Hepatitis - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES J AMES N. P ARKER , ...

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A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright Ó2003 by ICON Group International, Inc. Copyright Ó2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Hepatitis: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83704-X 1. Hepatitis-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on hepatitis. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications.

Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON HEPATITIS ................................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Hepatitis...................................................................................... 69 E-Journals: PubMed Central ..................................................................................................... 128 The National Library of Medicine: PubMed .............................................................................. 178 CHAPTER 2. NUTRITION AND HEPATITIS ..................................................................................... 269 Overview.................................................................................................................................... 269 Finding Nutrition Studies on Hepatitis .................................................................................... 269 Federal Resources on Nutrition ................................................................................................. 281 Additional Web Resources ......................................................................................................... 282 CHAPTER 3. ALTERNATIVE MEDICINE AND HEPATITIS ............................................................... 285 Overview.................................................................................................................................... 285 The Combined Health Information Database............................................................................. 285 National Center for Complementary and Alternative Medicine................................................ 286 Additional Web Resources ......................................................................................................... 303 General References ..................................................................................................................... 312 CHAPTER 4. DISSERTATIONS ON HEPATITIS ................................................................................. 313 Overview.................................................................................................................................... 313 Dissertations on Hepatitis ......................................................................................................... 313 Keeping Current ........................................................................................................................ 318 CHAPTER 5. CLINICAL TRIALS AND HEPATITIS ............................................................................ 319 Overview.................................................................................................................................... 319 Recent Trials on Hepatitis ......................................................................................................... 319 Keeping Current on Clinical Trials ........................................................................................... 345 CHAPTER 6. PATENTS ON HEPATITIS ............................................................................................ 347 Overview.................................................................................................................................... 347 Patents on Hepatitis................................................................................................................... 347 Patent Applications on Hepatitis............................................................................................... 380 Keeping Current ........................................................................................................................ 415 CHAPTER 7. BOOKS ON HEPATITIS ............................................................................................... 417 Overview.................................................................................................................................... 417 Book Summaries: Federal Agencies............................................................................................ 417 Book Summaries: Online Booksellers......................................................................................... 425 The National Library of Medicine Book Index ........................................................................... 440 Chapters on Hepatitis ................................................................................................................ 442 Directories.................................................................................................................................. 459 CHAPTER 8. MULTIMEDIA ON HEPATITIS..................................................................................... 463 Overview.................................................................................................................................... 463 Video Recordings ....................................................................................................................... 463 Audio Recordings....................................................................................................................... 473 Bibliography: Multimedia on Hepatitis ..................................................................................... 474 CHAPTER 9. PERIODICALS AND NEWS ON HEPATITIS .................................................................. 477 Overview.................................................................................................................................... 477 News Services and Press Releases.............................................................................................. 477 Newsletters on Hepatitis............................................................................................................ 481 Newsletter Articles .................................................................................................................... 482 Academic Periodicals covering Hepatitis................................................................................... 485 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 487 Overview.................................................................................................................................... 487

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U.S. Pharmacopeia..................................................................................................................... 487 Commercial Databases ............................................................................................................... 489 Researching Orphan Drugs ....................................................................................................... 489 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 493 Overview.................................................................................................................................... 493 NIH Guidelines.......................................................................................................................... 493 NIH Databases........................................................................................................................... 495 Other Commercial Databases..................................................................................................... 509 The Genome Project and Hepatitis............................................................................................. 509 APPENDIX B. PATIENT RESOURCES ............................................................................................... 515 Overview.................................................................................................................................... 515 Patient Guideline Sources.......................................................................................................... 515 Associations and Hepatitis......................................................................................................... 559 Finding Associations.................................................................................................................. 562 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 565 Overview.................................................................................................................................... 565 Preparation................................................................................................................................. 565 Finding a Local Medical Library................................................................................................ 565 Medical Libraries in the U.S. and Canada ................................................................................. 565 ONLINE GLOSSARIES ................................................................................................................ 571 Online Dictionary Directories ................................................................................................... 575 HEPATITIS DICTIONARY ......................................................................................................... 577 INDEX .............................................................................................................................................. 675

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with hepatitis is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about hepatitis, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to hepatitis, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on hepatitis. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to hepatitis, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on hepatitis. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON HEPATITIS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on hepatitis.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and hepatitis, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “hepatitis” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: ·

Cigarette Smoking and Hepatic Lesions in Patients with Chronic Hepatitis C Source: Hepatology. 34(1): 121-125. July 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: A possible hepatotoxicity (toxic to the liver) of cigarette smoke has been recently suggested by epidemiological and experimental studies. This article reports on a study undertaken to study the possible relationships between smoking and liver fibrosis (scarring) and activity in patients with chronic hepatitis C. The cross sectional study was performed in a group of 310 patients with chronic hepatitis C consecutively hospitalized for their first liver biopsy. The relationships between age, gender, alcohol consumption, route of contamination, tobacco consumption, and Knodell fibrosis and

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activity scores were examined in univariate, age adjusted, and multivariate analyses. Of the cohort, 176 patients (57 percent) were current smokers. Smokers were younger, more often of male gender, more often alcohol consumers, and more often had a history of intravenous drug use than never smokers. Smoking was related to increased fibrosis and activity scores in age adjusted and multivariate analyses. The authors conclude that smoking increases the severity of hepatic lesions in patients with chronic hepatitis C. 2 figures. 4 tables. 26 references. ·

Treatment of Chronic Hepatitis B in Australia and New Zealand Source: Journal of Gastroenterology and Hepatology. 15(Supplement): E79-E82. May 2000. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: Acute and chronic infections with hepatitis B virus (HBV) are a major public health problem in Australia and New Zealand. This article reviews the treatment of chronic hepatitis B in these countries. Although both countries have a low prevalence of the population with chronic HBV (less than 2 percent) infection, both have certain population groups with a high prevalence of the disease. In Australia, the highest rates are found among Aborigines and Torres Strait Islanders (approximately 10 to 25 percent) and immigrants from Southeast Asia and the Pacific Islands (5 to 15 percent). In New Zealand the cases of chronic HBV infection vary among groups: Chinese (10 percent), Maori (5.43 percent), Pacific Islanders (4.4 percent) and Europeans (0.43 percent). In New Zealand, a universal vaccination program was introduced, with hepatitis B vaccine being incorporated into the national childhood vaccination schedule in 1988. In both New Zealand and Australia, pregnant women are screened and HBV vaccine is administered to children of chronically infected mothers. Seronegative household members of families containing a member found to be acutely or chronically infected with HBV are vaccinated. Interferon therapy has been available since the late 1980s and is fully subsidized. Lamivudine has been prescribe preliver and postliver transplant as part of an international compassionate use program. Interferon, usually without steroid priming, has been the standard therapy, with trials showing a 41 percent response rate. 26 references.

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Therapy of Acute Hepatitis C Source: Hepatology. 36(5 Supplemental 1): S195-S200. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Acute hepatitis C has a high propensity to become chronic, which provides the rationale for treating patients with acute disease in an attempt to prevent chronic disease. This article reviews current strategies for therapy of acute hepatitis C. The authors note that almost all published studies on therapy of acute hepatitis C have been small in size, uncontrolled, and highly heterogeneous as to patient features, dose and duration of treatment, follow up evaluation, and criteria used to define efficacy and safety. The published studies on treatment of acute hepatitis C have used standard alfa or beta interferon monotherapy; none have evaluated combination therapy of interferon and ribavirin or peginterferon. Several meta-analyses of published studies have concluded that initiation of interferon monotherapy during the acute phase of hepatitis C virus (HCV) infection significantly reduces (by 30 to 40 percent) evolution to chronic

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hepatitis. The tolerability of interferon in acute hepatitis C has been excellent, even in symptomatic and icteric (with jaundice) patients; the side effects and adverse events being similar in type and frequency to those seen when treating chronic cases. Thus, currently available data support the treatment of patients with acute hepatitis C, but data are insufficient to draw firm conclusions about which patients to treat, when therapy should be started, or what regimen is optimal. Future studies of adequate size and design should focus on efficacy and tolerability of peginterferons and whether therapy should be started immediately after diagnosis or delayed for 2 to 4 months to avoid treatment of patients who spontaneously recover. 2 figures. 3 tables. 29 references. ·

Hepatitis C in Adults and Adolescents with Hemophilia: A Randomized, Controlled Trial of Interferon Alfa-2b and Ribavirin Source: Hepatology. 36(4 Part 1): 967-972. October 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Adolescents and adults with inherited disorders of coagulation have one of the highest prevalence rates of hepatitis C among known risk groups. Few data are available on the use of combination therapy with interferon and ribavirin in this population. This article reports on a study in which patients 13 years of age and older (n = 113) who were positive for hepatitis C virus (HCV) RNA and negative for HIV were randomized to receive interferon alfa-2b plus ribavirin or interferon alfa-2b alone for 48 weeks, with 24 weeks of posttreatment follow up. Patients started on interferon alone who remained positive for HCV RNA at week 12 crossed over to treatment with interferon plus ribavirin. Of the 113 patients, 37 were younger than 18 years. At the end of treatment, 18 of 56 patients (32 percent) treated with interferon plus ribavirin and 6 of 57 patients (11 percent) treated with interferon alone were negative for HCV RNA. Sustained virologic response in the combination arm was 29 percent (16 of 56) compared with 7 percent (4 of 57) for those started on interferon alone. Among adolescents younger than 18 years who were treated with combination therapy, 10 of 17 (59 percent) had sustained response compared with 6 of 39 (15 percent) of adult patients on the same regimen. The authors conclude that in this trial of therapy for HCV in patients with inherited bleeding disorders, sustained virologic response rate was significantly improved for patients treated with interferon and ribavirin compared with those started on interferon alone. Adolescents treated with combination therapy had a significantly higher sustained response than adults did on the same regimen. 1 figure. 5 tables. 25 references.

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Monitoring of Viral Levels During Therapy of Hepatitis C Source: Hepatology. 36(5 Supplemental 1): S145-S151. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Alpha interferon therapy of chronic hepatitis C is typically accompanied by a biphasic decrease in hepatitis C virus (HCV) RNA levels: an initial rapid decline during the first 24 to 48 hours, and a second more gradual decline during the following weeks. The rate of second-phase decline correlates with ultimate response to interferon treatment. Thus, assessment of early virological response (EVR) may predict outcome. This article describes data from two studies on the role of monitoring of viral levels during therapy for hepatitis C. Data from 2 large clinical trials of peginterferon and ribavirin were combined and analyzed to determine the optimal definition of an EVR

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which, if not achieved, was associated with a low likelihood of a sustained virological response (SVR). A fall in HCV RNA level to undetectable or by at least 2 log sub 10 units after 12 weeks was found to be the optimal definition of an EVR. Among 965 patients, 778 (80 percent) achieved an EVR by week 12, including all except 1 patient with genotypes 2 or 3. Among 187 patients without an EVR, only 3 (1.6 percent) had an SVR. These findings suggest that patients with genotype 1 who do not achieve an EVR should stop treatment after 12 weeks. Use of an early stopping rule reduces treatment costs by at least 16 percent and avoids the inconvenience and side effects of treatment in the 19 percent of patients without an EVR who have little chance of a lasting virological response. 3 tables. 27 references. ·

Relationship of Acute Transfusion-Associated Hepatitis to the Development of Cirrhosis in the Presence of Alcohol Abuse Source: Annals of Internal Medicine. 134(2): 120-124. January 16, 2001. Contact: Available from American College of Physicians. American Society of Internal Medicine. 190 North Independence Mall West, Philadelphia, PA 19106-1572. Website: www.acponline.org. Summary: Although concomitant (occurring at the same time) alcoholism is widely believed to enhance liver disease progression in persons with hepatitis C virus (HCV) infection, this relationship has not been well quantified. This article reports on a study undertaken to quantify the relationship of transfusion associated HCV infection and history of heavy alcohol abuse to the development of cirrhosis (liver scarring). The retrospective cohort study featured extensive followup of 1,030 patients in prospective investigations of transfusion associated viral hepatitis conducted in the United States between 1968 and 1980. Development of cirrhosis and history of heavy alcohol abuse were determined from review of interviews with patients or their proxies, medical records, death certificates, and autopsy and biopsy reports. The absolute risk for cirrhosis was 17 percent among patients with transfusion associated HCV; 3.2 percent among patients with transfusion associated nonA, nonB, nonC hepatitis; and 2.8 percent among controls. A history of heavy alcohol abuse was associated with a fourfold increased risk for cirrhosis. Hepatitis C virus infection plus a history of heavy alcohol abuse led to a substantial increase in risk for cirrhosis, compared with controls without such a history. The authors stress that this finding emphasizes the need to counsel such patients about their drinking habits. 2 tables. 19 references.

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Pilot Study of Interferon Alfa and Ribavirin Combination in Liver Transplant Recipients with Recurrent Hepatitis C Source: Hepatology. 36(5): 1253-1258. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Although interferon alfa (IFNa) and ribavirin are widely used in the treatment of hepatitis C, their role in the transplant recipient is unclear. This article reports on a pilot study conducted to determine the efficacy and safety of this therapy in transplant recipients with recurrent hepatitis C. Patients at least 6 months posttransplantation were treated with IFNa and ribavirin for 48 weeks followed by ribavirin monotherapy for 24 weeks. The primary end point was sustained virologic response, and secondary end points included biochemical, virologic, and histologic responses at the end of combination treatment. Thirty-eight patients initiated therapy, but 16 withdrew due to adverse effects, including 2 with myocardial infarction (heart

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attack). Median age was 50 years, 74 percent were men, and 91 percent had genotype 1 hepatitis C. On an intention-to-treat basis, 7 patients (18 percent) had a biochemical and 5 patients (13 percent) had a virological response at the end of combination treatment. Inflammatory activity did not change, but fibrosis worsened in virologic nonresponders. Ribavirin maintenance caused a further decrease in serum alanine aminotransferase levels, but hepatitis C virus (HCV) RNA levels increased. Only 2 of the 38 patients (5 percent) had a sustained virologic response. Several patients required treatment with erythropoietin for anemia. The authors conclude that IFN alfa and ribavirin are effective in a small proportion of liver allograft recipients with recurrent hepatitis C. 1 figure. 4 tables. 16 references. ·

Hepatitis: Still a Concern? Source: SCD. Special Care in Dentistry. 20(5): 209-212. 2000. Contact: Available from Federation of Special Care Organizations in Dentistry. 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2660. Summary: Although some forms of viral hepatitis were identified more than 50 years ago, hepatitis continues to have an impact on the practice of dentistry. This article reviews hepatitis, discussing possible transmission in the dental setting, management of the chronically ill, and legal issues related to treatment of infectious patients. Currently, seven viral forms of hepatitis are recognized. Those with predominantly enteral modes of transmission are of minor concern in the dental environment. Hepatitis B virus (HBV), the most infectious blood borne pathogen, has been largely controlled in this country by vaccination and the use of universal precautions. Hepatitis D virus (HDV) is an incomplete virus that has HBV infection as a prerequisite. Hepatitis C virus (HCV) is of great concern today for several reasons. A high percentage of HCV infections results in chronic disease. Most cases of HCV remain asymptomatic for an extended period of time, and many have no identifiable risk factors. Currently, no vaccination is available for HCV. Patients infected with HCV present a management challenge, because they may ultimately develop serious liver dysfunction. In fact, HCV infection is presently the most common reason for liver transplantation. By understanding the various forms of viral hepatitis and following recommended infection control and vaccination protocols, the dental health care worker can treat infected patients in a manner that is safe for both patients and dental health care workers. 1 table. 12 references.

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Chronic Hepatitis C: Update on Diagnosis and Treatment Source: Consultant. 40(9): 1590-1594, 1596. August 2000. Contact: Available from Cliggott Publishing Company. 55 Holly Hill Lane, Box 4010, Greenwich, CT 06831-0010. Summary: Although the number of new hepatitis C virus (HCV) infections dropped dramatically during the last decade, millions of Americans remain infected and at risk for fatal liver disease. Because chronic hepatitis is usually asymptomatic, many are unaware that they are infected. This article reviews the current guidelines for the diagnosis and treatment of HCV. The author recommends the testing of patients who have documented exposures to the disease, such as health care workers with needlestick injuries and children born to HCV positive women. Physicians should consider testing patients who have ever injected illicit drugs, received clotting factor concentrates before 1987 or blood transfusions or organ transplants before July 1992, undergone long term hemodialysis, had unexplained increases in alanine aminotransferases (ALT) or aspartate aminotransferase (AST) levels, or are HIV positive. Liver biopsy remains the

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best method of assessing disease severity. Combination therapy with interferon alpha and ribavirin produces sustained viral eradication in about 40 percent of patients; however, this therapy carries the risk of serious side effects and must be carefully monitored. The most common adverse reactions are flu like symptoms, which appear to decrease in severity as treatment continues. Anemia caused by ribavirin usually occurs in the first 2 months of therapy, but can also occur later. Viral genotype is the most important predictor of a successful response to combination therapy (infection with HCV genotype 1 is associated with lower response rates). Patients with chronic HCV infection and liver disease are at increased risk for fulminant (rapidly developing, often deadly) hepatitis A. One sidebar reviews the liver function test values that may show liver damage in patients with HIV; another reviews the role of liver biopsy in the decision to treat. 2 tables. 14 references. ·

Children with Hepatitis C Source: Hepatology. 36(5 Supplemental 1): S173-S178. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: An estimated 240,000 children in the United States have antibody to hepatitis C virus (HCV) and 68,000 to 100,000 are chronically infected with HCV. This article reviews the modes of acquisition, natural history, complications, and treatment of hepatitis C in children. Acute HCV infection is rarely recognized in children outside of special circumstances such as a known exposure from an HCV-infected mother or after blood transfusion. Most chronically infected children are asymptomatic and have normal or only mildly abnormal alanine aminotransferase levels. Although the natural history of HCV infection acquired in childhood seems benign in the majority of instances, the infection takes an aggressive course in a proportion of cases leading to cirrhosis (liver scarring) and end-stage liver disease during childhood; the factors responsible for a more aggressive course are unidentified. An optimal approach to management of hepatitis C in children would be prevention, particularly of perinatal transmission, which is now the major cause of new cases of hepatitis C in children. Obstetrical factors may be important determinants of transmission which, if confirmed, should lead to changes in the care of infected women. Therapy of HCV infection in children is also not well defined. There have been no large randomized, controlled trials of therapy in children with chronic hepatitis C. Small heterogeneous studies of interferon monotherapy have reported sustained virological response rates of 35 to 40 percent. There are few data regarding the use of combination therapy with interferon and ribavirin in children and no information on the use of peginterferon. 2 tables. 56 references.

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Infected and Unaware: Unmasking the Silent Epidemic of Hepatitis Source: Digestive Health and Nutrition. p. 22-25. March-April 2000. Contact: Available from American Gastroenterological Association. 7910 Woodmont Avenue, 7th Floor, Bethesda, MD 20814. (877) DHN-4YOU or (301) 654-2055, ext. 650. Email: [email protected]. Summary: An estimated 4 million people in the United States have chronic hepatitis and many of them are not even aware of their condition. This article familiarizes readers with the hidden epidemic of hepatitis, predominately hepatitis B and C viruses (HBC and HCV, respectively) that have become chronic infections. The author stresses that early diagnosis and treatment are curing some people with hepatitis and improving and

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prolonging the lives of others. Chronic hepatitis differs from the acute variety in the length of time an individual is affected. Treatment advances in the past few years for both HBV and HCV have produced drugs that reduce or eliminate evidence of the viruses from infected patients. Most hepatitis patients are referred by their primary care doctor. The patients most commonly are experiencing fatigue, but some may have more advanced symptoms such as jaundice and fluid retention. Only when the disease has done significant damage to the liver do the most serious symptoms appear, at which point a minority of patients seek medical help for the first time. Treatment options include lifestyle changes (particularly the avoidance of alcohol use), drug therapy, and liver transplantation. The author uses two case examples to show how chronic hepatitis can affect the lives of these patients. One sidebar reviews the physiology of the liver and its functions. The article concludes with a list of websites through which readers can obtain additional information. ·

Treatment of Chronic Hepatitis C in a State Correctional Facility Source: Annals of Internal Medicine. 138(3): 187-190. February 4, 2003. Summary: Approximately 1 in 4 of the nearly 2 million individuals in state and federal correctional facilities are infected with hepatitis C virus (HCV). Currently, there are few reports of treatment outcomes of this common infection in this setting. This article reports on a study undertaken to describe HCV therapy in the incarcerated population. The study included 93 inmates with chronic HCV infection who were treated with interferon alpha with ribavirin. Response rates are similar to previously published rates achieved in the community; 63 percent (50 of 79 patients) achieved viral clearance after 6 months of therapy, and 46 percent (26 of 57 patients) achieved sustained response 6 months after treatment. The authors conclude that the incarcerated population (which is disproportionately affected by addiction and psychiatric illness) can be effectively treated for HCV infection with interferon and ribavirin. 1 figure. 1 table. 13 references.

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Pathogenesis, Natural History, Treatment, and Prevention of Hepatitis C Source: Annals of Internal Medicine. 132(4): 296-305. February 15, 2000. Contact: Available from American College of Physicians. American Society of Internal Medicine. 190 North Independence Mall West, Philadelphia, PA 19106-1572. Website: www.acponline.org. Summary: Approximately 4 million persons in the United States and probably more than 100 million persons worldwide are infected with hepatitis C virus. This article reviews information presented at an NIH Clinical Staff Conference (held in March 1999) on the pathogenesis, natural history, treatment, and prevention of hepatitis C. The virus has the unique ability to cause persistent infection in susceptible hosts after parenteral or percutaneous transmission, and its underlying mechanisms are now well understood. The immunologic correlates of protection and viral clearance and the pathogenesis of liver injury are yet to be defined, but recent studies suggest the importance of cell mediated immune responses. Although 70 to 80 percent of infected persons become chronic carriers, most have relatively mild disease with slow progression. However, chronic and progressive hepatitis C carries significant morbidity and mortality and is a major cause of cirrhosis, end stage liver disease, and liver cancer. Development of an effective hepatitis C virus vaccine is not imminent, but recent advances in technology and basic knowledge of molecular virology and immunology have created some novel approaches to the fundamental problems encountered in vaccine development. Current therapy for hepatitis C, although effective in some patients, is problematic and still

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evolving. The authors conclude that advances in modern biology and immunology promise new therapies for this important disease. 5 figures. 3 tables. 77 references. ·

Hepatitis C, Cryoglobulinemia, and Cirrhosis: A Meta-Analysis Source: Hepatology. 36(4 Part 1): 978-985. October 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Approximately 40 percent of patients with chronic hepatitis C virus (HCV) infection develop detectable serum cryoglobulins or cryoprecipitates (CP), although most do not show clinical or physical signs of syndromic cryoglobulinemia. Although association of HCV with the extrahepatic (outside the liver) complications of cryoglobulinemia is widely recognized, the relationship of cryoglobulinemia with liver disease is unclear. This article reports on a study of the relationship between CP and cirrhosis that also determined whether the development of CP is a true covariate for progressive liver disease or a confounding variable that impacts cirrhosis because of patient age, duration of disease, or differences in gender. The authors performed a metaanalysis of 19 studies published between 1994 and 2001. The incidence of cirrhosis (liver scarring) was compared in patients with and without CP after adjustments for accepted risk factors for progressive liver disease, including age, gender, and estimated duration of disease (EDD). A total of 2,323 patients with chronic HCV were identified, with 1,022 (44 percent) having detectable CP. Cirrhosis was present in 40 percent of patients with CP but only 17 percent of patients with CP. After adjusted for age, gender, and EDD, the combined odds ratio for incidence of cirrhosis in patients CP positive versus CP negative was 4.87, indicating a highly significant association between cirrhosis and cryoglobulinemia. The authors conclude that cryoglobulins may be a useful prognostic indicator for increased risk of cirrhosis with chronic hepatitis C. 1 figure. 4 tables. 44 references.

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Autoimmune Hepatitis Source: Gastroenterology Nursing. 23(4): 157-159. July-August 2000. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (410) 528-8555. Summary: Autoimmune hepatitis (AIH) is a necro inflammatory disease that, untreated, carries a 3 year mortality (death) rate of approximately 50 percent. In this last of a series of three articles, the author reviews current knowledge about AIH. The mode of presentation of AIH is variable: insidious (hidden) onset with few if any symptoms, presenting with symptoms indistinguishable from that of any acute viral hepatitis, or onset with fulminant hepatitis. In AIH, hepatocytes become injured by various agents (such as a viral infection) and become antigenic, leading to a self perpetuating antigen/antibody response with subsequent chronic liver disease. AIH is the only type of hepatitis that is responsive to corticosteroids, but, complete withdrawal of steroids may not be possible. Occasionally, AIH develops after liver transplantation. In patients with AIH, there is a high frequency of other coexisting autoimmune disorders, particularly type 1 diabetes, vitiligo, glomerulonephritis, and autoimmune hemolytic anemia. Neither type of AIH is contagious, and with treatment, the adults and children affected can usually lead a near normal life. Medications metabolized in the liver and alcohol need to be avoided by these patients. 21 references.

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Cyclosporin A Is a Promising Alternative to Corticosteroids in Autoimmmune Hepatitis Source: Digestive Diseases and Sciences. 46(6): 1321-1327. June 2001. Contact: Available from Kluwer Academic Publishers. Customer Service Deparment, P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (781) 871-6600. Fax (781) 6819045. E-mail: [email protected]. Website: www.wkap.nl. Summary: Autoimmune hepatitis (AIH), a chronic T cell mediated liver injury, is treated with corticosteroids, with or without azathioprine. Corticosteroids are not universally effective and have serious side effects. Cyclosporin A was effective in refractory cases (those resistant to first lines of treatment). This article reports on a study undertaken to assess efficacy and safety of cyclosporin A (Neoral) in induction of remission in patients with AIH (n = 19). All 19 patients (nine as their first line of treatment) were treated with cyclosporin A in an open label trial and followed for 26 weeks. Liver biopsy was done and hepatitis activity index (HAI) determined at the beginning and end of treatment. Four patients did not complete the study for various reasons. Mean AST and ALT levels (measures of liver function) decreased from 948.77 to 100.6 and from 454.8 to 78.5, respectively. HAI decreased from 15.2 to 7.14. Serum creatinine did not change significantly. The authors conclude that low dose cyclosporin A appears to be safe and effective even in treatment nave autoimmune hepatitis patients. The authors call for randomized controlled trials to further test the use of this drug. 2 figures. 5 tables. 29 references.

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Management of Patients with Chronic Hepatitis B Source: Journal of Gastroenterology and Hepatology. 17(4): 406-408. April 2002. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: Better understanding of hepatitis B virus (HBV) replication and the natural history and immunopathogenesis of chronic hepatitis B, together with the introduction of effective agents with different mechanisms of action, are the basis for better therapeutic strategies against chronic hepatitis B. This article brings readers up to date on the current management of patients with chronic hepatitis B. Among currently available drugs, alpha interferon therapy gives a response rate of 30 to 40 percent, compared with 10 to 20 percent in matched controls, but patients with lower alanine aminotransferase (ALT), higher HBV-DNA, and immunosuppressed patients have a poorer response, and alpha interference can be dangerous in patients with cirrhosis (liver scarring). The author also reports on the use of thymosin alpha 1, lamivudine, and other drugs still in preliminary trials (adefovir dipivoxil, entecavir, emtricitabine, clevudine). The author concludes that further development of new drugs and new strategies, such as combination or sequential therapy, may help to better achieve the goals of treatment for chronic hepatitis B in the future. 1 table. 10 references.

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Cholestatic Presentation of Chronic Hepatitis C: A Clinical and Histological Study with a Review of the Literature Source: Digestive Diseases and Sciences. 46(10): 2066-2073. October 2001. Contact: Available from Kluwer Academic Publishers. Customer Service Deparment, P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (781) 871-6600. Fax (781) 6819045. E-mail: [email protected]. Website: www.wkap.nl. Distribution Centre, P.O. Box

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322, 3300 AH Dordrecht, The Netherlands. 31 78 6392392. Fax: 31 78 6546474. E-mail: [email protected]. Summary: Bile duct lesions are observed in the livers of chronic hepatitis C patients, but are inconstant and rarely associated with other features of chronic cholestasis (stoppage or suppression of the flow of bile) and progressive bile duct injury or loss. This article reports on a study in which the authors identified the clinical and biochemical characteristics of patients with chronic hepatitis C from their patient database (n = 620). The study was designed to determine if there is a correlation between histological evidence of bile duct injury and clinical or biochemical features observed in these patients. Of this patient population, 32 patients were identified as meeting the authors' criteria; 24 of these were excluded for the presence of other confounding factors and 2 for lack of liver biopsy. Of the remaining 6 patients, there were 2 men and 4 women, and their mean age was 47 years (plus or minus 9 years). Four of the six presented with pruritus, which was severe in 3 patients. Liver biopsy showed evidence of moderate to severe fibrosis in all but one patient. Evidence of bile duct injury was seen in all patients and tended to be more severe than in controls. Bile ductular proliferation and mild ductopenia were the most commonly observed findings. The authors conclude that a subset of patients with chronic hepatitis C may present with prominent cholestatic features. The majority of these patients present with pruritus and have histological evidence of bile duct injury, which may be progressive. 4 figures. 4 tables. 24 references. ·

Prophylactic Lamivudine Prevents Hepatitis B Reactivation in Chemotherapy Patients Source: Alimentary Pharmacology and Therapeutics. 16(11): 1939-1944. November 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: Chronic hepatitis B virus (HBV) carriers receiving chemotherapy develop a high hepatitis B virus reactivation rate (38 to 53 percent) with a high mortality (37 to 60 percent). Few studies have characterized the efficacy of lamivudine in the treatment of chemotherapy-induced HBV reactivation. This article reports on a study undertaken to determine whether lamivudine prophylaxis reduces chemotherapy-induced HBV reactivation and mortality. The medical records of all hepatitis B surface antigenpositive patients with malignancy treated with chemotherapy since 1995 at the National University Hospital of Singapore were identified and divided into those who received lamivudine prophylaxis before chemotherapy (P, n = 16) and those who did not (NP, n = 19). The baseline characteristics of the two groups were similar. Seven of the 19 patients in the NP group and none of the 16 patients in the P group developed HBV reactivation (36.8 percent versus 0 percent). Six of the seven patients in the NP group who developed reactivation received lamivudine at that time, but five died (mortality, 71.4 percent), whilst no patient in the P group died from reactivation. The authors conclude that prophylactic lamivudine appears to prevent hepatitis B virus reactivation and its associated mortality in patients treated with chemotherapy. 3 tables. 11 references.

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Adding to the Hepatitis B Virus Treatment Arsenal: Glucosidase Inhibitor Derivatives (editorial) Source: Hepatology. 33(6): 1544-1546. June 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000.

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Summary: Chronic hepatitis B virus (HBV) infection is a major cause of cirrhosis (scarring) and hepatocellular carcinoma (liver cancer) in the United States and worldwide. Eradication of the infection and prevention of complications of chronic infection are the dual goals of treatment. This editorial comments on an accompanying article which reports on the use of alfa glucosidase inhibitor derivatives in the drug therapy for HBV infections. The agents under consideration (N nonyl DNJ and N nonyl DGJ) appear to have a mechanism of action that is unique and potentially complementary to that of nucleoside analogues. As new agents for treatment of HBV infection become available for clinical use, combination treatment of chronic HBV infection can be anticipated. The editorial stresses that designing the optimal combination therapy for HBV will need to take into account drug potency, mechanism of drug uptake and activation, sites of drug action, effect on cccDNA, and specific viral mutations arising with prolonged therapy. The author concludes that it remains to be seen whether these imino sugars (N nonyl DNJ and N nonyl DGJ) will join the growing list of anti HBV drugs. However, if the present results can be reproduced in animal studies and clinical trials (with humans), this novel class of agents may be a welcome addition to the arsenal of anti HBV drugs. 1 figure. 1 table. 13 references. ·

Treatment of Hepatitis C Infection in Injection Drug Users Source: Hepatology. 34(1): 188-193. July 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Chronic hepatitis C is the most common infectious disease among injection drug users (IDUs). Because of the allegedly poor compliance of IDUs with treatment requirements and conditions, hepatologists (liver specialists) recommend treatment only if former IDUs have spent 6 to 12 months drug free. This article reports on a prospective study undertaken to investigate whether opiate dependent IDUs with chronic hepatitis C virus (HCV) infection can be treated successfully with interferon. Eligibility for the study meant IDUs had to be HCV RNA positive by polymerase chain reaction (PCR). Subsequently, 50 inpatients were enrolled during detoxification treatment. HCV treatment was started with interferon alfa 2a (through 1998) or a combined regimen consisting of interferon alfa 2a and ribavirin (begun in 1998). All patients were treated and supervised by specialized physicians in both hepatology and addiction medicine. The end point for this study was defined as a loss of detectable serum HCV RNA at week 24 after treatment. The rate of sustained virologic response was 36 percent. Sustained response rates were not significantly different for patients who relapsed and returned to treatment (53 percent), relapsed and did not return to treatment (24 percent), or who did not relapse (40 percent). During the 24 weeks after treatment, the authors were unable to detect any reinfection, even among patients who injected heroin during this period. The authors note that this surprising result should be examined in further studies. The authors conclude that HCV infected drug addicts with chronic HCV infection can be treated successfully with interferon alfa 2a and ribavirin if they are closely supervised by physicians specialized in both hepatology and addiction medicine (which improves the patients' compliance considerably). Effective treatment of HCV in IDUs could greatly reduce the general population's risk of becoming infected. 3 tables. 40 references.

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Chronic Hepatitis C: Implications for the Primary Care Clinician Source: JAAPA. Journal of the American Academy of Physician Assistants. 14(2): 41-44, 47-48, 63. February 2001.

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Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Fax (201) 573-4956. Summary: Chronic hepatitis C rarely causes acute illness, and may progress slowly without overt symptoms until the liver has been irreparably damaged. This article reviews the primary care considerations for managing patients with chronic hepatitis C. The authors cover the mechanism, natural history, and progression of infection with the hepatitis C virus (HCV); encourage readers to learn when to have a high index of suspicion for HCV infection; and summarize the clinical tools available to confirm diagnosis of HCV. The authors note that HCV is most often detected when elevated liver enzyme levels are found during a routine workup, health insurance screen, or preoperative evaluation. Risk factors for HCV infection include body piercing, child born to mother who has hepatitis C, hemodialysis, incarceration, injury with contaminated needles, intranasal cocaine use, IV drug use (even once), multiple sexual partners, sexual partners of hepatitis C patients, tattoos, and transfusion or infusion of blood products before 1992. Once infection has been diagnosed, liver biopsy is performed to assess the severity of disease. One of the most important roles of the primary care provider is to offer adequate patient education and support. The most important lifestyle modification for the patient is abstinence from alcohol. Alcohol kills liver cells and accelerates the progression to fibrosis and cirrhosis, and no amount of alcohol has been found safe for a patient who has chronic hepatitis C. Major lifestyle changes are not recommended, but patients should be counseled not to share razors, toothbrushes, or other items that may be contaminated with blood. Treatment (with interferon injections) is expensive, associated with multiple side effects, and varies widely in its effectiveness in eradicating the virus. The authors review five variables that can be considered to predict an individual's response to therapy and to guide the aggressiveness of that therapy. Appended to the article is a posttest with which readers can earn continuing education credit. 2 tables. ·

Association Between Hepatitis C Virus Infection and Type 2 Diabetes Mellitus: What Is the Connection? (editorial) Source: Annals of Internal Medicine. 133(8): 650-652. October 17, 2000. Contact: Available from American College of Physicians. American Society of Internal Medicine. 190 North Independence Mall West, Philadelphia, PA 19106-1572. Website: www.acponline.org. Summary: Chronic hepatitis C virus (HCV) infection and type 2 diabetes mellitus cause devastating long term complications in a significant minority of patients affected with these diseases. This editorial explores the potential link between these two disorders, noting that chronic HCV infection may cause cirrhosis (liver scarring), which, through insulin resistance, predisposes patients to diabetes mellitus. The author reviews a dozen studies that look at this connection, then introduces a research study published in the same journal issue as the editorial, which provides strong evidence for the association between HCV infection and type 2 diabetes mellitus. This latter study demonstrates that persons with HCV infection were more than three times more likely to have type 2 diabetes mellitus than those without HCV infection. Alcohol abuse did not seem to link the two disorders in this study. The editorial author addresses some of the potential limitations to this study, and suggests additional research that may further clarify the connection between the two diseases. The editorial concludes that the association between chronic HCV infection and type 2 diabetes mellitus seems genuine. However, numerous questions must still be addressed, most notably those regarding the nature of the link between the disorders. 19 references.

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Hepatocellular Carcinoma and Hepatitis C in the United States Source: Hepatology. 36(5 Supplemental 1): S74-S83. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Chronic infection with hepatitis C virus (HCV) is a major risk factor for the development of hepatocellular carcinoma (HCC). This article explores the interrelationship between HCC and hepatitis C. In general, HCC develops only after two or more decades of HCV infection and the increased risk is restricted largely to patients with cirrhosis (scarring) or advanced fibrosis. Factors that predispose to HCC among HCV-infected persons include male sex, older age, hepatitis B virus (HBV) coinfection, heavy alcohol intake, and possibly diabetes and a transfusion-related source of HCV infection. Viral factors play a minor role. The likelihood of development of HCC among HCV-infected persons is difficult to determine because of the lack of adequate long term cohort studies; the best estimate is 1 to 3 percent after 30 years. Once cirrhosis is established, however, HCC develops at an annual rate of 1 to 4 percent. Successful antiviral therapy of patients with HCV-related cirrhosis may reduce their future risk for HCC. The incidence of and mortality caused by all HCC has doubled in the United States over the past 25 years, an increase that has affected all ethnic groups, both sexes, and younger age groups. Given the current prevalence of HCV infection among persons 30 to 50 years of age, the incidence and mortality rates of HCC are likely to double in the United States over the next 10 to 20 years. Future research should focus on improving understanding of the incidence and risk factors for HCC, causes of HCV-related carcinogenesis (development of cancer), means of early detection, and better treatment for HCC. 5 figures. 3 tables. 88 references.

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Molecular Diagnosis of Viral Hepatitis Source: Gastroenterology. 122(6): 1554-1568. 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Website: www.gastrojournal.org. Summary: Chronic viral hepatitis is associated with significant morbidity and mortality and is considered a major public health problem in most areas of the world, raising the issues of the diagnosis, treatment, and prevention of these viral infections. Molecular biology-based assays are invaluable tools for the management of chronic viral hepatitis. These assays can be used to test blood donations, diagnose active infection, help to establish the prognosis, guide treatment decisions, and assess the virological response to therapy. This article reviews current molecular biology-based techniques and assays, and their practical use in the management of hepatitis B and C virus infection. The author concludes that further work is required to fully standardize assays and quantification units, improve automation, and better define clinically relevant thresholds that can be used to establish universal recommendations for patient care. The development of increasingly sensitive and accurate assays for detection and quantification will improve the assessment of the response to antiviral therapy and permit earlier detection of viral resistance. 4 figures. 3 tables. 103 references.

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Chronic Hepatitis C and G: Efficacy of Consensus Interferon in the Treatment of Chronic Hepatitis C Source: Journal of Gastroenterology and Hepatology. 15(12): 1418-1423. December 2000.

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Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: Consensus interferon (CIFN) is a newly developed type I interferon. This article reports on a study undertaken to investigate the safety and efficacy of CIFN in the treatment of patients with chronic hepatitis C and to determine the predictors for sustained response to the drug. Patients were randomized to receive 3 micrograms or 9 micrograms CIFN three times a week for 24 weeks, followed by 24 weeks of observation. There were no serious adverse effects related to CIFN therapy. Overall, 44 percent of patients receiving 3 micrograms and 48 percent of patients receiving 9 micrograms had normalization of serum transaminase levels and disappearance of HCV viremia (virus levels in the blood) at the end of treatment. At 24 weeks after stopping treatment, 16 percent of patients receiving 9 micrograms and 12 percent of patients receiving 3 micrograms had sustained responses. The histologic responses in patients receiving 9 micrograms and 3 micrograms were 60 percent and 36 percent, respectively. The necroinflammatory score was significantly reduced from baseline to week 48 in both groups. The authors also identified other predictors for sustained response to CIFN treatment (including bodyweight less than 60 kilograms and pretreatment serum HCV RNA levels less than 0.5). The authors conclude that 9 micrograms CIFN is safe and effective in the treatment of patients with chronic hepatitis C. 3 tables. 25 references. ·

Current and Novel Immunosuppressive Therapy for Autoimmune Hepatitis Source: Hepatology. 35(1): 7-13. January 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Corticosteroids alone or in conjunction with azathioprine represent the treatment of choice in patients with autoimmune hepatitis (AIH) and results in remission induction in over 80 percent of patients. This article reports on immunosuppressive therapy for AIH. Sustained response to this therapy may result in substantial regression of fibrosis even in advanced cases. The result of rapid withdrawal of immunosuppression (stopping the drugs) is disease relapse in many patients. Consequently, the use of 2 milligrams per kilogram per day of azathioprine as a sole agent to maintain remission has been widely accepted in clinical practice. Persistent severe laboratory abnormalities or histologic abnormalities such as bridging necrosis (tissue death) or multilobular necrosis are absolute indications for treatment based on controlled clinical trials, but debate exists as to whether all patients with AIH need treatment. Examination of liver tissue (by biopsy) remains the best method of evaluating both treatment response and need for treatment in patients who have little biochemical activity. Alternative strategies in patients who have failed to achieve remission on 'standard therapy' of corticosteroids with or without azathioprine or patients with drug toxicity include the use of cyclosporine, tacrolimus, or mycophenolate mofetil. Liver transplantation is the treatment of choice in managing decompensated disease. 1 figure. 2 tables. 50 references.

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Future Therapy of Hepatitis C Source: Hepatology. 36(5 Supplemental 1): S245-S252. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000.

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Summary: Currently available therapies for the treatment of chronic hepatitis C are effective in half of patients, but are expensive, often poorly tolerated, and unsuitable for certain patient populations. This article considers future strategies for therapy of hepatitis C. The authors note that the ideal therapy would be highly effective, orally bioavailable, have minimal side effects, be cost effective, and suitable for the majority of patients with hepatitis C. Recent advances in understanding the replication cycle of hepatitis C virus (HCV) and structural, crystallographic definitions of components of the viral polyprotein have improved the prospects for development of novel therapies. The lack of a small animal model of HCV infection continues to hamper progress in the preclinical evaluation of new antivirals and vaccines. Strategies to enhance response to current therapies include the development of novel interferons and delivery systems, nucleoside analogues that have reduced hemolysis compared with ribavirin, inosine 5 monophosphate dehydrogenase inhibitors, and other immuno-modulators that are being evaluated as adjunctive therapy to interferon-based regimens. Compounds in preclinical or early phase human trials include small molecules that inhibit virus specific enzymes or those that prevent translation initiation. Antifibrotic agents are also being developed in an attempt to prevent disease progression in patients in whom HCV RNA cannot be eradicated. The authors conclude that most of these newer therapies are unlikely to be available for routine clinical use in the next 3 to 5 years. 1 figure. 1 table. 24 references. ·

Hepatitis: An Update Source: FDA Consumer. 35(4): 25-29. July-August 2001. Contact: Available from Food and Drug Administration (HFI-40). 5600 Fishers Lane, Rockville, MD 20857. Summary: Despite many years of chronic infection, the majority of people infected with hepatitis C virus (HCV) do not develop severe liver disease, and some may not need treatment. This article offers an update on hepatitis C and its treatments. Most studies report that cirrhosis (liver scarring) develops in 10 to 20 percent of people with chronic HCV infection over a period of 20 to 30 years. Liver cancer develops in 1 to 5 percent of patients with chronic HCV infection. Those patients who do need treatment have more and better therapies available today then were available just a few years ago. For some people with mild hepatitis C, the only treatment needed may be eating a nutritious diet, avoiding alcohol, exercising regularly, and visiting a doctor regularly to monitor the disease. For others, the FDA (Food and Drug Administration) has approved two different treatment regimens: monotherapy (using a single drug, interferon) and combination therapy (using two drugs, interferon and ribavirin). The author reviews the results expected from these treatments, the problem of nonresponders, treatment side effects, patient selection (for treatment), diagnosis of HCV, risk factors for hepatitis C, and vaccination for hepatitis A and B. One sidebar describes how individuals infected with HCV can participate in a new research study; another lists resource organizations through which readers can obtain additional information (web sites are also provided). 3 figures.

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Long-Term Impact of Renal transplantation on Liver Fibrosis During Hepatitis C Virus Infection Source: Gastroenterology. 123(5): 1494-1499. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Website: www.gastrojournal.org.

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Summary: During hepatitis C virus (HCV) infection, liver fibrosis progression after renal (kidney) transplantation remains controversial. This article reports on a cohort study that compared liver histopathologic features during HCV infection between kidney transplant recipients and matched groups of hemodialysis patients or controls without renal disease and untreated for HCV> Each kidney transplant recipients (group 1, n = 30) was matched at first liver biopsy (LB) using the main factors known to influence progression of fibrosis, with one HCV hemodialyzed patient (group 2, n = 30) and one HCV-infected patients (nonhemodialyzed, nontransplanted; group 3, n = 30). The rate of fibrosis progression per year between the first and second liver biopsies was significantly lower in group 1 than group 3. The authors conclude that liver fibrosis progression is low in most HCV-infected kidney transplant recipients with moderate liver disease at baseline. 3 tables. 21 references. ·

Alcohol Use and Hepatitis C Source: Hepatology. 36(5 Supplemental 1): S220-S225. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Excess alcohol consumption can worsen the course and outcome of chronic hepatitis C. This article considers the interplay between alcohol use and hepatitis C. The authors stress that it is important to distinguish between alcohol abuse, which must be treated on its own merits, and the effect of alcohol use on the progression, severity, and treatment of hepatitis C. Most studies on the effects of alcohol on hepatitis C have focused on patients with high levels of daily alcohol intake. Indeed, the adverse effects of light and moderate amounts of alcohol intake on hepatitis C virus (HCV) infection have not been clearly shown, and only limited studies have been performed. Sex differences exist in the effect of alcohol on fibrosis as well as on the severity of hepatitis C. Alcohol use has been reported to be associated with lower responses to therapy and, in some studies, higher HCV RNA levels and increased HCV quasi-species. The authors conclude that many critical questions remain regarding the interactions between alcohol and hepatitis C. Currently, the evidence from the literature shows that heavy alcohol intake worsens the outcome of HCV infection. The literature is inadequate to provide definitive recommendations regarding the effect of light to moderate alcohol use in patients with hepatitis C. 1 table. 27 references.

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Hepatitis C Among Drug Users: Deja Vu All Over Again? Source: American Journal of Public Health. 91(1): 21-22. January 2001. Contact: American Public Health Association. 800 I Street, NW, Washington, DC 200013710. (202) 777-2742. Fax (202) 777-2534. E-mail: [email protected]. Website: www.ajph.org. Summary: Following HIV (and AIDS), hepatitis C virus (HCV) is the next emerging infectious disease epidemic to strike persons who inject psychoactive drugs. Like HIV, HCV is transmitted through the sharing of needles and syringes, and the majority of new HCV infections in the United States are associated with injection drug use. In this commentary, the authors stress that the current HCV epidemic among injection drug users challenges communities to learn from the mistakes that have been made (and are still being made) during the HIV epidemic. During the HIV epidemic, for example, stigmatization of drug users has blocked implementation of programs that could have greatly reduced HIV transmission. Approximately 80 percent of persons infected with HCV become chronic carriers, and HCV is readily transmitted through sharing of

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injection equipment. HCV is quite common in populations of injection drug users, with seroprevalence rates typically from 60 to 80 percent. At present there is no vaccine for HCV, and the rapid mutation rate of the virus will make it difficult to develop one. The extent to which behavior changes (or risk reduction) programs can reduce HCV transmission among injection drug users is an important question for continuing research. The authors report on current research work on epidemiology of HCV, ethical considerations, current treatments, and the increase in the population reaching end stage liver disease. The authors conclude that the HCV epidemic provides a rare second chance for courageous public health action, to implement strategies that are timely, effective, and just, and that transcend the politics of stigmatization. This article serves as an introduction to a number of related articles in the same journal issue. 9 references. ·

Is Severe Liver Disease a Common Outcome for People with Chronic Hepatitis C? Source: Journal of Gastroenterology and Hepatology. 17(4): 423-430. April 2002. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: For people with chronic hepatitis C, an assessment of their risk of progression to advanced liver disease is a major priority. Early studies of the natural history of chronic hepatitis C suggested that development of cirrhosis (liver scarring) was a relatively common outcome, even in the first 20 years of infection. More recent studies indicate that liver disease progression is generally slow, and that a minority of people with chronic hepatitis C will develop advanced liver disease. This article reports on a Markov model of liver disease progression that the authors developed based on an extensive review of studies reporting on chronic hepatitis C natural history. This model estimates that the risk of progression to cirrhosis in 7 percent and 20 percent after 20 and 40 years of infection, respectively. Corresponding estimates for hepatitis C related mortality (death) are 1 percent and 4 percent. However, liver disease progression is highly variable, and certain subgroups of people with chronic hepatitis C are at increased risk of advanced liver disease. Those groups include people with a heavy alcohol intake, those who have coinfection with HIV or HBV, and those who have already progressed to moderate to severe hepatic fibrosis. 6 figures. 2 tables. 61 references.

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Hepatitis B and C: Looking Beyond Traditional Therapy Source: Digestive Health and Nutrition. p. 23-25. November-December 2000. Contact: Available from American Gastroenterological Association. 7910 Woodmont Avenue, 7th Floor, Bethesda, MD 20814. (877) DHN-4YOU or (301) 654-2055, ext. 650. Email: [email protected]. Summary: For years, both hepatitis B and C have been treated mainly with one drug, interferon, that can cause a host of side effects and helps less than 50 percent of the people who take it. This article describes research into new drugs that indicates that many people with hepatitis C who do not respond to interferon alone may respond when it is combined with other drugs, and that some drugs may even take the place of interferon entirely for the treatment of hepatitis B. The author briefly reviews the different types of hepatitis, then notes the symptoms of hepatitis B and C, how they are transmitted, and prevention strategies. The author then focuses on interferon therapy. Interferon is a natural substance produced by the body to protect itself against infection, but, when infected with hepatitis, the body may not make enough interferon to fight the

20 Hepatitis

disease effectively. Injections of artificial interferon help stimulate the immune system to fight hepatitis. The author then describes the use of Rebetron (the trade name for a drug that combines interferon and ribavirin). Alone, ribavirin does not have much antiviral action, however, when taken with interferon, ribavirin boosts sustained response rates in hepatitis C patients to 40 percent. There are considerable side effects, so each patient must be cared for on an individualized plan. The article also describes the use of a modified form of interferon (pegylated interferon) which is expected to be approved by the Food and Drug Administration (FDA) in 2001 for treatment of hepatitis C (and perhaps later for hepatitis B). Another drug discussed is lamivudine, used to stop hepatitis B virus from reproducing. A final section discusses the role of some of these drugs in helping patients wait longer for a liver transplant. One sidebar reviews the impact of hepatitis on the liver and why it is so important to treat the disease when possible. ·

Noninvasive Monitoring of Patients with Chronic Hepatitis C Source: Hepatology. 36(5 Supplemental 1): S57-S64. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Hepatic (liver) fibrosis is the main determinant of clinical outcomes of chronic hepatitis C. Liver biopsy is frequently considered the gold standard for assessing hepatic fibrosis. However, liver biopsy is associated with sampling error, interobserver variability, and potential complications. This article considers the options for noninvasive monitoring of and assessing disease severity in patients with chronic hepatitis C. Clinical examination is unreliable in differentiating different stages of compensated liver disease. Among the routine laboratory tests, decreased platelet count, increase in the ratio of aspartate to alanine aminotransferase (AST ALT), and prolonged prothrombin time are the earliest indicators of cirrhosis and portal hypertension. Individual serum fibrosis markers (blood tests) have limited accuracy in predicting hepatic fibrosis. Indices composed of a panel of markers correlate better with histological fibrosis, but their reliability requires further validation. Currently, noninvasive monitoring of patients with chronic hepatitis C relies on clinical evaluation, routine laboratory tests, and ultrasound and endoscopic surveillance in patients with cirrhosis. Initial evaluation should focus on assessment of activity and stage of liver disease for prognosis and decisions regarding treatment, and to rule out coinfections and other causes of liver disease. Subsequent follow up should focus on detection of liver disease progression and the need for treatment. The frequency of monitoring and the tests used will depend on the patient's age, stage of liver disease, and comorbid conditions. The authors conclude that there is an urgent need to develop and validate noninvasive tests that can accurately reflect the full spectrum of hepatic inflammation and fibrosis in chronic hepatitis C. 5 tables. 37 references.

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Hepatic Steatosis in Chronic Hepatitis C Virus Infection: Prevalence and Clinical Correlation Source: Journal of Gastroenterology and Hepatology. 16(2): 190-195. February 2001. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: Hepatic steatosis (fatty liver) is a histological characteristic in patients with chronic hepatitis C virus (HCV) infection. This article reports on a study undertaken to

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evaluate the prevalence of hepatic steatosis in Chinese patients with chronic hepatitis C, and to look for possible correlation with various histopathological changes and to look for possible correlation with various clinical and pathologic variables. The study included 106 patients; patients with alcoholism or diabetes were excluded. Of the 106 patients with chronic hepatitis C, 55 patients (52 percent) had hepatic steatosis. Patients with hepatic steatosis had higher body mass index, and a higher incidence of obesity compared with patients without hepatic steatosis. No significant differences in serum HCF RNA titer and HCF genotype or the response to interferon therapy were noted between the two groups. Histological analysis showed patients with hepatic steatosis had a significantly higher mean fibrotic (scarring) score than patients without hepatic steatosis. There were no significant differences in the severity of necroinflammation, the presence of lymphoid aggregation or follicle or bile duct damage between the two groups. Multivariate logistic regression analysis showed that independent predictors associated with hepatic steatosis were obesity or a histology fibrotic score of greater than 2.2. 4 tables. 34 references. ·

Cost-Effectiveness of Hepatitis A Vaccination in Children, Adolescents, and Adults Source: Hepatology. 37(1): 44-51. January 2003. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Hepatitis A is a major public health problem in the United States and in other developed countries, largely because decreased natural immunity allows for increased susceptibility. This article reports on a review study undertaken to evaluate the costeffectiveness of routine vaccination of children, adolescents, and certain high-risk adults against hepatitis A. The author identified economic analyses of hepatitis A vaccination and also contacted experts in this field. Articles conforming to accepted standards of quality for health-economic studies were used to compile data on the vaccination of children, and the results are synthesized here. The authors notes that review of economic analyses of vaccine use in several developed countries shows costeffectiveness comparable with that of other vaccines in children and within accepted boundaries for adolescents and high risk adults. 6 tables. 69 references.

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Towards Control of Hepatitis B in the Asia-Pacific Region: Natural History of Hepatitis B Virus Infection in Children Source: Journal of Gastroenterology and Hepatology. 15(Supplement): E16-E19. May 2000. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: Hepatitis B virus (HBV) infection during childhood can cause acute, fulminant, or chronic hepatitis, liver cirrhosis (scarring), and liver cancer. This article reviews the natural history of hepatitis B infection in children, with a consideration of strategies towards control of hepatitis B in the Asia Pacific region. Approximately 90 percent of the infants of hepatitis B e antigen (HBeAg) seropositive mothers become hepatitis B surface antigen (HBsAg) carriers. Children chronically infected are mostly asymptomatic. Although liver damage is usually mild during childhood, severe liver disease, including cirrhosis and hepatocellular carcinoma, may develop insidiously for 2 to 7 years. Spontaneous HBeAg seroconversion occurs gradually as the age of the child increases. Viral replication is reduced during this process, which is usually preceded by

22 Hepatitis

an elevation of aminotransferases. In a long term followup study, the annual HBeAg seroconversion rate was 4 to 5 percent in children older than 3 years of age and less than 2 percent in children under 3 years. The annual seroconversion rate was very low (0.56 percent). Age at infection, maternal HBeAg and HBeAg status, host immune status, and possibly the HBV strain are the main factors determining the course of HBV infection in children. 22 references. ·

Treatment of Chronic Hepatitis B: Case Selection and Duration of Therapy Source: Journal of Gastroenterology and Hepatology. 17(4): 409-414. April 2002. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: Hepatitis B virus (HBV) infection is a major health burden in the Asia-Pacific region. This article addresses the treatment of chronic hepatitis B, focusing on case selection and duration of therapy. The author stresses that proper assessment and judicial introduction of therapy can suppress replication of HBV and resolve liver inflammation, thereby preventing the silent progression of chronic liver disease to end stage cirrhosis (liver scarring). The author discusses interferon (IFN) monotherapy, injection based therapies, lamivudine, administration and dosage, patient response, drug resistant mutations, the end point of treatment, combination therapy, herbal medicines, and patient indications for different drug therapies. The author concludes that preliminary data from IFN and lamivudine combination therapy show some promise, but there are conflicting results.

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Does the 'C' in Hepatitis C Stand for Complex? Source: Gastroenterology Nursing. 24(3): 120-126. May-June 2001. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (410) 528-8555. Summary: Hepatitis C is a disease usually found in asymptomatic adults. After diagnosis, these patients are instructed to start a therapy that encompasses oral medications and injections three times a week, involving a significant financial cost. Patients undergoing this therapy frequently experience unpleasant side effects. Unfortunately, there is no assurance the virus will respond to therapy. The sustained response rate is about 50 percent for this combination therapy. This article provides an overview of what is currently know about hepatitis C, treatment options, and the frequent side effects associated with therapy, focusing on the reasons why a person who has no outward sign of illness would want to go through this treatment. The author reviews the most common side effects of hepatitis C therapy and their treatments, including flu like symptoms, fatigue, depression, and hematologic (blood) disorders. The author concludes that there is no clear indications for the treatment of hepatitis C. Prevention is the key component to fighting hepatitis C. Once the virus is acquired, there are two choices: the patient may avoid therapy and wait to see if their liver disease progresses or they can start the recommended combination therapy. However, therapy is usually more successful with smaller viral loads. With therapy, there is a significant chance the patient will suffer side effects from the medications, though these side effects probably will not extend more than 1 year. The author stresses the importance of close teamwork between the patient, their primary care provider, and support services, including gastroenterology nurses (for whom this article serves as a continuing education source). 3 tables. 17 references.

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Chronic Hepatitis C: Implications for Health-Related Quality of Life Source: Gastroenterology Nursing. 24(4): 169-175. 2001. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (410) 528-8555. Summary: Hepatitis C viral (HCV) infection with its sequelae is a significant health care problem. Hepatitis C infects nearly 4 million Americans with almost half of these people unaware of their infection. Many of those individuals infected with hepatitis C develop chronic hepatitis C and in 15 percent of these patients, the infection will progress to cirrhosis (liver scarring) within 20 years. Several cross sectional and longitudinal studies have demonstrated the negative impact of chronic hepatitis C on health related quality of life (HRQOL). This review article describes what is currently known about the impact of chronic hepatitis C on health related quality of life during pharmacologic treatment and after liver transplantation. It is important to note that few studies have prospectively followed patients over time with respect to quality of life or examined other factors including symptoms, markers of disease progression, or host immune function. Studies suggest that patients with chronic hepatitis C, even without major disease related complications, perceive themselves to be unwell and have significant changes in their physical and mental well being. Such results have important implications for nursing care and management, including in such areas as alcohol consumption, fatigue reduction, and depression and psychological distress. The authors conclude that intervention studies focused on self care management with an emphasis on symptom reduction are warranted. 1 figure. 43 references.

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Hepatitis C: An Update on the Silent Epidemic Source: Journal of Clinical Gastroenterology. 30(2): 125-143. March 2000. Contact: Available from Lippincott Williams and Wilkins, Inc. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Summary: Hepatitis C virus (HCV) currently infects an estimated 2 to 3 million people in the United States and 175 million people globally. Over 80 percent of infected patients go on to develop chronic disease. This article offers an update on this 'silent epidemic,' noting that most patients remain asymptomatic despite insidious progression of the disease. The sequelae of HCV induced chronic liver disease accounts for 8,000 to 10,000 deaths annually in the United States and is currently the leading indication for liver transplantation. The cost of this epidemic to the United States was estimated in 1991 at $600 million in terms of medical expenses (excluding costs related to liver transplantation) and work lost. Over the last decade, since the viral genome of HCV was first sequenced in 1989, there has been a great increase in understanding of this infection. The authors discuss epidemiology of infection, viral characteristics, risk factors for disease, diagnostic testing, clinical manifestations, and therapeutic options. With modification of risk factors, aided by availability of accurate diagnostic tests and educational campaigns to target groups at risk, a decline in the incidence of acute HCV has already occurred. Therapeutic results are improving with combination interferon alpha and ribavirin, with sustained virologic response rates of 30 to 40 percent. The authors conclude that several disease modifiers may affect the natural history of HCV infection, leading to an accelerated clinical course and poorer therapeutic outcomes. Most important of these factors is continued alcohol use, which, even with modest consumption, may profoundly affect progression of liver disease in HCV infected patients. 5 figures. 4 tables. 176 references.

24 Hepatitis

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Southeast Asian Patients with Chronic Hepatitis C: The Impact of Novel Genotypes and Race on Treatment Outcome Source: Hepatology. 36(5): 1259-1265. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Hepatitis C virus (HCV) genotype and other host and viral factors influence treatment outcome in chronic HCV infection. This article reports on a study of the effect of race and genotype on interferon and ribavirin treatment outcome in 70 Southeast Asian (SEA) and 50 white patients. Twenty-six SEA genotype 7, 8, or 9 patients (79 percent) and 10 SEA true genotype 1b patients (59 percent) achieved a sustained virologic response (SVR) compared with 15 (34 percent) white genotype 1b patients. The authors conclude that a proportion of SEA patients classified by line probe assay as genotype 1b were in reality genotype 7, 8, or 9. HCV core sequencing was necessary to determine genotype accurately in persons potentially exposed to HCV genotypes 7, 8, or 9. This study also supports the concept that race and ethnicity are important determinants of treatment outcome in HCV infected patients. 2 figures. 2 tables. 42 references.

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Extrahepatic Manifestations of Hepatitis C Among United States Male Veterans Source: Hepatology. 36(6): 1439-1445. December 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Hepatitis C virus (HCV) has been associated with several extrahepatic conditions. To date, most studies assessing these associations involved small numbers of patients and lacked a control group. Using the computerized databases of the Department of Veterans Affairs, the authors of this article carried out a hospital-based case-control study that examined all cases of HCV-infected patients hospitalized during 1992 to 1999 (n = 34,204) and randomly chosen control subjects without HCV (n = 136,816), matched with cases on the year of admission. The inpatient and outpatient files were searched for several disorders involving the skin (porphyria cutanea tarda, vitiligo, and lichen planus); the kidney (membranous glomerulonephritis [GN] and membranoproliferative glomerulonephritis); the blood (cryoglobulin, Hodgkin's and non-Hodgkin's lymphoma [NHL]); the endocrine system (diabetes, thyroiditis); and rheumatologic (Sjogren's's syndrome). The association between HCV and these disorders was examined in analyses that controlled for age, gender, ethnicity, and period of military service. Patients in the case group were younger in age (45 versus 57 years), were more frequently nonwhite (39.6 percent versus 26.3 percent), and were more frequently male (98.1 percent versus 97.0 percent). A significantly greater proportion of HCV-infected patients had porphyria cutanea tarda (PCT), vitiligo, lichen planus, and cryoglobulinemia. There was a greater prevalence of membranoproliferative GN among patients with HCV but not membranous GN. There was no significant difference in the prevalence of thyroiditis, Sjogren's syndrome, or Hodgkin's or NHL. However, NHL became significant after age adjustment. Diabetes was more prevalent in controls than cases, but no statistically significant association was found after adjustment for age. The authors conclude that patients presenting with PCT, lichen planus, vitiligo, cryoglobulinemia, membranoproliferative GN , and NHL should be tested for HCV infection. 3 tables. 50 references.

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Natural History of Hepatitis C Virus Infection: Host, Viral, and Environmental Factors Source: JAMA. Journal of the American Medical Association. 284(4): 450-456. July 26, 2000. Summary: Hepatitis C virus (HCV) infection may resolve (viral clearance), persist without complications, or cause end stage liver disease (ESLD). The frequency and determinants of these outcomes are poorly understood. This article reports on a study undertaken to assess the incidence and determinants of viral clearance and ESLD among persons who acquired HCV infection from injection drug use. The community based prospective cohort study used enrollment in 1988 to 1989, with a followup of 8.8 years. The study featured a total of 1,667 persons aged 17 years or older with a history of injection drug use and an HCV antibody positive test result during followup. Viral clearance was observed in 90 persons who were compared with 722 with persistent viremia, while the viremia of 107 was not resolved. Viral clearance occurred more often in nonblacks and those not infected with human immunodeficiency virus (HIV). Forty cases of ESLD were observed throughout followup. In analysis, the risk of ESLD was higher for persons aged 38 years or older at enrollment and who reported ingestion of more than 260 g of alcohol per week. Of 210 patients without ESLD randomly selected for biopsy, only 2 had cirrhosis. The authors conclude that although HCV infection can be self limited or associated with ESLD, the majority of adults have persistent viremia, without clinically demonstrable liver disease. Further research is needed to explain the less frequent clearance of HCV infection among black persons and to improve utilization of treatment for those infected in the context of injection drug use. 3 tables. 44 references.

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Progress Against Hepatitis C Infection Source: Patient Care. 36(3): 11-12, 14-15, 19-20. February 15, 2002. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Fax (201) 573-4956. Summary: Hepatitis C virus (HCV) infection, the most frequently encountered cause of chronic viral hepatitis in the developed world, often results in the development of chronic infection (in 55 to 85 percent of patients infected). This article reports on progress against hepatitis C infection. The most common method of detecting HCV infection is via elevated liver enzyme levels, often discovered in conjunction with a routine physical examination. However, many people do not have routine physical examinations, and HCV infection may be present for decades before symptoms or physical signs are noted, so screening of high risk persons is key to detection. Treatment of HCV infection is aimed primarily at prevention of progressive liver disease, which may culminate in cirrhosis or liver cancer. Quality of life can be affected at an earlier disease stage, making therapy an option even for patients whose disease is not progressing quickly. As treatment efficacy continues to improve, some experts now offer treatment to all patients with HCV infection. The best results have been achieved with a regimen of peginterferon plus ribavirin given for 6 months to 1 year. Such an approach makes early detection by the primary care physician more important than ever. 1 figure. 2 tables. 20 references.

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Hepatitis C Virus Infection Source: New England Journal of Medicine. 345(1): 41-52. July 5, 2001.

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Summary: Hepatitis C virus (HCV) infects an estimated 170 million persons worldwide and thus represents a viral pandemic, one that is five times as widespread as infection with HIV. This article reviews recent advances in understanding the pathogenesis (development) of the infection and improvements in treatment options. The author notes that the institution of blood screening measures in developed countries has decreased the risk of transfusion associated hepatitis to a negligible level, but new cases continue to occur mainly as a result of injection drug use and, to a lesser degree, through other means of percutaneous or mucous membrane exposure. Progression to chronic disease occurs in the majority of HCV infected persons, and infection with the virus has become the main indication for liver transplantation. HCV infection also increased the number of complications in persons who are coinfected with HIV. The authors conclude that the best hope for a solution to the epidemic of HCV infection is the development of an effective vaccine. Although the recent demonstration of apparent immunologic clearance of virus in some persons with acute infection provides hope that a vaccine may someday be developed, it is not likely to be available soon. For those who are already infected with HCV, new therapeutic approaches can be expected in the future. Persons who have no response to therapy and who have a high risk of imminent progression to decompensated liver disease might benefit from therapies (such as interleukin 10) that halt disease progression until better therapies become available. 3 figures. 3 tables. 106 references. ·

Hepatitis C Virus (HCV) Infection and Liver-Related Mortality: A Population-Based Cohort Study in Southern Italy Source: International Journal of Epidemiology. 29(5): 922-927. October 2000. Contact: Available from Oxford University Press. Journals Subscription Department, Great Clarendon Street, Oxford OX2 6DP, UK. 44 (0)1865 267907. Fax 44 (0)1865 267485. Summary: Hepatitis C virus (HCV) is a common cause of chronic liver diseases but the degree to which these diseases contribute to liver related mortality (death) is not well established. This article reports on a study undertaken to estimate the absolute and relative effects of HCV infection on liver related mortality. A population random sample of 2,472 subjects aged greater than 30 years was enrolled and followed up from 1985 to 1996. At enrollment, a structured interview and a clinical evaluation were performed. Serum samples were tested using HCV ELISA and RIBA HCV. Crude overall and liver related mortality rates were 7.66 and 0.9 per 10 cubed person years, respectively. For HCV infection effect, incidence rate ratio and difference (per 10 cubed person years), risk ratio and difference were 27.5 and 0.06, respectively. All measures were adjusted for age at death, sex, and daily alcohol intake. The results show a strong relative but weak absolute effect of HCV infection on liver related mortality in the 10 year period considered. The authors conclude with a brief discussion of the potential impact of interferon and other antiviral therapies. 4 tables. 46 references.

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Hepatitis C and Minorities Source: Practical Gastroenterology. 25(11): 14, 16, 19-20, 23. November 2001. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435. Summary: Hepatitis C virus (HCV) is a major cause of chronic liver disease in the United States and the leading indication for liver transplantation. This review article summarizes the impact of racial and ethnic factors on different aspects of HCV infection. Most of the published data relates to blacks and very little information is available on

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other minorities. HCV infection rate is higher in blacks and Hispanics than in whites. Blacks have a higher rate of cirrhosis, hepatocellular carcinoma and death due to HCV related liver disease. There are no racial differences with respect to baseline liver test abnormalities and HCV RNA titers. However, blacks have a higher infection rate with HCV genotype 1 that responds less well to treatment compared to other genotypes. The overall response to anti-viral therapy is lower in blacks compared to whites. Finally, blacks are less likely to get a liver transplant, and those who get transplanted have lower survival rates than whites. 29 references. ·

Mother-to-infant Transmission of Hepatitis C Virus Source: Hepatology. 34(2): 223-229. August 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Hepatitis C virus (HCV) is acquired through transfusion of infected blood or blood products or through routes not related to transfusion, classified as community acquired disease. The rate of mother to infant HCV transmission is critical to predicting the burden of HCV infection in future generations (particularly after the implementation of blood product screening in 1991). The factors that determine whether or not an infant actually becomes infected need to be identified. This article reports on a review of published studies (n = 77, 1992 to 2000) of mother to infant transmission of HCV. The number of anti HCV positive mother-infant pairs ranged from 10 to 1,338 per study. The articles in this review reported a total of 363 cases of mother to infant transmission; the majority of studies originated from Italy and Japan. The prevalence of anti HCV positive women among all pregnant women varied widely across these studies, from 0.6 percent to 95.4 percent, reflecting the heterogeneity of the populations studied. For example, the 3 studies with highest prevalence were limited to intravenous drug users (IVDU). The reported rate of mother to infant HCV transmission ranged from 0 to 35 percent among children born to anti HCV positive women. HCV transmission patterns may differ among certain groups and, indeed, the definition of mother to infant transmission differed among studies. The rate of mother to infant HCV transmission appears increased among women coinfected with human immunodeficiency virus (HIV) compared with women without HIV infection. Between infants delivered vaginally versus by Cesarean section, overall rates of mother to infant transmission were similar. Overall rates of mother to infant transmission between breast fed and non breast fed infants were similar. Suggested viral factors such as genotype and viral titer were not consistently measured across studies; hence, their roles as significant risk factors in mother to infant transmission remain to be conclusively shown. Inconsistent follow up among studies resulted in only sporadic description of clinical outcome for infected infants. The authors conclude that, based on observational data from these 77 cohort studies, maternal risk factors for increased mother to infant transmission of HCV include coinfection with HIV, history of IVDU, and maternal viremia greater than 10 to the 6th power copies per milliliter. 2 tables. 102 references.

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Prevention of Spread of Hepatitis C Source: Hepatology. 36(5 Supplemental 1): S93-S98. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Hepatitis C virus (HCV) is transmitted by percutaneous or permucosal exposure to infectious blood or blood-derived body fluids. This article summarizes

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highlights of the epidemiologic data used to support recent recommendations on the prevention and control of HCV infection. Based on the results of cohort and acute case control studies, risk factors associated with acquiring HCV infection in the United States have included transfusion of blood and blood products and transplantation of solid organs from infected donors, injecting drug use, occupational exposure to blood (primarily through contaminated needle sticks), birth to an infected mother, sex with an infected partner, and multiple heterosexual partners. Nosocomial and iatrogenic transmission of HCV primarily are recognized in the context of outbreaks, and primarily have resulted from unsafe injection practices. Transmission from HCV-infected health care workers to patients is rare. Transfusions and transplants have been virtually eliminated as sources for transmission, and most (68 percent) newly acquired cases of hepatitis C are related to injecting drug use. The primary prevention of illegal drug injecting will eliminate the greatest risk factor for HCV infection in the United States. Other prevention strategies that need to be widely implemented include risk reduction counseling and services, and review and improvement of infection control practices in all types of health care settings. Testing for HCV infection should be routinely performed for persons at high risk for infection or who require postexposure management. There are no recommendations for routine restriction of professional activities for HCV-infected health care workers, and persons should not be excluded from work, school, play, and child care or other settings on the basis of their HCV infection status. 1 figure. 27 references. ·

Hepatitis C Infection and the Patient with End-Stage Renal Disease Source: Hepatology. 36(1): 3-10. July 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Hepatitis C virus (HCV) remains common in patients with end stage renal (kidney) disease (ESRD) and is an important cause of liver disease in this population. This article considers HCV infection and the patient with end stage renal disease. Acquisition of HCV infection continues to occur in dialysis patients because of nosocomial (due to medical procedures or settings) spread. The natural history of HCV in dialysis patients remains controversial because the course of HCV typically extends over decades, whereas dialysis patients have higher morbidity and mortality (death) rates than those of the general population, limiting long term follow up. However, recent reports suggest that HCV infection affects the survival of chronic dialysis patients as well as renal transplant (RT) recipients. The severity of preexisting liver disease on pretransplantation liver biopsy may provide useful prognostic information about clinical outcome after RT; liver biopsy should be incorporated in the evaluation and management of RT candidates with HCV. Use of renal grafts from HCV-infected donors in recipients with HCV does not appear to result in a greater burden of liver disease. There is only limited data about interferon (IFN) therapy in chronic dialysis patients, although sustained responses are reported. Preliminary data on IFN plus ribavirin therapy in dialysis patients with hepatitis C have given encouraging results, but randomized trials are needed. 1 figure. 3 tables. 51 references.

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Chronic Hepatitis D: A Vanishing Disease? An Italian Multicenter Study Source: Hepatology. 32(4, Part 1 of 2): 824-827. October 2000. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000.

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Summary: Hepatitis delta virus (HDV) was responsible for a high proportion of cases of acute and chronic liver disease in Southern Europe during the 1970s. Some data suggest that by the 1990s, HDV circulation had substantially declined. This article reports on a study that assessed the prevalence of HDC infection and its clinical impact in 834 Italian hepatitis B surface antigen (HBsAg) carriers in 1997. Anti-HDV antibodies were sought in all consecutive chronic HBsAg carriers observed in 14 referral liver units throughout Italy. Risk factors for anti HDV positivity were evaluated. Anti HDV antibodies were found in 69 of 834 (8.3 percent) HBsAg positive patients. Cohabitation with an anti HDV positive subject, intravenous drug addiction, residence in the South of the country, and the presence of cirrhosis were independently associated with the presence of anti HDV antibodies. The overall prevalence of anti HDV antibodies was lower than those observed in two multicenter surveys performed in 1987 and 1992 (23 percent and 14 percent, respectively). By 1997, the percentage of anti HDV positive subjects had sharply decreased in the 30 to 50 years age group, whereas it was almost unchanged in subjects over 50 years of age. The highest prevalence of anti HDC antibodies (11.7 percent) was found in patients with cirrhosis. This prevalence was as high as 40 percent in the 1987 study. The circulation of HDV sharply decreased in Italy, by 1.5 percent per year, from 1987 to 1997. This decrease resulted mainly from the reduction in chronic HDV infections in the young, for whom high morbidity and mortality rates were recorded in the past. The authors conclude that the results anticipate the almost complete control of HDV infection in the near future. 1 figure. 5 tables. 15 references. ·

Non-Transferrin-Bound Iron in Untreated and Ribavirin-treated Chronic Hepatitis C Patients Source: Alimentary Pharmacology and Therapeutics. 16(8): 1555-1562. August 2002. Contact: Available from Alimentary Pharmacology and Therapeutics. Blackwell Science Ltd., Osney Mead, Oxford OX2 OEL, UK. +44(0)1865 206206. Fax +44(0)1865 721205. Email: [email protected]. Website: www.blackwell-science.com. Summary: In patients with chronic hepatitis C, elevations in serum iron levels, hepatic iron content, and oxidative stress-related molecules have been reported. Treatment with ribavirin induces an increases in hepatic (liver) iron concentration. In situations of iron overload, non-transferrin-bound iron can appear. This article reports on a study that determined non-transferrin-bound iron levels in untreated chronic hepatitis C patients and in patients during interferon-ribavirin treatment. In 10 untreated and 19 interferonribavirin-treated chronic hepatitis C patients, the authors examined non-transferrinbound iron levels by a colorimetric method using nitrilotriacetic acid as a ligand and sodium triscarbondatecobalt (III) to block free iron binding sites on transferrin. Despite the presence of high serum iron saturation and ferritin levels, non-transferrin-bound iron was absent in the majority of hepatitis C virus patients (25 of 29 patients, 86 percent). There was no difference in non-transferrin-bound iron levels between untreated and treated patients. Four patients with high non-transferrin-bound iron levels were distinguished by higher serum iron levels. In two of these patients, hepatocytic iron was present on liver biopsy. 2 figures. 2 tables. 31 references.

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Hepatitis C and Human Immunodeficiency Virus Infection Source: Hepatology. 36(5 Supplemental 1): S201-S209. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000.

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Summary: In the United States, an estimated 200,000 persons are infected with both hepatitis C virus (HCV) and human immunodeficiency virus (HIV). This article explores the epidemiology, natural history, and management of hepatitis C in the HIV-infected person; the author uses the available literature to provide recommendations and to highlight areas of controversy. As the lives of HIV infected persons have been prolonged by use of highly active antiretroviral therapy, liver disease has emerged as an important, and in some settings, the leading, cause of morbidity and mortality. HIV infection appears to adversely affect all stages of hepatitis C infection, leading to increased viral persistence and accelerated progression of HCV-related liver disease. In turn, hepatitis C may affect the management of HIV infection, increasing the incidence of liver toxicity caused by antiretroviral medications. The medical management of hepatitis C in HIV-infected persons remains controversial, in part because of the complexity of both infections and potential drug interactions, but chiefly because there is so little published information. Nonetheless, the burden of liver disease is too high to delay management of HIV and HCV co-infected persons while awaiting better data. Instead, the management of hepatitis C today must be based on data generated on persons without HIV and an understanding of both infections. Properly designed studies of therapy in HIV and HCV co-infected persons are needed to help guide management of these patients in the future. 2 figures. 1 table. 92 references. ·

Hepatitis C: How to Reduce the Risk of Infection Source: Consultant. 40(2): 245-248. February 2000. Contact: Available from Cliggott Publishing Company. 55 Holly Hill Lane, Box 4010, Greenwich, CT 06831-0010. Summary: In the United States, hepatitis C is now the most common chronic blood borne infection. Because the early stages of the disease are usually asymptomatic, many persons with chronic HCV infection are unaware that they are infected and may unknowingly expose others to the virus. This article brings primary care physicians up to date on current recommendations for reducing the risk of infection with hepatitis C. The author begins by reviewing those groups who are more at risk for contracting the disease: transfusion and transplant recipients, injection and other illegal drug users, patients undergoing dialysis, health care workers, persons with tattoos or body piercing, persons with multiple sex partners, long term sex partners of HCV positive persons, household contacts of HCV positive persons, and children of HCV positive mothers. The author offers recommendations for determining who should be tested for HCV infection. The article concludes with a section of suggestions for the prevention of HCV transmission, in the categories of blood, blood products and transplanted organs and tissues; illegal drug use; high risk sexual practices; occupational exposure to blood; home infusion therapy; long term hemodialysis; and tattooing and body piercing. These recommendations are highlights of the recently issued CDC recommendations aimed at reducing the transmission of HCV and lowering the risk of serious liver disease in persons with chronic HCV infection. 4 tables. 1 reference.

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Cost-Effectiveness of Hepatitis A Vaccination in Patients with Chronic Hepatitis C Source: Hepatology. 31(4): 834-839. April 2000. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Infection with hepatitis A virus (HAV) occasionally leads to acute liver failure and has a higher fatality rate in patients with chronic hepatitis C virus (HCV).

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Vaccination of patients with HCV against HAV is effective and well tolerated. This article reports on a study that examined the cost effectiveness of HAV vaccination in North American patients with HCV. The authors constructed a decision analysis model to compare three HAV vaccination strategies in adult patients with chronic HCV over a period of 5 years: vaccinate no patients (treat none); vaccinate only susceptible (anti HAV negative) patients (selective); or vaccinate all patients without prior testing of immune status (universal). Probabilities and direct costs were estimated from hospital data and the literature. The cost per patient for the three vaccination strategies were: treat none, $2.00; selective, $56.00; and universal, $82.00. For every 1 million patients with HCV vaccinated over a 5 year period, the selective strategy prevented 128 symptomatic cases of HAV, 3 liver transplantations, and 3 deaths owing directly to HAV compared with the treat none strategy. In addition, the selective strategy costs an additional $427,000 per patient with HAV prevented, and $23 million per HAV related death averted, compared with the treat none strategy. The results were most sensitive to the incidence of HAV infection; vaccination increased costs if the annual rate of infection was less than 0.56 percent. The authors conclude that vaccination of North American patients with chronic HCV against HAV infection is not a cost effective therapy. 3 figures. 3 tables. 35 references. ·

Therapy for Acute Hepatitis C Source: New England Journal of Medicine. 345(20): 1495-1497. November 15, 2001. Summary: Infection with the hepatitis C virus (HCV) is now the most frequent cause of chronic hepatitis (liver inflammation or infection), cirrhosis (liver scarring), and hepatocellular carcinoma (liver cancer) in the United States and most Western nations. Although hepatitis C has been described as an epidemic and a national emergency, the epidemic reflects the identification of chronic cases rather than a large outbreak of new cases. This editorial reviews the current treatment strategies for acute hepatitis C, which is no longer very common in the United States. The decrease in incidence of acute HCV is due to the near-elimination of post-transfusion hepatitis as a result of screening donor blood, increased use of aseptic techniques and universal precautions, and a decrease in injection drug use. This editorial serves as an introduction to a research study published in this journal issue that reported on the use of a standardized 24 week course of interferon alfa to treat acute HCV. The research study results showed a dramatic response rate to therapy (98 percent). The editorial notes that in spite of these data, treatment recommendations for acute HCV are hard to make. The data is still preliminary and there is still no single, reliable diagnostic test for acute HCV. The author discusses the diagnostic criteria, the side effects of interferon therapy, monotherapy with interferon versus combination therapy with interferon and ribavirin, and patient selection considerations. 15 references.

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Hepatitis C, E, F, G, and Non-A-G Source: Gastroenterology Nursing. 23(2): 67-72. March-April 2000. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (410) 528-8555. Summary: Inflammation of the liver is known as hepatitis. Six or seven viruses, hepatitis viruses A through G, are responsible for most cases of viral hepatitis. In this second of a series of three articles, current knowledge regarding hepatitis C, E, F, G, and Non A G is reviewed. For each type, the author discusses the virus itself, how it manifests clinically (including associated malignancies, where applicable), transmission, outbreaks,

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prevention and control (including vaccines), and treatment. Up to 80 percent of patients infected with hepatitis C progress to chronic liver disease. Hepatitis E is an enteric hepatitis that is endemic in Asia. Hepatitis F may be a mutant hepatitis C. Hepatitis G is a posttransfusion hepatitis. Non A G hepatitis consists of all the hepatitis viruses awaiting identification. All of these viruses discussed cause an identical acute clinical syndrome of varying degrees after different incubation periods. Patients present with myalgias, arthralgias, anorexia (lack of appetite), nausea, and abdominal tenderness; in the more severe cases, jaundice with dark urine and light colored stools develop. The author emphasizes that every phase of patient care improves when health care professionals are knowledgeable regarding the illnesses of their clients. 1 table. 43 references. ·

Outcome of Hepatitis E Virus Infection in Indian Pregnant Women Admitted to a Tertiary Care Hospital Source: Indian Journal of Medical Research, Indian Council of Medical Research. Ansari Nagar, New Delhi 1120029. 6515497/6866258. Fax 6868662. Contact: Available from Indian Council of Medical Research. Ansari Nagar, New Delhi 110029. 6515497 or 6866258. Fax 6868662. Summary: Information on the incidence and prevalence of hepatitis E virus (HEV) infection in Indian pregnant women is scanty. Only a few studies have been done so far to document the vertical route (from mother to fetus during pregnancy or to child during birth) of transmission of this virus. This article reports on a study undertaken to determine the prevalence of HEV infection in pregnant women (n = 50) with hepatitis and to note the outcome of their pregnancies. After informed consent, their blood samples were tested for potential causes of hepatitis including hepatitis A, B, C, and E infections. Of the 50 cases, 20 patients (40 percent) were found to be positive for IgM anti HEV (group A) and 30 (60 percent) ewre negative for IgM anti HEV antibodies (group B). Overall, 19 patients were in their second trimester, while 30 were in their third trimester. Of those in the second trimester, 52.6 percent (10 out of 19) had fulminant liver (hepatic) failure (FHF). Of those in their third trimester, 50 percent (15 of 30 patients) had FHF. Only one patient presented in the first trimester; she had acute viral hepatitis (AVH) and recovered completely. Of the HEV infected women (n = 20), 70 percent were in their third trimester and the remaining 30 percent were in their second trimester of pregnancy. A similar percentage (i.e., 14 of 20 or 70 percent) manifested with FHF while 6 (30 percent) had acute hepatitis leading to recovery. The percentage of women with FHF and acute hepatitis was 36.6 and 63 percent, respectively, in group B. Upon follow up, 13 of the 14 HIV infected patients with FHF died before delivery, while one died just after delivering her baby, thus all had fatal outcome. The fatality rate in HEV infected patients was not different between the second and third trimesters (66.6 percent versus 71.43 percent, respectively). The authors conclude that HEV causes high mortality in pregnant women compared to non HEV infected pregnant women. This pilot study indicates that steps should be taken to prevent HEV infection during pregnancy. 2 tables. 14 references.

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Risk Factors for Hepatitis C Virus Infection in United States Blood Donors Source: Hepatology. 31(3): 756-762. March 2000. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000.

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Summary: Injection drug use (IDU) is a known risk factors for hepatitis C virus (HCV) infection, but the strength of other parenteral and sexual risk factors is unclear. This article reports on a case control study of 2,316 HCV seropositive blood donors and 2,316 seronegative donors matched on age, sex, race or ethnicity, blood center, and first time versus repeat donor status. Questionnaires were returned by 758 (33 percent) of the HCV positive subjects and 1,039 (45 percent) of the control subjects. The final multivariate model included only the following independent HCV risk factors: IDU, blood transfusion in non IDU, sex with an injection drug user, having been in jail more than 3 days, religious scarification, having been stuck or cut with a bloody object, pierced ears or body parts, and immunoglobulin injection. Although drug inhalation and a high number of lifetime sex partners were significantly more common among HCV seopositives, they were not associated with HCV after controlling for IDU and other risk factors. The authors conclude that, among United States blood donors, IDU, blood transfusion among non IDU, and sex with an injection drug user are strong risk factors for HCV. Weaker associations must be interpreted with caution. 1 figure. 3 tables. 40 references. ·

Prevalence and Duration of Hepatitis C Among Injection Drug Users in San Francisco, Calif Source: American Journal of Public Health. 91(1): 46-47. January 2001. Contact: American Public Health Association. 800 I Street, NW, Washington, DC 200013710. (202) 777-2742. Fax (202) 777-2534. E-mail: [email protected]. Website: www.ajph.org. Summary: Injection drug users are the population most affected by the hepatitis C virus (HCV); an estimated 60 percent of HCV transmission in the United States is attributed to injection drug use. This article briefly reports on a study of the prevalence and duration of hepatitis C among injection drug users in San Francisco, California. The authors tested stored serum (blood) samples collected in 1987 from 372 injection drug users for HCV antibody. Of these 372 samples, 353 (95 percent) tested positive for HCV antibody. This proportion is higher than the 72 percent found in Sacramento in 1987 to 1989 and the 89 percent found in a Baltimore study at the same period. As in those studies, HCV prevalence was strongly associated with length of injection career. Of those injecting for 2 years or less, 75.9 percent were infected. Of those injecting for more than 10 years, 98.8 percent were infected. There were no significant differences in prevalence by race, sex, or frequency of injection. The median year of initiating injection drug use was 1972. Because most injection drug users test positive for HCV antibody within 2 years of commencing injection drug use, the majority of injection drug users in this sample were most likely infected by the mid 1970s and are now well into their third decade of infection. Thus, large numbers of injection drug users may be developing liver disease at this time. Current national guidelines recommend that only injection drug users who have ceased to use drugs receive HCV therapies; however, the capacity of the drug treatment system in the United States is sufficient for only 10 to 20 percent of the people who could use it. The authors suggest an alternative to the present guidelines: that HCV related treatment decisions be made by the physician and the individual drug user on a case by case basis and with consideration of such issues as potential for adherence, possible drug interactions, and the risk of reinfection. In addition, strategies (such as outreach, incentives, and community based treatment sites) that have proven successful in other public health arenas should be used in developing HCV treatment programs for injection drug users. 1 figure. 7 references.

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Prevention and Treatment of Hepatitis C in Injection Drug Users Source: Hepatology. 36(5 Supplemental 1): S210-S219. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Injection drug users constitute the largest group of persons infected with the hepatitis C virus (HCV) in the United States, and most new infections occur in drug users. Controlling hepatitis C in the U.S. population, therefore, will require developing, testing, and implementing effective prevention and treatment strategies for persons who inject drugs. This article reviews the substantial body of research and clinical experience that exists on the prevention and management of chronic viral diseases among injection drug users. The author stresses that the need to implement interventions to stop the spread of HCV among drug users is critical. The capacity of substance-abuse treatment programs needs to be expanded to accommodate all who want and need treatment. Physicians and pharmacists should be educated in how to provide access to sterile syringes and to teach safe injection techniques, both of which are lifesaving interventions. The treatment of hepatitis C in drug users requires an interdisciplinary approach that brings together expertise in treating hepatitis and caring for drug users. Treatment decisions should be made individually by patients with their physicians, based on a balanced assessment of risks and benefits and the patient's personal values. Physicians should carefully assess, monitor, and support adherence and mental health in all patients, regardless of whether drug use in known or suspected. 1 figure. 5 tables. 93 references.

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Side Effects of Therapy of Hepatitis C and Their Management Source: Hepatology. 36(5 Supplemental 1): S237-S244. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Interferon and ribavirin combination therapy for chronic hepatitis C produces a number of well-described side effects that are dominated by fatigue, influenza-like symptoms, hematologic abnormalities, and neuropsychiatric symptoms. Combination therapy with pegylated interferons yields an adverse event profile similar to standard interferon, although the frequency of certain adverse events may vary by preparation. This article reviews the frequency and management of side effects reported with the use of peginterferon and ribavirin for the treatment of chronic hepatitis C, based on data from 2 large registration trials that compared these agents with standard interferon and ribavirin combination therapy. Premature withdrawal from therapy due to adverse events was required in 10 to 14 percent of participants in registration trials of these agents. Most adverse events were safely and effectively managed by dose reduction using predetermined criteria. The most common indications for dose reduction were hematologic abnormalities, such as anemia and neutropenia, with the latter more frequent in peginterferon treatment arms. Recent data suggest that maintaining adherence to a prescribed treatment regimen can enhance antiviral response. Strategies to maximize adherence are being developed and, in the future, may include early identification of and therapy for depression and the selective use of hematopoietic growth factors to ameliorate hematologic abnormalities. 3 figures. 5 tables. 61 references.

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Low Incidence of Hepatitis C Virus Transmission Between Spouses: A Prospective Study Source: Journal of Gastroenterology and Hepatology. 15(4): 391-395. April 2000. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: Interspousal transmission of hepatitis C virus (HCV) has been documented; however, the annual risk of interspousal transmission remains unclear. This article reports on a long term prospective study undertaken to define the risk of interspousal transmission of HCV. The index patients (n = 112) with chronic hepatitis C and their anti-HCV seronegative spouses were enrolled. The mean followup period was 45.9 months. Antibodies were tested for in each seronegative spouse every year. Seroconversion of anti HCV occurred in only one spouse, 2 years after enrollment, with a concomitant acute hepatitis. This subject and his spouse were infected with HCV genotype 1b. Nucleotide sequence comparison of the hypervariable region of their HCV genomes showed a homology of 98 percent. Further phylogenetic analysis suggested that they had virtually the same isolate. Accordingly, the annual risk of interspousal transmission of HCV infection was 0.23 percent per year. The authors conclude that their findings suggest a low incidence of interspousal transmission of HCV; however, the risk may be cumulative and such couples should be educated to avoid HCV infection from their spouses. 1 figure. 20 references.

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Assessment of Fatigue and Psychologic Disturbances in Patients with Hepatitis C Virus Infection Source: Journal of Clinical Gastroenterology. 32(5): 413-417. May-June 2001. Contact: Available from Lippincott Williams and Wilkins, Inc. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Summary: It is a common clinical impression that fatigue is a frequent, and often debilitating, symptom in patients with chronic hepatitis C virus (HCV) infection. However, despite its obvious clinical importance, several aspects of fatigue, including its relationship with the underlying liver disease and the presence of psychological disturbances, have not been well examined. This article reports on a study carried out to assess these issues. The subjects (n = 149) were assigned to one of the following study groups: healthy controls (n = 31), chronic HCV infection (n = 24), combined HCV infection and chronic alcohol abuse (n = 32), alcoholic liver disease (n = 22), and chronic non liver diseases (n = 40). All subjects were administered investigator assisted questionnaires designed to analyze the presence of severity of fatigue and psychological abnormalities. The means fatigue scores in patients with chronic HCV infection, alcoholic liver disease, mixed liver disease, and chronic non liver diseases were significantly greater compared to healthy subjects. The total fatigue scores were higher in HCV infected subjects compared with the other patient groups, but the differences failed to reach statistical significance. Moreover, the fatigue experienced by patients with HCV did not improve with rest as effectively as in the other study groups. All patient groups had higher scores for psychological disturbances compared with health subjects. Patients with HCV infection were shown to be more depressed and harbor greater feelings of anger and hostility compared with those with non liver chronic diseases. The authors conclude that these observations are important because proper management of the psychological symptoms may have a favorable impact on the quality of life of patients with HCV infection. 3 tables. 30 references.

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Clinical Trial of Lamivudine in Children with Chronic Hepatitis B Source: New England Journal of Medicine. NEJM. 346(22): 1706-1713. May 30, 2002. Summary: Lamivudine therapy is effective for chronic hepatitis B virus (HBV) infection in adults. This article reports on a study that evaluated the efficacy and tolerability of lamivudine as a treatment for chronic infection with HBV in children. Of the 403 children screened, 191 were randomly assigned to receive lamivudine and 97 to receive placebo. The rate of virologic response at week 52 was higher among children who received lamivudine than among those who received placebo (23 percent versus 13 percent). Lamivudine therapy was well tolerated and was also associated with higher rates of seroconversion from hepatitis B e antigen (HBeAg) to hepatitis B e antibody, normalization of alanine aminotransferase levels, and suppression of HBV DNA. 2 figures. 4 tables. 20 references.

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Transplantation in the Patient with Hepatitis C Source: JASN. Journal of the American Society of Nephrology. 11(7): 1343-1353. July 2000. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-6423. Summary: Liver disease is one of the leading causes of death in long term survivors after kidney (renal) transplantation. Hepatitis C virus (HCV) infection is currently the main cause of chronic liver disease in this group. This article discusses the use of transplantation in the patient with hepatitis C. The authors first review the basics of HCV infection: the virus, epidemiology, diagnostic tests, natural history, extrahepatic manifestations, and treatment. The authors then consider these same topics for HCV in patients on dialysis. Factors that may influence the risk of HCV infection in dialysis patients include the number of blood units transfused, the length of dialysis therapy, and the type of renal replacement therapy used. The management of HCV infection in dialysis patients on the waiting list has not been completely standardized. Morbidity and mortality from HCV infection after kidney transplantation are marked, affecting both patient and graft (transplant) survival. In the evaluation of the severity of HCV infection, liver tests, liver biopsy, and virologic tests are helpful. The rate of response to interferon therapy is usually higher in dialysis patients than in the general population. In patients with severe chronic hepatitis, a second liver biopsy may be required before entry on the waiting list for a kidney transplantation. Patients with liver cirrhosis (scarring) are considered for simultaneous liver and kidney transplantation. In HCV positive patients, administration of immunosuppression posttransplant should be reduced to the lowest possible levels, and close monitoring for infections is mandatory. Although the long term survival rates are lower in HCV positive compared with HCV negative graft recipients, kidney transplantation still remains the best option for HCV positive patients with end stage renal disease (ESRD). 1 figure. 4 tables. 91 references.

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Combination of Interferon-Alpha and Ribavirin Therapy for Recurrent Hepatitis C Virus Infection After Liver Transplantation Source: Transplantation Proceedings. 32(4): 714-716. June 2000. Contact: Available from Appleton and Lange. P.O. Box 86, Congers, NY 10920-0086. (203) 406-4623. Summary: Liver transplantation (LT) used as treatment for hepatitis C virus (HCV) infection is almost universally associated with a recurrence of infection. More than 60

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percent of patients show clinical and histological signs of hepatitis within 1 year of transplantation, and in several studies a rapid development of fibrosis and cirrhosis was reported. This study was undertaken to examine the efficacy, safety, and tolerability of the combination of interferon (IFN) and ribavirin for recurrent HCV infection after LT. Five patients (3 men and 2 women, age range 43 to 63 years) were included in the study; the median time between LT and initiation of treatment was 20 months (range, 10 to 24 months). Only one patient completed the 6 months of combination therapy. He had a normal serum ALT level at the end of the course, but remained serum positive for HCV, and 3 months after completing therapy, his serum ALT increased again. In the other four patients, therapy was discontinued after 1 to 3 months. All four had severe symptomatic hemolysis (breakdown of red blood cells); two patients required blood transfusions. Decreasing the ribavirin dose did not yield an increase in serum hemoglobin level, and ribavirin had to be withdrawn in all 4 patients. No episodes of rejection were recorded. All patients retained stable graft function 3 to 5 years after transplantation. The authors conclude that, despite the small sample size, the study suggests that the combination therapy with IFN and ribavirin after LT for recurrent HCV infection is associated with a high rate of severe side effects necessitating withdrawal of therapy. 1 table. 9 references. ·

Understudied Populations with Hepatitis C Source: Hepatology. 36(5 Supplemental 1): S226-S236. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Managing patients with hepatitis C virus (HCV) infection consists primarily of antiviral treatment, currently with peginterferon and ribavirin. Unfortunately, treatment recommendations derive largely from trials that have focused on highly selected patient populations. As a consequence of the strict inclusion and exclusion criteria in these studies, more than half of all HCV-infected patients would be ineligible for enrollment. Even among the selected patients enrolled into studies, only 50 percent achieve a sustained virological response (SVR). This article considers understudied populations with hepatitis C and the applicability of research results to the general population with hepatitis C. Patients not eligible for current therapies include those with mild disease and normal alanine aminotransferase (ALT) levels, patients with advanced and decompensated liver disease, children, the elderly, patients with ongoing or recent alcohol and substance abuse, renal disease, human immunodeficiency virus (HIV) infection, severe psychiatric or neurologic illness, autoimmune disorders, solid organ transplant, and other significant comorbid conditions. Because these patients have been excluded from most clinical trials, little is known about the safety or efficacy of therapy in these populations. The expense and side effects of therapy are also an impediment to treatment of patients who are on public assistance, in prisons, and in institutions. The author calls for new efforts and new approaches to expand the eligibility for antiviral therapy of hepatitis C and to make treatment more available for understudied populations with this disease. 92 references.

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Maternal-Infant Transmission of Hepatitis C Virus Infection Source: Hepatology. 36(5 Supplemental 1): S106-S114. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000.

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Summary: Mother-to-infant transmission of hepatitis C virus (HCV) is comparatively uncommon. This article considers the role of mother to infant transmission of HCV infection, including issue relating to pregnancy itself. The prevalence of antibody to HCV (anti-HCV) in pregnancy women is 0.1 percent to 2.4 percent, although in some endemic areas it is much higher. The proportion of women with anti-HCV who have active infection with viremia (virus in the blood) is 60 to 70 percent. Transmission of HCV occurs only when HCV RNA is detectable and may be related to higher levels. The rate of mother-to-infant transmission is 4 to 7 percent per pregnancy in women with HCV viremia. Co-infection with HIV (human immunodeficiency virus) increases the rate of transmission 4 to 5 fold. The actual time and mode of transmission are not known. Elective Cesarean section is not recommended for women with chronic HCV infection alone. The role of treatment to prevent transmission is limited by the fetal toxicity of currently available medications for hepatitis C. Breast feeding poses no important risk of HCV transmission if nipples are not traumatized and maternal hepatitis C is quiescent. Pregnancy women at high risk for HCV infection should be screened for anti-HCV and HCV RNA testing should be performed if anti-HCV is positive. Infants of women with hepatitis C should be tested for HCV RNA on two occasions, between the ages of 2 and 6 months, and again at 18 to 24 months, along with serum anti-HCV. The natural history of mother-to-infant hepatitis C remains uncertain, especially the course in the first year of life when some infants appear to have spontaneous resolution. 3 tables. 71 references. ·

Efficacy of Granulocyte-Macrophage Colon-Stimulating Factor or Lamivudine Combination with Recombinant Interferon in Non-Responders to Interferon in Hepatitis B Virus-Related Chronic Liver Disease Patients Source: Journal of Gastroenterology and Hepatology. 17(7): 765-771. July 2002. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: Non-response to interferon (IFN) monotherapy is a major therapeutic problem in the management of chronic hepatitis B virus (HBV) infection. This article reports on a study in which the effectiveness of combination therapy to enhance the immunomodulatory effect of IFN by combining GMCSF (granulocyte-macrophage colony stimulating factor) or decreasing viral load by adding an antiviral agent such as lamivudine was evaluated prospectively. The study included 24 patients with chronic hepatitis B who were non-responders to previous IFN therapy were randomized to receive an IFN and GMCSF (group A, n = 10) or IFN and lamivudine (group B, n = 14) combination for 6 months. All patients successfully completed both the treatment schedules. At the end of treatment, there was a significant decrease in mean ALT levels. The HBV-DNA and HBeAg loss was seen in six of 10 (60 percent) patients in group ! and seven of 15 (50 percent) patients in group B. During follow up, two of six patients (33 percent) in group A and three of seven (43 percent) patients in group B relapsed with HBV-DNA and HBeAg positivity, which meant an overall sustained response of 40 percent and 28 percent respectively. None of the factors such as HBV viral load, ALT levels or liver histology could predict the non-response to combination therapy or occurrence of relapse. The authors conclude that larger studies using such combination therapies would be helpful in improving treatment strategies for chronic hepatitis B. 4 tables. 34 references.

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Hepatitis B Infection in Patients with Acute Liver Failure in the United States Source: Hepatology. 33(4): 972-976. April 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Occult (hidden) hepatitis B virus (HBV) infection has been reported in 30 to 50 percent of patients with acute liver failure (ALF) in small case series. This article reports on a study undertaken to determine the prevalence of occult HBV infection in a large series of ALF patients in the United States and the prevalence of precore and core promoter variants in patients with ALF caused by hepatitis B. Sera (blood products) from patients in the US ALF study and liver, when available, were tested using nested polymerase chain reaction (PCR) with primers in the HBV S and precore regions. PCR positive samples were sequenced. Sera and or liver from 139 patients (39 males, 100 females; mean age 42 years) were studied between January 1998 and December 1999. Twelve patients were diagnosed with hepatitis B, one with hepatitis B, C, and D coinfection, and 22 had indeterminate etiology (cause). HBV DNA was detected in the sera of 9 patients (6 percent); all 9 had ALF caused by hepatitis B. HBV genotypes A, B, C, and D were present in 4, 3, 1, and 1 patients, respectively. Seven of these 9 patients had precore or core promoter variants. Liver from 19 patients were examined. HBV DNA was detected in the liver of 3 patients with ALF caused by hepatitis B, but in none of the remaining 16 patients with non B ALF. Contrary to earlier reports, occult HBV infection was not present in this large series of ALF patients in the United States. 1 appendix. 3 tables. 34 references.

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Chronic Hepatitis B Virus Infection in Asian Countries Source: Journal of Gastroenterology and Hepatology. 15(12): 1356-1361. December 2000. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: Of the estimated 50 million new cases of hepatitis B virus (HBV) infection diagnosed annually, 5 to 10 percent of adults and up to 90 percent of infants will become chronically infected. Of those who become chronically infected, 75 percent are in Asia where hepatitis B is the leading cause of chronic hepatitis (liver infection), cirrhosis (liver scarring), and hepatocellular carcinoma (liver cancer). This article offers detailed statistics on chronic HBV infection in Asian countries, including Indonesia, the Phillipines, Thailand, China, Taiwan, and Malaysia. In the highly endemic countries in Asia (places where HBV is found on a routine basis in the population), the majority of infections are contracted postnatally or perinatally (during birth). Three phases of chronic HBV infection are recognized: phase 1 patients are HBeAg positive with high levels of virus in the serum (blood) and minimal hepatic (liver) inflammation; phase 2 patients have intermittent or continuous hepatitis of varying degrees of severity; phase 3 is the inactive phase during which viral concentrations are low and there is minimal inflammatory activity in the liver. In general, patients who clear HBeAg have a better prognosis than patients who remain HBeAg positive for prolonged periods of time. The outcome after anti HBe seroconversion depends on the degree of preexisting liver damage and any subsequent HBV reactivation. Without preexisting cirrhosis, there may be only slight fibrosis or mild chronic hepatitis, but with preexisting cirrhosis, further complications may happen. The annual incidence of hepatic decompensation (reduction in liver function) in HBV related cirrhosis varies from 2 to 10 percent and in these patients, the 5 year survival rate drops dramatically to 14 to 35 percent. The annual risk

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of developing HCC (liver cancer) in patients with cirrhosis varies between 1 and 6 percent. Chronic hepatitis B is not a static disease and the natural history of the disease is affected by both viral and host factors. The prognosis is poor with decompensated cirrhosis and effective treatment options are limited. The authors conclude that prevention of HBV infection through vaccination is still therefore the best strategy for decreasing the incidence of hepatitis B associated cirrhosis and HCC. 1 table. 32 references. ·

Adherence to Combination Therapy Enhances Sustained Response in Genotype-1Infected Patients with Chronic Hepatitis C Source: Gastroenterology. 123(4): 1061-1069. October 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Website: www.gastrojournal.org. Summary: Patient adherence to prescribed antiviral therapy in HIV infection enhances response. This article reports on a study that evaluated the impact of adherence to combination therapy with interferon or peginterferon plus ribavirin in chronic hepatitis C patients. The authors assessed the effect of dose reduction on sustained virologic response (SVR) from prior trials with interferon plus ribavirin (n = 1010) or peginterferon plus ribavirin (n = 511). The actual treatment administered was verified from drug dispensing or return records and patient diaries. Two groups were identified: patients who receive at least 80 percent of both their total interferon and ribavirin doses for at least 80 percent of the expected duration of therapy, and patients who received reduced doses. The results showed that most patients were at least 80 percent compliant with their interferon and ribavirin or peginterferon and ribavirin therapy and had SVR rates of 52 percent and 63 percent, respectively, for the 2 regimens. This was most apparent for patients infected with hepatitis C virus (HCV) genotype 1. The authors conclude that patients who can be maintained on at least 80 percent of their drug therapy for the duration of treatment exhibit enhanced sustained response rates. These results suggest that adherence will enhance the likelihood of achieving an initial virologic response. Adherence beyond 12 to 24 weeks will be advantageous only for those patients who have achieved such an early virologic response. 5 figures. 2 tables. 22 references.

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Risk Factors for Hepatocellular Carcinoma: Synergism of Alcohol with Viral Hepatitis and Diabetes Mellitus Source: Hepatology. 36(5): 1206-1213. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Risk factors associated with hepatocellular carcinoma (HCC, liver cancer) are well documented, but the synergisms between these risk factors are not well examined. This article reports on a hospital-based, case-control study that included 115 HCC patients and 230 non-liver cancer control patients. Odds ratios were 15.3 for anti-HCV antigen, 12.6 for hepatitis B surface antigen (HBsAg), 4.5 for heavy alcohol consumption, and 4.3 for diabetes mellitus. Synergistic interactions on the additive model were observed between heavy alcohol consumption and chronic hepatitis virus infection and diabetes mellitus. Independent of the effect of HCV, HBV, and diabetes mellitus, heavy alcohol consumption contributes to the majority of HCC cases (32 percent), whereas 22 percent, 16 percent, and 20 percent were explained by HCV, HBV, and diabetes mellitus, respectively. The authors conclude that the significant synergy between heavy alcohol

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consumption, hepatitis virus infection, and diabetes mellitus may suggest a common pathway for hepatocarcinogenesis (development of liver cancer). 3 tables. 38 references. ·

Retreatment of Patients with Chronic Hepatitis C Source: Hepatology. 36(5 Supplemental 1): S128-S134. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Significant advances have been made in the treatment of chronic hepatitis C virus (HCV) infection during the past 5 years. As a consequence, there is continuing enthusiasm for retreating patients who did not achieve sustained virological response (SVR) with previous therapy. This article outlines strategies for retreatment of patients with chronic HCV. Retreatment of non-responders to standard interferon monotherapy using interferon and ribavirin has yielded SVR rates of 12 to 15 percent. Retreatment with peginterferon and ribavirin has been more effective, achieving SVR rates of 34 to 40 percent. Retreatment of patients who relapsed after interferon monotherapy using standard interferon and ribavirin yielded SVR rates of 47 percent, whereas retreatment with peginterferon and ribavirin resulted in an SVR rate of about 60 percent. The major factors associated with a higher likelihood of an SVR after retreatment include previous relapse, previous treatment with interferon monotherapy, HCV genotypes 2 or 3, lower serum levels of HCV RNA, and having a significant decrease in HCV RNA levels during the initial course of therapy. These results help to focus treatment with peginterferon and ribavirin on subsets of patients who are most likely to benefit. 2 figures. 3 tables. 23 references.

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Introduction to Therapy of Hepatitis C Source: Hepatology. 36(5 Supplemental 1): S114-S120. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Since the 1997 National Institutes of Health (NIH) Consensus Development Conference on the management of hepatitis C, there have been several important advances that have a significant impact on the therapy for this disease. This article offers an overview of these advances which include the availability of sensitive, specific, and standardized assays for identifying hepatitis C virus (HCV) RNA in the serum, the addition of ribavirin to alpha interferon, the pegylation of alpha interferon, and the demonstration that sustained virological response (SVR) is the optimal surrogate endpoint of treatment. Using pegylated interferon and ribavirin, virological response with relapse and nonresponse are less common, but remain poorly understood. Current studies are evaluating nonvirological endpoints of treatment, names biochemical response and histological response. To date, definitive treatment trials have primarily been conducted in adult patients with elevated aminotransferase levels, clinically compensated chronic liver disease, and no other significant medical disorder. Limited data are available from studies of other patient populations, and the safety of interferonbased treatment has not yet been established in several patient groups. The author calls for further research to elucidate the mechanisms of viral response and clearance, to develop effective therapies for interferon nonresponse or intolerance, to define the role of complementary and alternative medicine and other nonspecific therapies, and to develop strategies for the optimal management and treatment of special patient populations who probably represent the majority of persons with chronic hepatitis C in the United States. 4 figures. 2 tables. 29 references.

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Hepatitis A, Hepatitis B, and Combination Hepatitis Vaccines for Immunoprophylaxis: An Update Source: Digestive Diseases and Sciences. 47(6): 1183-1194. June 2002. Contact: Available from Kluwer Academic Publishers. Customer Service Department, P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (781) 871-6600. Fax (781) 6819045. E-mail: [email protected]. Website: www.wkap.nl. Distribution Centre, P.O. Box 322, 3300 AH Dordrecht, The Netherlands. 31 78 6392392. Fax: 31 78 6546474. E-mail: [email protected]. Summary: Since the publication of the last extensive review of hepatitis vaccines, use of inactivated hepatitis A vaccines has been extended to high-risk regions of the United States and specific patient groups, such as those with chronic liver disease, and use of the recombinant hepatitis B vaccines has been recommended for older adolescents. In addition, a combination hepatitis A and B vaccine, recently approved for licensure by the U.S. Food and Drug Administration (FDA), should increase convenience and compliance, reduce the costs of vaccination, and provide prolonged and dual protection for those at risk for hepatitis. This article considers these advances and their use for immunoprophylaxis. The author also briefly comments that although commercially available vaccines for hepatitis C, D, and E remain a distant goal, advances in vaccine and adjuvant technology, including immunization with DNA-based vaccines, hold promise for the future. 5 tables. 85 references.

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Sexual Activity as a Risk Factor for Hepatitis C Source: Hepatology. 36(5 Supplemental 1): S99-S105. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: The accumulated evidence indicates that hepatitis C virus (HCV) can be transmitted by sexual contact, but much less efficiently than other sexually transmitted viruses, including hepatitis B virus and human immunodeficiency virus (HIV). However, because sex is such a common behavior and the reservoir of HCV-infected individuals is sizable, sexual transmission of HCV likely contributes to the total burden of infection in the United States. This article considers the role of sexual activity as a risk factor for hepatitis C. Persons in long-term monogamous partnerships are at lower risk of HCV acquisition (0 to 0.6 percent per year) than persons with multiple partners or those at risk for sexually transmitted diseases (0.4 to 1.8 percent per year). This difference may reflect differences in sexual risk behaviors or differences in rates of exposure to nonsexual sources of HCV, such as injection drug use or shared razors and toothbrushes. In seroprevalence studies in monogamous, heterosexual partners of HCVinfected, HIV-negative persons, the frequency of antibody-positive and genotypeconcordant couples is 2.8 percent to 11 percent in Southeast Asia, 0 percent to 6.3 percent in Northern Europe, and 2.7 percent in the United States. Among individuals at risk for sexually transmitted diseases (STDs), the median seroprevalence of antibody to HCV (anti-HCV) is 4 percent. HIV coinfection appears to increase the rate of HCV transmission by sexual contact. Current recommendations about sexual practices are different for persons with chronic HCV infection who are in steady monogamous partnerships versus those with multiple partners or who are in short-term sexual relationships. 2 figures. 3 tables. 37 references.

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ACIP Recommendations for the Prevention of Hepatitis A Through Immunization Source: American Family Physician. 61(7): 2246-2248, 2255-2256. April 1, 2000. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. Summary: The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention has developed recommendations for the prevention of hepatitis A infection through active or passive immunization. This article offers practice guidelines that have been extracted from the original report. The ACIP recommendations are an updated version of a 1996 ACIP report on the prevention of hepatitis A through immunization. The new report includes new data on the epidemiology of hepatitis A; recent findings about the effectiveness of community based hepatitis A vaccination programs; and recommendations for the routine vaccination of children living in areas with rates of hepatitis that are at least twice the national average from 1987 through 1997. The author first describes the rationale for the prevention of hepatitis A through routine active immunization. Vaccination is recommended for persons who travel to or work in countries that have high or intermediate presence of hepatitis A virus (HAV) infection; for men who have sex with men; for persons who use injecting or noninjecting illegal drugs; persons who have occupational risk for infection with HAV; persons who have clotting factor disorders; and persons who have chronic liver disease. The author notes that when deciding to vaccinate for outbreak control, the characteristics of hepatitis A epidemiology in the community and existing hepatitis A vaccination programs should be considered. The author briefly discusses outbreaks in communities that have high, intermediate, or low rates of HAV infection, and outbreaks in other settings, such as day care centers, hospitals, institutions, and schools. The article concludes with information for readers who wish to obtain copies of the complete ACIP statement ($5.00 from Massachusetts Medical Society, C.S.P.O. Box 9120, Waltham, MA 02254-9120). 1 table.

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Association Between Administration of Hepatitis B Vaccine at Birth and Completion of the Hepatitis B and 4:3:1:3 Vaccine Series Source: JAMA. Journal of the American Medical Association. 284(8): 978-983. August 2330, 2000. Summary: The association between infant age at initiation of hepatitis B vaccination and completion of the 3 dose hepatitis B vaccination series is unclear. This article reports on a study undertaken to assess the association between administration of the first dose of hepatitis B vaccine within 7 days of birth and completion of the hepatitis B vaccine series and the 4:3:1:3 vaccine series (4 doses of diphtheria tetanus pertussis vaccine, 3 doses of polio vaccine, 1 dose of measles containing vaccine, and 3 doses of Haemophilus influenzae type b vaccine). The study included an analysis of data from the 1998 National Immunization Survey, a random digit dialing telephone survey (n = 34,480 complete interviews) of parents of children aged 19 to 35 months from 50 states and 28 selected urban areas in the United States that included a provider record check mail survey. Overall, 86.9 percent of children 19 to 35 months of age in 1998 received 3 or more doses of hepatitis B vaccine, and 79.9 percent completed the 4:3:1:3 vaccine series. Analysis indicated that, compared with children who received the first hepatitis B vaccine dose within 7 days of birth, odds ratios for not completing the 3 dose hepatitis B vaccine series increased as the time from birth increased. The authors hypothesize that the significant association between age at administration of the first dose of hepatitis B vaccine and completion of the 3 dose series may reflect clinician concerns about parental

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resistance to multiple injections during a single visit. The authors conclude that administration of the first dose of hepatitis B vaccine at birth is associated with increased likelihood of completion of the hepatitis B vaccination series. Because of this and other advantages, providers should strongly consider a hepatitis B vaccination schedule that initiates vaccination at birth. 1 figure. 2 tables. 23 references. ·

Comparison of Clinical, Virologic and Pathologic Features in Patients with Acute Hepatitis B and C Source: Journal of Gastroenterology and Hepatology. 16(2): 209-214. February 2001. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: The clinical outcomes of adult acquired acute infection of hepatitis C virus (HCV) and hepatitis B virus (HBV) are quite different. This article reports on a comparison of clinical, biochemical, virologic, and pathologic pictures in 22 adults patients with acute hepatitis C and 16 adult patients with acute hepatitis B. Liver biopsies were performed within 3 months of acute onset of the illness in each of these patients. The results showed that a significantly younger age; a higher ratio of the clinical symptoms of jaundice, nausea, vomiting, and poor appetite; a higher mean serum (blood) level of alanine transaminase; aspartate transaminase, and total bilirubin were present in patients with acute hepatitis B, compared to those with acute hepatitis C. There was a significantly higher degree of periportal inflammation and total necroinflammatory activity in the acute hepatitis B patients. Fifteen (68.2 percent) of the 22 patients with acute hepatitis C had detectable serum HCV RNA, but only two (14.3 percent) of the 14 tested patients with acute hepatitis B had detectable serum HCV DNA, detected by using the branched DNA signal amplification assay. Eighteen (82 percent) of the 22 acute hepatitis C patients and none of the 16 acute hepatitis B patients progressed into a chronic hepatitis stage. 3 tables. 35 references.

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Hepatitis B Immunization and Postimmunization Serology Source: Journal of the Canadian Dental Association. 66(10): 551-552. November 2000. Contact: Available from Canadian Dental Association. 1815 Alta Vista Drive, Ottowa, ON K1G 3Y6. (613) 523-1770. E-mail: [email protected]. Website: www.cda-adc.ca. Summary: The development of hepatitis vaccines in the 1980s has substantially decreased dental workers' risk of acquiring hepatitis B virus (HBV). This article reports on hepatitis B immunization and postimmunization serology, focusing on dental workers in Canada. A recent survey of dentists in Canada showed that more than 90 percent had completed an immunization series and an additional 3 percent had natural immunity. However, rates of immunization among dental assistants and hygienists was found to be much lower. The author discusses the vaccines themselves, the antibody levels required for protection, postimmunization testing for immunity, and the potential need for booster doses of hepatitis B vaccine. The author concludes that all nonimmune dental health care workers should receive immunization with recombinant hepatitis B vaccine. Postimmunization serology should be performed to ensure seroconversion and guide further immunization and postexposure prophylaxis. Following seroconversion, booster doses of vaccine are not required. 10 references.

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Interferon Therapy Prolonged Life Expectancy Among Chronic Hepatitis C Patients Source: Gastroenterology. 123(2): 483-491. August 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Website: www.gastrojournal.org. Summary: The effects of interferon therapy in chronic hepatitis C patients on survival are unclear. This article reports on a study that analyzed survival among a large cohort of chronic hepatitis C patients. The study included 2,889 patients with histologically proven chronic hepatitis C. Of these, 2,430 patients received interferon therapy and 459 patients were untreated. For intervention, the median dose and duration of interferon administration was 480 million units and 137 days, respectively. Results showed that 30 of 459 untreated patients, 7 of 817 virologic sustained responders, and 49 of 1,613 nonresponders died in 5.4 years of follow up. Of these 86 patient deaths, 58 (67 percent) were due to liver diseases (39 patients due to hepatocellular carcinoma, i.e. liver cancer). Compared with the general population, overall mortality was high among untreated patients, but not among interferon-treated patients. The risk of liver unrelated deaths remained unchanged. The authors conclude that interferon therapy improved the survival of chronic hepatitis C patients by preventing liver-related deaths. 1 figure. 7 tables. 29 references.

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Optimal Therapy of Hepatitis C Source: Hepatology. 36(5 Supplemental 1): S121-S127. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: The highest response rates to antiviral therapy for the treatment of chronic hepatitis C have been achieved using the combination of peginterferon and ribavirin. This article reviews current thinking on the optimal therapy of hepatitis C. Recentlycompleted controlled trials have reported rates of sustained virological response (SRS) between 50 and 60 percent in patients treated with higher doses of peginterferon and ribavirin, which was 5 to 10 percent higher than standard doses of interferon alfa and ribavirin. The major determinant of outcome of therapy is hepatitis C virus (HCV) genotype. With the combination of peginterferon and ribavirin, patients with genotype 1 achieve response rates of 40 to 45 percent, compared with rates approaching 80 percent with genotypes 2 or 3. Importantly, patients with HCV genotype 1 achieve higher rates of response with 48 weeks than with 24 weeks of therapy, whereas patients with genotypes 2 and 3 are adequately treated with a 24 week course. Furthermore, patients with genotypes 2 and 3 require only 800 milligrams of ribavirin daily to achieve optimal response rates, whereas 1,000 to 1,200 milligrams daily is needed for patients with genotype 1. The authors call for future studies to focus on optimizing the dose of peginterferon and ribavirin by patient characteristics, particularly on resolving the issue of weight-based dosing. For patients with good prognostic factors, a lower dose and shorter course of peginterferon may be adequate for full effect. 2 tables. 10 references.

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Kidney Transplantation in Patients with Chronic Hepatitis B Virus Infection: Is the Prognosis Worse? Source: Digestive Diseases and Sciences. 46(3): 469-475. March 2001. Contact: Available from Kluwer Academic/Plenum Publishers. 233 Spring Street, New York, NY 10013-1578. (212) 620-8000. Fax (212) 807-1047.

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Summary: The impact of hepatitis B virus (HBV) infection on the long term outcome of kidney transplant patients is controversial. This study included a total of 34 chronic hepatitis B surface antigen (HBsAg) carriers among 143 renal (kidney) allograft recipients (mean follow up period: 5.6 years plus or minus 3.3 years; range 1 to 13 years). During the follow up, one HBsAg positive recipient with preexisting cirrhosis died of liver failure, and seven (21 percent) others developed serious HBV related complications (4 had fulminant hepatitis, 2 hepatocellular carcinoma or liver cancer, and 1 cirrhosis), and four died. Although HBsAg positive recipients had a higher rate of liver related complications and deaths than HBsAg negative recipients did, there were no significant differences in the long term graft and patient survival between the two groups. The survival rates, liver related complications, and deaths in HBsAg positive allograft recipients and 28 HBsAg positive uremic patients under dialysis were similar. The authors conclude that HBV infection is not a contraindication to kidney transplantation. However, pretransplant candidates should be warned of potentially serious liver related complications. 3 figures. 4 tables. 28 references. ·

Chronic Hepatitis C: Latest Treatment Options Source: Nurse Practitioner. 27(4): 32-33, 37-40, 42, 47-49. April 2002. Contact: Available from Nurse Practitioner. Circulation Department, P.O. Box 5053, Brentwood, TN 37024-5053. (800) 490-6580. Fax (615) 377-0525. Summary: The most common chronic bloodborne infection in the United States, hepatitis C virus (HCV) is the most frequent reason for liver transplantation. Unfortunately, most infected individuals do not realize that they are HCV positive and only discover the disease after severe liver damage has occurred. This article updates nurses on the epidemiology, transmission, risk factors, diagnosis, clinical presentation, and management of chronic HCV. A patient treatment algorithm is provided. The author also focuses on counseling and quality of life issues for infected patients. 6 figures. 52 references.

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Management Issues in Chronic Viral: Hepatitis C Source: Journal of Gastroenterology and Hepatology. 17(4): 415-422. April 2002. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: The natural history of chronic hepatitis C virus (HCV) infection and intervention with antiviral therapy are closely linked issues that cause the greatest controversy and concern for the person infected with HCV, as well as for the clinician involved in the assessment and treatment of people with chronic HCV infection. This article explores these management issues. The outstanding challenge of natural history is to identify the person who is likely to develop serious liver disease, and to make that determination early in the course of chronic HCV infection when treatment is likely to be of the greatest benefit. Interferons are still the mainstay of antiviral therapy for chronic HCV infection. The combination of interferon and ribavirin has improved sustained virological response (SVR) by decreasing the relapse rate. Treatment responses vary according to host factors such as age and gender, fibrotic severity and to viral factors like genotype and viral load. Patients who relapse after an end-of-treatment response to interferon monotherapy have a good chance of responding to combination interferon and ribavirin given for 6 months, but a longer treatment course should be considered in less optimal cases. At present, the treatment of those with non-response is

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less clear, but there is interest in more intense forms of interferon therapy, such as induction dosing or pegylated interferon in combination with ribavirin. Clinicians need to be aware of the common side-effects of interferon and ribavirin so that appropriate counseling and testing can be instituted before and during therapy. 1 figure. 4 tables. 24 references. ·

Hepatitis C Virus in Blood and Dialysate in Hemodialysis Source: American Journal of Kidney Diseases. 37(1): 38-42. January 2001. Contact: Available from W.B. Saunders Company. Periodicals Department, 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: The prevalence of hepatitis C virus (HCV) positivity among hemodialysis patients remains high compared with that of the healthy population, and thus the issue of safety and environmental protection must be addressed. This article reports on a study undertaken to evaluate the dynamics of prehemodialysis and posthemodialysis blood HCV levels and HCV escape to spent dialysate (and thus to the environment). A serine protease inhibitor (nafamostat mesilate) was used as the anticoagulant for hemodialysis. High flux polysulfone membrane dialyzers were used; dialyzer reuse was not performed. A portion of total spent dialysate (the fluid used for dialysis) was continuously extracted to measure for HCV. No HCV extravasation to spent dialysis was found, although HCV copy numbers were reduced to a statistically significant level in postdialysis blood compared with predialysis levels. The need to establish standards for risk management in dialysis centers is evident. The data obtained in this study strongly suggest that to minimize the risk for HCV transmission, lower transmembrane pressure (TMP) should be used in the hemodialysis of HCV positive patients, with fresh polysulfone dialyzers and dialysis settings of 180 to 250 milliliters per minute for blood flow, 500 milliliters per minute for dialysate flow, and less than 1.872 mm Hg for TMP. 1 figure. 23 references.

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Hepatitis C: Latest Guidelines from the NIH Source: Consultant. 42(14): 1722-1728. December 2002. Contact: Available from Cliggott Publishing Company. 330 Boston Post Road, Darien, CT 06820-4027. (203) 661-0600. Summary: The recent advances in knowledge of hepatitis C led the National Institutes of Health in 2002 to hold a second Consensus Development Conference on this topic and issue updated recommendations. This article presents highlights from those recommendations. The consensus statement may be viewed in its entirety at www.consensus.nih.gov. Topics include natural history, assessment options (serologic tests, liver biopsy, screening for liver cancer and HIV co-infection), treatment considerations (including whom to treat), and prevention strategies in the areas of injection drug use, sexual transmission, needlestick injury, and perinatal transmission. 2 tables. 2 references.

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Role of Liver Biopsy in Chronic Hepatitis C Source: Hepatology. 36(5 Supplemental 1): S152-S160. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000.

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Summary: The report of the 1997 National Institutes of Health (NIH) Consensus Development Conference on hepatitis C endorse pretreatment liver biopsy. This article reviews the role of liver biopsy in chronic hepatitis C, addressing whether liver histology helps determine the urgency of, and predicts the likelihood of response to, antiviral therapy; and if surrogate markers can supplant histological assessment. Because the rate of progression of chronic hepatitis C is influenced by baseline histological grade or stage, patients can be stratified into those with moderate to severe hepatitis, who merit imminent therapy, and those with mild hepatitis, in whom therapy can be postponed until more effective or tolerable treatments become available. Less advanced baseline histology has been shown to be an independent predictor of responsiveness to antiviral therapy. Although the predictive value of biopsy is insufficient to withhold therapy from patients with advanced fibrosis, baseline biopsy helps gauge expectations for the outcome of therapy. Reports have been published recently suggesting that laboratory markers can predict distinctions between low-grade fibrosis and therapy-indicating septal fibrosis or cirrhosis (scarring). These indices, however, are insufficiently reliable to predict histological distinctions in populations with varying prevalence of fibrosis or cirrhosis or to provide anything more than broad qualitative distinctions, far short of the potential information in a liver biopsy. For most patients, the value of pretreatment liver biopsy outweighs its risks, provides information about the urgency of treatment, and should be retained. The authors call for studies to identify noninvasive laboratory markers of histological activity and stage, especially genetic predictors of accelerated disease progression. 5 tables. 59 references. ·

Serological and Molecular Testing in Viral Hepatitis: An Update Source: Canadian Journal of Gastroenterology. 15(3): 177-184. March 2001. Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. Fax (905) 829-4799. E-mail: [email protected]. Summary: The routine serological (by blood test) diagnoses of the three major forms of viral hepatitis (A, B, C, and also delta hepatitis) are important in the evaluation of acute and chronic viral hepatitis (liver inflammation). This article updates readers on serological and molecular virological tests that are used to evaluate patients with chronic hepatitis C. The authors focus on the use of genotype and viral load testing to plan individualized patient treatment approaches. Despite the increasing sophistication of these diagnostic techniques, the initial approach to the patient with suspected viral hepatitis is still determined by the clinical impression of whether infection is acute or chronic. For suspected acute viral hepatitis, hepatitis A and B remain the major differentials because acute hepatitis C is usually subclinical, whereas hepatitis C has become the major cause of chronic hepatitis. The authors discuss the possible role of genotyping to help determine which patients may respond to interferon monotherapy. 4 tables. 63 references.

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Health Profile Preferences of Hepatitis C Patients Source: Digestive Diseases and Sciences. 45(2): 345-350. February 2000. Summary: The side effects of interferon alpha for chronic hepatitis C are well known. Patients may differ with respect to their tolerance of these side effects and also with respect to their individual preferences. This article reports on a study in which the authors administered a brief questionnaire to 67 outpatients with hepatitis C virus infection. Patients were asked to make hypothetical choices between 6 month profiles of health. The results showed that patients preferred to expedite rather than postpone

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intervals of poor health; preferences of patients with low quality of life were quite similar to preferences of healthier patients; patients' choices satisfied transitivity; patients' choices satisfied preferential independence; and patients gave a variety of reasons for their choices. These results corroborate other investigations of health preferences, and serve to introduce the field of preference elicitation to gastroenterologists. Alerting physicians to the intricacies of patients' preferences can improve the quality and appropriateness of health care interventions. 3 figures. 1 table. 20 references. ·

Treatment of Alcoholic Hepatitis Source: Journal of Gastroenterology and Hepatology. 17(4): 448-455. April 2002. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: This article considers the treatment of alcoholic hepatitis, a common disease with an overall 1 year mortality (death rate) of 20 percent. Although the classic treatment for alcoholic hepatitis is abstinence, in some individuals abstinence alone is inadequate to promote survival and recovery. This is particularly true of patients with severe alcoholic hepatitis, who are identified by jaundice, coagulopathy, and neutrophilia. Within the last two decades, several agents have been examined as treatments for alcoholic hepatitis and cirrhosis (liver scarring). The compounds that offer the greatest survival benefit to patients with severe alcoholic hepatitis are corticosteroids. Several groups have reported excellent results with corticosteroids, but positive results are not uniform, and there remains some controversy over their efficacy. Consequently, other agents are being tested that have broader applicability to individuals with contraindications to steroids. In this regard, pentoxifylline shows some promise, as does enteral feeding with medium chain triglycerides. Other agents under study include anti-oxidants and drugs such as S-adenosyl-methionine. 4 figures. 2 tables. 47 references.

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HIV and Hepatitis B Infection and Risk Behavior in Young Gay and Bisexual Men Source: Public Health Reports; Vol. 112, March/April 1997. Contact: Boston University School of Public Health, Department of Epidemiology and Biostatistics, 80 East Concord St, Boston, MA, 02118, (617) 638-7718. Summary: This article describes a study conducted to estimate the prevalence of, and identify risks for, HIV type I (HIV-I) and hepatitis B virus (HBV) infections and unprotected anal intercourse among young homosexual and bisexual men. The authors performed a cross-sectional analysis of data from a prospective cohort of 508 gay and bisexual men aged 18-24. HIV-I seroprevalence was 2.4 percent with five of 390 college students and seven of 117 non-students infected. HIV-I infection was associated with having a history of a sexually transmitted disease (STD) other than HIV-I or hepatitis B. The prevalence of hepatitis B markers in unvaccinated men was 12.9 percent. This was significantly associated with Asian ethnicity, off-campus residence, and a history of an STD other than HIV-I or HBV. It was inversely associated with recent non-intravenous drug use. Eighteen percent of the participants reported having had sex with women during the previous 12 months, and 26.4 percent reported a history of unprotected anal intercourse during the previous 6 months. Men who reported unprotected anal intercourse were more likely to have a steady partner, to have met their partners in anonymous settings, and to be identified as probably alcohol-dependent. Although

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prevalence of HIV-I infection among young homosexual and bisexual men in Boston was relatively low, the high rates of unprotected anal intercourse suggest a potential for future HIV-I and HBV transmission. Interventions should focus on young men with histories of sexually transmitted diseases, alcohol abuse, and depression. ·

Use and Interpretation of Virological Tests for Hepatitis C Source: Hepatology. 36(5 Supplemental 1): S65-S73. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: This article describes the use and interpretation of four virological markers of hepatitis C virus (HCV) infection: HCV genotype, HCV RNA, HCV core antigen, and antibody to HCV (anti-HCV). The diagnosis of acute and chronic hepatitis C is based on both anti-HCV detection using enzyme immunoassays (EIA) and HCV RNA detection using a sensitive molecular biology-based technique. Other virological tools, including HCV genotype determination and HCV RNA quantification, are now used to tailor treatment to the individual patient and to determine its efficacy. The author reviews the kinetics of HCV markers during acute and chronic HCV infection, together with current assays and their practical use in the management of HCV-infected patients. 3 figures. 3 tables. 55 references.

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Fibrosis and Disease Progression in Hepatitis C Source: Hepatology. 36(5 Supplemental 1): S47-S56. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: This article discusses the progression of fibrosis in chronic hepatitis C, which determines the ultimate prognosis and thus the need and urgency of therapy. Fibrogenesis is a complex dynamic process, which is mediated by necroinflammation and activation of stellate cells. The liver biopsy remains the gold standard to assess fibrosis. Scoring systems allow a semiquantitative assessment and are useful for crosssectional and cohort studies and in treatment trials. The rate at which fibrosis progresses varies markedly between patients. The major factors known to be associated with fibrosis progression are older age at infection, male gender, and excessive alcohol consumption. Viral load and genotype do not seem to influence significantly the progression rate. Progression of fibrosis is more rapid in immunocompromised patients. Hepatic steatosis (fatty liver), obesity, and diabetes may also contribute to more rapid progression of fibrosis. There are no tests that reliably predict the rate of progression of fibrosis in an individual patient. Serum markers for fibrosis are not reliable and need to be improved and validated. Liver biopsy provides the most accurate information on the stage of fibrosis and grade of necroinflammation, both of which have prognostic significance. Repeating the liver biopsy, 3 to 5 years after an initial biopsy, is the most accurate means of assessing the progression of fibrosis. 4 figures. 2 tables. 63 references.

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Towards Control of Hepatitis B in the Asia-Pacific Region: Natural History of Chronic Hepatitis B Virus Infection Source: Journal of Gastroenterology and Hepatology. 15(Supplement): E20-E24. May 2000.

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Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: This article highlights four aspects of the natural history of chronic hepatitis B virus (HBV) infection that require clarification: the differences between Caucasians and Asians with chronic HBV infection; the relationship between HBeAg seroconversion and the onset of cirrhosis (liver scarring), the role of precore and core promoter mutations, and when patients develop hepatocellular carcinoma (HCC, or liver cancer) and other complications of cirrhosis. In chronic HBV infection acquired during adulthood, which is the type mostly seen in the Caucasian population, there is biochemical and histologic regression after HBeAg seroconversion, and the risk of death from hepatitis B related causes is low. In chronic HBV infection acquired during birth or early childhood, which is the type most commonly seen in the Asian population, there is a prolonged phases of immunotolerance. The immune clearance phase is characterized by multiple acute exacerbations preceded by elevations in serum HBV DNA levels, HBeAg concentration and HBeAg/anti HBe immune complexes. Of these patients, 2.4 percent may develop hepatic (liver) decompensation during the stage of HBeAg seroconversion. The development of cirrhosis occurs more frequently in patients with episodes of decompensation and with repeated severe acute exacerbations. However, progression to cirrhosis can be relatively silent and can occur even in children. After HBeAg seroconversion, precore and core promotor mutations occur frequently in the Asian population. However, there is little correlation between the occurrence of these mutations and alanine aminotransferase elevation in patients who are positive for anti HBe. Although cirrhosis develops during the process of HBeAg seroconversion, 68 percent of the complications of cirrhosis and of hepatocellular carcinoma occur after HBeAg seroconversion. These complications may still occur even after HBsAg seroclearance. 21 references. ·

Nonresponders to Hepatitis B Vaccine Source: Postgraduate Medicine. 107(3): 97-98. March 2000. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Summary: This article is one in a series of professional consultation clinical questions to which the author responds. In this article, the questioner notes that routine testing showed a health care worker in the clinic who was nonreactive for HbsAb (antibody to the hepatitis B surface antigen) after receiving the triple dose vaccine. The questioner asks for recommendations in handling this situation, both in regular daily settings and after a high risk exposure. The author replies by stating that treatment of health care workers who do not respond to hepatitis B vaccine is an important issue, because hepatitis B is the major infectious hazard among these personnel. Between 5 and 32 percent of people receiving the vaccine are nonresponders. The Centers for Disease Control (CDC) recommends that persons who do not respond to the initial vaccine series complete a second three dose series and get tested again. Current hepatitis B vaccines contain only recombinant HBsAg. However, a third generation hepatitis B vaccine is being reviewed for licensure that also contains proteins derived from the virus envelope. The author notes that this vaccine may offer an alternative for persons who do not respond to current vaccines. Some persons remain nonresponders, even to this new vaccine, suggesting that hepatitis B vaccine response may have a genetic basis. 1 reference.

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Tests for Acute and Chronic Viral Hepatitis: Finding Your Way Through the Alphabet Soup of Infection and Superinfection Source: Postgraduate Medicine. 107(2): 123-126, 129-130. February 2000. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Summary: This article is the second in a four article symposium that provides a practical approach to the diagnosis and management of common hepatic disorders encountered by primary care physicians. In this article, the authors review the serologic (blood) and molecular diagnosis of viral hepatitis. The authors note that viral causes of hepatitis are clinically indistinguishable from one another. This can be a problem because appropriate management often depends on the specific virus involved. The authors discuss five hepatitis viruses (A through E) and explain which tests are most helpful for deciding on management for each type. Diagnosis of acute hepatitis A virus (HAV) is made by detection of hepatitis A IgM antibody. IgG antiHAV develops after natural infection and provides lifelong immunity. Neither reinfection nor chronicity occurs with HAV. The hepatitis B virus (HBV) produces a number of proteins with corresponding antibodies that enable accurate diagnostic evaluation of the patient with suspected HBV infection. Hepatitis B surface antigen (HBsAg) is almost always detectable when the disease is first seen, and disappears in acute HBV infection after clearance of the virus. Acute hepatitis C virus (HCV) is usually subclinical (without apparent symptoms), but the likelihood of chronicity is high. The routine diagnosis of HCV is by antibody testing with an ELISA. Hepatitis D virus (HDV) is unable to replicate on its own and requires HBV; thus, it can cause disease only in patients with HBV infection. Diagnosis of HDV infection revolves around the identification of antibodies; however, these antibodies are detectable in only one third of HDV infections. Hepatitis E virus (HEV) is a very unusual cause of acute hepatitis in the United States. 7 tables. 10 references.

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Antiviral Therapy for Chronic Hepatitis B and C: Which Patients are Likely to Benefit from Which Agents? Source: Postgraduate Medicine. 107(2): 135-138, 141-142, 144. February 2000. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Summary: This article is the third in a four article symposium that provides a practical approach to the diagnosis and management of common hepatic disorders encountered by primary care physicians. In this article, the author discusses current therapies for chronic hepatitis B and C and provides insight into future medications. Antiviral therapy in chronic hepatitis can completely eradicate the virus and induce remission of liver disease. To achieve such benefits, however, therapy should be initiated before decompensated liver disease ensues; at that point, liver transplantation is the only available option. The author describes indications for and contraindications to antiviral therapy in chronic hepatitis. For chronic HBV infection, interferon alfa2b requires only a 4 month course. However, it has adverse effects and contraindications and does not produce a universal response. Another option for HBV infection is lamivudine, which is administered orally and causes few side effects. However, relapse may occur when treatment is discontinued, and mutant virus may emerge. For chronic HCV infection, interferon alfa2a, interferon alfa2b, consensus interferon, and interferon combined with ribavirin have been used. The combination alternative is emerging as the method of choice in patients who do not have contraindications to oral ribavirin. Adverse effects

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are common and durability of response varies according to HCV RNA level and genotype. 5 tables. 21 references. ·

Treatment of Patients with Hepatitis C and Cirrhosis Source: Hepatology. 36(5 Supplemental 1): S185-S194. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: This article offers guidelines for the treatment of patients with hepatitis C and cirrhosis (scarring of the liver). The author notes that determining recommendations for this patient population is difficult. Few prospective studies have focused on the treatment of patients with advanced disease, and response rates appear to be lower and serious side effects more frequent in patients with cirrhosis. In patients with compensated cirrhosis, combination therapy with interferon alfa and ribavirin results in a sustained virological response (SVR) in 33 to 41 percent of patients. Responses to combination therapy are not significantly higher using peginterferon alfa 1a or 2b, compared with standard interferon. In using peginterferon in combination therapy, the benefits of once weekly dosing need to be weighed against the higher risks of cytopenias and greater costs with the pegylated formulations. Combination therapy results in some degree of histological improvement even in patients who are virological nonresponders. These findings provide the scientific basis for ongoing studies of maintenance therapy with peginterferon to prevent complications of cirrhosis in nonresponders patients with hepatitis C. Recommendations for the management of decompensated cirrhosis and of recurrent hepatitis C after liver transplantation are difficult because of limitations of data, most of which are derived from uncontrolled case series. Combination therapy is poorly tolerated in both groups and rates of response are low. Thus, while the medical need is great, treatment of patients with decompensated cirrhosis or with recurrent hepatitis C after transplantation should be undertaken cautiously and only within the confines of prospective clinical trials. 2 figures. 1 table. 16 references.

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Update on Hepatitis C Infection Source: Patient Care. 35(5): 75-78, 81-84, 89. March 15, 2001. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Fax (201) 573-4956. Summary: This article offers readers an update on the hepatitis C virus (HCV), the most common chronic bloodborne infection in the United States. Chronic HCV is initially diagnosed using serologic (blood) tests that demonstrate the presence of HCV antibodies. The condition is typically diagnosed in asymptomatic patients when they donate blood, apply for life or health insurance, or when a routine chemistry panel is performed. The authors stress that the key to detection is identifying risk factors in a patient with liver disease. Liver biopsy is the best test to assess the severity of HCV disease, but biopsy can cause serious complications. The treatment of choice for chronic hepatitis C infection is the combination of interferon alfa 2b and ribavirin, although new pegylated interferons are becoming available. The major side effect of ribavirin is hemolytic anemia, which is reversible and usually stabilizes after 5 to 6 weeks of treatment. Interferon therapy can exacerbate existing depression and cause new onset depression. Patients with preexisting anemia usually cannot tolerate the degree of hemolysis that occurs with ribavirin therapy. There are currently no published guidelines on how to best manage patients with HCV infection who have HIV

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coinfection. Patients are usually treated with interferon and ribavirin, since patients with HIV are now living longer. Unfortunately, liver toxicity caused by some of the drugs used to treat HIV can sometimes make it necessary to avoid using the most effective combinations of drug therapy for HIV. Screening for liver cancer is recommended in patients with HCV who have liver cirrhosis (scarring). Patients with chronic HCV infection should be counseled to avoid excessive consumption of alcohol and to educate themselves about avoiding transmission of their infection. 5 tables. 28 references. ·

What You Need to Know About the Silent Epidemic: Hepatitis C Source: Stadtlanders Lifetimes. Issue 1: 15-17. 2001. Contact: Available from Stadtlanders Lifetimes. Stadtlanders Pharmacy, 600 Penn Center Boulevard, Pittsburgh, PA 15235-5810. E-mail: [email protected]. Summary: This article on hepatitis C is from a patient education newsletter for patients who have undergone transplantation. The hepatitis C virus (HCV) is an infection of the blood that targets the liver and can result in cirrhosis (scarring), liver failure, and liver cancer. HCV is the cause of 20 to 30 percent of all liver transplants. Many people have the virus for years but are unaware of their infection. A majority of HCV cases are caused by contact with blood or blood products that contain the virus. With early detection, damage to the liver may be slowed or minimized for some patients by prompt treatment with the proper medications. Early detection also allows patients to take steps to prevent spreading the virus to others. Detection can be accomplished by blood test, liver biopsy, and a home testing kit (blood test). People who have hepatitis C are more susceptible to damage from other viruses such as hepatitis A and B; patients can be vaccinated against the latter two viruses. Combination treatment with injection interferon and ribaviron (an oral drug) is the standard regimen against HCV. Unfortunately, this regimen is expensive and has more side effects than interferon alone. The author reiterates the importance of focusing on education, disease awareness and research to help stop the progression and spread of the hepatitis C virus. The article concludes with a list of websites and toll free telephone numbers through which patients can find more information.

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Burden of Hepatitis C in the United States Source: Hepatology. 36(5 Supplemental 1): S30-S34. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: This article on the burden of hepatitis C in the United States is from a special supplemental issue of Hepatology journal on the National Institutes of Health (NIH) Consensus Development Conference (June 2002) on the management of hepatitis C. According to the third National Health and Nutrition Examination Survey (NHANES), 3.9 million of the United States civilian population have been infected with hepatitis C virus (HCV), of whom 2.7 million (74 percent) have chronic infection. HCV infection is most common among non-Caucasian men, ages 30 to 49 years. Moreover, the prevalence of antibody to hepatitis C virus in groups not represented in the NHANES sample, such as the homeless or incarcerated, may be as high as 40 percent. The age-adjusted death rate for non-A, non-B viral hepatitis increased from 0.4 to 1.8 deaths per 100,000 persons per year between 1982 and 1999. In 1999, the first year hepatitis C was reported separately, there were 3,759 deaths attributed to HCV, although this is likely an underestimate. There was a 5-fold increase in the annual number of patients with HCV who underwent liver transplantation between 1990 and 2000. Currently, more than one

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third of liver transplant candidates have HCV. Inpatient care of HCV-related liver disease has also been increasing. In 1998, an estimated 140,000 discharges listed an HCV-related diagnosis, accounting for 2 percent of discharges from non-federal acute care hospitals in the United States. The total direct health care cost associated with HCV is estimated to have exceeded $1 billion in 1998. Future projections predict a 4-fold increase between 1990 and 2015 in persons at risk of chronic liver disease (i.e., those with infection for 20 years or longer), suggesting a continued rise in the burden of HCV in the U.S. in the foreseeable future. 3 figures. 2 tables. 18 references. ·

Course and Outcome of Hepatitis C Source: Hepatology. 36(5 Supplemental 1): S21-S29. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: This article on the course and outcome of hepatitis C is from a special supplemental issue of Hepatology journal on the National Institutes of Health (NIH) Consensus Development Conference (June 2002) on the management of hepatitis C. The hepatitis C virus (HCV) is a small enveloped RNA virus belonging to the family flaviridae and genus hepacivirus. The HCV replicates at a high rate in the liver and has marked sequence heterogeneity. There are 6 genotypes and more than 90 subtypes of HCV, the most common in the United States being 1a and 1b (approximately 75 percent), 2a and 2b (approximately 15 percent), and type 3 (approximately 7 percent). Acute hepatitis C is marked by appearance of HCV RNA in serum within 1 to 2 weeks of exposure followed by serum alanine aminotransferase (ALT) elevations, and then symptoms and jaundice. Antibody to HCV (anti-HCV) tends to arise late. However, 55 percent to 85 percent of patients do not clear the virus, but develop chronic hepatitis C. Chronic hepatitis C is often asymptomatic, but is usually associated with persistent or fluctuating elevations in ALT levels. The chronic sequelae of hepatitis C include progressive hepatic fibrosis, cirrhosis (liver scarring), and hepatocellular carcinoma (HCC, liver cancer). Extra-hepatic (outside the liver) manifestations include sicca syndrome, cryoglobulinemia, glomerulonephritis, and porphyria cutanea tarda. The author concludes that knowledge of the course and outcome of hepatitis C is important in developing approaches to management and therapy. 5 figures. 80 references.

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Natural History of Chronic Hepatitis C Source: Hepatology. 36(5 Supplemental 1): S35-S46. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: This article on the natural history of chronic hepatitis C is from a special supplemental issue of Hepatology journal on the National Institutes of Health (NIH) Consensus Development Conference (June 2002) on the management of hepatitis C. The author notes that much controversy surrounds the issue of the natural history of hepatitis C virus (HCV) infection. Many authorities view the disease as inexorably progressive with a high chance of progressing over time to cirrhosis (liver scarring) and occasionally hepatocellular carcinoma (HCC, liver cancer) and, therefore, likely to be responsible for causing death. Others regard chronic hepatitis C as having a variable outcome, the majority of infected persons not dying from the disease, but more likely from the comorbid conditions that so often accompany infection by this agent, or from more common medical conditions. Disagreements probably derive from the manner of conduct of the study and the populations studied. Efforts to determine natural history

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are handicapped by the primary characteristics of the disease, namely that its onset rarely is recognized and its course is prolonged exceedingly. Thus, different outcomes have come from retrospective rather than from prospective studies, but both have concluded that at least 20 percent of chronically infected adults develop cirrhosis within 20 years. More recent studies that used a retrospective and prospective approach, focusing largely on young infected individuals, have produced different results. Among these young people, particularly young women, spontaneous resolution of the viral infection is more common than previously thought and cirrhosis has been identified in 5 percent or fewer of them. The major failing for all groups studied, young and old, is that natural history studies have rarely exceeded the first 2 decades, so that outcome beyond this time is not known, other than through modeling. The author concludes that several host-related and extraneous factors probably affect the natural history. 6 figures. 4 tables. 96 references. ·

Factors Associated with Prevalent Hepatitis C: Differences Among Young Adult Injection Drug Users in Lower and Upper Manhattan, New York City Source: American Journal of Public Health. 91(1): 23-30. January 2001. Contact: American Public Health Association. 800 I Street, NW, Washington, DC 200013710. (202) 777-2742. Fax (202) 777-2534. E-mail: [email protected]. Website: www.ajph.org. Summary: This article reports on a study that examined correlates of prevalent hepatitis C virus (HCV) infection among young adult injection drug users in 2 neighborhoods in New York City. Injection drug users aged 18 to 29 years were street recruited from the Lower East Side and Harlem. Participants were interviewed about drug use and sex practices; venipuncture (blood testing) was performed for hepatitis B virus (HBV), HCV, and HIV serologies. In both sites, testing positive for HCV antibody (anti HCV) was associated with having injected for more than 3 years. Additionally, HCV infection was positively associated with injecting with someone known to have had hepatitis (but the association was significant only in the Lower East Side) and with sharing cotton (but the association was statistically significant only in Harlem). Being in drug treatment and older than 24 years were associated with HCV in the Lower East Side but not in Harlem. Receiving money for sex was associated with anti HCV positivity in Harlem but not in the Lower East Side. The authors conclude that several differences in factors associated with prevalent HCV infection existed among 2 populations of young injection drug users from the same city. Indirect transmission of HCV may occur. 1 figure. 3 tables. 30 references.

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Hepatitis C Virus Infection in a Community in the Nile Delta: Risk Factors for Seropositivity Source: Hepatology. 33(1): 248-253. January 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: This article reports on a study undertaken to identify risk factors for hepatitis C virus (HCV) infection in a rural village in the Nile Delta with a high prevalence of antibodies to HCV (anti HCV). One half of the village households were systematically selected, tested for anti HCV, and interviewed. Of this group (n = 3999), 973 (24.3 percent) were anti HCV positive, reflecting prior HCV infection but not necessarily current liver disease, with nearly equal prevalence among males and females. Anti HCV prevalence increased sharply with age among both males and females, from 9.3 percent

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in those 20 years of age and younger to greater than 50 percent in those older than 35 years of age. Among those over 20 years of age, the following risk factors were significantly associated with seropositivity: age, male gender, marriage, anti schistosomiasis injection treatment, blood transfusion, invasive medical procedure (surgery, catheterization, endoscopy, or dialysis), receipt of injections from 'informal' health care provider, and cesarean section or abortion. Exposures not significantly related to anti HCV positivity in adults included history of, or active infection with, Schistosoma mansoni; sutures or abscess drainage; goza smoking in a group; and shaving by community barbers. Among those 20 years old or younger, no risk factors were clearly associated with anti HCV positivity; however, circumcision for boys by informal health care providers was marginally associated with anti HCV. The authors note that prevention programs focused primarily on culturally influenced risks in rural Egyptian communities are being implemented and evaluated. 7 tables. 32 references. ·

National Institutes of Health Consensus Development Conference Statement: Management of Hepatitis C: 2002: June 10-12, 2002 Source: Hepatology. 36(5 Supplemental 1): S3-S20. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: This article reprints the introduction to the National Institutes of Health (NIH) Consensus Development Conference on the management of hepatitis C, that was held in Washington, D.C., in June 2002. The conference was convened with the aim of reviewing the most recent developments regarding management, treatment options, and the widening spectrum of potential candidates for treatment, and for updating the 1997 Consensus Statement on hepatitis C. The author of this executive summary briefly reports the consensus statements on the six questions posed to the Panel: What is the natural history of hepatitis C? What is the most appropriate approach to diagnose and monitor patients? What is the most effective therapy for hepatitis C? Which patients with hepatitis C should be treated? What recommendations can be made to patients to prevent transmission of hepatitis C? and What are the most important areas for future research? The article concludes with a list of 12 recommendations regarding hepatitis C, information about the NIH Consensus Development Program, and a list of the members of the Panel.

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Prevalence of Syphilis, Hepatitis B Virus (HBV), and Human Immunodeficiency Virus (HIV) Infection in New Arrestees at the Lake County Jail, Crown Point, Indiana Source: Journal of Prison & Jail Health; Vol. 12, no. 2, Winter 1993. Contact: Eli Lilly and Company, Eli Lilly Corporate Center, Indianapolis, IN, 46285, (317) 276-2000, http://www.lilly.com. Summary: This article reviews a study conducted to determine the prevalence in arrestees of syphilis, hepatitis B virus (HBV), and HIV infection by demographic and behavioral characteristics, and to evaluate the costs associated with universal screening for these sexually transmitted diseases compared with a theoretical targeted screening program. Three hundred and nineteen arrestees were screened for syphilis, HBV, and anonymously for HIV infection. The prevalence of syphilis was 2.5 percent; hepatitis B surface antigen prevalence was 1.6 percent; the prevalence of past or present HBV infection was 21.9 percent; and the prevalence of HIV infection was 1.6 percent. Targeted screening for sexually transmitted diseases was found to be more costeffective.

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Current Treatment Strategies for Chronic Hepatitis B and C Source: in Coggins, C.H.; Hancock, E.W., Eds. Annual Review of Medicine: Selected Topics in the Clinical Sciences, Volume 52. Palo Alto, CA: Annual Reviews Inc. 2001. p. 29-49. Contact: Available from Annual Reviews Inc. 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303-0139. (800) 523-8635. Fax: (415) 855-9815. PRICE: $47. ISBN: 0824305450. Summary: This article reviews current treatment strategies for chronic hepatitis B and hepatitis C, two types of liver inflammation caused by the hepatitis virus. For chronic hepatitis B, treatment with a 4 month course of interferon alfa-2b can achieve hepatitis B e antigen seroconversion, normalization of aminotransferase levels, reduced hepatic inflammation, and possibly reduced progression to cirrhosis (liver scarring), and improvement in survival in 20 to 30 percent of patients. Similar results can be achieved with a 12 month course of lamivudine, with response rates increasing to 40 to 65 percent after 3 years of therapy. Interferon can also be used in early cirrhotic patients, and lamivudine can be used in people with advanced cirrhosis and in immunosuppressed patients. Combination interferon and lamivudine therapy does not confer additional benefits. For chronic hepatitis C, the combination of interferon alfa-2b and ribavirin in the treatment of choice, offering superior sustained response rates (40 percent) compared with interferon alone (15 percent). Therapy should be administered for 12 months to patients with genotype 1 virus but for only 6 months to patients with genotypes 2 and 3. Patients experiencing relapse after 6 months of interferon monotherapy can be re-treated with interferon and ribavirin or high-dose interferon, with 45 to 56 percent sustained response rates. However, relatively few patients who are prior nonresponders to interferon monotherapy will have sustained response to further interferon-based treatments, including combination therapy with ribavirin. Successful therapy not only leads to the eradication of viral RNA but also may delay progression to cirrhosis and hepatocellular carcinoma (HCC, liver cancer). Interferon combined with polyethylene glycol (PEG) shows promise as an improved formulation of interferon with yet higher sustained response rates. 1 figure. 6 tables. 99 references.

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Non-Alcoholic Steato Hepatitis (NASH) Source: Practical Gastroenterology. 26(1): 34, 37-40, 42. January 2002. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435. Summary: This article reviews non alcoholic steato hepatitis (NASH), a common and increasingly recognized liver disease characterized by elevated liver enzymes and hepatic (liver) histology similar to alcoholic hepatitis in patients without significant alcohol consumption. Most common risk factors include: obesity, type 2 diabetes, metabolic disorders, and medications. The majority of patients are asymptomatic and the diagnosis is made after exclusion of viral and autoimmune hepatitis as well as other metabolic, toxic, or genetic causes of liver disease. The role of liver biopsy to confirm the diagnosis in clinical practice is a matter of controversy, although it remains the gold standard to assess disease severity and progression. There is increasing evidence that NASH is not as benign as originally thought with a significant number of patients progressing to cirrhosis. The mainstay of current treatment is modification of risk factors concentrating on weight loss for obese patients and tight control of glycemia and lipidemia in patients with diabetes and lipid disorders. Many experimental therapies are currently under investigation, but more effective treatments will require a better understanding of the disease pathogenesis. 3 tables. 17 references.

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Approach to the Patient with Chronic Hepatitis C Virus Infection Source: Annals of Internal Medicine. 136(10): 747-757. May 21, 2002. Contact: Available from American College of Physicians. American Society of Internal Medicine. 190 North Independence Mall West, Philadelphia, PA 19106-1572. Website: www.acponline.org. Summary: This article reviews the approach to a patient with chronic hepatitis C virus (HCV) infection, a common and often asymptomatic disease. Antibodies against HCV are a highly sensitive marker of infection. Molecular testing for HCV is used to confirm a positive result on antibody testing and to provide prognostic information for treatment; however, quantitative HCV RNA does not correlate with disease severity or risk for progression. Chronic HCV infection is most frequently associated with remote or current intravenous drug use and blood transfusion before 1992, although as many as 20 percent of infected patients have no identifiable risk factor. In an estimated 15 to 20 percent of persons infected with HCV, the infection progresses to cirrhosis (liver scarring); alcohol intake is an important cofactor in this progression. Most specialists prefer to include an examination of liver histology (by biopsy) in the management of patients with chronic HCV infection to aid prognostic and treatment decision. The current standard of drug therapy for chronic HCV is weekly subcutaneous peginterferon in combination with daily oral ribavirin, which results in sustained virologic response in approximately 55 percent of chronically infected patients. Side effects of interferon therapy include myalgias, fever, nausea, irritability, and depression. The cost-effectiveness of interferon therapy is similar to that of many commonly accepted medical interventions. The author concludes that the primary care physician serves a vital role in identifying patients with chronic HCV infection, educating patients about risk factors for transmission, advising patients about the avoidance of alcohol, and aiding patients in making treatment decisions. 4 tables. 100 references.

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Vaccination Against Hepatitis B: Current Challenges for Asian Countries and Future Directions Source: Journal of Gastroenterology and Hepatology. 15(4): 396-401. April 2000. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: This article reviews the current status of hepatitis B immunization programs as well as future issues concerning hepatitis B immunization in Asian countries. The literature was identified via in house and MEDLINE (1980 to 1999) searches and references cited in published articles. Results showed that chronic hepatitis B infection is responsible for 75 to 90 percent of primary hepatocellular carcinoma (liver cancer), one of the 10 most common cancers worldwide. Hepatitis B and its chronic sequelae can potentially be eradicated through vaccines that have been shown to be 95 to 99 percent effective in preventing development of the disease or the carrier state in immunized infants. Approximately 75 percent of the world's hepatitis B carriers live in Asian countries wherein wide variations in immunization strategies exist. Vaccination programs in hyperendemic Asian countries have elicited decreases in the incidence of acute and chronic infections as well as a decrease in chronic carriers in the unvaccinated population. Decreases in the incidence of hepatocellular carcinoma have been recorded in Taiwan and Singapore after at least 10 years of universal hepatitis B immunization programs. The authors conclude that, in Asian countries currently without nationwide hepatitis B programs, utilization of the existing vaccination infrastructure (for

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administration of other World Health Organization vaccines) will provide the most economical and efficient means of administration of the hepatitis B vaccine. 3 tables. 40 references. ·

Alcoholic Hepatitis: A Diagnosis of Exclusion Source: Physician Assistant. 25(7): 42-44. July 2001. Contact: Available from Springhouse Corporation. Physician Assistant, P.O. Box 908, Springhouse, PA 19477. (215) 646-8700. Fax (215) 646-4399. Website: www.pajournal.com. Summary: This article reviews the diagnosis of alcoholic hepatitis, generally thought to be a diagnosis of exclusion. The author first presents the case of a 41 year old Hispanic man who was referred to the gastroenterologist (specialist in the gastrointestinal tract) for evaluation of jaundice (yellowing of the skin and eyes, caused by extra bilirubin in the blood) of 2 weeks' duration. The author describes the patient's symptoms and the results of the diagnostic tests, noting that given the patient's clinical picture and longstanding history of alcohol abuse, a presumptive diagnosis of alcoholic hepatitis (inflammation of the liver) was made. The patient was admitted to the hospital for close monitoring and further evaluation; his final diagnosis was alcoholic hepatitis with underlying alcoholic cirrhosis (scarring of the liver). He remained stable throughout his 3 day hospital stay and was discharged from the hospital to be closely followed as an outpatient. The cornerstone of his treatment is abstinence, the same treatment for all forms of alcoholic liver disease (ALD). Because of his liver cirrhosis, complications need to be managed symptomatically until a transplant liver is available. The author notes that most transplant programs require at least 6 months abstinence from alcohol before a patient is considered for liver transplant candidacy. 3 references.

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Treatment of Patients with Hepatitis C and Normal Serum Aminotransferase Levels Source: Hepatology. 36(5 Supplemental 1): S179-S184. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: This article reviews the treatment of patients with hepatitis C and normal serum aminotransferase levels. Approximately 30 percent of patients with chronic hepatitis C have normal serum alanine aminotransferase (ALT) levels and another 40 percent have ALT levels that are less than twice the upper limit of the normal range. Most patients with normal ALT levels have mild degrees of inflammation with mild or no fibrosis, and the rate of disease progression is reduced compared with that in patients with elevated ALT levels. Some patients with normal ALT levels have advanced fibrosis and cirrhosis (scarring) on liver biopsy. Treatment of patients with normal ALT levels with either interferon monotherapy or interferon and ribavirin combination therapy has shown sustained virological response (SVR) rates that are equivalent to those achieved for patients with elevated ALT levels. Thus, patients with chronic hepatitis C should not be excluded from therapy based on ALT levels alone. The decision to initiate therapy with interferon and ribavirin should be based on a combination of factors independent of ALT levels, including amount of fibrosis on liver biopsy, hepatitis C virus (HCV) genotype and viral level, patient age and motivation, and co-morbid conditions. 2 tables. 23 references.

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National Institutes of Health Consensus Development Conference: Management of Hepatitis C: 2002 Source: Hepatology. 36(5 Supplemental 1): S1-S2. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: This article serves as an introduction to a special supplement of the journal Hepatology, which summarizes the National Institutes of Health Consensus Development Conference on the management of hepatitis C, held in Washington, D.C., in June 2002. This article reviews the six questions that formed the basis of the conference: What is the natural history of hepatitis C? What is the most appropriate approach to diagnose and monitor patients? What is the most effective therapy for hepatitis C? Which patients with hepatitis C should be treated? What recommendations can be made to patients to prevent transmission of hepatitis C? and What are the most important areas for future research? The author notes that this special supplement includes the final statement of the Consensus Panel, as well as overview summaries of the 28 oral presentations made at the conference. The author also thanks the members of the Consensus Panel and a number of organizations and individuals that made this work possible. 5 references.

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Characteristics of and Current Treatment Options for Hepatitis B and Hepatitis C Source: Journal of the Canadian Dental Association. 66(10): 537. November 2000. Contact: Available from Canadian Dental Association. 1815 Alta Vista Drive, Ottowa, ON K1G 3Y6. (613) 523-1770. E-mail: [email protected]. Website: www.cda-adc.ca. Summary: This brief article reviews the characteristics of and current treatment options for hepatitis B and hepatitis C, focusing on the risks to health care workers, including dental professionals. The author provides information about the natural history, therapeutic choices, and future directions of therapy for these two forms of hepatitis. Not all patients who test positive for hepatitis B surface antigen (HbsAg) require antiviral therapy; many people have circulating HBsAg without evidence of significant hepatitis. These people are chronic carriers and account for the majority of hepatitis B cases. Treatment options include alpha interferon or oral lamivudine; however, conversion to negative status is achieved in only approximately 20 percent of cases with either therapy. Hepatitis C is a common condition affecting approximately 2 percent of Canadians; of patients with chronic hepatitis C, approximately 20 percent experience serious liver complications. These complications can include cirrhosis, need for liver transplantation, hepatocellular carcinoma (liver cancer), or death. Standard treatment for hepatitis C is alpha interferon and ribavirin; sustained remission occurs in approximately 40 percent of cases. The article concludes with the website for the Canadian Association for the Study of the Liver (www.lhsc.on.ca/casl/summ.htm ).

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Confirming the Diagnosis of Hepatitis C Virus Infection Source: Journal of Critical Illness. 15(7): 350. July 2000. Contact: Available from Cliggott Publishing Company. 55 Holly Hill Lane, Greenwich, CT 06831-0010. (203) 661-0600. Summary: This brief article reviews the strategies undertaken to confirm the diagnosis of hepatitis C virus (HCV) infection. The first line test for diagnosing HCV infection is the HCV antibody test, an enzyme linked immunosorbent assay that is easy to perform,

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cost effective, and highly sensitive for detecting HCV infection in a patient who is not immunocompromised. Currently, the second generation anti HCV test is used by most institutions; a third generation assay with improved sensitivity has been approved but is not yet widely used. In general, patients should undergo HCV antibody testing if they admit to any of the risk factors for hepatitis C or if they have elevated liver enzyme levels, regardless of the degree of elevation. When a positive test result is obtained in a patient with risk factors for hepatitis C and elevated liver enzyme levels, the diagnosis of hepatitis C is more than 95 percent certain. To confirm ongoing viremia (virus status in the blood), testing for HCV RNA by polymerase chain reaction (PCR) is recommended. PCR testing is not recommended for first line testing because it is expensive, difficult to perform, and can yield both false positive and false negative results. One chart lists the indications (risk factors) for testing for hepatitis C virus. 1 table. 1 reference. ·

Hepatitis B e Antigen: The Dangerous Endgame of Hepatitis B. (editorial) Source: New England Journal of Medicine. NEJM. 347(3): 208-210. July 18, 2002. Summary: This editorial familiarizes readers with the complication of hepatitis B that results in the hepatitis B e antigen (HBeAg). Shortly after the discovery of hepatitis B virus (HBV), the striking epidemiological association between HBV infection and liver cancer (hepatocellular carcinoma) was noted. Subsequent research demonstrated that the risk of liver cancer was increased by a factor of 10 among men who were positive for HBsAg (hepatitis B surface antigen) alone and by a factor of 60 among those who were positive for both HBsAg and HBeAg. Older age, the presence of antibodies against hepatitis C virus, cigarette smoking, and use of alcohol were also identified as independent risk factors for the development of liver cancer. The author explores the evidence for the role of HBeAg and notes that although this proposed role of HBeAg may contribute to the development of liver cancer, it is most likely that its role as a marker of active virus replication is associated with the increased risk in cancer. The author also briefly considers the pathogenesis of HBV-associated liver cancer, the role of environmental hepatotoxins (liver toxins), and the strategies used to fight HBV (vaccination and drug therapy). 1 figure. 16 references.

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Viral Hepatitis A to E and Beyond Source: Practical Gastroenterology. 26(7): 43-44. July 2002. Contact: Available from Shugar Publishing. 12 Moniebogue Lane, Westhampton Beach, NY 11978. (516) 288-4404. Fax (516) 288-4435. Summary: This fact sheet, designed to be photocopied and distributed to patients, reviews the various types of viral hepatitis. Hepatitis is inflammation of the liver. Several different viruses cause viral hepatitis: the hepatitis A, B, C, D, and E viruses. For each type, the fact sheet notes how the disease is spread (transmission), people who are at particular risk for getting the disease, prevention strategies, and treatment options. All of these viruses cause acute, or short term, viral hepatitis. The hepatitis B, C, and D viruses can also cause chronic hepatitis, in which the infection is prolonged, sometimes lifelong. The fact sheet also notes the symptoms of viral hepatitis, which can include jaundice (yellowing of the skin and eyes), fatigue, abdominal pain, loss of appetite, nausea, diarrhea, and vomiting. However, some people do not have symptoms until the disease is advanced. The fact sheet concludes with a simple line illustration of the digestive tract showing the location of the liver. The contact information for three resource organizations is also provided. 1 figure.

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Preventing Transmission of HIV and Hepatitis B in Day Care Source: Epidemiology Bulletin; Vol. 93, No. 2. Contact: Oklahoma State Department of Health, Disease & Prevention Services, HIV/STD Service, 1000 NE 10th St, Oklahoma City, OK, 73117-1299, (405) 271-4636, http://www.health.state.ok.us/program/hivstd/index.html. Summary: This journal article presents prevention measures for avoiding the spread of HIV and Hepatitis B in day care settings. Methods of exposure and transmission are discussed, with an emphasis on the fact that exposure does not necessarily lead to infection. The minimal risk of transmission in day care is indicated. A fact sheet lists precautions for day care centers to follow, with a recommendation that these become general policy for all centers in the State of Oklahoma. The list includes suggestions on staff training, sanitation, and the handling of blood. Guidelines for dealing with infected children are also provided. These recommend against exclusion from day care, and urge that other parents or uninvolved staff members not be informed. Suggestions are made for managing aggressive behavior, such as biting, that could result in transmission. Other suggestions involve what to do should a potentially infectious event occur.

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Hepatitis C-Associated Autoimmune Disorders Source: Rheumatic Disease Clinics of North America. 24(2): 353-374. May 1998. Summary: This journal article provides health professionals with information on hepatitis C virus (HCV) infection, HCV-associated immune and autoimmune disorders, and therapeutic strategies and toxicities documented in patients with HCV-associated disorders. The article begins with a discussion of the possible role of the immune system in HCV infection and an explanation of how the HCV infection is diagnosed. This is followed by data on the prevalence of HCV-associated autoimmunity. The article then describes the serologic and clinical correlates of HCV infection to illustrate an emerging picture of autoimmune disease spectra. Correlates include autoantibody formation, cryoglobulinemic manifestation, vasculitis, vascular thrombosis and antiphospholipid antibody syndrome, glomerulonephritis, systemic lupus erythematosus, rheumatoid arthritis, polymyositis, dermatomyositis, Sjogren's syndrome, autoimmune thyroid disease, and autoimmune hepatitis. In addition, the article discusses the treatment of HCV infection with interferon alpha. Although this drug has been shown to reduce cryoglobulins and improve associated proteinuria, vasculitis, and neuropathy, it may have no effect on, precipitate, or exacerbate other autoimmune diseases. The article concludes that further epidemiologic and virologic investigations controlling for HCV risk factors, HCV subtype, human leukocyte antigen genotype, and geographic and environmental variables will be needed to clarify a potential causal relationship for HCV infection in autoimmune disease. 1 figure, 2 tables, and 177 references.

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Treatment of Chronic Hepatitis C: A Systematic Review Source: Hepatology. 36(5 Supplemental 1): S135-S144. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: This review article addresses three issues regarding current treatments for chronic hepatitis C: efficacy and safety in treatment-naive patients; efficacy and safety in selected subgroups of patients; and effects on long term clinical outcomes. The authors search electronic databases for articles from January 1996 to March 2002. Additional articles were identified by searching references in pertinent articles and recent journals

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and by questioning experts. Articles were eligible for review if they reported original human data from a study that used virological, histological, or clinical outcome measures. The review found that the combination of high dose peginterferon and ribavirin was more effective than standard interferon and ribavirin in persons infected with hepatitis C virus (HCV) genotype 1. Ranges of SVR rates were higher with peginterferon than with standard interferon monotherapy in naive patients. Reports were consistent in showing treatment with interferon and ribavirin was more effective than interferon monotherapy in treatment-naive persons and previous nonresponders and relapsers. Studies were moderately consistent in showing that treatment decreases the risk for hepatocellular carcinoma (HCC, liver cancer). The evidence on treatment in important subgroups was limited by a lack of randomized controlled trials. 2 figures. 2 tables. 62 references. ·

Role of Liver Biopsy in Management of Chronic Hepatitis C: A Systematic Review Source: Hepatology. 36(5 Supplemental 1): S161-S172. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: This review article considers two topics pertinent to the need for pretreatment liver biopsy in patients with chronic hepatitis C: how liver biopsy results predict treatment outcomes; and how well biochemical blood tests and serological measures of fibrosis predict biopsy findings in chronic hepatitis C. The authors searched MEDLINE and other electronic databases from January 1985 to March 2002. Additional articles were sought in references of pertinent articles and recent journals and by querying experts. Articles were eligible for review if they reported original human data from a study that used virological, histological, pathologic, or clinical outcome measures. Studies suggested that advanced fibrosis or cirrhosis (scarring) on initial liver biopsy is associated with a modestly decreased likelihood of a sustained virological response (SVR) to treatment. Also, studies relatively consistently showed that serum aminotransferases have modest value in predicting fibrosis on biopsy; that extracellular matrix tests hyaluronic acid and laminin may have value in predicting fibrosis; and that panels of tests may have the greatest value in predicting fibrosis or cirrhosis. Biochemical and serologic tests were best at predicting no or minimal fibrosis, or at predicting advanced fibrosis or cirrhosis, and were poor at predicting intermediate levels of fibrosis. Thus, evidence suggests that liver biopsy may have some usefulness in predicting efficacy of treatment in patients with chronic hepatitis C, and biochemical blood tests and serologic tests currently have only modest value in predicting fibrosis on liver biopsy. 2 tables. 81 references.

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Management of Viral Hepatitis B Source: Journal of Gastroenterology and Hepatology. 17 (Supplement): S125-S145. February 2002. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: This review article discusses hepatitis B virus (HBV) infection, a major global health concern and the most common cause of chronic liver disease worldwide. The natural history and clinical outcomes of chronic HBV infection are determined by the viral replication cycle and the host immune responses. Treatment of chronic hepatitis B is directed at interrupting the natural history of suppressing HBV replication before

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development of any significant irreversible liver cell damage. Two major classes of antiviral therapeutic agents that have been approved for treatment of chronic hepatitis B are immunomodulating agents (i.e., interferon) and the nucleoside analogs (i.e., lamivudine). A major problem of antiviral treatment is the emergence of drug resistance. Many new immunomodulatory therapies and antiviral agents are in various stages of clinical development and have shown some promise. Among newer HBV antivirals, adefovir dipivoxil, entecavir, emtricitabine, DAPD, and clevudine appear to be at least as potent as lamivudine in suppressing HBV replication. The author hypothesizes that combinations of an immunomodulatory agent and nucleoside analog may improve the therapeutic efficacy and reduce the emergence of drug resistance. Nevertheless, combinations of interferon and lamivudine therapies do not confer such additional benefits. The next challenge for HBV treatment is to use antivirals in combination or cyclical therapy to minimize the emergence of drug resistance and increase efficacy, particularly to achieve sustainable post treatment suppression of HBV. 4 tables. 147 references. ·

Hepatitis B Viral Genotypes: Clinical Relevance and Molecular Characteristics Source: Journal of Gastroenterology and Hepatology. 17 (6): 643-650. June 2002. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E- mail: [email protected]. Website: www.blackwell-science.com. Summary: This review article focuses on hepatitis B virus (HBV) infection, a global health problem. The clinical outcome of chronic HBV infection depends on the frequency and severity of hepatitis flares in the immune clearance phase. Currently, four subtypes and seven genotypes of HBV are identified and most have specific geographic distributions. The impact of HBV genotypes on the clinical outcome of chronic HBV infection has been partially clarified. The author provides numerous examples from Taiwan, Japan and China. The author concludes that pathogenic (how the disease develops) and therapeutic differences do exist among HBV genotypes, and determining the genotype in patients with chronic HBV infection would help gain further information for etiologic (causative), clinical, virologic, and anthropologic investigations. 1 figure. 2 tables. 61 references.

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Outcome of Hospital Care of Liver Disease Associated with Hepatitis C in the United States Source: Hepatology. 33(1): 201-206. January 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: This study describes mortality and resource utilization for inpatient (hospital) care of hepatitis C (HCV) in comparison to alcohol induced liver disease (ALD) in the United States. The study also identifies factors that affect outcomes. The Healthcare Cost and Utilization Project database, a national inpatient sample was used to identify hospitalization records with diagnoses related to liver disease from HCV and ALD. Outcomes of hospitalizations was analyzed in terms of inhospital deaths and health care resource utilization. For 1995, the authors estimate that there were 26,700 hospitalizations and 2,600 deaths in acute, nonfederal hospitals in the United States for liver diseases caused by HCV. Total charges for these hospitalizations were $514 million. In comparison, ALD was associated with 101,200 hospitalizations; 13,400 deaths, and $1.8 billion in charges. Simultaneous HCV and alcohol abuse was associated with

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younger ages at the time of hospitalization and death compared with HCV or ALD alone. In analyses, alcohol abuse and HIV infection were associated with an increased risk of death among those with HCV. Liver transplantation and patient death were associated with the largest increase in hospitalization charges. Major complications of cirrhosis (such as variceal bleeding, encephalopathy, and hepatorenal syndromes) and sociodemographic factors (such as race and health insurance) were also significantly associated with the risk of death and hospitalization charges, which were similar in HCV and ALD. The authors provide new estimates regarding the public health impact of HCV, for use in health policy decision and cost effectiveness analyses of preventive and therapeutic interventions. 6 tables. 21 references. ·

Screening Tests for Hepatocellular Carcinoma in Patients with Chronic Hepatitis C: A Systematic Review Source: Hepatology. 36(5 Supplemental 1): S84-S92. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: This systematic review article addresses two areas: the efficacy of using screening tests for hepatocellular carcinoma (HCC, liver cancer) in improving outcomes in chronic hepatitis C (HCV); and the sensitivity and specificity of screening tests for HCC in chronic HCV infection. The authors searched MEDLINE and other electronic databases for publications between January 1985 and March 2002. Additional articles were identified by reviewing pertinent articles and journals and by querying experts. Data collection involved paired reviewers who assessed the quality of each study and abstracted data. One nonrandomized prospective cohort study suggested that HCC was detected earlier and was more often resectable in patients who had twice yearly screening with serum alpha-fetoprotein (AFP) and hepatic ultrasound than in patients who had usual care. Twenty-four studies, which included patients with chronic hepatitis B or C or both, addressed the sensitivities and specificities of screening tests. They were relatively consistent in showing that the sensitivity of serum AFP for detecting HCC usually was moderately high at 45 percent to 100 percent, with a specificity of 70 to 95 percent. The few studies that evaluated screening with ultrasound reported high specificity, but variable sensitivity. The authors conclude that screening of patients with chronic hepatitis C with AFP and ultrasound may improve detection of HCC, but studies are needed to determine whether screening improves clinical outcomes. 2 figures. 1 table. 51 references.

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Treatment of Chronic Hepatitis B Virus Infection in Special Groups of Patients: Decompensated Cirrhosis, Immunosuppressed and Paediatric Patients Source: Journal of Gastroenterology and Hepatology. 15(Supplement): E71-E78. May 2000. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: Treatment of special groups of patients (i.e., patients with decompensated cirrhosis, immunocompromised patients, and children) is challenging and requires different treatment strategies. This article explores the management of chronic hepatitis B in these special populations. Patients with decompensated liver disease have a poor prognosis and are difficult to treat. Chances of survival for this group are limited without liver transplantation. Interferon alpha (IFN alpha) is presently the

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recommended treatment for patients with clinically stable chronic hepatitis B. The aim of treatment is to permanently suppress or eliminate HBV infection and thereby induce remission of liver disease. The author notes that there is increasing interest in the use of nucleoside analogues in the treatment of decompensated liver disease and those going for liver transplantation. The author discusses the use of thymosin alpha 1 and lamivudine as treatment options. Chronic hepatitis B is common in immunosuppressed patients, including antiHIV positive patients, patients with chronic renal failure, and patients undergoing organ transplantation. Unfortunately, their response to IFN therapy is poor, mostly because of high level viraemia (levels of virus in the blood) and depressed cell mediated immunity. The prevalence of hepatitis B in Asian children is probably similar to that in adults. Infection acquired early in life may not progress to liver disease until later in childhood or early adulthood. However, both cirrhosis and liver cancer (hepatocellular carcinoma, or HCC) have been documented in children. It is therefore important to consider effective therapy for children with chronic HBV infection and to monitor these children closely for HCC. 64 references. ·

Recombinant Alfa-Interferon Plus Ribavirin Therapy in Children and Adolescents with Chronic Hepatitis C Source: Hepatology. 36(5): 1280-1284. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Treatment with alfa-interferon alone yielded poor results in children with chronic hepatitis C and is not generally recommended. This article reports on a study undertaken to evaluate the effectiveness and tolerability of alfa-interferon 2b in combination with ribavirin in children with chronic hepatitis C with different routes of viral transmission. In an uncontrolled pilot study, 41 children and adolescents ranging from 3 to 16 years were treated with alfa-interferon in combination with oral ribavirin for 12 months. The mode of infection was unknown in 4 children, parenterally transmitted in 16 children, and vertically transmitted (from mother to child during pregnancy or birth) in 21 children. Forty patients completed the study. Eleven children, who remained hepatitis C virus (HCV) RNA positive 6 months after the beginning, discontinued therapy. One boy stopped treatment because of side effects. At the end of treatment, 25 patients were HCV-RNA negative (61 percent). All individuals remained HCV-RNA negative during the 6 month follow up period. Nine of 15 children with parenteral (56.3 percent), 14 of 21 with vertical (66.6 percent) and 2 of 4 with unknown route of infection responded. Side effects included minor clinical signs such as fever, flulike symptoms, anorexia, and more severe signs (21.4 percent) such as the development of thyroid autoantibodies and impairment of thyroid function. The authors conclude that the combination of alfa-interferon with ribavirin seems to be an important advance in the treatment of chronic hepatitis C in children and adolescents. 1 figure. 1 table. 26 references.

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Pegylated Interferons in the Treatment of Patients with Hepatitis C Source: Numedx. 3(2): 66-67. Summer 2000. Contact: Available from Numedx, Inc. One Columbus Place, Suite N36D, New York, NY 100019. (877) Numedx-1. Fax (646) 349-1752. Website: www.numedx.com. Summary: Until two years ago, interferon alpha monotherapy was the mainstay for treating patients with chronic hepatitis C. However, only 15 to 20 percent of patients achieve a sustained response to this therapy. This brief article explains the use of

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pegylated interferons in the treatment of patients with hepatitis C virus (HCV) infections. Pegylation involves the attachment of a polyethylene glycol (PEG) molecule part (a moiety) to an interferon molecule. The resulting (Peginterferon alpha 2a or Pegasys) interferon decreases the rate of kidney clearance of the drug, producing a 10 fold increase in serum half life compared with unmodified interferon alpha 2a. Thus, Pegasys circulates in the blood much longer than the unmodified drug does. Clinical trials of Pegasys in patients with chronic hepatitis C have shown this drug to be effective and safe; it provides a new alternative for patients. The author briefly reports on the clinical studies that were conducted on Pegasys. A number of other ongoing trials with Pegasys are examining the role of this therapy (in combination with ribavirin and other agents) among patients with chronic hepatitis C who have not responded to interferon or who relapsed following treatment with interferon. The authors also briefly comment that Pegasys may offer some additional help for patients with chronic hepatitis C who are also HIV positive. 17 references. ·

Chronic Hepatitis C and G: Chronic Hepatitis C Is Mild in Menstruating Women Source: Journal of Gastroenterology and Hepatology. 15(12): 1411-1417. December 2000. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: [email protected]. Website: www.blackwell-science.com. Summary: Women with chronic hepatitis C may have a slower rate of disease progression than men. The authors of this article have previously demonstrated a relationship between hepatic iron concentration and liver fibrosis in patients with chronic hepatitis C. Their aim in this current study was to compare hepatic histologic findings, iron status, and other factors possibly capable of determining the severity of chronic hepatitis between menstruating women and men of comparable age. The authors studied 21 consecutive hepatitis C virus (HCV) RNA positive menstruating women and 24 consecutive HCV RNA positive men of comparable age, who underwent liver biopsy for chronic hepatitis C. Alcohol intake was recorded and laboratory tests were evaluated. Menstruating women showed lower grading and significantly lower staging scores than men of comparable age. Among the factors supposedly capable of determining the severity of chronic hepatitis, only the hepatic iron concentration correlated with the hepatic histologic staging in a multivariate analysis. Iron depleted women showed significant lower hepatic (liver) histologic grading and staging scores than women with normal iron status. The authors conclude that menstruating women with chronic hepatitis C may have a milder disease compared to men of comparable age, possibly because of menstrual blood loss and lower hepatic iron concentration. Women with chronic hepatitis C and iron deficiency have a milder disease compared to women with normal iron status, suggesting that iron deficiency results in a slower rate of disease progression. 4 figures. 3 tables. 27 references.

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Hepatitis C Virus Infection and Needle Exchange Use Among Young Injection Drug Users in San Francisco Source: Hepatology. 34(1): 180-187. July 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Young injection drug users (IDUs) in San Francisco may be at high risk for hepatitis C virus (HCV) infection, despite access to several needle exchange venues. This article reports on a cross sectional study conducted from 1997 to 1999 in San Francisco to

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estimate the prevalence and incidence of antibody to HCV (anti HCV) among street recruited IDUs under age 30, and to examine risk behaviors and sources of sterile needles. Among 308 participants, the prevalence of anti HCV was 45 percent. Using statistical modeling, incidence of HCV infection was estimated to be 11 per 100 person years. Independent risk factors for anti HCV included age, years injecting, years in San Francisco, first injected by a sex partner, injected daily, ever borrowed a needle, bleached last time a needle was borrowed, snorted or smoked drugs in the prior year, and injected by someone else in the prior month. In the prior month, 88 percent of the study used at least 1 of several needle exchange venues, and 32 percent borrowed a needle. The authors conclude that anti HCV prevalence is lower than in previous studies of older IDUs, but 11 percent incidence implies high risk of HCV infection in a long injecting career. Despite access to sterile needles, borrowing of needles persisted. 1 figure. 5 tables. 60 references.

Federally Funded Research on Hepatitis The U.S. Government supports a variety of research studies relating to hepatitis. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to hepatitis. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore hepatitis. The following is typical of the type of information found when searching the CRISP database for hepatitis: ·

Project Title: A PATHOGENESIS

CHICKEN

MODEL

TO

STUDY

HEPATITIS

E

VIRUS

Principal Investigator & Institution: Meng, Xiang-Jin; Assistant Professor of Molecular Virolog; Biomedical Scis/Pathobiology; Virginia Polytechnic Inst and St Univ 460 Turner Street, Suite 306 Blacksburg, Va 24060 Timing: Fiscal Year 2002; Project Start 15-JUN-2002; Project End 31-MAY-2006 Summary: (provided by applicant): Hepatitis E virus (HEV), the causative agent of hepatitis E, is an important public health problem in developing countries. HEV is also endemic in the U.S. The mortality rate is reportedly up to 20% in infected pregnant women. Due to the lack of a practical animal model and an in vitro cell culture system, the replication and pathogenesis of HEV is poorly understood and a vaccine for HEV is still not available. This proposal is based on our recent discoveries of a novel avian HEV from chickens in 2000 and a novel swine HEV from pigs in 1997. Both avian HEV and swine HEV are antigenically and genetically related to human HEV. We have shown 2

Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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that swine HEV infects non-human primates and a U.S. human strain of HEV infects pigs, and that pig handlers are at risk of zoonotic HEV infection. Avian HEV causes a hepatitis disease in chickens that is similar to human hepatitis E. The central hypotheses of this proposal are that hepatitis E is a zoonosis and that, like pigs, chickens are also animal reservoirs for HEV, and that chickens are a useful animal model system for HEV. The long-term objectives of the project are to define and understand the mechanism of HEV replication and pathogenesis by using HEV infection in chickens as an animal model system and by using avian-swine, avian-human and swine-human HEV chimeras to identify genes that are functionally important for these processes. In this proposal, we aim to: 1) systematically characterize the course of HEV replication and pathogenesis in a homologous model (avian HEV infection in chickens), 2) to identify the initial and extrahepatic sites of HEV replication in infected chickens, 3) to construct an infectious cDNA clone of avian HEV for future study of the structural and functional relationship of HEV genes by using HEV chimeras, and 4) to evaluate the potential risk of zoonotic infection by avian HEV. This will be accomplished by using standard techniques including in situ hybridization, PCR, cloning and sequencing, gene expression, and serological and pathological methods. The proposed studies will significantly advance our understanding of the mechanisms of HEV replication, pathogenesis and natural history. The information gained will be very useful for developing small animal models for HEV research and for devising strategies to prevent and control this important disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: A NOVEL APPROACH TO STUDY HEPATITIS C VIRUS ENTRY Principal Investigator & Institution: Singh, Ila R.; Pathology; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Hepatitis C virus infects 4 million Americans and an estimated 2-4% of the world's population, causing chronic hepatitis in most of those infected. A sizable fraction subsequently develops cirrhosis or hepatocellular carcinoma. This proposal describes the use of a novel approach to perform a mutational analysis of regions of the Hepatitis C virus (HCV). The objective is to delineate, at an unprecedented resolution, the role of specific sequences, both viral and cellular, in viral entry. Conventional approaches to the study of viral entry consist of morphological and biochemical studies of replication intermediates. While these approaches have been very useful for many viruses, they suffer from some drawbacks. Since viral entry is an inefficient process, with only one out of hundreds or thousands of virions following the productive pathway of infection, the non-productive particles tend to severely obscure morphological analysis and limit interpretation of biochemical studies. It also becomes difficult to get an adequate signal with physiologically relevant multiplicities of infection. This is especially pertinent to the study of the early steps of viral infection, before there is any amplification from viral expression. These problems make it necessary to complement conventional studies with the genetic approach of making and analyzing mutations that disrupt viral functions. The mutational approach is a proven and well-established strategy for the study of gene function. However, most current methods involve the isolation, storage and characterization of each mutant separately, making the process very time consuming and labor intensive. Genetic footprinting is a novel method that allows for efficient construction and parallel functional analysis of thousands of mutations in a cloned gene. The specific aims of this research are: 1) Creation of libraries of mutations in the E1 and E2 envelope glycoproteins of HCV,

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using a transposon-based mutagenesis method, followed by their analysis. 2) Genetic footprinting of the HCV IRES, to determine regions necessary for its function. Preliminary data showing the successful generation of libraries is presented. These libraries will be analyzed en masse to determine what regions of the glycoproteins are necessary for viral binding and fusion, and to determine what regions of the IRES are essential for translation of viral proteins. A comprehensive and detailed knowledge of the process of HCV entry gained from this study will be important for understanding the mechanism of viral infection and for the development of new preventive and therapeutic approaches against HCV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ACUTE HEPATITIS C INFECTION FOLLOWING CD8 DEPLETION Principal Investigator & Institution: Cawthon, Andrew G.; Children's Research Institute 700 Children's Dr Columbus, Oh 43205 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: (provided by the applicant): The hepatitis C virus (HCV) infects approximately 2% of the global population. The majority (70%) of individuals exposed to the virus develop a persistent, life-long infection that over a period of years can result in cirrhosis of the liver or even hepatocellular carcinoma. It is thought that T cell mediated immune responses are important for spontaneous resolution of infection but the relative contribution of CD4+ and CD8+ subsets are not known. In order to directly address the role of CD8+ T cells during acute HCV infection, chimpanzees will be temporarily depleted of CD8+ T cells prior to challenge with HCV. This experimental approach will address the following aims: 1) To assess how HCV replication and liver pathology is altered by depletion of CD8+ T cells prior to infection, 2) To study the evolution of the CD4+ T cell response to acute HCV infection during the absence and recovery of the CD8+ T cell compartment, and 3) To determine if eliminating the selective pressure mediated by CDS+ T cells alters the evolution of class I and class II MHC restricted HCV epitopes. Results from the experiments proposed in this research plan should contribute to our understanding of HCV pathogenesis by providing a detailed temporal analysis of the kinetics of viral replication and liver pathology during the absence and recovery of the CDS+ T cell compartment following HCV infection. These studies will also provide important new information as to the relative importance of CD8+ and CD4+ T cell responses in the control of HCV infection while determining if a correlation exists between the emergence of antigen specific T cells, the evolution of escape mutations, and the kinetics of virus replication in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ADDICTION MEDICINE PHYSICIANS AND CARE FOR HEPATITIS C Principal Investigator & Institution: Gourevitch, Marc N.; Psychiatry and Behavioral Scis; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAY-2004 Summary: (provided by applicant): Drug users are heavily and disproportionately affected by hepatitis C, yet they face numerous barriers to healthcare that place them at risk for substantially lower levels of hepatitis C care than non-drug users. Because of their continuous contact with individual drug users and their knowledge of and experience with the intricacies of their healthcare, physicians practicing addiction medicine are in a unique position to facilitate drug users' access to and success with

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hepatitis C treatment. However, no data exists to describe the knowledge, attitudes and experience of addiction medicine physicians regarding hepatitis C care for drug users. We propose to nationwide survey of over 800 physician members of the American Society of Addiction Medicine (ASAM). Non-ASAM physicians practicing medicine in methadone maintenance treatment programs New York State will also be surveyed and compared to ASAM members to determine the generalizability of findings derived from the latter cohort. The proposed study will address the following specific aims: Aim 1: To describe the knowledge of and attitudes towards eligibility guidelines for hepatitis C treatment among physicians in addiction medicine, and determine the association between these attitudes and the physicians' provision of hepatitis C treatment to DUs, either direct or by referral; Aim 2: To determine the association between provision of HIV care by physicians in addiction medicine and the provision of hepatitis C treatment to DUs, either direct or by referral; Aim 3: To determine the association between the availability of onsite primary medical care in drug treatment programs and provision of hepatitis C treatment to DUs, either direct or by referral, by physicians in addiction medicine. The survey will focus on physicians' knowledge and attitudes surrounding treatment eligibility criteria, such as duration of abstinence from drug and alcohol use and history of depression. It will query physicians about their experience with hepatitis C treatment for drug users, either by referral or by direct management themselves, and their access to treatment resources. It will also inquire about their clinical practice setting and their professional background. The proposed study will identify strengths and weaknesses in the delivery of hepatitis C healthcare by addiction medicine physicians to drug users, and it will focus on collecting data useful for the development of interventions designed to improve drug users' access to hepatitis C treatment. Data from this study will have relevance to both drug abuse treatment policy and clinical practice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ADULT AIDS CLINICAL TRIALS UNIT Principal Investigator & Institution: Balfour, Henry H.; Professor of Laboratory Medicine, Pathol; Lab Medicine and Pathology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 01-MAR-1992; Project End 31-DEC-2004 Summary: (adapted from the application's abstract): The Minnesota AIDS Clinical Trials Unit (ACTU) requests to continue to be a unit of the Adult AIDS Clinical Trials Group (AACTG). The Minnesota ACTU is committed to the Scientific Agenda of the AACTG, in which they have participated continuously since January 1, 1987. In addition to recruiting and retaining a cohort of new HIV-infected patients in clinical trials (estimated to be 85 patients in main studies and 54 patients in substudies annually), the Minnesota ACTU plans to contribute to the Group Scientific agenda with the following specific aims: (1) to correlate the quantity and replication competence of HIV at the cellular level in lymphoid tissue (LT), peripheral blood fractions and other compartments; (2) to develop more sensitive methods to detect HIV and apply these to selection of more effective therapies; (3) to define the natural history of cytomegalovirus (CMV) disease in the era of potent antiretroviral therapy and determine the best assays (virologic and immunologic) to monitor its clinical course (AACTG 360); (4) to identify and properly manage the patients who are at risk for complications of the dyslipidemias associated with potent antiretroviral therapy; (5) to identify resistant CMV strains and assess their pathogenicity; (6) to study relationships between the production of neurotoxins in plasma and cerebrospinal fluid of HIV-infected patients, neuronal loss as

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measured by proton magnetic resonance spectroscopy and the development or progression of HIV-associated dementia (HAD); and (7) to understand and characterize pharmacokinetic behavior, including drug-drug interactions, of antiretrovirals and other HIV-related drugs in biologic fluids. To help achieve these specific aims, the Minnesota ACTU has both Virology and Pharmacology Advanced Technology Laboratories (ATL). The Virology ATL is focusing on quantitation and characterization of HIV in lymphoid tissue and other body compartments. This laboratory also has expertise in HIV and CMV resistance. The Pharmacology ATL is developing assays for simultaneous determination of levels of protease inhibitors and measurement of intracellular antiretroviral anabolites. The Nebraska subunit has a special interest in neuroAIDS and has identified neurotoxins putatively responsible for pathology in HAD. The Iowa subunit has expertise in the detection of hepatitis C and will be collaborating in studies of the pathogenesis of coinfection with HIV and hepatitis C. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ANTIVIRAL DRUG DELIVERY WITH LYOPHILIZED PLATELETS Principal Investigator & Institution: Fischer, Thomas H.; Research Associate Professor; Pathology and Lab Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The overall goal of the proposed research program is to deliver antiviral therapeutics to macrophages that are infected with the single strand RNA viruses that cause hemorrhagic fevers and hepatitis. Our strategy is to use rehydrated, lyophilized (RL) platelets to deliver ribavirin to the macrophages of the reticuloendothelial system (RES) that are involved in the initial stage of viral infection, as well as macrophages at sites of vascular injury in the later acute-hemorrhagic phase of infection. Viruses of the Arenaviridea (e.g., Lassa fever virus), Filoviridae (e.g., Ebola and Marburg viruses), Bunyaviridae (e.g., Rift Valley virus) and Flaviviridae (e.g., Yellow fever virus) families cause viral-induced cellular damage to vascular tissues that result in hemorrhage. Similarly, hepatitis C virus (a Flaviviridae family member) propagation is frequently associated with bleedingintensive hepatic surgeries. Ribavirin, as a broad-spectrum antiviral RNA mutagen, holds promise for the treatment of these hemorrhage-associated viruses. However, adverse toxicities have limited the clinical use of this ribonucleoside as an antiviral chemotherapeutic. We seek to increase the therapeutic efficacy of ribavirin by using RL platelets to deliver the ribonucleoside. The intrinsic hemostatic function of RL platelets will thus concentrate the ribavirin in the microenvironment of the virus for increased chemotherapeutic efficacy; in RES and vascular wound site macrophages. Goal of the proposed research- Two specific research aims are proposed in this application. First, we will optimize the method for covalently attaching ribavirin to RL platelets in a form that is releasable in the low pH environment of the macrophage phagosome Secondly, the pharmokinetics of ribavirin delivery to elements of the RES and wound sites will be characterized. Overall Scope of the program. We anticipate that the proposed research will form the basis for studies (beyond the scope of this proposal) with non-human primates that will access the therapeutic utility of ribavirin loaded RL platelets as antiviral agents for the treatment of hemorrhagic fevers. The results of this research program hold promise for providing badly needed therapeutics for hemorrhagic fevers and hepatitis, and thus have biodefense as well as first and third worm public health implications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIOLOGY OF PEDIATRIC HEPATITIS C INFECTION Principal Investigator & Institution: Borkowsky, William; Professor of Pediatrics; Pediatrics; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2001; Project Start 15-FEB-1997; Project End 31-JAN-2002 Summary: (Adapted from the Investigator's Abstract): The goal of this proposal is to study the factors influencing the transmission of hepatitis C (HCV) from HIV- and HCV-infected mothers to their offspring, describing the natural history of this process, including the virologic, immunologic, and the genetic factors at play in both preventing transmission and modifying any infection which is not prevented. The following aims are planned: AIM 1) To describe the natural history of infection by identifying HCVinfected pregnant women and studying their offspring for evidence of HCV infection. This will include the quantitation of HCV during pregnancy in cell-free and cellassociated blood compartments, quantitation of CD4 and HIV viral load, and their correlation with whether HCV transmission occurs. The offspring will be studied prospectively from birth for evidence of HCV infection using PCR and serologic methodologies. The transmission rate in children born to HIV-uninfected mothers will be compared to that in HIV-infected and -uninfected children born to HIV-infected mothers. The effect of HCV infection on liver function will be measured. AIM 2) To assess the distribution of quasispecies using the heteroduplex mobility assay on plasma and peripheral blood mononuclear cells from HCV-infected mothers during pregnancy, peripartum, and in their respective HCV-infected children. This will determine whether the child is infected with a selected few or unselected viruses present in the mother. AIM 3) To measure humoral and cell-mediated responses to HCV in both HCV infected and uninfected children born to infected mothers prospectively from birth. The presence or absence of such responses will be correlated with infection status and disease status. The presence or absence of these responses will be correlated with viral diversification that occurs in the child as described in AIM 2. AIM 4) To determine the HLA status of the HCV-infected mothers and their offspring. The prevalence of alleles in the mother and child will be correlated with whether transmission of HCV occurs. The influence of both maternal and child alleles on transmission will be assessed. The correlation of immune responses measured in AIM 3 and the clinical outcome of HCV infection with HLA alleles in the child will be studied. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INFECTION

CELLULAR

IMMUNITY

OUTCOME

HEPATITIS

C

VIRUS

Principal Investigator & Institution: Chang, Kyong-Mi M.; Assistant Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: (adapted from the application) Up to 3% of the world population is infected with hepatitis C virus (HCV), a hepatotropic RNA virus that causes acute and chronic hepatitis as well as cirrhosis and hepatocellular carcinoma. HCV infection results in chronicity in most cases (85%) despite the presence of antiviral immune response. While the basis for high rate of persistent infection is not well defined, the role of cellular immunity in the outcome of HCV infection can be directly examined by comparing patients with HCV clearance, persistence and resistance The central hypothesis in this application is that viral clearance is mediated by phenotypically distinct T cell response and that these features are present in patients with spontaneous viral clearance, in patients who successfully eradicate the virus after antiviral therapy and in resistant

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individuals who remain uninfected despite recurrent high risk exposures. Furthermore, the role of virus sequence heterogeneity in modifying this process is examined. The four hypotheses being tested in this application are as follows: First, HCV clearance is mediated by phenotypically distinct Thl/Tcl type T cell responses; Second, HCV clearance during antiviral therapy is mediated by a switch in the phenotype of virusspecific T cell response; Third, viral epitope sequence variations modify HCV-specific CTL response; Fourth, protective cellular immunity to HCV is present in individuals who remain uninfected despite frequent exposure. It is hoped that a better understanding of the cellular immune response during successful viral clearance would lead to development of strategies to eliminate chronic HCV infection and prevent its long term sequelae. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: CHIMERIC VIRUS PRIMATE MODEL OF HEPATITIS C Principal Investigator & Institution: Lemon, Stanley M.; Professor & Dean, Sch. of Medicine; Clinical Research Center; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2006 Summary: (Provided by the applicant): Chronic HCV infection is a major threat to the public health. Current therapies have limited efficacy, but the search for more effective treatments is hampered by the lack of available animal models of HCV infection. The chimpanzee (Pan troglodytes) is the only animal species permissive for infection with this virus. This deficiency will be addressed by developing a small nonhuman primate model of hepatitis C involving the closely related, unclassified flavivirus GBV-B. GBV-B replicates to high titers, is hepatotropic, and causes liver disease in susceptible tamarins (Saquinus sp.). Since tamarins are more readily available than chimpanzees for such studies, GBV-B infection of these animals represents a potentially useful surrogate for studies of hepatitis C. However, although GBV-B among all animal viruses has the closest phylogenetic relationship to HCV, its proteins still share only approximately 25% identity at the amino acid level. Moreover, unlike HCV, GBV-B does not appear capable of establishing persistent infection in these animals. These features of GBV- B limit its usefulness. To overcome these limitations, the applicants will construct chimeric genome-length GBV-B cDNA clones in which specific functional domains of HCV are inserted in lieu of homologous GBV-B sequence. The hypothesis is that the close phylogenetic relationship between GBV-B and HCV will allow the rescue of viable chimeric viruses from these clones, and that these viruses will represent uniquely valuable resources to the research community since they will allow the in vivo evaluation of candidate inhibitors of critical HCV replication functions in a readily available and relatively inexpensive small, nonhuman primate species. Under Aim 1, the investigators have constructed a fulllength, infectious cDNA copy of the GBV-B genome. The infectivity of RNA transcribed from this clone has been demonstrated following intrahepatic injection of the RNA in a susceptible tamarin. In Aim 2, the investigators are constructing infectious chimeric flavivirus cDNAs containing the following HCV domains within a GBV-B background: the internal ribosome entry site (IRES), the major proteinase (NS3) with its cofactor molecule (NS4A), the RNA helicase (NS3) and the RNA dependent, RNA polymerase (NSSB). In Aim 3, chimeras in which the structural proteins of GBV-B and HCV are placed within the genetic background of the alternate virus will be constructed. For both Aims 2 and 3, the applicants will assess the ability of RNAs transcribed from these chimeric cDNA clones to induce infection in tamarins following intrahepatic inoculation, and determine the extent to which the

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viruses rescued from these clones cause acute or chronic liver disease on subsequent passage in these nonhuman primates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: CHRONIC HEPATITIS C: MOLECULAR & CELLULAR MARKERS Principal Investigator & Institution: Farrell, Geoffrey C.; University of Sydney Main Quadrangle, Bld A14 Sydney, 2006 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: Only a minority of HCV-infected individuals have progressive forms of chronic hepatitis that will result in cirrhosis in 20 to 30 years. This project is concerned with the biological basis of disease progression in chronic hepatitis C. We have noted that, to date, viral factors and the systemic immune response to HCV are poorly correlated with disease progression. The key pathobiological process that determines progression of liver disease in chronic hepatitis C is fibrogenesis, with hepatocyte cell death and proliferation playing lesser roles. In the present proposal, these processes are conceptualized as responses to hepatic inflammation and oxidative stress causing activation of hepatic stellate cells and liver cell injury. Thus our overall objective is to characterize how interactions between HCV, the hepatic inflammatory response and liver cells promote fibrogenesis and disease progression in chronic hepatitis C. In particular, we will test the hypothesis that, in the early stages of chronic HCV infection, an intrahepatic "molecular map" can be created to identify subsets of individuals who will develop progression of liver disease. We will then seek to identify patterns of hepatic gene expression that correlate with the pathogenesis of fibrosis, hepatocyte death and proliferation. A particular focus will be on the identification of genes not previously known to be associated with individual susceptibility to HCV. A unique feature of these studies is that they will be performed on serial liver biopsy samples obtained at 3 to 5 year intervals from 200 patients with mild to moderate chronic hepatitis C who will be followed prospectively and monitored by quantitative liver functional assessments. The Specific Aims are: 1) To establish the relationship between cytokine mediators of the hepatic inflammatory response, macrophage activation and the presence of oxidative stress in the liver, and to compare these with characteristics of the HCV infection in hepatocytes and other cell types; 2) To determine whether expression of these cytokines and/or oxidative stress correlate with the activity of hepatic fibrogenesis, using both cross-sectional and prospective longitudinal approaches. 3) To identify hepatic genes previously not known to be associated with a progressive course for hepatitis C. The findings may allow those individuals most at risk of progressive liver disease from HCV to be identified at a time when they are most likely to respond to antiviral therapy. It will also allow the design of adjunctive treatments more appropriately targeted towards the key pathogenic processes that determine disease progression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CLINICAL CENTER FOR BILIARY ATRESIA: ETIOPATHOGENESIS A* Principal Investigator & Institution: Bezerra, Jorge A.; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-MAY-2007 Summary: (provided by applicant): We propose to develop a Biliary Atresia Clinical Center to perform translational research focused on diagnosis, pathogenesis, and novel

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therapeutic modalities for biliary atresia and neonatal hepatitis. These disorders are the main causes of neonatal cholestasis, with biliary atresia accounting for -50% of the indications for liver transplantation in children. The application is a logical extension of the long-standing mission of the applicant Center to provide exceptional care to any child with liver disease through comprehensive care and research. To pursue this mission, a clinical service focused exclusively on pediatric liver disease was created in 1985; since, then, we have served as a referral center for regional medical groups and institutions. We also performed clinical and patient-directed laboratory research to define specific causes of neonatal hepatitis and to explore novel therapeutic modalities for affected infants. Recently, we applied functional genomics to identify immunologic pathways that may regulate pathogenesis of biliary atresia. Despite these accomplishments, we recognize that further advances will depend directly on the access to a large patient population in a prospective manner for adequately powered studies. Therefore, we set two goals for the applicant Center: 1) to establish and maintain the infrastructure of a Clinical Center that will work in collaboration with other centers of the Biliary Atresia Clinical Research Consortium, and 2) to actively use the resources provided by the consortium to carry out studies on children with biliary atresia and neonatal hepatitis. To accomplish these goals, we propose an administrative structure jointly shared by medical and surgical faculty of the Center, a network of regional collaborators that will assure access to patients, and a database to gather clinical and laboratory information based on the natural history of biliary atresia. Using a model of translational research that is focused on the child with biliary atresia, we propose two studies to be carried with the approval by the Research Consortium. The first is a shortterm study applying basic science technology to further defines the pathogenesis of this disease. The second is a 3-year open-label randomized study to establish the efficacy of corticosteroids in improving biliary flow following surgical portoenterostomy in infants with biliary atresia. Execution of these studies and access to a critical amount of clinical information and serum/tissues will facilitate research and generate hypotheses on pathogenesis and optimal treatment for children with biliary atresia and neonatal hepatitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: CONTINUITY OF CARE FOR DRUG-ADDICTED OFFENDERS IN RI Principal Investigator & Institution: Friedmann, Peter D.; Associate Professor; Rhode Island Hospital (Providence, Ri) Providence, Ri 02903 Timing: Fiscal Year 2002; Project Start 25-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): This cooperative agreement application proposes to develop a Rhode Island Research Center to participate in NIDA's National Criminal Justice Drug Abuse Treatment Services Research System (CJ-DATS). The mission behind the CJ-DATS is to improve the public safety, drug-related, public health, health and psychosocial outcomes of drug-involved offenders. Thus, this application aims to develop research infrastructure to support rigorous, multisite studies of integrated approaches to the treatment of individuals with drug abuse or addictive disorders, including models of treatment in jail or prison and as part of community re-entry; to support research on continuity of care models integrated with re-entry programs for drug-involved offenders returning to their communities, including services for health problems such as HIV, tuberculosis, or hepatitis infections and mental health problems; and to enrich the collaborations among the criminal justice, treatment, and academic communities in Rhode Island. Our Research Center will build on the strong, existing clinical and research partnerships among the Lifespan Hospitals/Brown University

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investigators, the Department of Corrections and 4 community addiction treatment programs already situated in the Rhode Island prison. These 4 programs deliver a comprehensive range of treatment modalities and ancillary services. The Rhode Island Research Center offers at least 4 specific advantages to the National CJ-DATS Cooperative: (1) Investigators and treatment partners with substantial research and clinical experience regarding the organization and integration of substance abuse treatment and health services, especially continuity of care models for community reentry of inmates afflicted with health problems such as HIV, tuberculosis, or hepatitis infections, and mental health disorders; (2) Strong, existing ties among the Rhode Island partners from prior collaborative research and clinical endeavors; (3) A small state with a unified correctional system, all divisions and facilities on a single campus and an administration highly supportive of research; and (4) An accessible population of addicted persons in which we have achieved high rates of enrollment and follow-up in prior investigations. The Rhode Island Research Center would lead rigorous multisite studies that draw on our expertise in the development, delivery and evaluation of linkages to community health services, with an initial focus on hepatitis C and methadone treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: DEFECTIVE INTERFERENCE OF HEPADNAVIRUS IN NATURE Principal Investigator & Institution: Shih, Chiaho; Professor; Pathology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001; Project Start 23-DEC-1996; Project End 31-DEC-2004 Summary: Our long-term goal is to understand the pathobiology associated with viral hepatitis and liver cancer. Hepatitis B virus (HBV) is the 4th most common infectious agent in humans. Chronic infection with HBV is tightly associated with the development of liver cancer. Although both hot immune and viral factors are believed to contribute to the establishment of chronic infection, the mechanism of HBV chronic infection remains to be fully explored. Defective interfering (DI) particles have been found in many RNA and DNA viruses of bacteria, plants, and animals, and are known to be associated with persistent infection in tissue culture. However, the existence of DI particles has not yet been demonstrated in human natural infections since their first discovery in influenza virus by von Magnus (1947) in the laboratory setting. Using a new approach, we provided the first experimental evidence for the existence of DI-like viruses in human chronic HBV carriers. Functional characterization of these naturallyoccurring "core intentional deletion variants" (CID) of HBV reveals all of the characteristic features of DI particles. In this application, we propose to study the biological significance of CID variants in patients and woodchuck animal model. We will investigate the phenomenon of fluctuating titers of HBV CID variants in human patients. In addition, we propose to investigate if woodchuck hepatitis virus (WHV) core internal deletion variants, which we have found recently (manuscript submitted) also behave like DI particles in tissue culture. Finally, we will continue our studies of the mechanism of defective interference of HBV CID variants by both genetic and biochemical approaches. A "repressor-like model" versus a "preferential replication" model will be distinguished. Successful completion of this work will have important implications for chronic viral hepatitis which leads to the development of highly malignant liver cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DENDRITIC IMMUNOTHERAPY

CELL

TARGETED

HEPATITIS

C

79

VIRUS

Principal Investigator & Institution: Mohamadzadeh, Mansour; Medicine; Tulane University of Louisiana New Orleans, La 70118 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Hepatitis C is one of the worlds most pandemic and insidious diseases. Less than 41% of patients respond to the current treatment, and a large fraction is ineligible for therapy. Thus, there is an urgent need for new therapeutic strategies. Clearance of hepatitis C virus (HCV) is correlated with the level of HCVspecific CD4+ T cells, and viral escape mutations have been identified in immunodominant CD4+ T-cell epitopes. These results suggest that an immunotherapy designed to increase and broaden HCV-specific CD4+ T cells could provide a new therapeutic approach. Dendritic cells (DCs), the most important class of professional antigen presenting cells, possess the ability to elicit both humoral and cellular immune responses. These cells are poised to capture pathogens, migrate to draining lymph nodes, and select antigen-specific CD4+ T cells to regulate T, B, and NK cells, all of which may contribute to protective immunity. The objective of this proposal is to develop a novel vaccine strategy targeting the HCV nonstructural protein 3 (NS3) directly to DC subsets, e.g., Langerhans Cells (LCs). Recently we showed that LCs can be generated by culturing monocytes with GM-CSF+IL15. Such LCs induce significant T-cell activation in vivo. Furthermore, we have generated peptides that bind specifically to LCs or interstitial DCs from a phage display peptide library. We hypothesize that targeting NS3 directly to DCs will increase the level and duration of specific immune responses. Thus, we will target NS3 to DCs by coupling or fusing it to DC-specific peptides. We further hypothesize that NS3 can be structurally modified in order to eliminate the immunodominant epitopes and therefore recruit new T cells against HCV. Specific aims are: 1) To determine whether targeting NS3 specifically to DC subsets enhances specific immune responses against HCV by analyzing T-cell proliferation/activation in humanized SCID mice; and 2) To augment the development of IFN3 gamma-producing NS3-specific CD4+ T cells by engineering the threedimensional structure of HCV NS3. Alternative modes of loading DC subsets will be explored, including via recombinant Lactobacillus sp. that express and secrete DCtargeted NS3. A needle-less and non-toxic immunotherapy would provide a treatment for hepatitis C patients who currently have none. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: DETERMINANTS OF HEPATITIS C & E MORBIDITY IN EGYPT Principal Investigator & Institution: Strickland, George T.; Epidemiology and Prev Medicine; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 15-SEP-2000; Project End 31-AUG-2005 Summary: By using new molecular virological techniques, Non-A Non-B hepatitis patients have now been categorized into those infected with hepatitis C virus (HCV), a parenterally transmitted flavivirus, and hepatitis E virus (HEV), a fecal-oral transmitted "hepatitis E-like virus." WHO estimates that 170 million are infected with HCV, the most common cause of chronic viral hepatitis (CVH), post-necrotic cirrhosis of the liver and hepatocellular carcinoma (HCC). HEV is primarily transmitted in developing countries where it is the most common cause of acute viral hepatitis (AVH) and fulminating hepatitis, particularly in pregnant women. We and others have documented that the highest prevalence of HCV, and also possibly HEV, in the world occurs in Egypt. We

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have established a Network of Egyptians and Americans who are studying viral hepatitis and its cost to the country. In this ICIDR proposal, we will extend the work of this Network to include investigations of: (1) the effect that the host genome has on chronicity and cirrhosis following HCV infection (Project 1); (2) the host, viral, and environmental determinants of HCC and (because HCV is lymphotrophic as well as hepatotrophic) non-Hodgkins lymphoma (NHL, Project 2); and the epidemiology and complications of HEV (Project 3). Projects 1 & 2 will have case-control studies. The former will compare: (a) chronic carriers of HCV RNA vs. subjects who clear infection and (b) those with HCV who develop cirrhosis vs. those that show no signs of disease; while the latter compares HCC or NHL cases vs. age- and gender-matched controls. Projects 1-3 will have prospective cohort studies of 10,000 inhabitants of two villages with prevalence of anti-HCV of 9% and 24% and anti-HCV of 51 and 70%, respectively. Their goals will be to determine incidence of, and risk determinants for cirrhosis (Project 1), HCC and NHL (Project 2), and HEV infection and disease (Project 3). A cohort of pregnant women and children will be studied to assess HEV morbidity in pregnancy and exposures and disease in infancy. Domestic animals and peri-domestic rodents will be studied to determine whether HEV has a zoonotic component in Egypt. Viral genotypes, host class I and II alleles and candidate genes, e.g., chemokine receptors and HDL, a possible HCV receptor, and environmental exposures and their impact on host genes (p53 genetic fingerprinting) will be assayed. Because the scientific, administrative, logistic and laboratory network is in place and both HCV and HEV have such a high prevalence in Egypt, these investigations have a high probability of early success. Explanations for these very important questions can be obtained at a fraction of the cost and time as they could be found elsewhere, and the results should lead to the development of better interventions to prevent the two most important causes of liver disease in the world. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: DEVELOPMENT OF HEPATITIS C VIRUS ENTRY INHIBITORS Principal Investigator & Institution: Gardner, Jason P.; Progenics Pharmaceuticals, Inc. 777 Old Saw Mill River Rd Tarrytown, Ny 10591 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The development of new therapeutic agents for hepatitis C virus (HCV) infection is a major public health priority. We have selected HCV entry as a target for the discovery and development of novel antiviral agents. The overall goal of this Phase I project is to develop a novel cell-based membrane fusion assay that accurately recapitulates HCV entry, using well characterized, biologically relevant cellular reagents.During the Phase I project, we will develop stable cell lines that express fusogenic forms of native HCV envelope glycoproteins, and use these cells to adapt a cell-based membrane fusion assay for HCV entry. We will generate stable human hepatocyte cell lines as appropriate targets for fusion, and optimize the assay for reproducibility, sensitivity and suitability for high-throughput screening (HTS). We will also probe the mechanism of HCV entry using monoclonal antibodies and cell lines expressing putative attachment receptors.Success in the Phase I project will enable the HCV membrane fusion assay to be utilized in Phase II for HTS of libraries of structurally diverse small molecules, in order to identify potent inhibitors of HCV entry. Lead compounds will be screened for in vivo inhibition of HCV infection in a novel transgenic mouse model and mechanisms of action will be probed. Promising compunds will be developed for clinical application for HCV infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EARLY DETECTION OF LIVER CANCER AND HEPATITIS Principal Investigator & Institution: Block, Timothy M.; Professor and Director; Biochem & Molecular Pharmacol; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: The goal of this proposal is to develop methods for the early detection of hepatocellular carcinoma (HCC) and hepatitis. The hypothesis that changes in the amount or modification of serum polypeptides correlate with the onset of HCC or hepatitis will be determined. Individuals chronically infected with hepatitis B or C virus (HBV, HCV) are at high risk for the development of HCC and hepatitis, with disease progression occurring after many years. Serum polypeptides from individuals at different stages in the disease continuum will be resolved by "Proteomic" 2-dimensional gel analysis. Our preliminary evidence and the work of others demonstrate that 2D gel technology has advanced to the point where expressed protein profiles of biological samples can be reproducibly resolved. Polypeptides that correlate (by their appearance, disappearance or post translational modification) with disease status will be identified. Correlating polypeptides will be characterized by a variety of methods available to us: data base reference, immunological methods or micro sequencing. Identification of biomarkers that help in the diagnosis and prediction of liver disease in this high-risk population will have enormous public health benefit, given the limitations on current methods. It will also provide insights about the mechanisms of progression of this disease family and offer a platform technology for the use of proteome diagnostics in other areas of cancer detection and liver decompensation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENZYMATIC DIFFERENCES AMONG HEPATITIS C VIRUS GENOTYPES Principal Investigator & Institution: Frick, David N.; Biochem and Molecular Biology; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2003; Project Start 15-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): Almost one in every fifty-five Americans have been exposed to the Hepatitis C Virus (HCV), but most are unaware of their infection because the virus causes few acute symptoms. If left untreated, the majority of HCV infections lead to chronic active hepatitis that eventually progresses to cirrhosis, cancer, or liver failure. Current therapies involving the drugs interferon and ribavirin are costly and produce debilitating side effects, frequently worse than the symptoms produced by HCV itself. Newer treatments are, however, quite effective against certain viral genotypes. This proposal will examine the HCV proteins most directly involved in viral replication, the NS3 Helicase and NS5B polymerase, as putative targets for the drug ribavirin and as targets for new antiviral agents. In addition to its established role as a modulator of the immune system, ribavirin has been proposed to eliminate viruses as a mutagen or through direct effects on viral replicative proteins. One popular hypothesis states that ribavirin's enhancement of the already high HCV mutation rate leads to a catastrophe of errors and subsequent virus elimination. Here, ribavirin effects will be examined in vitro, in enzyme assays, and in vivo, using a novel HCV replicon that should allow the assessment of replication fidelity. To attempt to relate ribavirin effects to genotype-specific drug response, all experiments will be repeated with the three most common American HCV genotypes, two that normally do not respond to therapy (la and lb) and one that frequently responds to therapy (2a). The polymerase and helicase

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proteins from each genotype will also be characterized to define conserved and divergent properties. A rigorous biochemical approach will be used to define enzyme differences because sequence data alone does not accurately predict protein structure or function. Preliminary data show that different genotypes encode enzymes with markedly different properties, hampering current rational drug design efforts. Structure-based site-directed mutagenesis will be used to determine the genetic basis for HCV enzyme variability. The biological consequences (i.e. replication rate, fidelity, protein expression) of HCV genetic variation will then be analyzed in a replicon system. The delineation of genetic variations responsible for certain phenotypes might allow the prediction of patient response to current or future HCV therapies, and the clear identification of conserved HCV enzyme properties will aid future HCV drug development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: EPIDEMIOLOGY AND IMPACT OF HEPATITIS C IN THE COMMUNITY Principal Investigator & Institution: Kim, W R.; Assistant Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2003; Project Start 15-MAR-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Hepatitis C virus (HCV) is the most common chronic blood-borne infection in the US: an estimated 2.7 million Americans have been infected with the virus. Although the prevalence of HCV infection in the population is well established, the public health impact of liver disease caused by HCV remains uncertain. Based on established resources for population-based research in Olmsted County (the Rochester Epidemiology Project), we have already established a registry of all community residents presently diagnosed with HCV. In this study, we propose to screen community residents for HCV and then determine the impact of HCV infection in the community. In Aim 1, we will measure the prevalence of HCV which has not previously been diagnosed by screening the serum of Olmsted County residents of ages 30 to 49 years for HCV. For screening, we will utilize an established method to obtain serum samples from the majority of the target population in the community. In Aim 2, we will compare the prevalence and severity of liver disease, health status, quality of life and comorbidity profile among three groups of community residents, namely those with established HCV diagnosis, those with HCV infection discovered only by screening, and those without HCV infection. In Aim 3, based on these three groups, we will measure community-wide healthcare resource utilization related to HCV, independent of effects of comorbid conditions, particularly substance abuse and mental health problems. The results of this work will address the substantial gap between patient outcome data derived from referral patient samples and prevalence data based on population surveys, by providing key information about the impact of HCV on morbidity and health of the majority of Americans whose HCV infection remains undetected. My long-term goal is to establish a comprehensive patient-oriented research program in viral hepatitis and liver disease, encompassing epidemiology, survival statistics, quality of life, and health services research. Resources created by the current project, namely detailed clinical information and biologic specimens from a large cohort of community residents with HCV, will provide future opportunities to study natural history, virologic and host prognostic determinants of progression, and effectiveness of community-based interventions on HCV outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EPIDEMIOLOGY OF HEP E VIRUS INFECTIONS IN BANGLADESH Principal Investigator & Institution: Nelson, Kenrad E.; Epidemiology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Hepatitis E virus (HEV) infections cause serious morbidity and mortality, especially in pregnant women. Few population-based studies have characterized HEV epidemiology. Proposed is a two-year, multi-component, population-based study to describe the epidemiology and quantify the burden of HEV infections and disease in rural Bangladesh (Matlab District). These studies will be nested within a population of 105,000 under intensive longitudinal health surveillance since 1966. This unique research setting, maintained by the International Center for Diarrheal Disease Research, represents the most accurate and oldest population health surveillance in the developing world. Evidence suggests Bangladesh is HEV endemic, yet no known studies have examined HEV there. The age-specific population prevalence of 1gM and lgG antibodies to HEV will be determined using a random sample of 1030 individuals from the Matlab cohort. A large proportion of the population is under age 15, allowing a description of HEV antibody prevalence among children using improved, reliable assays. Data will be collected at baseline, 12, and 18 months. Incidence of HEV infection and disease will be calculated from HEV seroconversion rates and by extracting reports of hepatitis disease from surveillance system records. A ratio of asymptomatic HEV infections to clinical HEV will be estimated. A nested case-control study is also proposed during the 18-month period to identify potential risk factors associated with sporadic HEV disease. Contaminated water is known to precipitate HEV outbreaks, but risk factors for sporadic HEV are unknown. A visual algorithm will identify potential HEV cases near the time of infection. Only anti-HEV 1gM positive cases will be enrolled. Two HEV-naive controls will be age-matched to a case. A questionnaire will assess potential behavioral, animal and environmental risk factors associated with incident HEy. Multiple logistic regression will be used to model risk factors. Using GIS, cases will be analyzed for spatial or temporal clustering. Virus isolates from acute cases will be sequenced for a phylogenetic analysis of Bangladesh HEy. These studies in a well-defined South-East Asian population will provide a comprehensive epidemiologic profile of endemic and epidemic HEV in a high risk population, and could form the basis for future preventive interventions, such as vaccine trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ESTABLISHMENT OF A BREEDING AND RESEARCH PROGRAM Principal Investigator & Institution: Couch, Ronald C.; Coulston Foundation 1300 La Velle Rd Alamogordo, Nm 88310 Timing: Fiscal Year 2001; Project Start 30-SEP-1986; Project End 31-MAY-2001 Summary: The Coulston Foundation proposes to continue a self-sustaining chimpanzee breeding colony of-animals which will produce 10-15 animals per year. Approximately 50% will he retained each year to serve as eventual breeders. The remaining infants will he provided to research programs of national importance. Two long-standing programs continue to support the offspring of this colony through governmental research efforts in Hepatitis at CDC, FDA, NIAID and AIDS vaccine development program with NCI and NIAID through Program Resources Institute. The 113 animals proposed include 65 confirmed breeders, 28 potential breeders. and 20 of other status. The consolidation of two primate facilities offers the influx of new genetic material into the NCBRP program

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by inclusion of breeders from the population housed at the La Velle facility and vice versa after appropriate screening. With the recommendation from the genetic consultants, this will maximize the genetic diversity of the entire inventory. Animals continue to be aggressively tested to ensure the animals are free from hepatitis. All the tests are currently being performed in-house; these include Hepatitis B, Hepatitis C antibody and PCR, liver enzyme assays, and when appropriate, liver biopsies, assuring a disease-free colony. A transition to a family group housing unit is planned to be completed in the next five years. Two populations will be maintained, formed from a genetic strategy provided, designating animals to either research and breeding pools, thus creating a purpose bred chimpanzee. Each family unit is provided an indoor/outdoor den (consisting of 6 animals) with access to play yards. The facilities supporting the remaining colony will undergo a renovation to enhance socialization expediting their move to the new facility as new buildings are built. Monies have been designated to renovate the isolettes with plans to expand BSL-3 experimental space to augment the current level of MDS vaccine research. Further congressional support is being sought to complete the remaining two phases that will complete the chimpanzee retirement housing and additional animal holding associated support areas (experimental and veterinary). Infants designated as breeding replacements will be left in family units as long as population dynamics allowing a comprehensive behavioral management program, multi-phasic in design, to incorporate plans for environmental enrichment, breeding, and normal sexual development. The project receives support by a talented group of experienced technicians and state-of-the-art clinical chemistry. hematology, microbiology, virology and immunology and pathology laboratories. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ETIOLOGY AND PREVENTION OF BLOOD BORNE VIRUSES IN IDUS Principal Investigator & Institution: Hagan, Holly C.; Deputy Director; National Development & Res Institutes Research Institutes, Inc. New York, Ny 10010 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-MAR-2007 Summary: (provided by applicant): The etiology and prevention of blood-borne viral infections in injection drug users (IDUs) have not been fully characterized, and many questions remain regarding which injection practices may result in I infection. Viral hepatitis infections in IDUs are among the most frequently occurring 81ood-bornel l infections in humans; in low HIV-prevalence settings, morbidity and mortality in IDUs attributable to l hepatitis virus infections may exceed that for HIV. Hepatitis C virus (HCV) is highly prevalent in IDU- populations, and is more efficiently transmitted l abouty injection than HIV. Because sexual HCV transmission is relatively rare, it may serve as a highly sensitive biologic marker of direct percutaneous exposure to these infections in drug injectors, and may contribute to understanding the mechanism of transmission of other infections via injection practices. The long-term goal of our research is to advance knowledge of the epidemiology, etiology and-prevention of HIV and hepatitis infections in IDUs. We propose studies that will make new contributions toward our long-term goal: Aim 1. Examine the extent to which HCV prevention education at the Seattle needle exchange program has reduced the risk of HCV infection. Aim 2. Measure the risk of HCV seroconversion associated with specific injection risk behaviors, and calculate the risk of HCV attributable to these practices in the IDUpopulation. Aim 3. Compare reporting of socially-undesirable or stigmatized injection and sexual risk behavior collected by A-CASI to interviewer-administered data collection methods. Aim 4. Assess the feasibility and disease control benefits of HBV

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and HCV partner notification for IDUs. Aim 5. Study whether changes in hepatitis C reporting laws are associated with increased reporting in IDUs. The significance of this research is its potential contribution to our understanding of the etiology of these l infections, and examines many practical questions related to the effectiveness of public health surveillance and prevention programs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ETIOLOGY AND TREATMENT OF BILIARY ATRESIA AND INH Principal Investigator & Institution: Sokol, Ronald J.; Professor; Pediatrics; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Biliary atresia and idiopathic neonatal hepatitis are two cholestatic disorders occurring in the first 3 months of life that account for 60-70% of all infants with neonatal cholestasis, which have similar clinical presentations but disparate outcomes. Diagnosis of biliary atresia is frequently delayed; the Kasai portoenterostomy procedure may extend an infant's life, but in most cases is not curative. Thus liver transplantation becomes necessary in 70% of infants with biliary atresia in North America, accounting for 40-50% of all pediatric liver transplants. In idiopathic neonatal hepatitis, on the other hand, recovery occurs in 80% of patients with supportive care alone. The etiology and pathogenesis of these two disorders is currently poorly understood; consequently few effective therapies have been developed over the past three decades. The development of new therapeutic strategies will require a thorough understanding of the causes and mechanisms of tissue injury in these disorders. Because both these disorders are rare, a network of centers will be essential to achieve effective investigation. Consequently, the objective of this grant application is to be chosen as one of the Clinical Centers in the Biliary Atresia Clinical Research Consortium and participate in all investigations initiated by this consortium. We specifically will test the hypothesis that perinatal/acquired cases of biliary atresia and idiopathic neonatal hepatitis are distinct phenotypes caused by similar viral-induced immune injury of extrahepatic and entrahepatic bile ducts and hepatocytes in the genetically and immunologically susceptible infant. The specific aims of this proposal are: (1) To develop a database and tissue/serum bank of human specimens from infants with biliary atresia, idiopathic neonatal hepatitis, and appropriate control cholestatic and non-cholestatic infants, in order to define the natural history and better understand the pathogenesis of these disorders. (2) To determine the role of specific viral infections in the etiology of biliary atresia and idiopathic neonatal hepatitis. (3) To conduct a Phase I/Phase II study of treatment with an antioxidant solution designed to reduce injury, and ultimately fibrosis, in infants with biliary atresia. Our Center has extensive experience in clinical care, investigation, and development of novel therapies for biliary atresia and related cholestatic disorders, and is committed to the scientific development of and participation in clinical investigations and trials initiated by the Biliary Atresia Clinical Research Consortium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FUNCTIONAL GENOMICS AND HCV-ASSOCIATED LIVER DISEASE Principal Investigator & Institution: Katze, Michael G.; Professor; Microbiology; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAY-2007

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Summary: (provided by applicant): In this application for a Core Support Center, we propose to apply the technologies of functional genomics to the study of hepatitis C virus (HCV)-associated liver disease, a public health problem that is a direct consequence of drug abuse and addiction. This center will be composed of a diverse group of NIH-funded investigators, including experts in viral hepatitis, liver disease and transplantation, global gene expression analysis, proteomics, and advanced information technologies. The unifying theme is the desire to gain a detailed understanding of the molecular mechanisms underlying the progression from chronic HCV infection to end-stage liver disease, including cirrhosis and hepatocellular carcinoma. The University of Washington provides an exceptional environment that has fostered a high level of expertise in all these venues, and it is only through a Core Support Center that such a multidisciplinary group of researchers can be brought together to focus their expertise on a single problem. The proposed center will consist of four cores: Microarray & Virology, Proteomics & Modeling, Bioinformatics & Biostatistics, and Administration. Investigators from basic and clinical science will participate in the Microarray & Virology Core, providing a primary human hepatocyte cell culture system and access to unique patient populations, including biopsy material from patients with recurrent HCV after liver transplantation, and from patients coinfected with HCV and human immunodeficiency virus. An established infrastructure is in place for microarray analysis, including extensive experience in gene expression analysis during virus infection. The Proteomics & Modeling core will be located at the Institute for Systems Biology, one of the world's leading proteomics centers. Specialists in computational biology, bioinformatics, and statistics will provide the essential functions of data management, analysis, and statistical evaluation. This group will also develop a national database resource of gene expression and proteomics data that can be accessed via the World Wide Web. This multidisciplinary approach provides a unique opportunity to advance our understanding of viral hepatitis and liver disease to a level far in excess of that which could be obtained by any of these investigators working individually. The Core Support Center provides the mechanism to bring this outstanding group of scientists together and to attract additional scientists of the highest quality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: GBV-B-- A SMALL PRIMATE MODEL FOR HEPATITIS C INFECTION Principal Investigator & Institution: Lanford, Robert E.; Scientist; Southwest Foundation for Biomedical Res San Antonio, Tx 782450549 Timing: Fiscal Year 2001; Project Start 15-AUG-2000; Project End 31-JUL-2003 Summary: (Adapted from the applicant's abstract): HCV is a major health problem with as many as 3.9 million Americans chronically infected. As the population ages, these patients will be increasingly at risk for developing liver disease and hepatocellular carcinoma. The current model for HCV study, the chimpanzee, is too large and too expensive for many studies of HCV replication. An alternative surrogate model for HCV infection is replication of GBV-B in tamarins. GBV-B is closely related to HCV to the degree that the GBV-B protease cleaves an HCV protein substrate. GBV-B is believed to be a tamarin virus that causes an acute, self-limiting hepatitis. The virus can be transmitted via infectious plasma causing a readily reproducible hepatitis. The applicants hypothesize that GBV-B is so closely related to HCV that the study of GBV-B in tamarins and in tamarin hepatocyte cell cultures will provide data on replication, pathogenesis and the immune response that will be useful in understanding HCV

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infections in humans, and that furthermore this animal model will be of great value in the testing of antiviral drug strategies for HCV. A model system for study of GBV-B in tamarins will be initiated by generating and titering a pool of serum containing GBV-B. The course of GBV-B infections in normal and immunosuppressed tamarins will be monitored by reverse transcriptase PCR (RT-PCR) and ELISA assays being developed for this purpose. The host range of GBV-B will be examined by infecting squirrel, owl, and spider monkeys with infectious GBV-B serum to determine the optimal host for future investigations. A tissue culture system for hepatocytes isolated from naive tamarins will be used for in vitro infectivity studies. Immortalized hepatocyte cell lines will be developed from primary tamarin hepatocytes in an effort to establish continuous hepatocyte cell lines susceptible to GBV-B infection. A preliminary investigation of the humoral immune response to GBV-B infections in tamarins will be undertaken with emphasis on identifying the major viral antigenic regions responsible for eliciting the antibody response. An in vitro neutralization assay will be developed for use in preliminary examination of the requirement of the GBV-B neutralization. GBV-B and GBV-B/HCV hybrid molecular clones will be tested for infectivity following injection into tamarin liver or electroporation into primary hepatocytes or continuous hepatocyte cell lines. It is anticipated that a viable surrogate model for HCV infection will be developed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: HBV INDUCED LIVER PATHOGENESIS Principal Investigator & Institution: Siddiqui, Aleem A.; Professor; Microbiology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2001; Project Start 01-APR-1996; Project End 31-MAR-2006 Summary: (provided by applicant): Hepatitis B virus infections are one of the leading causes of chronic hepatitis. Infection results in a broad range of clinical symptoms from mild, nonapparent disease to fulminant hepatitis to hepatocellular carcinoma. Due to lack of in vitro infection system for HBV, the events of infectious processes are poorly understood. HBV encodes a regulatory protein termed HBx. While many functions have been attributed to HBx, a clear picture of how this protein participates in establishing infectious process has not emerged. In this competing renewal grant application, the focus of our study will be on the detailed characterization of HBx s association with mitochondria and exploring the functional consequences of that association. First, we propose to identify the mitochondrial targeting domain within HBx protein. Using those mutants, which fail to associate with mitochondria, further characterization of various possible functions of HBx within mitochondria will be investigated. These include, the ability of HBx via its interaction with the outer membrane channel VDAC to alter mitochondrial membrane potential (delta-psim), generation of reactive oxygen species (ROS). Ca+2 homeostasis. and permeability transition among others. Alteration of these functions will be correlated with induction of gene expression via NF-kB, AP-1, NF-AT and STAT-3 transcription factors. The results of these studies will delineate the molecular mechanisms in the induction of HBV-induced liver disease pathogenesis including hepatocellular carcinoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HCV-ALCOHOL EPIDEMIOLOGY

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Principal Investigator & Institution: Stapleton, Jack T.; Professor; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 31-AUG-2003 Summary: Hepatitis C is the commonest cause of chronic hepatitis in the US and can lead to progressive liver injury with the development of cirrhosis, liver failure and liver cancer. Liver injury may be caused by an interaction of the virus with the host immune response leading to inflammation and fibrosis in the liver. We plan to examine the mechanism of HCV induced liver injury in three distinct groups of patients: 1) those with chronic HCV infection and evidence of moderate to severe necroinflammatory disease, who are at average risk of progression to cirrhosis; 2) those with persisting viremia but normal or minimally elevated transaminases and normal or mildly inflamed liver biopsies, who are at low risk of progression to cirrhosis; and 3) patients with chronic HCV liver disease and active daily alcohol use (greater than 50 gm/day), who are at the highest risk of progression of liver disease. Specifically, we propose to evaluate the role of intrahepatic viral load on immune response and liver injury by measuring liver derived CTL response and cytokine production and correlating the immune response to the degree of liver injury. The response in the liver will be compared with that seen in the periphery to determine whether there is compartmentalization of immune responses and whether peripheral immune response can correlate with the injury and immune response seen in the liver. The role of antiviral therapy and alcohol on these responses will also be studied. These studies may lead to insights on the mechanism of liver injury and help define those patients who are most likely to have progressive liver injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: HELIOBACTER INDUCED HEPATITIS AND TUMORIGENESIS Principal Investigator & Institution: Fox, James G.; Director and Professor; Div of Comparative Medicine; Massachusetts Institute of Technology Cambridge, Ma 02139 Timing: Fiscal Year 2001; Project Start 01-MAY-1995; Project End 31-DEC-2003 Summary: Helicobacter hepaticus is responsible for a new murine disease, "H. hepaticus induced hepatitis". We have reproduced this type of chronic active hepatitis experimentally in both SPF inbred mice and outbred germfree mice and determined that H. hepaticus is widespread in mouse colonies and causes a persistent hepatitis in susceptible strains of mice. H. hepaticus also persistently colonizes the lower gastrointestinal tract of both A/JCr susceptible and resistant C57Bl/6 mice but does not cause liver lesions in resistant strains of mice. In the A/JCr and B6C3F1 the organism induces hepatic adenomas and hepatocellular carcinomas. We have determined the morphological stages of the H. hepaticus induced liver lesions in the A/JCr which consist of a series of progressive changes beginning with chronic active hepatitis and vasculitis leading to bile duct and oval cell hyperplasia with increased hepatocyte proliferation and hepatomegaly, development of clear cell foci and nodular hyperplasia and finally culminating in adenomas and hepatocellular carcinoma. Several key features of H.hepaticus' role in carcinogenesis have been recently elucidated which strongly suggest H. hepaticus acts as a tumor promoter. Experiments designed to further characterize and elucidate mechanisms responsible for H. hepaticus biological effects will continue to explore in vivo molecular events operable in establishing chronic hepatitis and promotion of tumorigenesis. In this proposal we plan to 1) Utilize isogenic

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mutants of H. hepaticus lacking putative virulence determinants to determine effects of these bacterial gene products on chronic hepatic inflammation and promotion of tumorigenesis. 2) Utilize congenic recombinant mice to characterize and map the genetic difference(s) responsible for determining the differential susceptibility of strains A/J and C57BL/6 to H. hepaticus induced hepatitis and liver tumors and 3) Determine if H. hepaticus infection promotes onset and progression of hepatitis and tumor formation in mice initiated with hepatic carcinogens and ascertain whether the sequential events operable in tumor induction can be interrupted by eradication of H. hepaticus at different stages of infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: HEPATITIS B AND C AMONG HOMELESS ADULTS Principal Investigator & Institution: Gelberg, Lillian; Family Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2004 Summary: Applicant's Abstract Persons infected with the hepatitis B virus (HBV) or hepatitis C virus (HCV) are at high risk for serious long-term health problems, and they are potentially infectious to others. Because of the seriousness of these infections, the NIH has developed a national agenda for preventing the spread and consequences of HBV and HCV. This agenda includes early detection, treatment, and prevention efforts for high-risk and infected persons. Homelessness has reached crisis proportions in the US today. Recent research by our team and others suggests that homeless adults in urban areas are a group at particularly high risk for HBV and HCV infections due to high rates of risky drug use and risky sexual behaviors. Despite the apparent high risk, however, there is only limited research on viral hepatitis in this group. We propose to conduct epidemiologic and health services research regarding HBV and HCV in a population-based sample of 500 homeless adults. We will recruit a probability sample of homeless adults with oversampling of injection drug users from 30 shelters and meal programs in the Skid Row area of Los Angeles. Respondents will undergo a two-hour interview (including the Diagnostic Interview Schedule-DIS-IV) and blood draw for hepatitis serology. We will estimate the prevalence of HBV and HCV and identify risk factors for each. We will evaluate whether homeless adults with histories of injection and non-injection drug use, risky sex, serious alcohol or mental disorders, or chronic homelessness have an elevated risk for these infections. We will also conduct health services research in which we will describe the respondents' past history of HBV/HCV testing, awareness of infection status, medical care for HBV and HCV, and willingness to return for HBV/HCV test results. Further, we will identify utilization of medical and non-medical settings to identify sites for future screening, treatment, and prevention efforts. We will provide hepatitis B immunization to those that test negative for hepatitis B. We will bridge the gap between research and prevention by using the Theory of Planned Behavior to understand protective behaviors used by homeless adults to avoid exposure to infectious diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HEPATITIS C CLEARANCE AND HOST GENETIC FACTORS Principal Investigator & Institution: Thio, Chloe L.; Assistant Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005

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Summary: (Applicant's Abstract) The candidate is completing a three year Infectious Diseases fellowship and has devoted the last two years to studying associations of the human leukocyte antigen complex to hepatitis B virus outcomes in a multi-cohort study. Through this grant, the candidate will use molecular genetics tools in an epidemiologic setting and will thus bridge the gap between the epidemiologists and basic scientists in an effort to understand immunopathogenic mechanisms of infectious diseases. Long-term, the candidate would like to establish herself as a faculty member interested in understanding infectious disease outcomes by examining the geneticallydetermined variability of the host response. In particular, in the short-term, this candidate is interested in studying host genetic factors that affect hepatitis C outcomes to elucidate mechanisms of hepatitis C virus pathogenesis, which eventually may have therapeutic and vaccine implications. The work will be performed under the guidance of Dr. David Thomas who has expertise in hepatitis C and epidemiology. In collaboration with Dr. David Vlahov, the epidemiologist who established the ALIVE cohort, and with Dr. Mary Carrington, a leader in the field of genetics, the candidate will have the collaborative resources necessary for the successful completion of this project. The candidate will complement her research by attending 2 hours per week of infectious diseases and hepatitis related conferences, attending weekly hepatitis C research meetings, and seeing patients in an infectious diseases/hepatitis clinic one half-day per week. She also plans to take courses in epidemiology, genetics, and virology. Over 170 million people worldwide are infected with hepatitis C virus (HCV), 85 percent of them have a persistent infection and the remainder clear the virus. This heterogeneous outcome difference is not explained by viral or environmental factors. As has been shown in other chronic viral infections, it is likely that host factors, which may be genetically programmed determine these outcomes. In the past, these host-virus interactions have been difficult to explore because of limited knowledge of HCV biology and lack of molecular tools to explore the human genome. However, HCV biology is unfolding and the recent advances in molecular biology permit detection of human genomic variability on a large scale. Using the ALIVE cohort of injection drug users, the candidate will study 131 individuals who have cleared the virus and 262 matched controls with persistent HCV infection. She will test polymorphisms in the human leukocyte antigen alleles and putative pathogenic genes for distortions in allele frequency between the clearance and persistently infected individuals. Where possible, the allele frequencies will be checked for Hardy-Weinberg equilibrium distortions. Chisquare analysis and univariate and multivariate conditional logistic regression will be performed. The associations will also be assessed with regards to HCV genotype. Success is anticipated since the cohort is well-characterized, the molecular tools exist, and the collaborations have proven to be productive in HBV studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: HEPATITIS C IN CENTRAL EUROPE Principal Investigator & Institution: Krekulova, Laura; Nusle Clinic Taborska 57 Prague, Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2007 Summary: (provided by applicant) This is a reentry grant proposal being submitted by an investigator who has undergone Fogarty International Center (FIC)-supported training at the University of California, Berkeley in molecular epidemiology of viral hepatitis. The study will focus on hepatitis C in Prague, Czech Republic. Hepatitis C is a major emerging infectious disease problem in Central and Eastern Europe, especially among young adults who engage in injection drug use (IDU) practice. IDU practice itself has become an epidemic in the last 10 years in Prague, Czech Republic. We wish to take

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advantage of this epidemic to characterize the natural history, clinical response to therapy, and epidemiology of hepatitis C in Prague. One unique feature of the current hepatitis C epidemic in Prague is that the hepatitis C viral (HCV) subtype diversity is limited, compared to those cities in the US or Western Europe, where IDU has been in practice for a much longer time. Hence, we wish to determine if any sets of viral strain types can be shown to be associated with adverse clinical outcome and response to antiviral therapy. To do so, we plan to 1) compare prospectively HCV genotype and subtype distribution, and evolution of the viral subtypes among cohorts of IDU and non-IDU subjects undergoing treatment for HCV infection in Prague, and determine if such characteristics are associated with certain treatment outcomes; 2) study the natural history of the HCV epidemic among untreated IDU populations for viral subtype distribution, evolution, and clinical outcomes among newly infected subjects in Czech Republic; and 3) create a registry of a database related to viral strain type, patient clinical characteristics, and therapeutic response rates that may be used to evaluate the long-term consequences of HCV infection (cirrhosis, hepatocellular carcinoma) for future use. In the process, we wish to learn about the epidemiology of hepatitis C in Prague and provide new data that may be ultimately used for designing better intervention strategies, including the identification of new antiviral drug targets and HCV vaccine candidates. We also believe that what we learn in Prague will have relevance to other regions in Central and Eastern Europe, including Russia where similar epidemics of IDU are occurring. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: HEPATITIS C IN CLINICALLY DISCORDANT HEMOPHILIC SIBLINGS Principal Investigator & Institution: Fried, Michael W.; Associate Professor of Medicine; Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: The clinical spectrum of hepatitis C is variable and the factors responsible for these divergent outcomes with chronic hepatitis C infection remain unknown. We propose to study a cohort of hemophilic siblings infected with hepatitis C to define the natural history, immunologic, and genetic factors that influence its clinical outcome. Patients with hemophilia have a prevalence rate of hepatitis C as high as 90 percent. The sex-linked pattern of inheritance of hemophilia allows us to identify a cohort of siblings both of who have been infected with hepatitis C. Hemophilic siblings are an attractive population to study because: 1) They are all males; 2) Siblings will be relatively close in age; 3) The mode of HCV acquisition is identical; 4) The age at acquisition of hepatitis C is similar 5) The date of acquisition can be confidently estimated upon their factor replacement history; 6) Hemophilic sibs share significant amounts of genetic material. Hemophilic siblings with hepatitis C will undergo a detailed clinical evaluation to stage their liver disease and to identify sibling pairs with clinically and/or histologically discordant levels of disease activity. These siblings pairs will be further studied to define antigen recognition patterns of peripheral CD8 plus CTL and CD4 plus cells and determine their functional significance. Using peripheral blood mononuclear cells, CD8 plus cells will be assayed for CTL activity against three overlapping vaccinia/HCV constructs covering the entire HCV genome followed by fine cloning to identify HCVspecific CTL epitopes. Peripheral CD4 plus cells will be tested for their ability to proliferate to HCV antigens. Using stimulation index, we will quantitate the presence and magnitude of this response. We will also try to identify immunodominant regions

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targeted by cytotoxic T cells using HLA class I matched hemophilic siblings. Finally, we will identify specific host genes that are preferentially expressed or repressed in patients with delayed progression of their HCV disease. We will quantitate the expression of mRNAs encoding host antiviral defense and immunoregulatory elements in peripheral blood mononuclear cells (PBMCs) and liver tissue from sibling pairs that have discordant chronic hepatitis C using mRNA libraries that will be screened by high density oligonucleotide arrays. The expression levels of these genes (including, but not limited to, interferon alpha, beta, and gamma; IRF-1 and IRF-2; interferon induced protein kinase; the cellular protein activator of PKR (PACT) RNase L; interferoninducible RNA-specific adenosine deaminase; a ribonuclease specific for inosinecontaining RNA; chemokine receptors CCR1, CCR3, CCR5, and their signal transduction elements; 2'-5'-oligoadenylate synthetase; tumor necrosis factor; FAS receptor; signal transduction components of these antiviral pathways, and both type 1 and 2 cytokines) will be correlated with delayed progression and diminished pathogenesis in paired hemophilic siblings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: HEPATITIS C VIRAL QUASISPECIES WITHIN THE LIVER Principal Investigator & Institution: Di Bisceglie, Adrian M.; Professor of Internal Medicine; Internal Medicine; St. Louis University St. Louis, Mo 63110 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: This application proposes to examine the biological significance of liverspecific hepatitis C viral (HCV) quasispecies variants. HCV is a positive single-stranded blood-borne RNA virus which infects humans and may cause chronic liver injury including hepatitis, cirrhosis and hepatocellular carcinoma through chronic infection. The liver is the major site of replication of HCV although HCV RNA is also found in the blood of infected individuals. The genome of HCV varies considerably in nucleotide sequence from isolate to isolate, allowing HCV to be divided into genotypes and subtypes. However, multiple isolates from a single infected individual may also have considerable variability in nucleotide and amino acid sequence, particularly within the hypervariable region (HVR1) of the envelope gene. HRV1 is a sequence of approximately 27 amino acids at the likely N terminus of the HCV E2 glycoprotein. Variations in HRV1 provide markers for identification and tracing of HCV quasispecies variants. Quasispecies arise because of the high error frequency associated with viral RNA replication and immune pressure appears to be a factor in their selection. Preliminary experiments conducted by the applicants have shown that a greater number of HCV quasispecies variants are found within the liver compared to serum, even allowing for differences in viral load and that some liver-specific variants appear to be present. The applicants hypothesize that an excess of HCV quasispecies variants are continually being produced by errors in replication of HCV RNA within hepatocytes, some of which are cleared from serum by neutralizing antibodies, leaving behind in the circulation those variants which have escaped immune clearance. The significance of these differences will be examined through cloning and sequencing quasispecies variants present in both serum and liver. Changes in HCV quasispecies over time will be sought by comparing nucleotide sequence in HRV1 region before and after liver transplantation. The presence of possible neutralizing antibodies in serum directed against liver-specific quasispecies variants will be sought by enzyme-linked immunoassays based on peptides synthesized according to nucleotide sequences of the various cloned quasispecies. In addition, immunoreactivity to the whole of the E1 and E2 proteins cloned and expressed in mammalian cells will be determined. Differences in

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presence, titer and reactivity of antibodies against quasispecies will be compared to determine whether neutralizing antibodies account for clearance of some quasispecies from serum but not liver. These studies have great potential significance for understanding of viral clearance, development of persistent infection and for the development of a vaccine against HCV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: HEPATITIS C VIRUS IN ETIOLOGY OF WA RHEUMATOID FACTORS Principal Investigator & Institution: Agnello, Vincent; Lahey Clinic 41 Mall Rd Burlington, Ma 01805 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: We have established the association of hepatitis C virus (HCV) infection with type II cryoglobulinemia (MC-II) and with the WA crossidiotype (XId) positive monoclonal rheumatoid factors (WA mRF), and the selective concentration of HCV and very low density lipoprotein (VLDL) in these cryoglobulins. We have also established that the LDL receptor mediates endocytosis of HCV and other members of the Flaviviridae family and that the apolipoprotein E epsilon2 allele in HCV infected patients increases the risk of developing MC three-fold. The broad, long-term objective of this proposal is to investigate how WA mRF are produced in MC-II and how they may affect chronic HCV infection. Two hypotheses will be tested: 1) In patients with MC-II associated with HCV infection, the WA mRF is produced as a result of chronic stimulation of B cells by complexes of HCV and VLDL. It is postulated from this hypothesis that initially a WA+ RF- IgM is produced and that rheumatoid factor activity arises as a result of a point mutation in the CDR3 with chronic HCV infection. It will be determined whether: a) WA+ RF- IgM has antibody activity to HCV VLDL, b) WA mRFs ve cross reactivity with the same antigen, and c) cells producing WA mRF- IgM are the precursors of those producing WA mRF+ IgM. Lymphoid aggregates in liver biopsies from HCV infected patients with mixed cryglobulinemia will be examined for the presence of WA+ RF- and WA+ RF+ B cells and the results compared to DNA and mRNA analysis for WA sequences from the same liver biopsies and paired peripheral bloods. 2) LDL receptor endocytosis is a major route of HCV infection of hepatocytes. The main physiologic role of WA antibodies is to block endocytosis of HCV VLDL complexes by the LDL receptors. The retarded endocytosis of HCV-VLDL complexes containing apolipoprotein E2 via the LDL receptor is the mechanism underlying the apo E2 risk factor for developing MC-II. Flow cytometry, in situ hybridization, and quantitative PCR assays will be used to study the endocytosis of HCV-lipoprotein complexes to determine a) the rate of endocytosis of HCV-VLDL of various apo E phenotypes and various HCV genotypes and b) the effect of WA mRF and WA+ RF-IgM on the rates of endocytosis. In addition, the role of lipoprotein concentration, apo E phenotypes and HCV genotypes on the distribution of HCV among lipoproteins in HCV infected individuals with and without cryoglobulinemia and on the selective concentration on VLDL with HCV in MC-II will be determined. The proposed studies may provide insights into the etiology of MC-II, the mechanism of HCV infection, and the role of natural antibody systems in the immune response to HCV, and may lead to better therapy, early detection and prophylaxis of the disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HEPATITIS C VIRUS INDUCED IL-8 & INHIBITION OF INTERFERON Principal Investigator & Institution: Polyak, Stephen J.; Assistant Professor, Research; Laboratory Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Hepatitis C virus (HCV) infects an estimated 3% of the world's population, and is a significant cause of liver disease. The interactions that occur between HCV proteins, cellular proteins and signal transduction machinery have a significant influence on virus replication, persistence, pathogenesis, and the outcome of antiviral therapy. Mutations in HCV proteins correlate with clinical responses to IFN therapy, and affect HCV replication in vivo and in vitro. HCV proteins also inhibit the antiviral actions of interferon (IFN). We have found that the HCV NS5A protein induces the pro-inflammatory CXC chemokine, interleukin 8 (IL-8), which is associated with inhibition of the IFN system. The in vivo significance of this finding is shown by elevated IL-8 levels in persons with chronic hepatitis C. In the HCV replicon system, we have also found that HCV replication is associated with increased production of IL-8 and attenuated IFN-induced transcriptional responses. Furthermore, exogenous IL-8 stimulates HCV protein production in HCV replicons. In this proposal, we hypothesize that HCV induced IL-8 inhibits the antiviral actions of IFN, promotes HCV replication, and contributes to HCV pathogenesis. To address this hypothesis, we propose 2 specific aims (SA) to determine the mechanisms of HCV induction of IL-8, and to determine the mechanisms of IL-8's anti-IFN activity. SA1 will focus on HCV induction of IL-8 via both transcriptional activation of the IL-8 promoter and stabilization of IL-8 mRNA. SA2 will focus on IL-8 mediated inhibition of the IFN-induced 2'-5' oligoadenylate synthetase/RNase L system, as well as cross-talk between IL-8 induced mitogen activated protein (MAP) kinases and IFN induced STAT-JAK pathways. The characterization of a new mechanism for modulation of the IFN system by a chemokine may be relevant to pathogenesis of chronic hepatitis C and many other viral and nonviral diseases. Moreover, IL-8 or its receptors may prove to be suitable targets for therapeutic intervention in chronic hepatitis C. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HEPATITIS C VIRUS PERSISTENCE AND PATHOGENESIS Principal Investigator & Institution: Lai, Michael M.; Distinguished Professor; Molecular Microbiol and Immun; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2001; Project Start 01-AUG-1996; Project End 31-JUL-2005 Summary: This application seeks continuing funding for the Hepatitis C Cooperative Research Center (HC-CRC) at the University of Southern California (USC) to coordinate and advance research toward understanding the replication infection. HCV is currently the major cause of chronic hepatitis in this country. Options for therapeutic intervention and prevention are limited. Continued funding will facilitate and expand the longstanding collaborative research activities at the USC HC-CRC. Four specific projects are proposed: 1. Study of the effects of HCV proteins on host functions. Emphasis will be placed on the effects of HCV proteins on the interferon activities, particularly the effect of viral E2 and NS5a proteins on host proteins mediating interferon actions. 2) Study of the immune modulation by the HCV core protein. By using an experimental model of adenovirus infection of mouse, we will study the effects of HCV core protein on TNF signaling, induction of cytotoxic T cells, antigen presentation and NK cell function in the

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liver. 3) Study of the mechanisms of HCV replication. We will develop in vitro cell culture systems for studying HCV replication. We will also study a novel HCV gene product discovered in Dr. Jing-Hsiung Ou's laboratory. 1) Study of the role of E2 and NS5a sequence variations in interferon resistance in patient populations. Furthermore, we will also study the role of NS5b mutations in the clinical resistance to ribavirin. These projects are expected to contribute to the understanding of viral pathogenesis and further improvement in therapies for HCV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: HEPATITIS C VIRUS REPLICATION AND LIVER INJURY Principal Investigator & Institution: Fausto, Nelson; Professor and Chairman; Pathology; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from application): Hepatitis C is an emerging infectious disease of major public health importance. Approximately 2% of the population of the USA and Europe are chronically infected with hepatitis C virus (HCV). Although major progress has been made in studies of the HCV genome and its encoded protein, basic aspects of the mechanisms of HCV pathogenesis are still poorly understood. One of the major difficulties has been the lack of an adequate tissue culture in which to study the interactions between HCV and hepatocytes, its natural host. Furthermore, the mechanisms of viral persistence and quasispecies evolution in HCV infected patients as well as the relationships between viral replication and disease progression remain to be determined. This application seeks to study the relationships between HCV replication and hepatocyte injury in a newly developed tissue culture system for human fetal hepatocytes (HFH) as well as in the human host. It is hypothesized that cell killing by apoptosis, preservation of permissive cells in which the virus persists and activation of cytokine signaling are events that occur in HCV infection and can be modified by the virus, the hepatocyte as its natural host or by interaction between virus and host cells. The application consists of 3 projects and 2 cores. Project 1 proposes to analyze HCV replication and the mechanisms of HCV-induced apoptosis in cultures transfected with full length HCV RNA or a 3'deleted virus used as control as well as in HFH cultures infected with patient sera. Project 2 will use cDNA microarrays to conduct a comprehensive analysis of gene expression in HFH transfected with full length and mutant HCV RNAs and investigate the effects of interferon on these cells. Project 3 will investigate the relationships between HCV replication, quasispecies evolution and hepatitis C disease progression in a population of Alaskan Native Americans (ANA cohort) from which serum, liver biopsies and clinical and epidemiological data have been collected. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HEPATITIS C: IFN-ALPHA, IL-12 AND IMMUNOREGULATION Principal Investigator & Institution: Karp, Christopher L.; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: The high failure rates associated with the use of IFNalpha clearly show the need for novel therapeutic strategies for chronic hepatitis C. IFNalpha probably directly inhibits hepatitis C virus (HCV) production or release. IFNalpha also has potent immunoregulatory activities, however, that likely play an important role in the overall response to its use in HCV infection. Interleukin 12 (IL-12) is an immunoregulatory

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cytokine which is central to the development of cell-mediated immune responses. Production of IL-12 by monocyte/macrophages and other antigen presenting cells is critical for immunity to a wide variety of viral and other pathogens. The immunology of chronic HCV infection, and the immunology of HCV therapy, strongly suggests that endogenous IL-12 plays an important role in successful viral clearance in this infection. We have shown that IFNalpha is a potent inhibitor of IL-12 production by monocyte/macrophages in vitro. IL-12 production is also reported to be suppressed in patients with HCV during IFNalpha therapy. Furthermore, successful therapeutic clearance of HCV with IFNalpha appears to be associated with maintained IL-12 responses, although this has not yet been definitively addressed. The central hypothesis underlying these studies is that therapeutic use of IFNalpha in chronic hepatitis C is compromised by suppression of the production of the critical immunoregulatory cytokine IL-12. The ultimate goal of this research is to use knowledge of the molecular mechanisms underlying IFNalpha- mediated alterations in IL-12 responses to devise novel therapeutic strategies for this disease. The studies in this proposal aim to further characterize the effects of therapeutic IFNalpha on in vivo and ex vivo IL-12 production, and to characterize, in vitro, the molecular mechanism(s) responsible for IFNalphamediated suppression of IL-12 production. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: HEPATITIS C: STUDIES OF IMMUNITY AND PATHOGENESIS Principal Investigator & Institution: Rice, Charles M.; Lab/Virology & Infect Diseases; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2001; Project Start 01-AUG-1996; Project End 31-JUL-2005 Summary: Hepatitis C virus (HCV) is an important cause of chronic liver disease, cirrhosis and hepatocellular carcinoma in most parts of the world. Its fastidious nature and limited host range have made it difficult to study. In this program, four separate groups of investigators join forces to attack the hepatitis C virus from a variety of different but interrelated vantage points. The four groups (PIs H. Greenberg, C. Rise, T. Wright, and M. Kay) have a well-documented history of collaborations in the general areas of hepatitis viruses and bring a pathogenesis and immunity and will range from clinically based investigation to fundamental analysis of the interaction of the HCV genome and the host. By combining resources, reagents and ideas, the program team hopes to advance the state of knowledge concerning HCV pathogenesis. The individual projects in this program are briefly outlined. Dr. Greenberg who is the overall program director, will carry out studies on the class I restricted CD8+ T cell response to HCV in patients with acute and chronic hepatitis and in patients undergoing liver transplant. He will take advantage of several new assay systems (tetramers and intracellular cytokines) to study responses in peripheral blood and the liver and will work closely with Drs. Wright and Kay to carry out these studies. Dr. Wright will continue her longitudinal analysis of two groups of patients: examine the contributions of virologic and immunologic variables to disease progression and will work collaboratively with Drs. Greenberg and Rice to study host immune responses and hepatocyte response to HCV infection. Dr. Kay will continue to develop his murine model for HCV replication. This model involves the engraftment of human hepatocytes on immunodeficient mice treated with antibody to c-met. Once established, Drs. Kay and Wright to study HCV strain variation phenotypes in the grafts. Finally, Dr. Rice will collaborate with Dr. Greenberg to study hepatocytes and other liver cell transcriptional responses to HCV using microarray techniques. These studies will involve cells in culture which express HCV proteins under the control of an inducible promoter, hepatocytes in vivo derived

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from chimpanzees and humans, and, when feasible, infected hepatocytes engrafted in our mouse model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: HEPATITIS DELTA VIRUS REPLICATION AND PATHOGENESIS Principal Investigator & Institution: Lazinski, David W.; Assistant Professor; Molecular Biol & Microbiology; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2001; Project Start 01-JAN-1997; Project End 31-DEC-2002 Summary: The principal investigator is interested in the mechanisms by which human pathogenic viruses replicate and establish chronic infections. For the past five years, such interests have been directed toward studies of the replication of hepatitis delta virus (HDV). This subviral human pathogen establishes acute and chronic infections of the liver and uses a helper, hepatitis B virus (HBV), to provide envelope proteins needed for virus assembly. The 25 million carriers worldwide who are chronically infected with HDV suffer a greater incidence of active hepatitis, liver cirrhosis and hepatocellular carcinoma than do those infected with the helper virus alone. The mechanisms responsible for such HDV-associated pathogenicity remain poorly understood and there are currently no effective treatments for HDV-infected individuals. A more detailed understanding of the molecular details involved in HDV replication will be essential if such antiviral therapies are to be developed. In addition to its clinical importance, HDV is also of scientific significance. Unlike all other infectious agents of animals, HDV contains a circular, single-stranded RNA genome that encodes ribozymes. These ribozymes self-cleave multimeric replication intermediates into unitlength species and the resulting termini are joined in a ligation reaction to generate the monomeric circular species. HDV also expresses a protein, the delta antigen, that binds viral RNA to form a ribonucleoprotein (RNP) complex. Like the RNA processing reactions, both the assembly of this RNP and its subsequent incorporation into HBV envelope particles represent essential steps in the viral life cycle that are logical targets for antiviral intervention. Both biochemical and genetic methods will be used in an effort to otter understand the process by which the delta antigen specifically identifies and assembles on its target RNA. Additional experiments are proposed to determine the domain within the helper virus envelope protein responsible for RNP packaging. This will be accomplished by making hybrids with a relative of HBV, duck hepatitis B virus, which is unable to package the HDV RNP. Such experiments may also enable the development of a new animal model useful for the study of HDV pathogenesis. Finally, the principal investigator has previously established a role for host-specific factors in the processing of HDV RNA. To better understand their role in both HDV and host RNA maturation, these factors will be cloned and biochemically characterized. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HEPATITIS DELTA VIRUS RNA EDITING Principal Investigator & Institution: Casey, John L.; Microbiology and Immunology; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2001; Project Start 15-FEB-1999; Project End 31-JAN-2003 Summary: RNA editing plays a central role in the life cycle of hepatitis delta virus, a subviral human pathogen. A cellular protein, likely a double- stranded RNA adenosine deaminase, is responsible for editing the antigenomic RNA at the amber/W site. This process changes the function of the viral protein from one of supporting RNA replication to one of facilitating virion formation and inhibiting RNA replication.

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Editing is highly specific, and requires a particular structure in the HDV RNA. The longterm objectives of the proposal are to expand our understanding of RNA editing via adenosine deamination, and the particular mechanisms through which this process is utilized by HDV. Post-transcriptional regulation by adenosine deamination is increasingly recognized as an important biologic regulatory mechanism that specifically controls the expression of viral and cellular protein variants that have altered functions. The identification and characterization of the RNA structures required, the deaminase enzymes responsible for the modifications, and accessory factors that might influence editing rates and specificity, remain important goals in advancing our understanding of this process. The specific aims are 1) to define the RNA structures required for editing HDV genotype I RNA; 2) to identify the RNA structures required for editing HDV genotype III RNA; 3) to evaluate the effects of modulating RNA adenosine deaminase expression on HDV RNA editing, RNA replication, virion formation, and genetic stability; and 4) to examine the mechanisms and implications of the inhibition of editing by hepatitis delta antigen, the sole viral protein. These aims will be addressed by a combination of approaches, including site- directed mutagenesis, analysis in vitro of editing and RNA-protein interactions, and evaluation of editing and its consequences in transfected cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: HEPATITIS VIRUS, ALCOHOL EXPOSURE AND OXIDATIVE STRESS Principal Investigator & Institution: Hassan, Manal M.; Gastrointestinal Med Oncology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant) Hepatitis C virus (HCV) infection and alcohol abuse are the 2 major risk factors for hepatocellular carcinoma (HCC) in this country. The higher prevalence of HCV infection in the general population has resulted in a significant increase of the incidence of HCC in the United States. Although both HCV and alcohol can independently induce liver disease, exposure to both agents may accelerate the course of liver pathology and/or lead to more severe injury. The mechanism underlying the synergistic effect of HCV and alcohol intake is not well understood. One hypothesis is that both HCV and alcohol intake may contribute to chronic hepatitis, cirrhosis and subsequent liver cancer through enhanced oxidative stress. It is known that alcohol could induce oxidative stress and lipid peroxidation. Interestingly, a recent study has reported that HCV encodes a selenium (Se)-dependent antioxidant enzyme, glutathione peroxidase, GPx, and GPx may have a regulatory role in HCV replication. The virus-induced overexpression of GPx may lead to a decreased level of Se in the host due to the competition of HCV for Se. In fact, patients with HCV have been shown to have a significant decline in their serum Se. On the other hand, the hepatotoxicity of ethanol and its associated malnutrition will further reduce the cellular Se level. This additive decline in the Se level will make the cell more susceptible to reactive oxygen species (ROS). Previous studies have shown an association between oxidative DNA damage and either alcohol exposure or chronic viral infection. It seems that chronic HCV infection may lead to an increased ROS, overexpression of GPx and reduced serum level of Se. When the Se-GPx level is low, the virus will be more provoked for replication, leading to a higher viral load in the infected cell. Eighty newlydiagnosed HCC patients will be recruited from University of Texas MD Anderson Cancer Center (UTMDACC). The current project will explore the effect of dietary selenium intake and its interaction with HCV and alcohol intake in HCC in a case-

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control study. Eighty healthy individuals (first control group), matched with cases by age, sex and ethnicity, will be recruited from the patients non-blood relatives and friends from UTMDACC. To have a control group with comparable prevalence of HCV infection, 80 patients with liver cirrhosis, who have no evidence of HCC (second control group), will be recruited from Baylor College of Medicine. Information on alcohol intake, dietary Se intake and other risk factors will be collected by a questionnaire. The frequency and profile of hepatitis B virus (HBV) and HCV infection will be determined by measuring serum HBsAg, anti-HBC, anti-HCV, and HCV-RNA. Oxidative stress will be evaluated by measuring the levels of serum Se, GPx activity, lipid peroxides, and 8hydroxy-deoxyguanosine (8-OH-dG), a marker of oxidative DNA damage. The expression of GPx and the level of 8-OH-dG will also be measured in tissue samples from cirrhotic and HCC patients. Serum Se, GPx activity, lipid peroxides and oxidative DNA damage will be measured in relation to HCV and alcohol intake history. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: HIV AND HEPATITIS IN YOUNG INJECTORS: A COMMUNITY STUDY Principal Investigator & Institution: Moss, Andrew R.; Adjunct Associate Professor; Epidemiology and Biostatistics; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 25-SEP-1999; Project End 31-AUG-2003 Summary: Hepatitis C virus (HCV) infection is common in young injection drug users in San Francisco even though most use sterile syringes. HIV infection is relatively uncommon, and may be contained by the use of sterile equipment. We propose an epidemiological and ethnographic study to investigate this anomaly, and to study HIV and hepatitis infections in young injectors. First, we will examine HIV infection crosssectionally in 1200 injectors aged 29 and under. We will explore risk factors for prevalent HIV infection in this needle exchange-using population. Second, we will carry out a prospective cohort study of HCV seroconversion. The principal aim of the proposed research is to estimate the seroconversion rate for HCV in the young injector population and to determine the reasons for seroconversion. In particular, we will examine the sharing of drug doses and of injection equipment other than syringes as the main reason for ongoing HCV transmission. We will accrue a cohort of 300 HCV seronegative injectors from among the 1200 persons screened and will follow them for one year. We will record HCV seroconversion prospectively. We will also identify individuals with early HCV infection, using a viral RNA amplification technology. Third, we will carry out a randomized controlled trial of a method to improve vaccination against hepatitis B virus (HBV) in young injectors. We will randomize eligible cohort members to either an accelerated vaccine schedule, which may be effective in achieving rapid immunity in young IDUs, or the standard schedule, and will study the development of immunity. Fourth, because little is known about detailed injection and sharing practices among young injectors, we will complement the epidemiological studies with an ethnographic investigation of the injecting practices of street-based youth in their natural context. We will examine how the moral economy of mutual dependency in a street-based youth culture promotes frequent paraphernalia sharing among network members, but direct needle sharing between running partners. We will explore aspects of the cultural, economic and social-status determinants of risktaking that may explain the differential HCV and HIV infection rates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HIV HCV COINFECTION--ANTIVIRAL THERAPY AND FIBROSIS Principal Investigator & Institution: Thomas, David L.; Associate Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 20-SEP-2000; Project End 31-JUL-2005 Summary: (Applicant's Abstract) Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections occur with alarming frequency in persons who misuse alcohol and illicit drugs. In East Baltimore, 80 percent of HIV-infected injection drug users also have HCV infection and one-half acknowledges regular, heavy alcohol use. This disease cluster may cause cirrhosis since HIV infection and heavy alcohol use are the two conditions that accelerate progression of hepatitis C. Recently the significance of these cofactors has been magnified by improved anti-retroviral treatments that dramatically reduce other opportunistic infections but may themselves cause liver toxicity. Accordingly, the 1999 US Public Health Service guidelines for management of HIV opportunistic infections considered hepatitis C but withheld recommendations for medical management because of the paucity of supporting data. In this investigation, we hypothesize that treatment of HIV and HCV infections will reduce progression of liver disease, after controlling for alcohol use. To test the hypothesis, we will first examine the success of prior anti-retroviral use with respect to liver fibrosis and then the change in fibrosis over three years of anti-retroviral experience. In addition, we will examine the effect of alfa-interferon based treatment for HCV infection with respect to fibrosis changes and eradication of HCV. Innovative tools will be tested to assess liver fibrosis (morphometrics), predict liver fibrosis (markers), and measure use of alcohol and medical adherence (A-CASI). Given the experience of the investigative team and the extensive preliminary data, we anticipate providing data that will directly affect forthcoming guidelines for the medical management of HIVHCV coinfected persons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HIV RISK BEHAVIORS AMONG URBAN NOMAD DRUG INJECTORS Principal Investigator & Institution: Des Jarlais, Don; Director of Research; National Development & Res Institutes Research Institutes, Inc. New York, Ny 10010 Timing: Fiscal Year 2001; Project Start 05-SEP-2000; Project End 31-JUL-2004 Summary: The global diffusion of HIV, hepatitis B and hepatitis C among injecting drug users (IDUs) shows both that they engage in substantial travel and that research is needed on their travel patterns. Previous research makes it clear that IDUs travel regionally, nationally, and internationally, but has not adequately described travel patterns nor the factors that influence IDUs' HIV risk behavior when they travel. Through our street-based research with IDUs in New York City, we have developed considerable familiarity with a large group of highly mobile, young IDUs, self-defined as "urban nomads", who travel frequently and widely throughout the U.S. These urban nomads are often homeless, but are conceptually and behaviorally distinct from "locally homeless" drug injectors who are not geographically mobile. The specific aims include both methodological and substantive objectives: (Aim 1) Analytically describe a large sample (n = 800) of "urban nomad" young IDUs, including their demographics, drug use histories, travel histories, HIV risk behaviors and serostatus. Identify factors associated with (a) HIV risk behaviors and (b) frequency of intercity travel. (Aim 2) Identify patterns of drug use and HIV risk behavior during travel by urban nomad IDUs, including numbers of "person-trips" (a trip by a person to another metropolitan area),

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the geographic distribution of person- trips where HIV risk behaviors do and do not occur, and factors that differentiate person-trips with and without HIV risk behavior. Aims 1 and 2 will be achieved through interviews with 600 urban nomad IDUs recruited in New York City and 200 urban nomad IDUs recruited at collaborating research sites across the country. (Aim 3) Implement and assess a long-distance telephone follow-up interview system for collecting data from urban nomad IDUs in their travels. Subjects will be intensively prepared to maintain telephone contact with researchers. Longdistance telephone interviewing will be supplemented by referrals to local research studies for HIV counseling and testing, by referrals to syringe exchange programs, and by e-mail and web site communication. (Aim 4) Determine potential biases in loss to follow-up in using these techniques. Estimated biases can then be used to adjust estimates of continuing drug use and risk behaviors. Aims 3 and 4 will be achieved through a cohort study of 300 subjects recruited in New York. Drug use and HIV risk behavior among IDUs are often viewed as local phenomena, with drug practices, risk behaviors and HIV epidemics occurring within defined geographic areas. The proposed research will provide data and research technologies for a complementary perspective that sees drug use practices and blood-borne pathogens diffusing within a loosely integrated nation-wide "system" of illicit drug use. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: IDENTIFICATION OF HEPATITIS C VIRUS BINDING PROTEINS Principal Investigator & Institution: Gale, Michael J.; Assistant Professor; Microbiology; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Hepatitis C virus (HCV) is a hepatotropic RNA virus that infects more than 200 million people worldwide. HCV is transmitted via percutaneous exposure to contaminated blood or blood products. Acute exposure to HCV most often leads to chronic infection characterized by persistent virus replication, hepatitis and the development of fibrosis and cirrhosis. The molecular basis for the hepatotropism of HCV has not been defined, in part, because of the lack of a suitable culture system by which to propagate native HCV infection. HCV binding and entry into the host cell is thought to occur through specific interactions of the HCV surface glycoproteins, E1 and E2, with surface proteins expressed on the target cell. We have adapted and developed new strategies by which to identify candidate HCV receptor proteins, and by which to assess the role of each candidate receptor in mediating the processes of virus binding and entry that direct HCV infection. We will utilize these novel strategies to investigate the hypothesis that HCV tropism is mediated by E1 and/or E2 glycoprotein interactions with liver-specific cell surface receptor proteins. In Aim 1 of this proposal we will utilize a cell-based expression/binding assay system to screen a liver-specific cDNA library for candidate cellular receptors that bind to one or both HCV glycoproteins. Aim 2 will employ a novel HCV-pseudotyped virus system to assess the role of each candidate receptor protein in supporting HCV binding and entry into the host cell. This pilot project will identify cellular HCV-binding proteins that direct viral tropism and that participate in the processes of HCV binding and entry. The proposed studies will provide novel insights into the HCV infectious cycle, and will establish a foundation for future work aimed at understanding the virus-cell interactions that confer HCV tropism and infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IDENTIFYING DETERMINANTS OF HCV TROPISM Principal Investigator & Institution: Dragic, Tatjana; Assistant Professor; Microbiology and Immunology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2008 Summary: (provided by applicant): It is estimated that 170 million people worldwide are infected with the Hepatitis C virus (HCV) and are at risk of developing chronic hepatitis or cirrhosis, the latter often leading to hepatocellular carcinoma. There is currently no vaccine and licensed therapies are associated with modest efficacies and significant toxicities. Despite the urgency of this worldwide public health problem, our basic understanding of HCV replication and pathogenesis remains poor due to a lack of key experimental models. For example, difficulties in culturing the virus in vitro and expressing native, fusogenic envelope glycoproteins have greatly limited studies of HCV tropism and entry. These are critical aspects of viral biology because the host range and pathogenesis of enveloped virus infection is largely determined by the selective interaction of viral envelope glycoproteins with cell-surface receptors. A major goal in HCV research is to understand how HCV targets the liver and by what mechanism it enters host cells. Recently, a major breakthrough in the field has been the development of retroviruses pseudotyped with HCV envelope glycoproteins that specifically mediate infection of primary hepatocytes, as well as certain other human cells. We will use this new experimental system to study HCV entry into target cells. Alterations in naturally occurring HCV envelope glycoproteins may predicate differences in receptor usage and target cell tropism in vivo. To investigate the range of HCV cellular tropism, pseudotypes incorporating envelope glycoproteins from clinical HCV isolates will be tested for their ability to enter relevant primary cells and cell lines. A functional cDNA cloning approach will be used to identify cell-surface receptors that specifically mediate HCV entry into different target cells. However, these receptors may be ubiquitously expressed and HCV targeting to different cell types may be determined by another mechanism. We recently demonstrated that L-SIGN and DC-SIGN are specific HCVcapture receptors and we will explore whether they mediate infection of target cells in trans, thereby determining HCV tropism. The major objective of our work is to identify the basic protein interactions that mediate HCV tropism, which will serve as a foundation for detailed structure/function analyses of HCV receptors and envelope glycoproteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMMUNITY TO HEPATITIS C IN LIVER TRANSPLANT RECIPIENTS Principal Investigator & Institution: Koziel, Margaret J.; Assistant Professor; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 01-JUN-1997; Project End 31-MAY-2002 Summary: (Adapted from the applicant's abstract) Hepatitis C virus (HCV) is a significant cause of end stage liver disease in the United States, and in most transplant centers is a major indication for transplantation. Following liver transplantation, HCV viremia occurs in nearly 100% of HCV-infected individuals. Approximately half of infected liver transplant recipients will develop clinically significant hepatitis, which has a more rapid progression than HCV hepatitis in the immunocompetent host. A subset of HCV infected transplant recipients may have rapid graft loss and impaired survival. The only currently licensed therapy for HCV infection, interferon-alpha (IFNa), has a low sustained response rate and increases the risk of chronic rejection in allograft recipients. Given the impact of HCV on transplant recipients, there is a need for

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a greater understanding of pathogenesis of this infection. Neither the viral nor the host factors which determine outcome are defined. At present, there is no small animal model for HCV infection; so examination of host responses in infected individuals is critical to understanding the possible role of host factors in determining clinical outcome. Cellular immune responses are a crucial component of host defenses in most viral infections and are attenuated in transplant recipients. In particular, cytotoxic T lymphocytes (CTL) are an important element of protective host immunity, but under certain circumstances may induce host tissue damage without clearing viral infection. By comparing the immune response against HCV in immunocompetent hosts and transplant recipients, it may be possible to determine which host factors are important in controlling viremia and which host factors may be responsible for accelerated disease. The goal of this proposal is understanding the role of cytotoxic T lymphocytes in limiting viral replication. The specific aims of this proposal are to: 1) define HCVspecific cellular immune responses in transplant recipients; 2) correlate the spectrum of HCV-specific CTL responses with disease activity in transplant recipients; and 3) characterize the role of cytokines in HCV-specific CTL responses in transplant recipients. These studies will provide the necessary scientific background for the development of vaccines or immunotherapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: IMMUNOGENICITY OF HEPATITIS C VIRUS (HCV) LIKE PARTICLES Principal Investigator & Institution: Barber, Glen N.; Associate Professor; Microbiology and Immunology; University of Miami Box 016159 Miami, Fl 33101 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JAN-2008 Summary: (provided by applicant): Hepatitis C virus [HCV], a member of the Flaviviridae, is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Acute infection with HCV is associated with persistent viral replication in approximately 80-90% of cases, with an estimated 200 million people infected worldwide. Presently, the only effective therapy against HCV infection is type I interferon [IFN] currently in combination with the nucleoside analogue ribavirin. However, response rates vary from 5% to 50%, depending on race and gender, thus leaving many infected individuals untreatable. Presently, there is no vaccine for HCV and therefore a collective need to develop preventive strategies as well as new therapies. The search for effective vaccines is hampered, however, by the inability to grow candidate HCV vaccine preparations in vitro and by the prevalence of numerous HCV quasispecies that have evolved due to the virus lacking a proof reading mechanism while replicating. Since HCV cannot be efficiently manufactured for vaccine assessment, we have synthesized, in mammalian cells, highly immunogenic, non-infectious HCVlike particles comprised of the core, E1 and E2 products of HCV. This was achieved by cloning the core/El/E2 genomic region of HCV into the relatively simple, nonpathogenic negative-stranded virus, vesicular stomatitis virus (VSV). Following infection of tissue cultured mammalian cells with VSV/HCV recombinant viruses, high levels of authentic core/El/E2 HCV proteins were generated that autoassembled into HCV-virus-like particles (VLPs). Importantly, our preliminary data further indicates that VSV/HCV induced cell-mediated and humoral activity to all the structural proteins in immunized mice. Thus, our HCV expression system may have the capacity to generate effective, multivalent immune respones to a variety of HCV encoded proteins. Given this data, we aim to analyze the potency of the rVSVs system that expresses HCV gene products or purified HCV-like particles themselves, in vaccine studies designed to

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further evaluate whether robust cell-mediated and humoral responses can be safely and effectively obtained to multiple HCV epitopes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: INCIDENT HIV INFECTION AND IMMUNE RESPONSE TO HCV Principal Investigator & Institution: Cox, Andrea L.; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Dr. Cox is an infectious disease fellow at the Johns Hopkins University (JHU) and has spent the last two years working with her mentors, Drs Thomas, Ray, and Pardoll on the cellular and humoral immune responses to hepatitis C virus (HCV) infection. Through this award, Dr. Cox hopes to conduct basic science research on HCV immunology as a faculty member in the Division of Infectious Diseases. To elucidate the effects of HIV infection of CD4+ T cell on the immune response to chronic hepatitis C virus (HCV) infection, she plans to characterize the humoral and cellular immune responses to HCV in the same subjects before and after HIV infection. Her hypothesis is that HIV infection alters CD4+ T cell by destruction or dysregulation, an effect that in turn modifies B cell and CD8+ T cell activity. Through the sponsor's research, cells, plasma, and serum have been collected before and after HIV infection from individuals with chronic HCV. Humoral responses to each HCV protein at multiple time points before and after HIV infection will be assessed using an ELISA assay optimized for the measurement of end-point titers of IgM, IgG, and the four IgG subtypes specific for HCV CD8+ T cell responses will be measured at multiple time points before and after HIV infection using an Elispot assay for the detection of gamma interferon. Finally, the cytokine secretion profiles of CD4+ T cell will be assessed to determine if alterated cytokine production is correlated with any observed changes in B cell or T cell function. We anticipate that this study will provide insight into the impact of HIV infection on CD4+ T cell effector function, will increase understanding of HCV immune responses and control of HCV viremia, and will enhance future research aimed at elucidating the mechanisms of interaction between HIV and HCV that lead to differences in the pathogenesis and control of HCV seen with HIV co-infection. Since no direct patient contact is anticipated, Dr. Cox plans to conduct these studies through a K08 award. Dr. Cox will attend immunology, virology, and infectious disease seminars. This, along with excellent mentorship and the supportive and rich environment at JHU, will provide Dr. Cox with the skills she needs to develop into an independent researcher studying HIV/HCV coinfection immunology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INDUCIBLE TRANSGENIC MOUSE MODEL FOR HEPATITIS C Principal Investigator & Institution: Chan, Tehsheng; Microbiology and Immunology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): The long-range goal of this research is to develop animal models for use in elucidating the mechanism of hepatitis C, as well as in preclinical studies of candidate therapeutics. The transgenic mice that constitutively express hepatitis C virus (HCV) proteins in the liver have been valuable in some studies in the past. However, they have been less useful as a model for hepatitis due to their inherent tolerance to the viral antigens expressed in the liver. We have taken advantage of the cre/IoxP technology, and developed several transgenic mouse lines with

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inducible expression of the HCV core, E1, and E2 proteins in the liver. In this grant application, we propose studies aimed at establishing a suitable murine hepatitis C model through much improved induction technologies. We will evaluate a novel hydrodynamics-based transfection protocol. The efficiency of HCV gene induction and potential adverse effects will be examined. In addition, a cell-permeable cre fusion protein will be assessed for its function as the catalyst for HCV transgene recombination in the liver. We will then test the hypothesis that transgenic mice conditionally expressing the HCV proteins will mount immune response to the viral antigens and develop hepatitis. In the event that HCV gene expression alone is not sufficient to result in T cell homing and hepatocellular injuries, we will co-transfect the liver with a plasmid DNA encoding the co-stimulatory signal molecule CD80 or CD86 to increase the level of antigen presentation. The antibody and T cell responses against HCV antigens will then be assessed. The results obtained from these proposed studies will be the bases for future NIH RO1 grant applications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: INNOVATIVE FORMULATION

SINGLE-DOSE

HEPATITIS

B

VACCINE

Principal Investigator & Institution: Kitchell, J P.; Director, Biodegradable Implants; Biotek, Inc. 21-C Olympia Ave Woburn, Ma 01801 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JAN-2004 Summary: (provided by applicant): Hepatitis B (HBV) is a serious viral disease that can result in acute massive hepatic necrosis, chronic active hepatitis, and cirrhosis of the liver. HBV vaccines are commercially available and HBV vaccination is now recommended for all infants, adolescents, health workers and others who may be exposed to the virus through their work. Three HBV vaccine injections are required to generate protective immunity. Compliance depends on completing three visits to the healthcare provider. Incomplete vaccination is common and often attributed to scheduling difficulties. The vaccination success rate could be improved if only one dose were needed for full protection. There have been many attempts to address the need for single dose formulations for vaccines. Kitchell and Crooker (1997) studied the physicochemical properties of alum, the adjuvant used in the approved HBV vaccine, and they made an important observation about the hydration behavior of this material. Their discovery led to a simple and elegant method of formulating alum-adjuvanted hepatitis A vaccine as a single-dose injection giving multiple delayed pulses. This innovative approach to reformulation is also appropriate for the HBV vaccine. BIOTEK believes that it has gained further insight into the techniques needed to prepare a single dose HBV vaccine which provides three discrete pulses of vaccine exposure. The formulation will utilize the established HBV vaccine antigen and adjuvant, and a FDA approved biodegradable polymeric excipient. The specific aims of the Phase I project are to prepare and test in vivo both one month and four month delayed pulse formulations. PROPOSED COMMERCIAL APPLICATIONS: The technology, first directed at an improved hepatitis B vaccine formulation, could be transferred to hepatitis A vaccine and to the childhood DPT vaccination series. One important application in the future may be with an AIDS vaccine, where relaible single-dose protection for high risk populations may be especially important. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TREATMENT

INTEGRATED

DUAL

DIAGNOSIS/INFECTIOUS

DISEASE

Principal Investigator & Institution: Rosenberg, Stanley D.; Professor; Psychiatry; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2003 Summary: (adapted from the applicant's abstract): People with severe mental illness (SMI), and particularly those dually diagnosed with comorbid substance use disorder (SUD), are at extremely elevated risk for several serious blood-borne infections, including HIV, Hepatitis B and Hepatitis C. One third of dually diagnosed clients in many mental health service settings are likely to have one of these infections, and the rate of co-infection is very high. However, the field lacks effective and feasible models for responding to this problem, and neither infected nor high-risk clients receive services that meet authoritative standards. Indeed, infected clients may be the least likely of all people with SMI to receive adequate medical care. By and large, mental health providers are not well informed regarding these issues, and do not systematically provide the necessary interventions to help clients understand and cope with these risks and diseases. Providers do, however, express interest and willingness to respond by increasing staff education and by adding services for their high-risk clients. To date, no such innovation has been reported in any state mental health system, even in those states with known high rates of seroprevalence. Barriers to dissemination and provision of best practices have been identified, and include providers' underestimation of the problem in clients they serve, and confusion about how to best respond to information about clients' risk and infection status. To implement and sustain best practices interventions for this vulnerable group of clients, integrated procedures to change the knowledge, attitudes, training resources and practices of community mental health providers are required. Procedures for dealing with blood-borne pathogens should be structured to be a standard part of multidisciplinary team treatment. They should include a very basic set of evidence based practices for HIV, Hepatitis B and Hepatitis C, including screening, diagnosis, counseling, risk reduction, immunization, linkage with appropriate medical providers, and support for clients through treatment. We propose, in this Exploratory/ Developmental Grant application (R21), to develop an easily disseminated intervention, packaged as a "toolkit" and supported by implementation assistance, to enhance the knowledge, attitudes and practices of typical community mental health providers so that they will achieve sustainable, best practices standards for their infected and at-risk clients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: INTERFERON-GAMMA TO TREAT CHRONIC HCV INFECTION Principal Investigator & Institution: Muir, Andrew J.; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 21-SEP-2001; Project End 31-AUG-2003 Summary: (adapted from the application) Current treatment options for chronic hepatitis C infection remain limited and unsatisfactory. Treatment with interferon-alpha and ribavirin leads to a sustained response in the minority of patients, and many patients may not be eligible for treatment due to side effects associated with these medications. Other treatment options are clearly necessary for chronic hepatitis C infection. A major complication of chronic hepatitis C infection is fibrogenesis, ultimately leading to development of cirrhosis. Animal models have demonstrated that interferon-gamma reduces fibrogenesis through its effect on stellate cells. A recent

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report in patients with idiopathic pulmonary fibrosis found that interferon-gamma was well-tolerated and led to improved pulmonary function, ostensibly due to a reduction in fibrogenesis. Given these data, we postulate not only that interferon-gamma will be effective for treatment of hepatitis C mediated fibrogenesis, but also that it will be safe. We have therefore proposed a phase I study to assess the effectiveness of interferongamma in twenty patients with chronic hepatitis C infection. The patients will include those who have failed previous therapy with interferon-alpha or are not candidates for interferon-alpha therapy. Men or women 18 years of age or older are eligible. Other inclusion criteria are serum positive for hepatitis C virus by PCR; liver biopsy consistent with chronic hepatitis and with a fibrosis score of at least one on the Knodell scale; compensated liver disease; and informed, written consent obtained prior to entry. All patients will receive 200 micrograms of interferon-gamma three times a week for twelve months. Patients will undergo liver biopsy prior to treatment and at the end of treatment. Safety and tolerance will be evaluated at weeks 1, 2, 4, 8 and then every 4 weeks during treatment and at weeks 4 and 12 following the completion of therapy. Serum HCV-RNA will be evaluated prior to initiating therapy and at the end of therapy. The primary endpoint of this study will be the histological response of patients with chronic hepatitis C infection to treatment with interferon-gamma. Secondary endpoints include the biochemical response, inflammatory and regulatory cytokine levels, and quality of life during treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: INTERNATIONAL CONFERENCE ON THE HEPATITIS B VIRUSES Principal Investigator & Institution: Tavis, John E.; Molecular Microbiol and Immun; St. Louis University St. Louis, Mo 63110 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2004 Summary: (provided by applicant): The 350 million chronic carriers of Hepati tis B Virus (HBV) worldwide are at risk of hepatitis, cirrhosis, and hepatocellular carcinoma. A recombinant subunit vaccine is available, but it has a 5-10% failure rate, and there is no widely effective therapy for HBV infection. The development of effective therapies could be advanced more rapidly by a better understanding of the mechanisms of pathogenesis, the immune response, and function of the proteins involved in HBV replication. This conference will gather about 200 scientists who study different aspects of HBV, animal hepadnaviruses, and Hepatitis Delta Virus for discussions of the latest conceptual and technical advances. This meeting has been held annually since 1985, and is the only basic science HBV and HDV meeting of its kind. The primary goal of this application is to raise funds to support travel grants for junior scientists. The 2003 HBV Meeting will be organized by Drs. Antonio Bertoletti and John Tavis. The meeting will be modeled on the successful traditions of this series: intimate interactions through small size, presentation of work-in-progress, and a focus on training younger scientists. The meeting will have 9 oral sessions, two poster sessions, a keynote speaker, and one workshop. The oral session will be: New Models & Viral Entry, RNA & DNA Synthesis, Assembly, Morphogenesis & Trafficking, Regulatory Proteins and Variants, Immune Responses, Pathogenesis, Hepatitis Delta Virus, Hepatocellular Carcinoma & Oncogenesis, and Antivirals & Immunomodulation. Involvement of women and minorities in leadership positions will be emphasized. Each session will have approximately 7 talks selected through peer-review by the organizers of submitted abstracts. Posters for each topic will be presented in the poster sessions. A theme of the meeting will be to compare and contrast HBV with Hepatitis C Virus (HCV), the other most medically important hepatitis virus. The keynote speaker, Dr. Raft Bartenschlager,

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will contrast the molecular biology of HCB with that of HBV. The workshop will compare HBV and HCV immunology and pathogenesis. This conference will advance HBV research by introducing ideas from the HCV field, promoting constructive interactions between researchers, encouraging exchange of unpublished data and key reagents, and educating graduate students and post-doctoral trainees. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: JOHNS HOPKINS ADULT AIDS CLINICAL TRIALS UNIT Principal Investigator & Institution: Flexner, Charles W.; Associate Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-JAN-2000; Project End 31-DEC-2004 Summary: (adapted from applicant's abstract): Johns Hopkins University has had an ACTU since its inception in 1986. The Unit is administratively within the Division of Infectious Diseases as a component of the Johns Hopkins HIV Care Program, but it is configured to make maximum use of relevant institutional resources with investigators from multiple departments and divisions including Pharmacology, Neurology, Ophthalmology, Gynecology, Pathology and Internal Medicine. The Hopkins ACTU has provided leadership to the ACTG scientific agenda and has provided HIV clinical trials to Baltimore, a city that ranks ninth among metropolitan areas in AIDS rates. The performance record for the last grant cycle shows average enrollment, data performance and a rank of No. 3 in scientific contributions. Assets of this ACTU include leadership and scientific expertise in virology (B. Jackson), immunology (H. Lederman, T. Quinn, R. Bollinger), quality of life assessment (A. Wu), neurology (J. McArthur), pharmacology (C. Flexner), CMV retinitis (D. Jabs), and mycobacteriology (R. Chaisson). This unit has a subunit in the prison system, has developed an ACTG study of tuberculosis in Haiti and has high enrollment of injection drug users and African-Americans. This application proposes to continue a scientific portfolio that has depth and diversity to support the ACTG scientific agenda and a clinical trials program that includes good data performance and the enrollment of high priority participants. All current investigators will continue in their present roles as will the three advanced technology laboratories. Three new investigators, Dr. R. Siliciano (latent reservoirs of HIV), Dr. Richard Moore (HIV outcomes, cost and cost effectiveness), and Dr. David Thomas (hepatitis C coinfection) will be added. Preference will be given to protocols that reflect emphasis areas of the Hopkins ACTU, especially pharmacology, neurology, immunology, mycobacteriology, hepatitis C, long-term outcomes (quality of life and cost analyses) and simplified ART regimens (to better serve the patients). There will be emphasis on enhanced enrollment with a new peer recruiter and a new subunit to increase the catchment area. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LIVER-TARGETED PRODRUGS FOR THE TREATMENT OF HEPATITIS C Principal Investigator & Institution: Van Poelje, Paul D.; Metabasis Therapeutics, Inc. 9390 Towne Centre Dr, Ste 200 San Diego, Ca 921213026 Timing: Fiscal Year 2003; Project Start 01-AUG-2001; Project End 31-AUG-2005 Summary: (provided by investigator): The long-term objective of this application is to identify a potent, efficacious and safe drug for the treatment of hepatitis C virus (HCV) through the use of our proprietary HepDirect prodrug technology. It is estimated that >170 million people are infected with Hepatitis C virus worldwide. Despite recent

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improvements in HCV drug formulations, a large segment of the patient population is still under treated. In the first phase of our SBIR grant support we demonstrated the potential of HepDirect prodrugs in selectively delivering high levels of phosphorylated nucleoside analogues to the liver. The work led to the identification of a development candidate (HepDirect-adefovir), which recently completed its initial Phase I clinical study and is expected to begin Phase 1/2 in early 2003. We now propose to continue the exploration of the HepDirect technology and its applications to a large and structurallydiverse set of nucleosides, with the goal of identifying a potent and selective inhibitor of HCV replication. Most nucleosides designed to be specific inhibitors of viral replication as the nucleoside triphosphate (NTP) fail as a result of poor recognition by the nucleoside kinases responsible for converting the nucleoside to the NTP. The HepDirect technology overcomes this limitation and allows us to pursue nucleoside analogues that are easily overlooked or discarded by companies pursuing standard drug discovery approaches. The specific aims of this application include the synthesis of a large number of HepDirect prodrugs of diverse nucleoside analogues, the production of the corresponding NTP library via the biological conversion of the prodrugs in hepatocytes, and the screening of this library for the inhibition of HCV replication. To support the antiviral activity determinations, a key aim is the development of a cellular assay compatible with the prodrug technology as well as a novel human tissue based HCV replication model. Following the identification of a lead inhibitor, the HepDirect prodrug moiety is optimized for intracellular activation efficiency, oral bioavailability, pharmacokinetics, as well as liver targeting. The final aim is to complete the requisite studies to launch the compound identified into full development for the treatment of HCV including second species pharmacokinetics, pilot animal toxicology, pilot in vitro and in vivo genetic toxicology and general safety pharmacology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MALIGNANT COMPLICATIONS OF CHRONIC HEPATITIS C VIRUS Principal Investigator & Institution: Loffredo, Christopher A.; Assistant Professor; Oncology; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2001; Project Start 29-SEP-1999; Project End 31-JUL-2004 Summary: Chronic infection with hepatitis C virus (HCV) is a major public health problem, particularly in Egypt, where the prevalence of HCV infection is high. Among the long-term complications of HCV are hepatocellular carcinoma (HCC) and nonHodgkin's lymphoma (NHL), but, particularly for NHL, few prospective studies have been done; hence, the incidence of malignant complications of chronic HCV is largely unknown. The contribution of other cancer risk factors also needs to be taken into account in assessing the HCV-associated risk of HCC and of NHL. Such factors include environmental exposures to carcinogens and inherited genetic susceptibilities, and new research is needed to investigate whether these risk factors can interact with HCV to modify the risks of malignancies in persons with chronic infections. In addition, the role of tumor suppressor genes in the biology of HCC and NHL cells needs to be addressed more fully. To fill these gaps in knowledge, this proposal builds upon an ongoing collaborative infrastructure of American and Egyptian scientists and research institutions to investigate the epidemiology of HCV- associated malignancies in Egypt. We propose to conduct: (1) a case-control study of the interrelationships among viral, genetic, and environmental risk factors for these two cancers; (2) a prospective study to estimate the incidence of HCC and NHL in persons with chronic HCV; and (3) a study of the mutational spectrum of the p53 gene in the tumor tissues of patients with HCC

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and NHL. Given the high prevalence of both HCV and HCV- related cancers in Egypt, the high potential for environmental exposures to carcinogenic chemicals there, and our demonstrated ability to collect biological samples and to obtain high-quality data from study subjects in Egypt, this proposal represents a unique opportunity to address important questions concerning the role of hepatitis C in these types of cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MECHANISMS OF CHRONIC HEPATITIS B INFECTION Principal Investigator & Institution: Milich, David R.; President; Vaccine Research Institute of San Diego San Diego, Ca 92109 Timing: Fiscal Year 2001; Project Start 01-MAY-1984; Project End 31-MAR-2006 Summary: (Adapted from applicant's abstract): The hepatitis B virus (HBV) is a major cause of infectious liver disease throughout the world. There are 1.2 million carriers of HBV in the U.S. and approximately 300 million worldwide. Neonatal HBV infection is rarely cleared and as many as 90 percent of perinatally infected children become chronically infected. Therefore, in addition to worldwide vaccine programs to prevent new infections, methods for treating HBV chronic carriers will be necessary to eradicate this disease. This application is focused on understanding the mechanisms responsible for inducing and maintaining chronic HBV infection, and specifically the role of HBV nucleoprotein antigens, the nucleocapsid (HBcAg) and the secreted non-particulate HBeAg. The specific aims are addressed through the use of HBc/HBeAg-expressing and HBV replicating transgenic (Tg) mice, the eight recently developed HBc/HBeAg-specific T cell receptor (TCR)-Tg lineages and various combinations of "double and triple-Tg" hybrids. The specific aims are: (1) production and characterization of TCR-Tg lineages; (2) development of models to explore the relationship between chronicity and perinatal infection; (3) examine the potential of the secreted HBeAg to elicit and maintain immune tolerance and promote chronicity; (4) explore mechanisms that allow HBc/HBeAgspecific CD4+ T cells to escape tolerance induction and co-exist with viral antigens; (5) examine mechanisms by which residual (i.e., non-tolerized) HBc/HBeAg-specific CD4+ T cells cause liver injury; and (6) use the models of liver injury to screen HBc/HbeAgspecific immunotherapies potentially useful in the treatment of chronic infection. It is anticipated that the results of these studies will have diagnostic, therapeutic, and vaccine applications and will provide a better understanding of basic immune mechanisms responsible for viral persistence and clearance in chronic HBV infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF LIVER INJURY BY HEPATITIS C AND ALCOHOL Principal Investigator & Institution: Weinman, Steven A.; Professor of Internal Medicine and Physi; Physiology and Biophysics; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001; Project Start 27-SEP-2000; Project End 31-AUG-2005 Summary: Hepatitis C is the most common form of chronic liver disease in the U.S. with an estimated 4-5 million people infected. The disease is characterized by hepatic inflammation and progressive fibrosis leading to eventual development of cirrhosis and/or hepatocellular carcinoma in as many as 20-30% of individuals. Alcohol consumption greatly increases the severity and rapidity of disease progression but the mechanism of alcohol/HCV synergy is unknown. Development of new therapeutic approaches has been hampered by the limited experimental models systems available and a lack of understanding of the pathogenic mechanisms involved. The long-term

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objective of this study is to characterize a transgenic mouse model which expresses HCV proteins in the liver and to use this model to determine the role of oxidative stress and mitochondrial dysfunction in producing the increased liver toxicity of alcohol in chronic hepatitis C. The specific aims are 1. To examine the mechanisms and consequences of HCV protein-induced stimulation of ROS production. These experiments will use cell culture expression systems to determine the effects of HCV core protein on basal and TNF-induced ROS production and examine the source of abnormal ROS. The consequences of core-induced ROS changes to cell survival and its modification by antioxidants and NF-XB activation will be determined. Changes in gene expression induced by HCV protein expression in cell lines will be measured using RNase protection assays. 2. To determine the effects of HCV protein expression on ethanolinduced liver injury. Chronic alcohol feeding of normal and a-ansgenic mice will be performed and liver histology and oxidant injury compared. Alcohol induced changes in liver gene expression will be measured using DNA microarrays. 3. To evaluate antioxidant based approaches to modify HCV/alcohol-induced cell and liver injury. Ethanol-fed transgenic animals and cell culture systems will be used to determine the potential to modify HCV/alcohol -induced liver injury with antioxidants and anti-TNF antibodies. Successful completion of these studies will result in the development of a new model for the study of HCV-induced liver injury, new insight into the role of oxidative stress in HCV/alcohol induced liver injury, and a preliminary evaluation of potential therapeutic modalities for this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MID-ATLANTIC BANH CONSORTIUM SITE Principal Investigator & Institution: Haber, Barbara A.; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-MAY-2007 Summary: (provided by applicant): The aim of this proposal is to demonstrate that the group of physicians and scientists at Children's Hospital of Philadelphia (CHOP) have the interest, infrastructure and resources to be an outstanding participant in the Biliary Atresia Neonatal Hepatitis Clinical Consortium to conduct investigations of the pathogenesis, natural history and pathophysiology of Biliary Atresia and Neonatal Hepatitis. Progress in the care of Biliary Atresia and Neonatal Hepatitis is hampered by many factors including the difficulty in recruiting adequate numbers of children with these diagnoses at a single center, diversity of conditions that are all labeled neonatal hepatitis and the absence of a national database. There are few efforts at collaboration in pediatric liver research at the national level, unlike that instituted to accelerate the pace of progress in pediatric cancer or AIDS. Success in addressing these problems through a national collaborative network will depend on the scientific leadership and operational performance of the centers involved in the Consortium. Our proposal is composed of four sections. Section I: A description of the facilities, resources and participation of the team of physicians and scientists at Children's Hospital of Philadelphia and University of Pennsylvania. Section II: A strategy and description of the development of a comprehensive database. Section III: A three-year research protocol to identify therapy to improve growth in children with Biliary Atresia. Section IV: A one-year research protocol to examine Jagged 1 as a modifier gene in children with Biliary Atresia. In summary, the CHOP team has the infrastructure, facilities, subject availability, clinical investigators and scientific investigators to be a dedicated and productive member of the Biliary Atresia Neonatal Hepatitis Clinical Consortium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MODELING VIRAL AND T LYMPHOCYTE DYNAMICS Principal Investigator & Institution: Perelson, Alan S.; Staff Member; None; University of Calif-Los Alamos Nat Lab Ms G758 Los Alamos, Nm 87545 Timing: Fiscal Year 2001; Project Start 19-APR-1991; Project End 31-MAR-2005 Summary: Mathematical modeling combined with experiment has led to increased understanding of the processes that underlie HIV-1 infection in humans and the development of improved therapies. Nevertheless HIV has not been eradicated from infected individuals and various reservoirs including latently-infected cells, virus trapped on folliculary dendritic cells (FDC), and virus in semen have been identified. This application proposes to continue the development of more realistic models of HIV infection with particular emphasis on events that occur in lymphoid tissue. The applicants propose to develop models that explicitly take into consideration infection in blood and tissue, the role of FDC, and possible incomplete penetrance of drugs into various cell populations and tissues. The primary health-related effects of HIV infection are consequences of CD4+ T cell depletion. Nevertheless, the population dynamics of T cells in vivo are poorly characterized. It is proposed to develop theory and analyze data from in vivo labeling studies that will help characterize the rates of proliferation and death of T cells in uninfected, HIV-infected, and HIV-infected individuals under potent antiretroviral treatment. Infection by hepatitis C virus (HCV) and hepatitis B virus (HBV) continue to cause liver failure and hepatocellular carcinoma in many infected individuals. Antiviral therapy for these agents lags behind developments in HIV. The applicants propose to use the modeling and analysis tools that they have developed for HIV to increase understanding of the in vivo kinetics of HCV and HBV infection and the effects of antiviral therapy. In addition to gaining basic understanding, this approach aims to put information into a practical setting, and the applicants hope to interact with clinical groups in the design and evaluation of new treatment protocols. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MODULATION OF OXIDATIVE DAMAGE BY TEA POLYPHENOLS Principal Investigator & Institution: Wang, Jia-Sheng; None; Texas Tech University Health Scis Center Health Sciences Center Lubbock, Tx 79430 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant) The primary objective of this research project is to study the modulating effects of green tea polyphenols on reducing hepatocarcinogeninduced oxidative damages in high-risk human populations. Oxidative damage induced by reactive oxygen species in vivo plays important roles in human hepatocarcinogenesis primarily caused by chronic infection of hepatitis B/C viruses and exposure to dietary aflatoxins. The level of 8-hydroxy-2'- deoxyguanosine, a biomarker for oxidative DNA damage, increases in hepatitis B virus surface antigen positive and aflatoxin-exposed humans and in aflatoxin- treated animals. Dietary antioxidants are important components of cancer modulating agents, which have been proven to effectively target carcinogen biomarkers, including oxidative damages, in high-risk human populations. Among various identified dietary associated antioxidants, green tea and its polyphenols have been shown to be safe and highly effective in inhibition of a variety of carcinogeninduced oxidative damages, mutagenesis, and tumorigenesis in in vitro bioassays and in vivo animal models. The general hypothesis underlying this proposal is that green tea polyphenols have a protective effect against oxidative stress or damage induced by aflatoxin and hepatitis B/C viruses through the mechanisms of modulating aflatoxin metabolism and oxidated DNA damage. The specific aims include: (1) to determine

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antioxidative role of green tea polyphenols in inhibition of the level of 8-hydroxy-2'deoxyguanosine in urine samples collected from an intervention study of 120 participants who are double positive for hepatitis B virus surface antigen and aflatoxinalbumin adducts, and (2) to determine the modulating effect of green tea polyphenols on excretion of carcinogen detoxifying product, aflatoxin Bl-mercapturic acid in urine samples collected from the study participants. The results of this proposed study will help to understand the mechanisms of antioxidative role of tea polyphenols in modulating human hepatocarcinogenesis caused by hepatitis B/C viruses and aflatoxins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MOLECULAR BIOLOGY OF THE HEPATITIS B TYPE VIRUSES Principal Investigator & Institution: Ganem, Don E.; Professor & Howard Hughes Investigator; Microbiology and Immunology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-SEP-1982; Project End 31-MAR-2003 Summary: Hepatitis B virus (HBV) and hepatitis D virus (HDV) are important causes of acute and chronic hepatitis in humans. Although much is known about the replication of these viruses, less is known about how replication causes disease. Evidence suggests that, in HBV infection, host immune responses trigger liver injury and affect viral replication. This application proposes studies to further examine the nature of these immune responses and to determine if similar responses can occur in HDV infection; the ability of such responses to affect HDV RNA replication will also be examined. In addition, detailed studies of the mechanisms of HDV RNA replication will be conducted, with emphasis on the involvement of host factors in this important reaction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NATURAL HISTORY OF HEPATITIS C INFECTION IN HIV DISEASE Principal Investigator & Institution: Craven, Donald E.; Professor; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: Each year more than 20 percent of the 3.5 million Americans infected with hepatitis C progress to cirrhosis and ten to fifteen thousand develop end-stage liver disease. Because hepatitis C and HIV disease share common modes of transmission, coinfection occurs in 8-10 percent of all HIV-infected individuals overall and is present in over 70 percent of those with parenteral risk factors. There are few data available on the natural history of HIV and HCV co-infection in specific risk groups, as most previous studies have not assessed the impact of confounding variables such as alcohol use, continuing substance abuse, malnutrition, duration of HCV infection, and degree of HIV-related immune suppression. Moreover, current data regarding the impact of HIV on HCV infection are changing rapidly due to the widespread use of highly active antiretroviral therapy (HAART). New cases of HIV and HCV are expected to continue to occur in substance abusers, since HIV infection is increasing rapidly in inner-city populations. The purpose of this study is to examine the natural history of HIV and HCV co-infection in a large inner city cohort who are predominately minority and have a history of polysubstance abuse. We will compare three groups: 1) HIV and HCV infected, 2) HCV infected alone, and 3) HIV infected alone. Epidemiologic studies will be conducted to explore the risk factors associated with HCV progression, morbidity, and mortality, using both standard clinical parameters and novel surrogate markers of

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liver fibrosis. Additional targeted substudies will examine the important clinical question of whether therapy of either the HCV or HIV disease alters progression of liver disease. Finally, immunologic studies aimed at increasing our understanding of the pathogenesis of liver injury and why it may be accelerated in HIV disease will be performed. The central hypothesis of this proposal is that alterations in immune function associated with HIV infection are the main determinant of poorer hepatitis C outcomes. The specific aims of this grant are: 1) to identify the variable(s) that impact the progression of HCV infection in HIV-infected individuals; 2) to determine the effect of HAART on HCV in dually infected persons; and 3) to define the immunologic variables that predict more rapidly progressive liver disease. These studies are expected to improve our understanding of the natural history and pathogenesis of HCV in immunosuppressed hosts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: NEW HEPATITIS B SMALL MOLECULE INHIBITORS Principal Investigator & Institution: Mehta, Anand D.; Synergy Pharmaceuticals, Inc. 2 Executive Dr, Ste 450 Somerset, Nj 08873 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant): The over-all goal of this "fast track" proposal is to develop a new class of orally available compounds for the treatment of chronic human hepatitis B virus (HBV) infection through a "proof of principle" Phase I/IIa Human clinical trial. With our colleagues, we have shown that alkylated imino sugars, called "alkovirs," are novel and effective in preventing HBV replication in tissue culture systems under conditions where there is no detectable cyto-toxicity. The alkovirs are previously undescribed synthetic (hence completely characterized) small molecules. Unlike the glucosidase inhibitors, (another class of imino sugars that we have been studying) alkovirs do not inhibit glucosidases, making them distinct and conferring certain advantages. Moreover, although alkovirs inhibit HBV replication, they do not target the viral polymerase, as do most nucleoside analogues. Thus, alkovirs should be effective against lamivudine "resistant" HBV mutants. The objectives of this "fast track" proposal are intended to be straightforward and defined by clear milestones: In phase I, the Alkovir(s) with the most potent anti-HBV activity against wild type virus and lamivudine resistant virus will be selected and tested for in vivo toxicity and pharmacokinetics in a rat model. In Phase II, the efficacy and toxicity of the candidate Alkovir(s) selected in Phase I will be evaluated in the woodchuck model of chronic hepatitis virus infection both as monotherapy and in combination with 3TClamivudine. Other work, to be performed in parallel with this study, will explore the precise mechanism of action of alkovirs and possibility that (a) they are effective against other viruses and (b) are a class of compounds to which mutant viruses do not frequently emerge. Accomplishment of these Aims will permit the introduction of alkovirs for human clinical trials. Given the need to find complements to nucleoside analogues, the introduction of new anti-hepatitis B virus agents as described here is extremely important. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NON-PARENTERAL TRANSMISSION OF HEPATITIS C Principal Investigator & Institution: Wang, Chia C.; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-JAN-2008

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Summary: (provided by applicant): This proposal will provide the applicant, Chia Wang, with training in the epidemiologic study of viral transmission. Dr. Wang is a board certified ID physician with a MS in Epidemiology. During her fellowship at the University of Washington, she studied heterosexual HIV transmission in Africa. This project formed the foundation of a long term interest in the epidemiology of transmission and acquisition of infection. This proposal describes her research interests in the area of non-parenteral transmission of hepatitis C virus (HCV). In Aim 1, we will study individuals with chronic infection in a longitudinal study of the prevalence and pattern of shedding of HCV RNA in saliva and genital tract fluids. Furthermore, information about oral and genital tract inflammatory conditions will be collected to investigate the hypothesis that such conditions may increase shedding. In Aim 2, we explore the hypothesis that transmission may occur more efficiently during the acute phases of HCV infection. We will establish early serum viral load dynamics and mucosal shedding patterns in incident cases of HCV identified from a local cohort of HCV negative current IDUs. Finally, in Aim 3, we will examine potential risk factors in individuals who deny parenteral modes of transmission by incorporating audio computer-assisted survey instrument (ACASI) technology to reduce under-reporting bias and specific survey techniques to reduce recall bias. The under-reporting rate of stigmatized behaviors such as intravenous drug use will be determined in subjects who deny such risk factors in traditional face-to-face interviews. Reporting of other potential non-parenteral risk factors for hepatitis C, such as intranasal cocaine use, will be compared to that of a control population derived from general medicine clinic. The mode of infection in 20-30% of hepatitis C-infected individuals remains poorly understood. The findings of the proposed research study may confirm suspected transmission routes such as sexual exposure, or may refute current figures suggesting that a substantial proportion of infections may occur non- parenterally. In addition, the proposed project will provide Dr. Wang with training in viral transmission research beyond her rather focused fellowship project, with the goal of establishing her expertise in this field and providing her with skills to pursue further independent studies in the transmission of hepatitis C and other viruses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: OXIDATIVE STRESS ROLE IN CHRONIC HEPATITIS C Principal Investigator & Institution: Matta, Jaime L.; Ponce School of Medicine G.P.O. Box 7004 Ponce, Pr 00731 Timing: Fiscal Year 2001; Project Start 30-SEP-1986; Project End 31-MAY-2005 Description (provided by applicant): This proposal addresses a fundamental question in hepatitis C research; what is the mechanistic role of oxidative stress in the progression of HCV infection? There is a limited knowledge on the mechanism(s) by which HCV causes liver and other types of damage. This study will test the hypothesis that oxidative stress is a mechanistic component of chronic HCV infection in Puerto Rican populations. This will serve as the first population based study that utilizes multiple markers of oxidative stress to test this hypothesis. This will be accomplished through the following aims: Specific Aim 1: The aim of these studies is to evaluate the role of the serum iron balance in the development of oxidative stress. Hypothesis: iron is a key component of oxidative stress in Puerto Ricans with chronic HCV. Specific Aim 2: The aim of these studies is to characterize the DNA adducts in leukocytes and to determine if different adducts are produced in HCV patients. Hypothesis 1: DNA adducts are markers in the chronic progression of HCV-related hepatitis. Hypothesis 2: DNA adducts are correlated with the serum iron balance. Specific Aim 3:The aim of these

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experiments is to evaluate whether manganese superoxide dismutase (MnSOD) is a suitable marker of oxidative stress in blood from HCV patients. Hypothesis: MnSOD specific activity is significantly increased in the leukocytes and erythrocytes of patients with chronic HCV infection. Specific Aim 4: The aim of these experiments is to determine whether patients with chronic HCV show higher plasma levels of lipid peroxidation. Hypothesis: Significantly higher levels of malonaldehyde and 4hydroxynonenal are found in the plasma of HCV positive patients when compared with controls. Data on HCV viral genotype, viral load, disease stage, activity of liver aminotransferases, type of pharmacological treatment will be statistically analyzed to determine whether correlations exist with these markers of oxidative stress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: PATHOGENESIS OF GROUND GLASS CELLS IN HEPATITIS B Principal Investigator & Institution: Yen, T.S. Benedict.; Professor; Northern California Institute Res & Educ San Francisco, Ca 941211545 Timing: Fiscal Year 2001; Project Start 05-MAR-1992; Project End 31-MAR-2006 Summary: (Adapted from the Investigator's abstract): Hepatitis B virus (HBV) causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC), and is especially common among minorities such as African Americans and Asian Americans. The mechanism by which HBV causes HCC is unclear, but it is likely that HCC results from both specific viral factors and non-specific mutagenesis due to constant cell turnover. One candidate viral factor is the large surface protein, since expression of this protein in transgenic mice results in HCC. We have recently shown that large surface protein can activate cellular genes at the transcriptional level, apparently by forming non-secretable particles in the endoplasmic reticulum (ER) and activating ER stress. Further preliminary data indicate that large surface protein causes cell death, probably by apoptosis. Since hepatocytes containing large surface protein particles within the ER ("ground glass cells") are seen in the livers of people with chronic hepatitis B, our results point to a specific mechanism whereby HBV may cause HCC. However, the reason for ground glass cell formation in infected livers is still unclear. For the next cycle of this project, we propose to study events both up-stream and down-stream of the formation of ground glass cells. First, we wish to validate our hypothesis that mutations in the viral genome can lead to ground glass cells, and determine if two common naturally occurring viral mutants can cause ground glass cells and HCC in transgenic mice. Second, we will clone out HBV genomes from human ground glass cells, and look for additional mutations that may be responsible for ground glass cell formation. Third, we will determine how large surface protein causes cell death, and whether it is by apoptosis. We will also determine if there is increased apoptosis of ground glass cells in transgenic mice, and look for activation of apoptotic pathways in human livers with ground glass cells. These experiments should give novel insights into the mechanism by which HBV causes liver disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PATHOGENESIS COINFECTION

OF

HEPATIC

INJURY

WITH

HCV/HIV

Principal Investigator & Institution: Groopman, Jerome E.; Chief; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006

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Summary: (provided by applicant) The primary objective of this proposal is to examine how the hepatitis C virus (HCV) and the human immunodeficiency virus (HIV) envelope proteins may act collaboratively to trigger signaling events that contribute to hepatocyte inflammation and apoptosis. Coinfection with HIV and HCV confers a poor prognosis, with progressive hepatic dysfunction that often results in cirrhosis and death. Both intravenous drug users and hemophiliacs have a high incidence of coinfection and face this grim outcome. Why do coinfected hosts have such high rates of progressive liver disease? The pathogenesis of HCV-related hepatitis is believed to be due, in part, to immune-mediated inflammation as well as the effects of direct infection of hepatocytes. Our preliminary data suggest a novel third potential mechanism for hepatic inflammation and apoptosis. We observed in both HepG2 cells and primary hepatocytes that treatment with the HCV envelope protein E2, in conjunction with HIV gpl20, induced the inflammatory chemokine interleukin-8 (IL-8) and triggered apoptosis. These functional outcomes occurred at nanomolar concentrations of E2 and gp 120 that correspond to the Kd's for the cognate ligands binding to their respective receptors, CDS1 and CXCR4, and were associated with activation of specific signaling molecules, including the Src family Lyn kinase, RAFTK/Pyk2, Erkl/2 and p38 MAP kinases, and Fas-ligand. These data indicate that proinflammatory and apoptotic events may occur due to dual exposure to HCV and HIV envelope proteins via an "innocent bystander" mechanism. This proposal seeks to characterize the molecular mechanisms of IL-8 induction and the program of apoptosis caused by HCV E2 and HIV gpl20. A focused experimental approach is presented to delineate signaling events that originate at specific cell surface receptors, are transduced through intermediate signaling molecules, and converge on transcriptional activators of the MAP kinase family. Elucidating how these HCV and HIV envelope proteins may interact with hepatocytes could not only further our understanding of the pathogenesis of disease in coinfected hosts but also lead to targeted therapeutic strategies to improve the currently poor prognosis of such individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: PROTEOMICS AND BIOMARKERS FOR HEPATOCELLULAR CANCER Principal Investigator & Institution: Afdhal, Nezam H.; Associate Professor of Medicine; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2003; Project Start 25-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Hepatitis C (HCV) is the commonest cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) in the United States. HCC occurs primarily in patients with advanced fibrosis and cirrhosis from HCV. Current screening techniques involve the use of serum alfafetoprotein and liver imaging with ultrasound performed in high risk patients on a 3 to 6 monthly basis. Early detection can improve outcomes with liver transplantation and perhaps non-surgical therapies. However screening is not very effective and many patients present with large tumors or multifocal HCC with a median survival of only 6 months. There is a definite clinical need for better non-invasive biomarkers for HCC which can lead to early detection and treatment. The specific aims of this exploratory R21 proposal are to utilize a proteomic approach to identify novel biomarkers for HCC and then evaluate these biomarkers in a cohort of patients with HCV at high risk for HCC. The initial step will be identification of a matching group of patients with a high risk of HCC and those who have developed HCC during the prospective COPILOT study. The COPILOT study provides a large cohort of patients with HCV and cirrhosis who are randomized to

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treatment with either low dose PEGylated interferon alfa 2b or colchicine and are followed for 4 years with rigorous clinical screening for HCC. The study is in year 2 and the incidence of HCC is approximately 5%. Serum from these patients prior to and after the development of HCC is stored and will be utilized for proteomic studies. Tissue from normal liver and HCC is available from these patients who have undergone liver transplant. A control disease serum bank from patients with HCC unrelated to HCV is also available at BIDMC. The serum and tissue will be examined by proteomics for identification of novel biomarkers using SELDI-TOF mass spectrometry. Careful clinical characterization and matching will assist in the bioinformatic approach necessary to identify candidate biomarkers. Novel proteins and peptide biomarkers will be sequenced and identified and an ELISA will be developed for any promising candidate biomarkers. The candidate biomarker ELISA will then be validated in the large HCV serum bank at BIDMC of patients with all stages of HCV and those in the COPILOT trial. These studies may lead to identification of more specific and sensitive biomarkers for HCC in HCV which can then be validated further in prospective clinical trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: PSEUDOTYPED VIRUS TO STUDY EARLY EVENTS IN HCV INFECTION Principal Investigator & Institution: Colston, Elizabeth M.; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2003 Summary: (adapted from applicant's abstract): This proposal outlines a five-year plan for the training of the applicant for an academic career studying hepatitis C virus (HCV) pathogenesis. The candidate received a Ph.D. in the laboratory of Dr. Vincent Racaniello, completed a residency training in Internal Medicine and a Clinical Fellowship in Infectious Diseases and is now working in the laboratory of Dr. Paul Bates, her sponsor. Dr. Colston`s research interests currently center on hepatitis C virus entry. She has a background in non-enveloped virus entry and seeks to gain the experience in enveloped viruses needed to attack questions of HCV entry independently. For this purpose, an integrated research and training program is outlined in the Division of Infectious Diseases and the Department of Microbiology. In addition to Dr. Bates, who works on retroviral receptors and viral entry, an advisory board will mentor the candidate`s career development. HCV is the major cause of nonA nonB hepatitis worldwide. There is currently no vaccine to protect against infection and available therapies often do not work well. HCV was cloned and sequenced over 10 years ago but there are many unanswered questions regarding viral pathogenesis. Limitations to the study of HCV are the lack of either a cell culture system or a small animal model. The proposed work is to incorporate HCV glycoproteins into retroviral particles and use these pseudotypes as a model system to study early events in viral infection. Specifically, these pseudotypes will be useful for analyzing HCV glycoprotein function, studying the mechanism of HCV entry, examining the immune response to viral glycoporteins and identifying a cellular receptor(s) for HCV. These studies aim to provide new insights into HCV infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PSYCHOLOGICAL STRESS AND IMMUNE RESPONSE TO VACCINATION Principal Investigator & Institution: Marsland, Anna L.; Pathology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260

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Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-MAY-2008 Summary: (provided by applicant): It is widely proposed that the influence of stress on immune function is the primary biological pathway linking stress to increased infectious disease susceptibility. However, the literature is missing empirical evidence for this pathway, in part because of a failure to focus on immune measures that are relevant for the development of host resistance. The broad objective of the proposed study is to identify pathways linking psychological stress to in vivo immune processes that are clinically relevant for the development and maintenance of resistance to infectious disease. For this purpose, a hepatitis B vaccination model is employed. This model permits the systematic exploration of behavioral and biological pathways linking stress to ability to mount and maintain primary and secondary antibody responses following exposure to a novel antigen. It also allows the exploration of the role that individual differences in the magnitude of biological responses to stress play in vulnerability to stress-immune relationship. In this regard, it has been demonstrated that individuals vary consistently in the magnitude of their cortisol and immune responses to acute stress, conceivably rending them more or less able to mount an antibody response to vaccination. One hundred and eight-two healthy males and females aged 40-60 years will be recruited to participate in the proposed longitudinal research, which includes a laboratory based physiological reactivity phase, a prospective surveillance phase and a follow-up period. In the reactivity phase, participant's immune and cortisol responses to an acute laboratory stressor will be measured to determine individual differences in the magnitude of immunologic reactivity to stress. During this phase, participants will also complete self-report measures of recent life stress and trait negative affect. In the surveillance phase, participants will be administered the three does of hepatitis B vaccine by standard protocol. They will also complete daily stress diaries for the seven days surrounding each dose of vaccine to assess levels of acute stress. Saliva samples for the assessment of cortisol levels will be collected at the time of each vaccination. Antibody responses will be measured at the time of the second and third does of vaccine and, during the follow-up period, 6 and 12 months following completion of the vaccination series. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: QUANTITATION OF HEPATITIS C VIRUS IN PERIPHERAL BLOOD Principal Investigator & Institution: Schmidt, Warren N.; Assistant Professor; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 01-MAR-1999; Project End 31-DEC-2001 Summary: Hepatitis C (HCV) is a parenterally transmitted RNA virus that has been shown to be responsible for the majority of cases of NonA-NonB chronic active hepatitis. The virus causes considerable morbidity and mortality worldwide. Since discovery of the virus, considerable progress has been made in the development of qualitative and quantitative assays for patient diagnosis and management during antiviral therapy. Although current serum or plasma quantitative assays for HCV have proven utility, their correlation with the pathogenesis of HCV is poor and they offer limited diagnostic information for clinical management of patients during antiviral therapy. Our laboratory has recently developed a method for the direct detection of HCV RNA in peripheral whole blood which is more sensitive than current plasma or serum based HCV assays. Consequently, characterization and standardization of quantitative methods for assay of HCV in whole blood is worthwhile and may provide a more reliable means to correlate whole blood viral load with hepatic pathology and treatment of chronic infection. This proposal will address this hypothesis with three

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specific aims: 1) Building on our past observations, we will develop and standardize assays for the quantitation of HCV in peripheral whole blood. 2). Quantitative whole blood assays for HCV will then be used to investigate the relationship of whole blood viral levels with hepatic histologic activity indices. 3). Finally, we will measure the whole blood viral load of patients before, during, and following antiviral therapy. These experiments will test whether quantitation of HCV in whole blood can potentially improve our ability to predict patient outcome after therapy. The overall goal of this proposal is to establish the feasibility and clinical utility of quantitative methods for measurement of the virus in peripheral whole blood. We hope that this new technology will improve patient evaluation and management, as well as increase our understanding of the pathogenesis of HCV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: RACIAL DIFFERENCE IN HCV/HOST INTERACTIONS Principal Investigator & Institution: Riely, Caroline A.; Professor; Medicine; University of Tennessee Health Sci Ctr Health Science Center Memphis, Tn 38163 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: The University of Tennessee, Memphis Hepatitis C Cooperative Research Center will use studies of HCV/host interactions to determine why African American patients with HCV respond poorly to standard therapy (interferon and ribavirin). Hepatitis C is common, 1.8% of all Americans, but is even more common among African Americans, and in persons living in poverty. In Memphis, 55% of the population is African American, 34% of whom live below the poverty line. In a previous study, we documented a response rate of only 5% in this population, contrasted with 40% in whites. We propose to systematically characterize the differences between African Americans and whites by allelic variations in cellular ligands/receptors for HCV (Project 1). In Project 2, we will continue to develop an in vitro system for studying HCV, a chimeric VSV virus with the hepatitis C E1 and E2 envelope proteins expressed on its surface. We will use this model to characterize virus/cell interactions, testing antibodies to specific dominant quasispecies, contrasting our African American patients with whites. We will further characterize the putative receptor for HCV, CD81, to define its associated proteins, possible co-receptors (Project 3). These data will interface back to our patients as we search for allelic variations between African Americans and whites to explain the differences in response to therapy. Using the surrogate virus model, we will also screen libraries of small molecules to search for compounds that can block E2/CD81 binding (Project # African American population responds so poorly. Understanding this phenomenon will provide insights into why present day therapy is still only moderately successful in all populations, will allow us to predict who is more likely to respond, and will pave the way to developing better therapy for this emerging health problem. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RECOMBINANT ATTENUATED SALMONELLA VACCINES FOR HUMANS Principal Investigator & Institution: Curtiss, Roy Iii.; Professor; Biology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Of the 18.9 million annual deaths (1997) due to infectious diseases, about 7.5 million, in addition to significant morbidity, are the result of infections by Salmonella typhi, S. paratyphi A, hepatitis B virus (HBV), Plasmodium

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falciparum, Streptococcus pneumoniae and Mycobacterium tuberculosis. In the belief that improving health, nutrition and economic well-being (the later dependant on the first two) provides the best means to enhance the quality of life globally and thus reduces conditions that result in warlike and terrorist behavior, we propose a vaccine development program based on our recent technical developments in using recombinant attenuated Salmonella vaccines. Our objectives include: (a) to design, construct and evaluate an attenuated derivative of S. paratyphi A that will serve as an antigen delivery vector by exhibiting regulated delayed lysis within effector lymphoid tissues in the immunized individual to release hepatitis B virus (HBV) core particles encoding (i) HBV pre $1, pre $2 and T-cell epitopes as a preventative/therapeutic vaccine against HBV and (ii) P. falciparum circumsporozoite epitopes as a vaccine against malaria; (b) to construct and evaluate the contribution of strain background and the RpoS* phenotype on immunogenicity of a recombinant antigen expressed by attenuated S. typhi vaccine strains; and (c) to design, construct and evaluate recombinant attenuated S. typhi vaccines to express and deliver protective antigens specified by genetic information from (i) S. pneumoniae to prevent pneumococcal disease caused by strains with diverse capsular serotypes and (ii) M. tuberculosis as a preventative/therapeutic vaccine. The S. paratyphi A and S. typhi recombinant vaccines should also provide immunity to infection by S. paratyphi A and S. typhL We will also develop our Master File, prepare and fully characterize candidate vaccine Master Seeds for stability and safety, prepare and submit protocols for IRB approvals, submit information necessary to obtain INDs, and perform any other work needed to arrange that the best candidate vaccines be clinically evaluated in human volunteers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: RECURRENT HEPATITIS B AFTER LIVER TRANSPLANTATION Principal Investigator & Institution: Lok, Anna S.; Professor; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2008 Summary: Hepatitis B accounts for approximately 5000 deaths/yr in the United States. Early results with orthotopic liver transplantation (OLT) for hepatitis B were poor with recurrence rates of >80% and 2-year mortality rates of 50%. Recent studies found that continuous high dose IV hepatitis B immune globulin (HBIG) can decrease the rate of reinfection to <20%. However, high dose HBIG is very expensive ($30,000-$50,000/yr) and the efficacy is low in patients with replicative infection pre-OLT. Pilot studies showed that lamivudine (LAM, an oral nucleoside analog which costs $1,200-$1,500 per yr) can decrease the rate of recurrent hepatitis B to <30% during the first post-OLT year but the long-term efficacy is limited by drug resistant mutants. Three pilot studies reported that combination therapy of HBIG and LAM is more effective than either agent alone with recurrence rates <5%, but it is not clear how long HBIG needs to be administered. Given the high costs and the inconvenience of life-long HBIG therapy, there is a need for a prospective, randomized controlled trial to determine if prophylaxis with LAM and short-term HBIG is as effective as LAM and long-term HBIG in the prevention of recurrent hepatitis B post-OLT. The use of antiviral agents with potential activity against LAM resistant HBV mutants, such as adefovir dipivoxil, also needs to be evaluated. The specific aims of our study are: (1) To compare the safety, efficacy and cost-effectiveness of combination therapy with LAM and a 6-month course of HBIG with LAM and a 3-yr course of HBIG in the prevention of recurrent hepatitis B postOLT. (2) To identify the epidemiological, clinical and virological factors that are

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associated with recurrent hepatitis B post-OLT. (3) To determine the safety and efficacy of adefovir dipivoxil in the suppression of HBV replication in patients who have developed LAM resistant HBV mutants and to compare the rate of recurrent hepatitis B post-OLT in patients with and without LAM resistant mutants prior to transplant. This is a prospective, randomized, multi-center clinical trial involving 20 liver transplant centers in N. America, to be conducted under an investigator IND 59,167. 290 patients with hepatitis B who are listed for OLT as UNOS status 1 or 2 will be enrolled. Open label LAM will be administered to decrease virus load pre-OLT. Patients will be randomized after OLT to Group I: LAM and 3 yr-course of HBIG or Group II: LAM and 6-month course of HBIG. Patients who develop LAM resistant mutants pre- or postOLT will additionally receive adefovir dipivoxil. The primary end-point of this trial is the rate of recurrent hepatitis B during the first 3 yr post-OLT. This trial will provide definitive answers whether combination therapy with LAM and a 6-mon course of HBIG is as efficacious and more cost-effective than LAM and a 3-yr course of HBIG in the prevention of recurrent hepatitis B post-OLT. In addition, crucial data will be generated on the efficacy of pre-OLT LAM in virus clearance, incidence and outcome of silent allograft infection, clinical outcome of patients with LAM resistant HBV mutants, and management of patients with LAM resistant mutants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ROLE OF HBX PROTEIN IN HBV REPLICATION Principal Investigator & Institution: Schneider, Robert J.; Professor; Biochemistry; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2001; Project Start 01-APR-1992; Project End 31-MAR-2006 Summary: (provided by applicant): The long term objectives of this proposal are to understand the roles of the hepatitis B virus (HBV) HBx gene in viral infection. Please note that the title of this grant has been changed from "Transcription and Transformation by Hepatitis B Virus HBx Protein," to" Role of HBx protein in HBV replication" to reflect the progression of our studies on HBx. AIM 1: Molecular mechanism for human hepatitis B virus (HBV) HBx protein action. HBx activates cytoplasmic signal transduction pathways. HBx activation of the Pyk2-Src tyrosine kinase signalling pathway represents an important activity for viral replication in hepatocytic cell lines. Studies are outlined to understand the molecular mechanism for HBx activation of Pyk2-Src signal transduction, since it is tightly linked to HBx stimulation of viral replication. In addition, HBx appears to possess nuclear functions that may stimulate viral transcription. Studies will also investigate the mechanism by which HBx functions in viral transcription, including a possible role in the nucleus, and its impact on viral replication. AIM 2: Role of HBx protein in HBVreplication. Studies are proposed to determine the molecular basis for HBx activation of HBV reverse transcription and DNA replication. Model systems have been developed for delivery of hepadnavirus genomes to differentiated hepatocytic cell lines and rodent primary hepatocytes in culture, that permit viral replication in an HBx-dependent manner. Studies will investigate the role of HBx in viral replication in a biologically relevant system, focusing on HBx induction of HBV core protein phosphorylation, control of the cell cycle, and induction of nucleotide metabolism. HBx-dependent HBV replication will also be studied in primary hepatocytes prepared from mice that are deficient in genes that impact on HBV replication, including knockouts of Src and Pyk2 kinases, to better understand their importance for viral replication. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF LIVER CYTOKINES IN HEPATITIS C VIRAL INFECTION Principal Investigator & Institution: Liu, Chen; Assistant Professor; Pathology, Immunol & Lab Med; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and liver cancer, and is the most common indication for liver transplantation in the United States. The hallmarks of the HCV infection are viral persistence and liver cell injury. The underlying molecular mechanisms remain poorly understood. Cytokines appear to play a critical role in viral clearance and liver tissue damage. The Long-Term Goal of our research program is to understand how antiviral cytokines modulate viral RNA replication and the predictive role of these cytokines in response to interferon alpha treatment. In support of this goal, our Preliminary Studies have 1) demonstrated that IFN` and FGF1 have a direct effect on HCV viral subgenomic RNA (replicon) replication in hepatoma cells; 2) identified several IFN` responsive genes potentially responsible for its antiviral activity in the replicon cell lines; 3) established a cytokine-related cDNA microarray system and established the feasibility of carrying out microarray experiment using liver biopsy tissues. These studies have led us to formulate a Central Hypothesis of this proposal, that antiviral cytokines such as IFN` or others are critical in viral clearance by direct inhibition of viral replication within hepatocytes; and the presence of these cytokines before IFN` treatment can predict the responsiveness to the therapy. In the Specific Aims we will: 1) determine the efficacy of cytokines such as IFN` and FGF1 on inhibiting HCV viral RNA replication and to identify the key intracellular signaling molecules responsible for this effect; and 2) identify cytokines that favor viral clearance versus viral persistence through analyzing HCV-infected liver tissues before and after IFN-based treatment. To address these aims, we will utilize the existing HCV replicon cell line for in vitro mechanistic studies and carry out microarray experiments using liver biopsy tissues to determine the role of antiviral cytokines in HCV-infected patients. This proposal will delineate how IFN` and FGF1 exert antiviral activity within hepatocytes, and will identify cytokines that predict viral clearance in HCV viral infection. This study will enhance our understanding of the host and hepatitis C virus interactions underlying the pathogenesis of viral chronic infection. The candidate's long-term career goal is to be an independent physician scientist conducting translational research. The immediate career goal is to develop the scientific reasoning and skills necessary for a successful research career by carrying out the current research proposal. Our institution provides an outstanding supportive environment for career development. This funding mechanism will give the candidate the opportunity to establish an independent research career. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SMALL ANIMAL MODEL FOR HEPATITIS C VIRUS REPLICATION Principal Investigator & Institution: Andrus, Linda; New York Blood Center 310 E 67Th St New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: The goal of this research is to develop a small animal model for hepatitis C virus (HCV) replication by transplantation of human fetal hepatocytes to immunodeficient mice. A number of different immunodeficient mouse strains will initially be compared for susceptibility to engraftment by hepatocytes directed to the recipient liver by intrasplenic injection. Engraftment will be assessed by serological assays for human alfa-fetoprotein in mouse plasma, by immunohistochemical staining

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for human proteins, and by PCR for human Alu Sb2 repeats from DNA recovered from engrafted tissues. In an attempt to overcome innate "natural immunity" in immunodeficient mice, which may provide a barrier to long-term engraftment with xenogeneic tissue, the effect of recipient gamma irradiation, natural killer (NK) cell depletion and macrophage depletion on transplant survival will be evaluated. The efficacy of endogenously generated hepatocyte growth hormone (HGF) in expanding the critical mass of transplanted human tissue, and in improving HCV viremia will also be assessed. Isolated hepatocytes will be infected in vitro with virus inocula containing known numbers of HCV RNA molecules. Following transplantation of cells to appropriately conditioned immunodeficient mice, HCV replication will be assessed by reverse transcription and PCR (RT-PCR) for both positive and negative strand HCV RNA in blood and transplanted tissues, and by quasispecies analysis of the viral variants which establish infection in these animals. Finally, serial passage of virus from infected to non-infected transplanted animals will be performed to provide definitive proof of HCV replication. The availability of a reliable small animal model for HCV replication will assist in the development of anti-viral drugs and the design of a vaccine for this leading cause of chronic liver disease and hepatocellular carcinoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: SOCIAL CAPITAL, SELF EFFICACY, AND SEX WORKER HEALTH Principal Investigator & Institution: Cohan, Deborah; Ob, Gyn and Reproductive Scis; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Deborah Cohan, MD, MPH is a full-time faculty member in the Department of Obstetrics, Gynecology and Reproductive Sciences at the University of California San Francisco (UCSF) and medical director of St. James Infirmary, a peer-based, multi-service clinic for male, female, and transgender sex workers. Dr. Cohan has just completed a two-year fellowship in Reproductive Infectious Disease and her Masters in Public Health. She proposes to build on her research skills by learning ethnographic techniques and advanced biostatistical methods, with the ultimate goal of becoming an independent clinical researcher. Dr. Cohan proposes to conduct a multi-level study to identify individual-level psychological factors and population-level network characteristics associated with risk of prevalent HIV-1, sexually transmitted infections (STIs), and hepatitis B (HBV) and C (HCV) among female sex workers in San Francisco. The study combines qualitative and quantitive methods, including ethnography, a cross-sectional survey using venue-based probability sampling, and social network analysis, to describe the sociopolitical, environmental, and psychological forces that underlie sexual and drug-using behavior among sex workers. She proposes three specific aims: (1) to characterize sexual and drug-using behavior and prevalence of HIV, STIs, HBV, and HCV, and to examine psychological risk factors associated with these infections among female sex workers in San Francisco; (2) to characterize social capital among networks of female sex workers in San Francisco; and (3) to investigate whether diminished social capital is associated with increased risk of prevalent HIV, STI and hepatitis among these networks. With these data, Dr. Cohan intends to develop and evaluate culturally-appropriate, communitydriven prevention interventions for sex workers. Dr. Cohan has assembled a multidisciplinary team spanning the fields of epidemiology, psychology, and medical anthropology to ensure success of this project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURAL ANALYSIS OF THE HEPATITIS C CORE PROTEIN Principal Investigator & Institution: Allaire, Marc; Brookhaven Science AssocBrookhaven Lab Brookhaven National Lab Upton, Ny 11973 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JAN-2006 Summary: (provided by applicant): Hepatitis C virus (HCV) infection is recognized as a worldwide health problem affecting over 170 million individuals. In the United States, over 4 million peoples have been infected and 12,000 deaths yearly are due to hepatitis C. HCV is the most common reason for liver transplantation and accounts for one-third of hepatocellular carcinoma. Prevention of the HCV infection is impeded by the lack of protective vaccines and current therapies against HCV are unsatisfactory. There is clearly an urgent need for the development of new drugs. The molecular mechanisms of viral replication and viral assembly of HCV are poorly understood. It has been shown recently that nucleocapsid-like particles of HCV can be assembled from the HCV core protein that are identical to the HCV nucleocapsid from sera of infected patients. The aim of this proposal is to characterize the HCV core and capsid using macromolecular crystallography and to characterize the packaging signal on the viral RNA. The HCV core protein is the viral subunit of the HCV capsid. It appeared in the last few years that this protein is also very important for the pathogenesis of the disease by inducing cancer, cirrhosis and inflammation of the liver tissue. The resolution of the threedimensional structure of this protein and the capsid will not only help us to characterize the protein-protein interactions between the proteins subunits, the interaction between the subunits and the nucleic acid but also to resolve the surface of the capsid that interacts with several host factors responsible for different aspects of the pathogenesis of the disease. Altogether, the determination of the structure of the capsid will facilitate the development of research programs that aim to inhibit the assembly of the virus, a novel and very promising target for drug development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STUDIES OF THE NATURAL HISTORY OF HEPATITIS C IN LIVER Principal Investigator & Institution: Carithers, Robert L.; Director of Hepatology Section; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: Chronic hepatitis C virus infection has emerged as the most important form of viral hepatitis in the United States. Although the disease often remains indolent for many years, approximately 20 percent of patients with chronic hepatitis C progress to cirrhosis within 20 years. As a consequence, liver failure from chronic hepatitis C has become the leading indication for liver transplantation both in the United States and Europe. Despite remarkable progress in our understanding of many aspects of this disease, the mechanism of hepatocellular injury in patients with chronic hepatitis C is not well understood. Unfortunately, neither efficient cell culture systems nor animal models are available to study the pathogenesis of the liver disease. Given these limitations, we have systematically examined the evolution of liver injury in patients with recurrent hepatitis C after liver transplantation. By correlating the degree of injury to the transplanted organ with detailed analyses of viral replication we hope to provide insights into the pathogenesis of liver cell injury in these chronically infected patients. This proposal is designed to examine the hypothesis that differing patterns of mutation in the genomic sequence of HCV RNA have a profound influence on the severity of liver injury in patients with recurrent hepatitis C after liver transplantation. Our Specific Aim 1 is to prospectively determine the relationship between evolution of HCV quasispecies

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and hepatocellular injury in patients with recurrent hepatitis C. In Specific Aim 2 we plan to intensively investigate the clonal evolution of quasispecies and to determine the tissue origin of these viral strains both in patients with severe recurrent hepatitis C and in those with mild hepatocellular injury after liver transplantation. We plan to test the hypothesis that the primary site of quasispecies replication is critical to the development of hepatocellular injury. We propose that emergence of nonpathogenic strains of virus after liver transplantation result from continuous extrahepatic replication of HCV, whereas pathogenic strains of HCV originate from intrahepatic replication of the virus. In Specific Aim 3 we plan to assess in impact of HCV genotype, circulating levels of virus, and evolution of HCV quasispecies on the long term evolution of histologic injury in the transplanted liver. By carefully correlating the evolution of the virus with the degree of hepatocellular injury experienced by patients who develop recurrent hepatitis C after liver transplantation, we hope to provide insights into to the pathogenesis of this important liver disease. From these detailed analyses we also hope to isolate pathogenic strains of virus which can later be tested in cell culture systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: TRANSLATION-INHIBITION OF HEPATITIS C AND POLIO VIRUSES Principal Investigator & Institution: Dasgupta, Asim; Professor; Microbiology and Immunology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: Picorna and Flaviviruses encompass a large variety of medically important human viruses which include those inducing poliomyelitis (poliovirus), infectious (Hep. A) and chronic hepatitis (hepatitis C), common cold (rhinovirus), and myocarditis and encephalitis (coxsackie) among others. A common feature of these viruses is the strategy they employ for synthesis of viral proteins. While cellular mRNAs are translated by capdependent "scanning" mechanism, the viral RNAs are translated by a distinct mechanism involving internal entry of ribosomes within the 5' untranslated region (5' UTR) of viral RNA (IRES-mediated translation). Two inhibitors (a small RNA, IRNA and a small peptide, LAP) which efficiently block hepatitis C and poliovirus IRESmediated translation (but not cellular translation) both in vivo and in vitro, will be studied. Both biochemical and genetic approaches will be used to determine the mechanism by which IRNA and LAP preferentially inhibit translation of HCV and PV RNAs over cellular mRNAs. Cellular proteins involved in IRES-mediated translation will be purified and their roles in HCV RNA translation will be determined. Structurefunction analysis of IRNA will be performed. The mechanism of entry of LAP into hepatocytes will be determined. Identity and normal function of IRNA in the yeast S. cerevisiae will be addressed by cloning and characterizing the IRNA gene. IRNA gene knockout will be performed to better understand the role of IRNA in yeast. We will examine whether IRNA-binding proteins in yeast play any role in IRES-mediated translation (in yeast). Finally, we will develop transgenic mice expressing IRNA and LAP to determine the long term expression of IRNA in animals as well as efficacy of IRNA in blocking virus infections in transgenic animals. It is hoped that the studies proposed here will not only further our understanding of the mechanism of internal initiation of translation in eukaryotic cells, but also provide novel strategies to develop antivirals effective against hepatitis C. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VIRAL HEPATITIS IN CHILDREN OF INJECTION DRUG USERS Principal Investigator & Institution: Schwarz, Kathleen B.; Associate Professor; Pediatrics; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: (Applicant's Abstract) Hepatitis B virus (HBV) and hepatitis C virus (HCV) are endemic among adult injection drug users (IDUs). Children of IDUs (CIDU) are known to be at risk for HBV and HCV because of maternal-fetal transmission, and possibly, other factors as well. CIDU often live below the poverty level and - 1/3 of homeless children are CIDU. Although both poverty and the condition of being homeless are associated with low immunization rates, strategies to improve immunization for HBV in CIDU have not been systematically studied, and the epidemiology of HCV in this high-risk population has not been characterized. Therefore, the specific aims of this project are: 1) To develop a new multi-component intervention strategy (culturally adapted CD ROM-based educational materials, reminder systems, and clinic/shelter-based vaccines) to improve HBV immunization rates in CIDU and compare this strategy to conventional strategies 2) To characterize the epidemiology of HCV in CIDU. In Baltimore, we have identified three large cohorts of CIDU which are well-suited to accomplish the aims of this proposal: 1) 900 homeless children 2) 100 CIDU in the AIDS Linked to Intravenous Experience (ALIVE) study of adult IDUs and 3) 200 CIDU in the ongoing Risk, Evaluation and Assessment of Community Health (REACH) study of young IDUs. 1. In the immunization studies, we will partner with Hepatitis Foundation International (HFI) and Johns Hopkins Medical Video to adapt HFI educational materials about viral hepatitis to age- and culturally appropriate CDROM based presentations. Subjects will be randomized as to a "standard" or "special" prevention approach and ongoing critique and validation of the materials will be performed. 2. The epidemiologic studies in CIDU will include determination of HCV prevalence and will utilize an Automated Computer Assisted Self Interview to investigate injection drug use by parents and children, and other potential correlates of HCV infection among CIDU (e.g., tattooing, piercing). The novel approach of using a salivary anti-HCV (S-anti-HCV) assay for non-invasive screening in CIDU will be studied, after first validating the test in 60 children with chronic HCV infection. CIDU who test S-anti-HCV+ will have blood assayed for serologic markers for HCV, HBV, and human immunodeficiency virus. It has been estimated that complete eradication of hepatitis B and C infection from all children in the U.S. could save at least $200 million over the next 10 years, Preventative strategies emanating from this proposal could contribute significantly to reduction of both the high medical costs and human suffering secondary to these infections in children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VITAMIN A THERAPY IN PRETERM INFANTS: VACCINE RESPONSE Principal Investigator & Institution: Ballow, Mark; Professor of Pediatrics; Pediatrics; State University of New York at Buffalo 402 Crofts Hall Buffalo, Ny 14260 Timing: Fiscal Year 2001; Project Start 15-SEP-1999; Project End 31-AUG-2003 Summary: The role of vitamin A as an immune modulatory factor has been the focus of many studies both in animals and man. Epidemiologic studies emphasize that vitamin A is essential for supporting the immune system against infection. Despite many therapeutic improvements in recent years, infection still remains a major problem in very low birth weight (VLBW) pre-term infants. Pre-term infants have lower plasma

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vitamin A (retinol) levels and limited hepatic reserves compared to full term infants. Vitamin A deficiency may lead to increased susceptibility to infection in pre-term infants. Hepatitis B immunization in the neonatal period offers an excellent opportunity to determine what effects vitamin A supplementation has in pre-term infants on their antibody immune response to this vaccine. VLBW pre-term infants less than 1500g (less than 32 weeks gestation) will be randomized into two treatment groups: vitamin A supplemented and placebo (saline). The vitamin A treatment group will receive 2000 IU of retinyl palmitate by intramuscular injection starting on postnatal day 2 and thereafter on alternate days for 28 days. Plasma vitamin A levels will be closely monitored for toxicity. Plasma immunoglobulins and antibodies to HbsAg and tetanus toxoid will be quantified by ELISA after the second and third doses of hepatitis B vaccine. These results will be correlated with changes in CD4+ T-cell subsets as defined by their cytokine secretion profile and the proportion of naive (CD45RA) to memory (CD45R0) T-cells as analyzed by flow cytometry. Acceleration in the maturation of T-cells (naive to memory), and augmentation in the proportion of intracellular cytokine producing Tcells will provide a mechanism for the enhancement in the humoral immune responses to hepatitis B vaccine by vitamin A supplementation. Finally, the type and number of infections in the NICU and to 9 months of age will be recorded to determine if vitamin A supplementation affects the incidence and severity of infection in early infancy. Vitamin A supplementation may be useful in pre-term infants in augmenting B-cell immune responses to infectious agents and in their response to vaccines. These factors could lead to decreased morbidity and mortality of pre-term infants during early postnatal life. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “hepatitis” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for hepatitis in the PubMed Central database: ·

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A Defective Interference-Like Phenomenon of Human Hepatitis B Virus in Chronic Carriers. by Yuan TT, Lin MH, Chen DS, Shih C.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=109410

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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A Dose Ranging Study of the Pharmacokinetics, Safety, and Preliminary Efficacy of Lamivudine in Children and Adolescents with Chronic Hepatitis B. by Sokal EM, Roberts EA, Mieli-Vergani G, McPhillips P, Johnson M, Barber J, Dallow N, Boxall E, Kelly D.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89731

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A family cluster of an immune escape variant of hepatitis B virus infecting a mother and her two fully immunized children. by Ho MS, Lu CF, Kuo J, Mau YC, Chao WH.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170234

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A Frequent, Naturally Occurring Mutation (P130T) of Human Hepatitis B Virus Core Antigen Is Compensatory for Immature Secretion Phenotype of Another Frequent Variant (I97L). by Yuan TT, Shih C.; 2000 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112021

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A new PCR-based seroneutralization assay in cell culture for diagnosis of hepatitis E. by Meng J, Dubreuil P, Pillot J.; 1997 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229751

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A novel form of hepatitis delta antigen. by Bichko VV, Khudyakov YE, Taylor JM.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190189

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A Serotyping Assay for Hepatitis C Virus in Southeast Asia. by Songsivilai S, Kanistanon D, Dharakul T.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95649

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A Small Yeast RNA Blocks Hepatitis C Virus Internal Ribosome Entry Site (HCV IRES)-Mediated Translation and Inhibits Replication of a Chimeric Poliovirus under Translational Control of the HCV IRES Element. by Das S, Ott M, Yamane A, Tsai W, Gromeier M, Lahser F, Gupta S, Dasgupta A.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=110227

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Abnormal Priming of CD4 + T Cells by Dendritic Cells Expressing Hepatitis C Virus Core and E1 Proteins. by Sarobe P, Lasarte JJ, Casares N, Lopez-Diaz de Cerio A, Baixeras E, Labarga P, Garcia N, Borras-Cuesta F, Prieto J.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136154

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Accuracy of perceptions of hepatitis B and C status: cross sectional investigation of opiate addicts in treatment. by Best D, Noble A, Finch E, Gossop M, Sidwell C, Strang J.; 1999 Jul 31; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28181

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Acute Hepatitis C Virus Structural Gene Sequences as Predictors of Persistent Viremia: Hypervariable Region 1 as a Decoy. by Ray SC, Wang YM, Laeyendecker O, Ticehurst JR, Villano SA, Thomas DL.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104053

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Algorithmic Approach to High-Throughput Molecular Screening for Alpha Interferon-Resistant Genotypes in Hepatitis C Patients. by Sreevatsan S, Bookout JB, Ringpis FM, Pottathil MR, Marshall DJ, De Arruda M, Murvine C, Fors L, Pottathil RM, Barathur RR.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104948

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Alpha Interferon Inhibits Hepatitis C Virus Replication in Primary Human Hepatocytes Infected In Vitro. by Castet V, Fournier C, Soulier A, Brillet R, Coste J, Larrey D, Dhumeaux D, Maurel P, Pawlotsky JM.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=155162

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Altered DNA Mutation Spectrum in Aflatoxin B1-Treated Transgenic Mice That Express the Hepatitis B Virus X Protein. by Madden CR, Finegold MJ, Slagle BL.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136763

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Amplification of Full-Length Hepatitis B Virus Genomes from Samples from Patients with Low Levels of Viremia: Frequency and Functional Consequences of PCRIntroduced Mutations. by Gunther S, Sommer G, Von Breunig F, Iwanska A, Kalinina T, Sterneck M, Will H.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104572

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An Indian strain of hepatitis E virus (HEV): cloning, sequence, and expression of structural region and antibody responses in sera from individuals from an area of high-level HEV endemicity. by Panda SK, Nanda SK, Zafrullah M, Ansari IH, Ozdener MH, Jameel S.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228549

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Analysis of hepatitis C virus isolates by serotyping and genotyping. by van Doorn LJ, Kleter B, Pike I, Quint W.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229115

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Analysis of Hepatitis C Virus-Inoculated Chimpanzees Reveals Unexpected Clinical Profiles. by Bassett SE, Brasky KM, Lanford RE.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=109692

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Antenatal Screening for Hepatitis B and Antibodies to Toxoplasma gondii and Rubella Virus: Evaluation of Two Commercial Immunoassay Systems. by Diepersloot RJ, Dunnewold-Hoekstra H, Kruit-den Hollander J, Vlaspolder F.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=96143

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Anticardiolipin Antibodies in Patients with Chronic Hepatitis C Virus Infection: Characterization in Relation to Antiphospholipid Syndrome. by Ordi-Ros J, Villarreal J, Monegal F, Sauleda S, Esteban I, Vilardell M.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95855

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Antigenic Diversity of Hepatitis B Virus Strains of Genotype F in Amerindians and Other Population Groups from Venezuela. by Blitz L, Pujol FH, Swenson PD, Porto L,

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Atencio R, Araujo M, Costa L, Monsalve DC, Torres JR, Fields HA, Lambert S, Van Geyt C, Norder H, Magnius LO, Echevarria JM, Stuyver L.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104602 ·

Antigenic Heterogeneity of the Hepatitis C Virus NS5A Protein. by Dou XG, Talekar G, Chang J, Dai X, Li L, Bonafonte MT, Holloway B, Fields HA, Khudyakov YE.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120141

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Antigenic variation of core, NS3, and NS5 proteins among genotypes of hepatitis C virus. by Neville JA, Prescott LE, Bhattacherjee V, Adams N, Pike I, Rodgers B, ElZayadi A, Hamid S, Dusheiko GM, Saeed AA, Haydon GH, Simmonds P.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230123

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Antigenicity and Immunogenicity of Novel Chimeric Hepatitis B Surface Antigen Particles with Exposed Hepatitis C Virus Epitopes. by Netter HJ, Macnaughton TB, Woo WP, Tindle R, Gowans EJ.; 2001 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114797

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Antisense Oligonucleotide Inhibition of Hepatitis C Virus (HCV) Gene Expression in Livers of Mice Infected with an HCV-Vaccinia Virus Recombinant. by Zhang H, Hanecak R, Brown-Driver V, Azad R, Conklin B, Fox MC, Anderson KP.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89075

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Antiviral Activities of Oral 1-O-Hexadecylpropanediol-3-Phosphoacyclovir and Acyclovir in Woodchucks with Chronic Woodchuck Hepatitis Virus Infection. by Hostetler KY, Beadle JR, Hornbuckle WE, Bellezza CA, Tochkov IA, Cote PJ, Gerin JL, Korba BE, Tennant BC.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89993

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Antiviral Activity of [beta]-l-2[prime prime or minute],3[prime prime or minute]Dideoxy-2[prime prime or minute],3[prime prime or minute]-Didehydro-5Fluorocytidine in Woodchucks Chronically Infected with Woodchuck Hepatitis Virus. by Le Guerhier F, Pichoud C, Jamard C, Guerret S, Chevallier M, Peyrol S, Hantz O, King I, Trepo C, Cheng YC, Zoulim F.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90426

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Antiviral Efficacy and Pharmacokinetics of Oral Adefovir Dipivoxil in Chronically Woodchuck Hepatitis Virus-Infected Woodchucks. by Cullen JM, Li DH, Brown C, Eisenberg EJ, Cundy KC, Wolfe J, Toole J, Gibbs C.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90725

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Antiviral l-Nucleosides Specific for Hepatitis B Virus Infection. by Bryant ML, Bridges EG, Placidi L, Faraj A, Loi AG, Pierra C, Dukhan D, Gosselin G, Imbach JL, Hernandez B, Juodawlkis A, Tennant B, Korba B, Cote P, Marion P, Cretton-Scott E, Schinazi RF, Sommadossi JP.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90266

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Assessment of Hepatitis B Virus DNA Stability in Serum by the Chiron Quantiplex Branched-DNA Assay. by Krajden M, Comanor L, Rifkin O, Grigoriew A, Minor JM, Kapke GF.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104546

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Assessment of Hepatitis C Virus Sequence Complexity by Electrophoretic Mobilities of Both Single-and Double-Stranded DNAs. by Wang YM, Ray SC, Laeyendecker O, Ticehurst JR, Thomas DL.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105098

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Assessment of Spontaneous Fluctuations of Viral Load in Untreated Patients with Chronic Hepatitis C by Two Standardized Quantitation Methods: Branched DNA and Amplicor Monitor. by Halfon P, Bourliere M, Halimi G, Khiri H, Bertezene P, Portal I, Botta-Fridlund D, Gauthier AP, Jullien M, Feryn JM, Gerolami V, Cartouzou G.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104981

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Assessment of the COBAS Amplicor HBV Monitor Test for Quantitation of Serum Hepatitis B Virus DNA Levels. by Lopez VA, Bourne EJ, Lutz MW, Condreay LD.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130700

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Assessment of Viral Loads in Patients with Chronic Hepatitis C with AMPLICOR HCV MONITOR Version 1.0, COBAS HCV MONITOR Version 2.0, and QUANTIPLEX HCV RNA Version 2.0 Assays. by Martinot-Peignoux M, Le Breton V, Fritsch S, Le guludec G, Labouret N, Keller F, Marcellin P.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87008

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Assessment, by Transcription-Mediated Amplification, of Virologic Response in Patients with Chronic Hepatitis C Virus Treated with Peginterferon [alpha]-2a. by Sarrazin C, Hendricks DA, Sedarati F, Zeuzem S.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88249

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Automated Multiplex Assay System for Simultaneous Detection of Hepatitis B Virus DNA, Hepatitis C Virus RNA, and Human Immunodeficiency Virus Type 1 RNA. by Meng Q, Wong C, Rangachari A, Tamatsukuri S, Sasaki M, Fiss E, Cheng L, Ramankutty T, Clarke D, Yawata H, Sakakura Y, Hirose T, Impraim C.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88264

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Automated RIBA Hepatitis C Virus (HCV) Strip Immunoblot Assay for Reproducible HCV Diagnosis. by Martin P, Fabrizi F, Dixit V, Quan S, Brezina M, Kaufman E, Sra ,K, DiNello R, Polito A, Gitnick G.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104547

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Baculovirus Expression of Chimeric Hepatitis B Virus Core Particles with Hepatitis E Virus Epitopes and Their Use in a Hepatitis E Immunoassay. by Touze A, Enogat N, Buisson Y, Coursaget P.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=84333

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Can Pooling Be Used for Seroprevalence Studies of Hepatitis C? by Stephens GM, Raboud JM, Karakas L, Sherlock CH.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87579

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CD8 + T Cells Mediate Viral Clearance and Disease Pathogenesis during Acute Hepatitis B Virus Infection. by Thimme R, Wieland S, Steiger C, Ghrayeb J, Reimann KA, Purcell RH, Chisari FV.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=140637

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Changes in anti-viral effectiveness of interferon after dose reduction in chronic hepatitis c patients: a case control study. by Bekkering FC, Neumann AU, Brouwer JT, Levi-Drummer RS, Schalm SW.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64636

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Characteristics of Hepatitis B Virus Isolates of Genotype G and Their Phylogenetic Differences from the Other Six Genotypes (A through F). by Kato H, Orito E, Gish RG, Sugauchi F, Suzuki S, Ueda R, Miyakawa Y, Mizokami M.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136184

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Characterization of a Strain of Infectious Hepatitis E Virus Isolated from Sewage in an Area where Hepatitis E Is Not Endemic. by Pina S, Jofre J, Emerson SU, Purcell RH, Girones R.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=106673

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Characterization of Hepatitis C Virus Quasispecies by Matrix-Assisted Laser Desorption Ionization-Time of Flight (Mass Spectrometry) Mutation Detection. by Ayers M, Siu K, Roberts E, Garvin AM, Tellier R.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130814

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Characterization of Hepatitis G Virus (GB-C Virus) Particles: Evidence for a Nucleocapsid and Expression of Sequences Upstream of the E1 Protein. by Xiang J, Klinzman D, McLinden J, Schmidt WN, LaBrecque DR, Gish R, Stapleton JT.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=109717

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Characterization of Low- and Very-Low-Density Hepatitis C Virus RNA-Containing Particles. by Andre P, Komurian-Pradel F, Deforges S, Perret M, Berland JL, Sodoyer M, Pol S, Brechot C, Paranhos-Baccala G, Lotteau V.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136313

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Characterization of Unusual Escape Variants of Hepatitis B Virus Isolated from a Hepatitis B Surface Antigen-Negative Subject. by Grethe S, Monazahian M, Bohme I, Thomssen R.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=110046

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Chronic Active Hepatitis in Transgenic Mice Expressing Interferon-[gamma] in the Liver. by Toyonaga T, Hino O, Sugai S, Wakasug S, Abe K, Shichiri M, Yamamura K.; 1994 Jan 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42999

134 Hepatitis

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Chronic Active Hepatitis Induced by Helicobacter hepaticus in the A/JCr Mouse Is Associated with a Th1 Cell-Mediated Immune Response. by Whary MT, Morgan TJ, Dangler CA, Gaudes KJ, Taylor NS, Fox JG.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=108325

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Chronic proliferative hepatitis in A/JCr mice associated with persistent Helicobacter hepaticus infection: a model of helicobacter-induced carcinogenesis. by Fox JG, Li X, Yan L, Cahill RJ, Hurley R, Lewis R, Murphy JC.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173960

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Classification of Hepatitis C Viruses Based on Phylogenetic Analysis of the Envelope 1 and Nonstructural 5B Regions and Identification of Five Additional Subtypes. by Stuyver L, Arnhem WV, Wyseur A, Hernandez F, Delaporte E, Maertens G.; 1994 Oct 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44972

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Clinical and Epidemiological Relevance of Quantitating Hepatitis E Virus-Specific Immunoglobulin M. by Seriwatana J, Shrestha MP, Scott RM, Tsarev SA, Vaughn DW, Myint KS, Innis BL.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=120059

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Clinical and Virological Aspects of Blood Donors Infected with Hepatitis B Virus Genotypes B and C. by Kao JH, Chen PJ, Lai MY, Chen DS.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120125

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Clinical characterization of a competitive PCR assay for quantitative testing of hepatitis C virus. by Miskovsky EP, Carrella AV, Gutekunst K, Sun CA, Quinn TC, Thomas DL.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229165

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Clinical course of hepatitis C virus during the first decade of infection: cohort study. by Harris HE, Ramsay ME, Andrews N, Eldridge KP.; 2002 Feb 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=65664

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Clinical Evaluation of the Automated COBAS AMPLICOR HCV MONITOR Test Version 2.0 for Quantifying Serum Hepatitis C Virus RNA and Comparison to the Quantiplex HCV Version 2.0 Test. by Yu ML, Chuang WL, Dai CY, Chen SC, Lin ZY, Hsieh MY, Wang LY, Chang WY.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87152

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Clinical Evaluation of Two Methods for Genotyping Hepatitis C Virus Based on Analysis of the 5[prime prime or minute] Noncoding Region. by Nolte FS, Green AM, Fiebelkorn KR, Caliendo AM, Sturchio C, Grunwald A, Healy M.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=153875

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Clinical Significance of Hepatitis C Virus Genotypes. by Zein NN.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=100152

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Coadministration of Gamma Interferon with DNA Vaccine Expressing Woodchuck Hepatitis Virus (WHV) Core Antigen Enhances the Specific Immune Response and Protects against WHV Infection. by Siegel F, Lu M, Roggendorf M.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114907

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Combination Therapy with Lamivudine and Adenovirus Causes Transient Suppression of Chronic Woodchuck Hepatitis Virus Infections. by Zhou T, Guo JT, Nunes FA, Molnar-Kimber KL, Wilson JM, Aldrich CE, Saputelli J, Litwin S, Condreay LD, Seeger C, Mason WS.; 2000 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112458

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Comparative Analysis of Translation Efficiencies of Hepatitis C Virus 5[prime prime or minute] Untranslated Regions among Intraindividual Quasispecies Present in Chronic Infection: Opposite Behaviors Depending on Cell Type. by Laporte J, Malet I, Andrieu T, Thibault V, Toulme JJ, Wychowski C, Pawlotsky JM, Huraux JM, Agut H, Cahour A.; 2000 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=110962

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Comparative Evaluation of Semiautomated COBAS AMPLICOR Hepatitis B Virus (HBV) MONITOR Test and Manual Microwell Plate-Based AMPLICOR HBV MONITOR Test. by Marin IJ, Poljak M, Seme K, Meglic-Volkar J, Maticic M, Lesnicar G, Brinovec V.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87814

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Comparative Pathogenesis of Infection of Pigs with Hepatitis E Viruses Recovered from a Pig and a Human. by Halbur PG, Kasorndorkbua C, Gilbert C, Guenette D, Potters MB, Purcell RH, Emerson SU, Toth TE, Meng XJ.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87850

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Comparative Sequence Analysis of the Core Protein and Its Frameshift Product, the F Protein, of Hepatitis C Virus Subtype 1b Strains Obtained from Patients with and without Hepatocellular Carcinoma. by Ogata S, Nagano-Fujii M, Ku Y, Yoon S, Hotta H.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130847

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Comparison and Application of a Novel Genotyping Method, Semiautomated Primer-Specific and Mispair Extension Analysis, and Four Other Genotyping Assays for Detection of Hepatitis C Virus Mixed-Genotype Infections. by Hu YW, Balaskas E, Furione M, Yen PH, Kessler G, Scalia V, Chui L, Sher G.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87116

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Comparison of a Chemiluminescent Immunoassay with Two Microparticle Enzyme Immunoassays for Detection of Hepatitis B Virus Surface Antigen. by Diepersloot RJ, van Zantvliet-van Oostrom Y, Gleaves CA.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95975

136 Hepatitis

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Comparison of a competitive combined reverse transcription-PCR assay with a branched-DNA assay for hepatitis C virus RNA quantitation. by Mayerat C, Burgisser P, Lavanchy D, Mantegani A, Frei PC.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229389

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Comparison of hepatitis B virus DNA extractions from serum by the QIAamp blood kit, GeneReleaser, and the phenol-chloroform method. by Kramvis A, Bukofzer S, Kew MC.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229395

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Comparison of Hepatitis C Viral Loads in Patients with or without Human Immunodeficiency Virus. by Matthews-Greer JM, Caldito GC, Adley SD, Willis R, Mire AC, Jamison RM, McRae KL, King JW, Chang WL.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=96128

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Comparison of methods for extraction of nucleic acid from hemolytic serum for PCR amplification of hepatitis B virus DNA sequences. by Klein A, Barsuk R, Dagan S, Nusbaum O, Shouval D, Galun E.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229868

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Comparison of plasma virus loads among individuals infected with hepatitis C virus (HCV) genotypes 1, 2, and 3 by quantiplex HCV RNA assay versions 1 and 2, Roche Monitor assay, and an in-house limiting dilution method. by Hawkins A, Davidson F, Simmonds P.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229536

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Comparison of Sequence Analysis and the INNO-LiPA HBV DR Line Probe Assay for Detection of Lamivudine-Resistant Hepatitis B Virus Strains in Patients under Various Clinical Conditions. by Aberle SW, Kletzmayr J, Watschinger B, Schmied B, Vetter N, Puchhammer-Stockl E.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88061

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Comparison of Serum Hepatitis C Virus RNA and Core Antigen Concentrations and Determination of Whether Levels Are Associated with Liver Histology or Affected by Specimen Storage Time. by Lagging LM, Garcia CE, Westin J, Wejstal R, Norkrans G, Dhillon AP, Lindh M.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=139660

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Comparison of the Second-Generation Digene Hybrid Capture Assay with the Branched-DNA Assay for Measurement of Hepatitis B Virus DNA in Serum. by Ho SK, Chan TM, Cheng IK, Lai KN.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=85256

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Comparison of Three Different Sensitive Assays for Hepatitis B Virus DNA in Monitoring of Responses to Antiviral Therapy. by Chan HL, Leung NW, Lau TC, Wong ML, Sung JJ.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87356

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Comparison of two quantitative hepatitis C virus reverse transcriptase PCR assays. by Roth WK, Lee JH, Ruster B, Zeuzem S.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228779

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Comprehensive Analysis of CD8 +-T-Cell Responses against Hepatitis C Virus Reveals Multiple Unpredicted Specificities. by Lauer GM, Ouchi K, Chung RT, Nguyen TN, Day CL, Purkis DR, Reiser M, Kim AY, Lucas M, Klenerman P, Walker BD.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136241

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Concentrations of Cytokines, Soluble Interleukin-2 Receptor, and Soluble CD30 in Sera of Patients with Hepatitis B Virus Infection during Acute and Convalescent Phases. by Monsalve-de Castillo F, Romero TA, Estevez J, Costa LL, Atencio R, Porto L, Callejas D.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=130099

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Concerted Action of the FasL/Fas and Perforin/Granzyme A and B Pathways Is Mandatory for the Development of Early Viral Hepatitis but Not for Recovery from Viral Infection. by Balkow S, Kersten A, Tran TT, Stehle T, Grosse P, Museteanu C, Utermohlen O, Pircher H, von Weizsacker F, Wallich R, Mullbacher A, Simon MM.; 2001 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=115123

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Conservation of the Conformation and Positive Charges of Hepatitis C Virus E2 Envelope Glycoprotein Hypervariable Region 1 Points to a Role in Cell Attachment. by Penin F, Combet C, Germanidis G, Frainais PO, Deleage G, Pawlotsky JM.; 2001 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114285

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Contamination of Foods by Food Handlers: Experiments on Hepatitis A Virus Transfer to Food and Its Interruption. by Bidawid S, Farber JM, Sattar SA.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=92070

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Cooperative Oligonucleotides Mediating Direct Capture of Hepatitis C Virus RNA from Serum. by O'Meara D, Yun Z, Sonnerborg A, Lundeberg J.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105143

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Correlation between Mutations in the Interferon Sensitivity-Determining Region of NS5A Protein and Viral Load of Hepatitis C Virus Subtypes 1b, 1c, and 2a. by Lusida MI, Nagano-Fujii M, Nidom CA, Soetjipto, Handajani R, Fujita T, Oka K, Hotta H.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88455

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Covalently closed circular viral DNA formed from two types of linear DNA in woodchuck hepatitis virus-infected liver. by Yang W, Mason WS, Summers J.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190393

138 Hepatitis

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CpG Oligodeoxynucleotides with Hepatitis B Surface Antigen (HBsAg) for Vaccination in HBsAg-Transgenic Mice. by Malanchere-Bres E, Payette PJ, Mancini M, Tiollais P, Davis HL, Michel ML.; 2001 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114371

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Critical contribution of liver natural killer T cells to a murine model of hepatitis. by Takeda K, Hayakawa Y, Van Kaer L, Matsuda H, Yagita H, Okumura K.; 2000 May 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25857

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Cross-Reactivity between Hepatitis C Virus and Influenza A Virus DeterminantSpecific Cytotoxic T Cells. by Wedemeyer H, Mizukoshi E, Davis AR, Bennink JR, Rehermann B.; 2001 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114725

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Decreased Frequency of the HLA-DRB1*11 Allele in Patients with Chronic Hepatitis C Virus Infection. by Yenigun A, Durupinar B.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=135873

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Deficiencies in the Acute-Phase Cell-Mediated Immune Response to Viral Antigens Are Associated with Development of Chronic Woodchuck Hepatitis Virus Infection following Neonatal Inoculation. by Menne S, Roneker CA, Roggendorf M, Gerin JL, Cote PJ, Tennant BC.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=135887

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Degenerate Immunogenicity of an HLA-A2-Restricted Hepatitis B Virus Nucleocapsid Cytotoxic T-Lymphocyte Epitope That Is Also Presented by HLA-B51. by Thimme R, Chang KM, Pemberton J, Sette A, Chisari FV.; 2001 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114890

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Depletion of neutrophils blocks the recruitment of antigen-nonspecific cells into the liver without affecting the antiviral activity of hepatitis B virus-specific cytotoxic T lymphocytes. by Sitia G, Isogawa M, Kakimi K, Wieland SF, Chisari FV, Guidotti LG.; 2002 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129753

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Detection and Characterization of Hepatitis C Virus RNA in Seminal Plasma and Spermatozoon Fractions of Semen from Patients Attempting Medically Assisted Conception. by Bourlet T, Levy R, Maertens A, Tardy JC, Grattard F, Cordonier H, Laurent JL, Guerin JF, Pozzetto B.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130669

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Detection and Quantitation of Hepatitis C Virus RNA in Feces of Chronically Infected Individuals. by Beld M, Sentjens R, Rebers S, Weel J, Wertheim-van Dillen P, Sol C, Boom R.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87401

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Detection and Sequence Analysis of Hepatitis B Virus Integration in Peripheral Blood Mononuclear Cells. by Laskus T, Radkowski M, Wang LF, Nowicki M, Rakela J.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=103945

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Detection by Reverse Transcription-PCR and Genetic Characterization of Field Isolates of Swine Hepatitis E Virus from Pigs in Different Geographic Regions of the United States. by Huang FF, Haqshenas G, Guenette DK, Halbur PG, Schommer SK, Pierson FW, Toth TE, Meng XJ.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=140370

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Detection of Antibodies to Hepatitis C Virus in Dried Blood Spot Samples from Mothers and Their Offspring in Lahore, Pakistan. by Parker SP, Khan HI, Cubitt WD.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=85032

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Detection of Antibody Against Antigen Expressed by Molecularly Cloned Hepatitis C Virus cDNA: Application to Diagnosis and Blood Screening for Posttransfusion Hepatitis. by Miyamura T, Saito I, Katayama T, Kikuchi S, Tateda A, Houghton M, Choo Q, Kuo G.; 1990 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53394

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Detection of Diverse Hepatitis C Virus (HCV)-Specific Cytotoxic T Lymphocytes in Peripheral Blood of Infected Persons by Screening for Responses to All Translated Proteins of HCV. by Wong DK, Dudley DD, Dohrenwend PB, Lauer GM, Chung RT, Thomas DL, Walker BD.; 2001 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114029

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Detection of hepatitis A virus RNA in oyster meat. by Cromeans TL, Nainan OV, Margolis HS.; 1997 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168541

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Detection of Hepatitis B Virus DNA in Sera from Patients with Chronic Hepatitis B Virus Infection by DNA Microarray Method. by Kawaguchi K, Kaneko S, Honda M, Kawai HF, Shirota Y, Kobayashi K.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=153866

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Detection of Hepatitis B Virus Infection in Wild-Born Chimpanzees (Pan troglodytes verus): Phylogenetic Relationships with Human and Other Primate Genotypes. by MacDonald DM, Holmes EC, Lewis JC, Simmonds P.; 2000 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=111941

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Detection of hepatitis E virus RNA in stools and serum by reverse transcription-PCR. by Turkoglu S, Lazizi Y, Meng H, Kordosi A, Dubreuil P, Crescenzo B, Benjelloun S, Nordmann P, Pillot J.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229066

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Detection of Hepatitis G Virus (HGV) RNA and Antibodies to the HGV Envelope Protein E2 in a Cohort of Hemodialysis Patients. by Perez-Gracia T, Galan F, GironGonzalez JA, Lozano A, Benavides B, Fernandez E, Rodriguez-Iglesias M.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87584

140 Hepatitis

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Detection of Sporadic Cases of Hepatitis E Virus (HEV) Infection in China Using Immunoassays Based on Recombinant Open Reading Frame 2 and 3 Polypeptides from HEV Genotype 4. by Wang Y, Zhang H, Li Z, Gu W, Lan H, Hao W, Ling R, Li H, Harrison TJ.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88551

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Detection of TT Virus DNA and GB Virus Type C/Hepatitis G Virus RNA in Serum and Breast Milk: Determination of Mother-to-Child Transmission. by Schroter M, Polywka S, Zollner B, Schafer P, Laufs R, Feucht HH.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=86193

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Determination of genotypes of hepatitis C virus in Venezuela by restriction fragment length polymorphism. by Pujol FH, Loureiro CL, Devesa M, Blitz L, Parra K, Beker S, Liprandi F.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229860

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Determination of Hepatitis C Virus Genotype by Direct Sequence Analysis of Products Generated with the Amplicor HCV Test. by Germer JJ, Rys PN, Thorvilson JN, Persing DH.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=85299

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Determination of hepatitis C virus genotypes in the United States by cleavase fragment length polymorphism analysis. by Marshall DJ, Heisler LM, Lyamichev V, Murvine C, Olive DM, Ehrlich GD, Neri BP, de Arruda M.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230140

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Development of a Primary Tamarin Hepatocyte Culture System for GB Virus-B: a Surrogate Model for Hepatitis C Virus. by Beames B, Chavez D, Guerra B, Notvall L, Brasky KM, Lanford RE.; 2000 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112459

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Development of a Quantitative Real-Time Detection Assay for Hepatitis B Virus DNA and Comparison with Two Commercial Assays. by Pas SD, Fries E, De Man RA, Osterhaus AD, Niesters HG.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87141

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Development of a Simple and Highly Sensitive Enzyme Immunoassay for Hepatitis C Virus Core Antigen. by Aoyagi K, Ohue C, Iida K, Kimura T, Tanaka E, Kiyosawa K, Yagi S.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=84955

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Diagnosis of Hepatitis C Virus (HCV) Infection Using an Immunodominant Chimeric Polyprotein to Capture Circulating Antibodies: Reevaluation of the Role of HCV in Liver Disease. by Chien DY, Choo Q, Tabrizi A, Kuo C, McFarland J, Berger K, Lee C, Shuster JR, Nguyen T, Moyer DL, Tong M, Furuta S, Omata M, Tegtmeier G, Alter H, Schiff E, Jeffers L, Houghton M, Kuo G.; 1992 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50267

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Diagnostic Value of Anti-Hepatitis C Virus (HCV) Core Immunoglobulin M in Recurrence of HCV Infection after Orthotopic Liver Transplantation. by Casino C, Lilli D, Rivanera D, Comanducci A, Rossi M, Casciaro G, Pecorella I, Alfani D, Mancini C.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=85330

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Diagnostic Value of Immunoglobulin G (IgG) and IgM Anti-Hepatitis E Virus (HEV) Tests Based on HEV RNA in an Area Where Hepatitis E Is Not Endemic. by Lin CC, Wu JC, Chang TT, Chang WY, Yu ML, Tam AW, Wang SC, Huang YH, Chang FY, Lee SD.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87517

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Different Levels of T-Cell Receptor Triggering Induce Distinct Functions in Hepatitis B and Hepatitis C Virus-Specific Human CD4 + T-Cell Clones. by Diepolder HM, Gruener NH, Gerlach JT, Jung MC, Wierenga EA, Pape GR.; 2001 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=115022

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Differential cytotoxic T-lymphocyte responsiveness to the hepatitis B and C viruses in chronically infected patients. by Rehermann B, Chang KM, McHutchinson J, Kokka R, Houghton M, Rice CM, Chisari FV.; 1996 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190761

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Differential prevalence of hepatitis C virus subtypes in healthy blood donors, patients on maintenance hemodialysis, and patients with hepatocellular carcinoma in Surabaya, Indonesia. by Soetjipto, Handajani R, Lusida MI, Darmadi S, Adi P, Soemarto, Ishido S, Katayama Y, Hotta H.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229426

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Direct sequencing of hepatitis A virus strains isolated during an epidemic in France. by Apaire-Marchais V, Robertson BH, Aubineau-Ferre V, Le Roux MG, Leveque F, Schwartzbrod L, Billaudel S.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=167705

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Distribution of Hepatitis B Virus Genotypes in Two Different Pediatric Populations from Argentina. by Mbayed VA, Lopez JL, Telenta PF, Palacios G, Badia I, Ferro A, Galoppo C, Campos R.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105331

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Diverging Effects of Human Recombinant Anti-Hepatitis C Virus (HCV) Antibody Fragments Derived from a Single Patient on the Infectivity of a Vesicular Stomatitis Virus/HCV Pseudotype. by Burioni R, Matsuura Y, Mancini N, Tani H, Miyamura T, Varaldo PE, Clementi M.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136746

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Diverse patterns of recognition of hepatitis C virus core and nonstructural antigens by antibodies present in Egyptian cancer patients and blood donors. by Attia MA, Zekri AR, Goudsmit J, Boom R, Khaled HM, Mansour MT, de Wolf F, el-Din HM, Sol CJ.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229382

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DNA Microarray Analysis of Chimpanzee Liver during Acute Resolving Hepatitis C Virus Infection. by Bigger CB, Brasky KM, Lanford RE.; 2001 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114434

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DNA Vaccine for Hepatitis B: Evidence for Immunogenicity in Chimpanzees and Comparison with Other Vaccines. by Davis HL, McCluskie MJ, Gerin JL, Purcell RH.; 1996 Jul 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38962

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DNA-Mediated Immunization in a Transgenic Mouse Model of the Hepatitis B Surface Antigen Chronic Carrier State. by Mancini M, Hadchouel M, Davis HL, Whalen RG, Tiollais P, Michel M.; 1996 Oct 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38020

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Dominant Role of Host Selective Pressure in Driving Hepatitis C Virus Evolution in Perinatal Infection. by Manzin A, Solforosi L, Debiaggi M, Zara F, Tanzi E, Romano L, Zanetti AR, Clementi M.; 2000 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=111950

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Dose Range Study of Pharmacokinetics, Safety, and Preliminary Antiviral Activity of Emtricitabine in Adults with Hepatitis B Virus Infection. by Gish RG, Leung NW, Wright TL, Trinh H, Lang W, Kessler HA, Fang L, Wang LH, Delehanty J, Rigney A, Mondou E, Snow A, Rousseau F.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=127249

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Dynamics of Persistent TT Virus Infection, as Determined in Patients Treated with Alpha Interferon for Concomitant Hepatitis C Virus Infection. by Maggi F, Pistello M, Vatteroni M, Presciuttini S, Marchi S, Isola P, Fornai C, Fagnani S, Andreoli E, Antonelli G, Bendinelli M.; 2001 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=116095

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Early changes in hepatitis C viral quasispecies during interferon therapy predict the therapeutic outcome. by Farci P, Strazzera R, Alter HJ, Farci S, Degioannis D, Coiana A, Peddis G, Usai F, Serra G, Chessa L, Diaz G, Balestrieri A, Purcell RH.; 2002 Mar 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122476

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Early Events in Hepatitis C Virus Infection of Chimpanzees. by Shimizu YK, Weiner AJ, Rosenblatt J, Wong DC, Shapiro M, Popkin T, Houghton M, Alter HJ, Purcell RH.; 1990 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54550

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Early treatment of acute hepatitis C infection may lead to cure. by Hoey J.; 2001 Nov 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=81686

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Effect of Multiple Freeze-Thaw Cycles on Hepatitis B Virus DNA and Hepatitis C Virus RNA Quantification as Measured with Branched-DNA Technology. by Krajden M, Minor JM, Rifkin O, Comanor L.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=84922

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Effect of Oral Administration of Emtricitabine on Woodchuck Hepatitis Virus Replication in Chronically Infected Woodchucks. by Korba BE, Schinazi RF, Cote P, Tennant BC, Gerin JL.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89954

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Effect of Retreatment with Interferon Alone or Interferon plus Ribavirin on Hepatitis C Virus Quasispecies Diversification in Nonresponder Patients with Chronic Hepatitis C. by Gerotto M, Sullivan DG, Polyak SJ, Chemello L, Cavalletto L, Pontisso P, Alberti A, Gretch DR.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104248

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Efficacy of the Carbocyclic 2[prime prime or minute]-Deoxyguanosine Nucleoside BMS-200475 in the Woodchuck Model of Hepatitis B Virus Infection. by Genovesi EV, Lamb L, Medina I, Taylor D, Seifer M, Innaimo S, Colonno RJ, Standring DN, Clark JM.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=106024

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Efficient Infection of Primary Tupaia Hepatocytes with Purified Human and Woolly Monkey Hepatitis B Virus. by Kock J, Nassal M, MacNelly S, Baumert TF, Blum HE, von Weizsacker F.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114913

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Efficient Site-Specific Nonribozyme Opening of Hepatitis Delta Virus Genomic RNA in Infected Livers. by Chang J, Moraleda G, Gudima S, Taylor J.; 2000 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=102025

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Elevated Levels of Interleukin-8 in Serum Are Associated with Hepatitis C Virus Infection and Resistance to Interferon Therapy. by Polyak SJ, Khabar KS, Rezeiq M, Gretch DR.; 2001 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114338

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Elimination of hepatitis C virus RNA in infected human hepatocytes by adenovirusmediated expression of ribozymes. by Lieber A, He CY, Polyak SJ, Gretch DR, Barr D, Kay MA.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190975

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Emergence of Drug-Resistant Populations of Woodchuck Hepatitis Virus in Woodchucks Treated with the Antiviral Nucleoside Lamivudine. by Zhou T, Saputelli J, Aldrich CE, Deslauriers M, Condreay LD, Mason WS.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89396

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Enhanced amplification of hepatitis C virus (HCV) cDNA by PCR: detection of HCV RNA in archival sera. by Beardsley AM, Gowans EJ, Burrell CJ, Marmion BP.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229070

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Enhanced Expression of Interferon-Regulated Genes in the Liver of Patients with Chronic Hepatitis C Virus Infection: Detection by Suppression-Subtractive Hybridization. by Patzwahl R, Meier V, Ramadori G, Mihm S.; 2001 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114039

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Enhancement of Hepatitis B Virus Infection by Noninfectious Subviral Particles. by Bruns M, Miska S, Chassot S, Will H.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=124627

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Enhancing B- and T-Cell Immune Response to a Hepatitis C Virus E2 DNA Vaccine by Intramuscular Electrical Gene Transfer. by Zucchelli S, Capone S, Fattori E, Folgori A, Di Marco A, Casimiro D, Simon AJ, Laufer R, La Monica N, Cortese R, Nicosia A.; 2000 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112441

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Epidemiological Dynamics of Hepatitis C Virus among 747 German Individuals: New Subtypes on the Advance. by Schroter M, Zollner B, Schafer P, Reimer A, Muller M, Laufs R, Feucht HH.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130918

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Epidemiology of Hepatitis B, C, E, and G Virus Infections and Molecular Analysis of Hepatitis G Virus Isolates in Bolivia. by Konomi N, Miyoshi C, La Fuente Zerain C, Li TC, Arakawa Y, Abe K.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=85549

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Evaluation of a New Rapid Test for the Combined Detection of Hepatitis B Virus Surface Antigen and Hepatitis B Virus e Antigen. by Clement F, Dewint P, LerouxRoels G.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=154615

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Evaluation of a New Serotyping Assay for Detection of Anti-Hepatitis C Virus TypeSpecific Antibodies in Serum Samples. by Gault E, Soussan P, Morice Y, Sanders L, Berrada A, Rogers B, Deny P.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154718

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Evaluation of a novel serotyping system for hepatitis C virus: strong correlation with standard genotyping methodologies. by Dixit V, Quan S, Martin P, Larson D, Brezina M, DiNello R, Sra K, Lau JY, Chien D, Kolberg J.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228618

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Evaluation of Accumulation of Hepatitis C Virus Mutations in a Chronically Infected Chimpanzee: Comparison of the Core, E1, HVR1, and NS5b Regions. by Lu L, Nakano T, Orito E, Mizokami M, Robertson BH.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=115927

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Evaluation of an Automated Sample Preparation Protocol for Quantitative Detection of Hepatitis C Virus RNA. by Stelzl E, Kormann-Klement A, Haas J, Daghofer E, Santner BI, Marth E, Kessler HH.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=140388

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Evaluation of commercially available and in-house reverse transcription-PCR assays for detection of hepatitis G virus or GB virus C. by Forns X, Tan D, Alter HJ, Purcell RH, Bukh J.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230044

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Evaluation of enzyme immunoassay for hepatitis B virus DNA based on anti-doublestranded DNA. by Garcia F Jr, Garcia F, Bernal MC, Leyva A, Piedrola G, Maroto MC.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=227958

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Evaluation of Hepatitis C Virus Glycoprotein E2 for Vaccine Design: an Endoplasmic Reticulum-Retained Recombinant Protein Is Superior to Secreted Recombinant Protein and DNA-Based Vaccine Candidates. by Heile JM, Fong YL, Rosa D, Berger K, Saletti G, Campagnoli S, Bensi G, Capo S, Coates S, Crawford K, Dong C, Wininger M, Baker G, Cousens L, Chien D, Ng P, Archangel P, Grandi G, Houghton M, Abrignani S.; 2000 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112206

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Evaluation of immunochromatographic assay systems for rapid detection of hepatitis B surface antigen and antibody, Dainascreen HBsAg and Dainascreen Ausab. by Sato K, Ichiyama S, Iinuma Y, Nada T, Shimokata K, Nakashima N.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229035

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Evaluation of performance of the RIBA processor system for automated analysis of the strip immunoblot assay for detection of antibodies to hepatitis C virus. by Icardi G, Bonanni P, Raffo AM, Masini A, Orione L, De Martini M, Crovari P.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229964

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Evaluation of SHARP signal system for enzymatic detection of amplified hepatitis B virus DNA. by Valentine-Thon E.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=227970

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Evaluation of the automated COBAS AMPLICOR hepatitis C virus PCR system. by Poljak M, Seme K, Koren S.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230102

146 Hepatitis

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Evaluation of Two New Automated Assays for Hepatitis B Virus Surface Antigen (HBsAg) Detection: IMMULITE HBsAg and IMMULITE 2000 HBsAg. by Weber B, Dengler T, Berger A, Doerr HW, Rabenau H.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=149549

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Evaluation of Urine as a Clinical Specimen for Diagnosis of Hepatitis A. by Joshi MS, Chitambar SD, Arankalle VA, Chadha MS.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=120033

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Evidence for Immune Selection of Hepatitis C Virus (HCV) Putative Envelope Glycoprotein Variants: Potential Role in Chronic HCV Infections. by Weiner AJ, Geysen HM, Christopherson C, Hall JE, Mason TJ, Saracco G, Bonino F, Crawford K, Marion CD, Crawford KA, Brunetto M, Barr PJ, Miyamura T, McHutchinson J, Houghton M.; 1992 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48889

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Evidence of Extrahepatic Sites of Replication of the Hepatitis E Virus in a Swine Model. by Williams TP, Kasorndorkbua C, Halbur PG, Haqshenas G, Guenette DK, Toth TE, Meng XJ.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88293

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Evidence that Rodents Are a Reservoir of Hepatitis E Virus for Humans in Nepal. by He J, Innis BL, Shrestha MP, Clayson ET, Scott RM, Linthicum KJ, Musser GG, Gigliotti SC, Binn LN, Kuschner RA, Vaughn DW.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=154618

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Evolution of Hepatitis C Virus Quasispecies in Hypervariable Region 1 and the Putative Interferon Sensitivity-Determining Region during Interferon Therapy and Natural Infection. by Polyak SJ, McArdle S, Liu SL, Sullivan DG, Chung M, Hofgartner WT, Carithers RL Jr, McMahon BJ, Mullins JI, Corey L, Gretch DR.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=109659

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Evolution of Hypervariable Region 1 of Hepatitis C Virus in Primary Infection. by Manzin A, Solforosi L, Petrelli E, Macarri G, Tosone G, Piazza M, Clementi M.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=110460

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Evolution of the Hepatitis C Virus Second Envelope Protein Hypervariable Region in Chronically Infected Patients Receiving Alpha Interferon Therapy. by Pawlotsky JM, Germanidis G, Frainais PO, Bouvier M, Soulier A, Pellerin M, Dhumeaux D.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112731

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Evolutionary Rate and Genetic Drift of Hepatitis C Virus Are Not Correlated with the Host Immune Response: Studies of Infected Donor-Recipient Clusters. by Allain JP, Dong Y, Vandamme AM, Moulton V, Salemi M.; 2000 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=111742

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Excretion of Hepatitis A Virus (HAV) in Adults: Comparison of Immunologic and Molecular Detection Methods and Relationship between HAV Positivity and

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Infectivity in Tamarins. by Polish LB, Robertson BH, Khanna B, Krawczynski K, Spelbring J, Olson F, Shapiro CN.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=85708 ·

Existence of Distinct GB Virus C/Hepatitis G Virus Variants with Different Tropism. by Fogeda M, Lopez-Alcorocho JM, Bartolome J, Arocena C, Martin MA, Carreno V.; 2000 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112324

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Existence of Hepatitis C Virus in Culex quinquefasciatus after Ingestion of Infected Blood: Experimental Approach to Evaluating Transmission by Mosquitoes. by Chang TT, Chang TY, Chen CC, Young KC, Roan JN, Lee YC, Cheng PN, Wu HL.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88344

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Exposure of Hepatitis C Virus (HCV) RNA-Positive Recipients to HCV RNA-Positive Blood Donors Results in Rapid Predominance of a Single Donor Strain and Exclusion and/or Suppression of the Recipient Strain. by Laskus T, Wang LF, Radkowski M, Vargas H, Nowicki M, Wilkinson J, Rakela J.; 2001 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114790

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Expression and self-assembly of empty virus-like particles of hepatitis E virus. by Li TC, Yamakawa Y, Suzuki K, Tatsumi M, Razak MA, Uchida T, Takeda N, Miyamura T.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=192060

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Expression of Hepatitis B Virus X Protein Does Not Alter the Accumulation of Spontaneous Mutations in Transgenic Mice. by Madden CR, Finegold MJ, Slagle BL.; 2000 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=110881

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Expression of Hepatitis C Virus Proteins Induces Distinct Membrane Alterations Including a Candidate Viral Replication Complex. by Egger D, Wolk B, Gosert R, Bianchi L, Blum HE, Moradpour D, Bienz K.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136238

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Expression of Hepatitis C Virus Proteins Inhibits Signal Transduction through the Jak-STAT Pathway. by Heim MH, Moradpour D, Blum HE.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112866

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Expression of Regeneration and Tolerance Factor Correlates Directly with Human Immunodeficiency Virus Infection and Inversely with Hepatitis C Virus Infection. by Sung CC, Boomer JS, Givens TS, DuChateau BK, Lepe MR, Feller A, Westerman MP, Gilman-Sachs A, Chedid A, Beaman KD.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95849

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Fast relapse and high drop out rate of 48 weeks daily interferon monotherapy in HIVinfected patients with chronic hepatitis C. by Bruno R, Sacchi P, Puoti M, Ciappina V, Zocchetti C, Brunetti E, Maffezzini E, Capelli A, Patruno SF, Malfitano A, Filice G.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128825

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Full-Length GB Virus C (Hepatitis G Virus) RNA Transcripts Are Infectious in Primary CD4-Positive T Cells. by Xiang J, Wunschmann S, Schmidt W, Shao J, Stapleton JT.; 2000 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=102111

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Fully Automated Detection of Hepatitis C Virus RNA in Serum and Whole-Blood Samples. by Kessler HH, Clarici AM, Stelzl E, Muhlbauer G, Daghofer E, Santner BI, Marth E, Stauber RE.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=130092

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Functional Characterization of Naturally Occurring Variants of Human Hepatitis B Virus Containing the Core Internal Deletion Mutation. by Yuan TT, Lin MH, Qiu SM, Shih C.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=109512

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Functional characterization of the interferon regulatory element in the enhancer 1 region of the hepatitis B virus genome. by Alcantara FF, Tang H, McLachlan A.; 2002 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=113846

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Functional Measurement of Hepatitis C Virus Core-Specific CD8 + T-Cell Responses in the Livers or Peripheral Blood of Patients by Using Autologous Peripheral Blood Mononuclear Cells as Targets or Stimulators. by Fang SH, Chiang BL, Wu MH, Iba H, Lai MY, Yang PM, Chen DS, Hwang LH.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88461

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Further evidence for association of hepatitis C infection with parenteral schistosomiasis treatment in Egypt. by Rao MR, Naficy AB, Darwish MA, Darwish NM, Schisterman E, Clemens JD, Edelman R.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139974

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GEMHEP multicenter quality control study of PCR detection of GB virus C/hepatitis G virus RNA in serum. by Bogard M, Buffet-Janvresse C, Cantaloube JF, Biagini P, Duverlie G, Castelain S, Izopet J, Dubois M, Defer C, Lepot I, Coste J, Marcellin P, Martinot-Peignoux M, Halfon P, Gerolami V, Frangeul L, Pawlotsky JM, RoudotThoraval F, Dussaix E, Loiseau P, Ravera N, Lewin P, Lamoril J, Lerable J, Lebon P.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230166

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Genetic and Experimental Evidence for Cross-Species Infection by Swine Hepatitis E Virus. by Meng XJ, Halbur PG, Shapiro MS, Govindarajan S, Bruna JD, Mushahwar IK, Purcell RH, Emerson SU.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=110481

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Genetic and Serological Evidence for Multiple Instances of Unrecognized Transmission of Hepatitis C Virus in Hemodialysis Units. by Mizuno M, Higuchi T, Kanmatsuse K, Esumi M.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105089

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Genetic Characterization and Sequence Heterogeneity of a Canadian Isolate of Swine Hepatitis E Virus. by Pei Y, Yoo D.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=139705

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Genetic Clustering of Hepatitis C Virus Strains and Severity of Recurrent Hepatitis after Liver Transplantation. by Gigou M, Roque-Afonso AM, Falissard B, Penin F, Dussaix E, Feray C.; 2001 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114714

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Genetic Diversity and Tissue Compartmentalization of the Hepatitis C Virus Genome in Blood Mononuclear Cells, Liver, and Serum from Chronic Hepatitis C Patients. by Navas S, Martin J, Quiroga JA, Castillo I, Carreno V.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=124648

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Genetic Heterogeneity of Hypervariable Region 1 of the Hepatitis C Virus (HCV) Genome and Sensitivity of HCV to Alpha Interferon Therapy. by Sandres K, Dubois M, Pasquier C, Payen JL, Alric L, Duffaut M, Vinel JP, Pascal JP, Puel J, Izopet J.; 2000 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=111585

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Genome Variability and Capsid Structural Constraints of Hepatitis A Virus. by Sanchez G, Bosch A, Pinto RM.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=140588

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Genomic organization of GB viruses A and B: two new members of the Flaviviridae associated with GB agent hepatitis. by Muerhoff AS, Leary TP, Simons JN, Pilot-Matias TJ, Dawson GJ, Erker JC, Chalmers ML, Schlauder GG, Desai SM, Mushahwar IK.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189418

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Genotypes and Clinical Phenotypes of Hepatitis B Virus in Patients with Chronic Hepatitis B Virus Infection. by Kao JH, Chen PJ, Lai MY, Chen DS.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=140384

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Genotypic distribution of hepatitis C virus in different regions of Thailand. by Kanistanon D, Neelamek M, Dharakul T, Songsivilai S.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229839

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Genotyping of hepatitis C virus in South Africa. by Smuts HE, Kannemeyer J.; 1995 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228247

150 Hepatitis

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Genotyping of Hepatitis C Virus Isolates using CLIP Sequencing. by Ross RS, Viazov SO, Holtzer CD, Beyou A, Monnet A, Mazure C, Roggendorf M.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87440

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Genotyping of Hepatitis C Virus Types 1, 2, 3, and 4 by a One-Step LightCycler Method Using Three Different Pairs of Hybridization Probes. by Schroter M, Zollner B, Schafer P, Landt O, Lass U, Laufs R, Feucht HH.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130695

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Greater diversity of hepatitis C virus genotypes found in Hong Kong than in mainland China. by Zhang YY, Lok AS, Chan DT, Widell A.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228609

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Helicobacter canis isolated from a dog liver with multifocal necrotizing hepatitis. by Fox JG, Drolet R, Higgins R, Messier S, Yan L, Coleman BE, Paster BJ, Dewhirst FE.; 1996 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229299

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Hepatitis A vaccine: Is it being used to best advantage? by Scheifele DW, Ochnio J.; 2002 Jul 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=116641

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Hepatitis A Virus Inhibits Cellular Antiviral Defense Mechanisms Induced by Double-Stranded RNA. by Brack K, Berk I, Magulski T, Lederer J, Dotzauer A, Vallbracht A.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136892

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Hepatitis A: Old and New. by Cuthbert JA.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88961

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Hepatitis associated with Kava, a herbal remedy for anxiety. by Escher M, Desmeules J, Giostra E, Mentha G.; 2001 Jan 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26591

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Hepatitis B or Hepatitis C Virus Infection Is a Risk Factor for Severe Hepatic Cytolysis after Initiation of a Protease Inhibitor-Containing Antiretroviral Regimen in Human Immunodeficiency Virus-Infected Patients. by Saves M, Raffi F, Clevenbergh P, Marchou B, Waldner-Combernoux A, Morlat P, Le Moing V, Riviere C, Chene G, Leport C.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90223

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Hepatitis B Virus (HBV) Mutations Associated with Resistance to Lamivudine in Patients Coinfected with HBV and Human Immunodeficiency Virus. by Thibault V, Benhamou Y, Seguret C, Bochet M, Katlama C, Bricaire F, Opolon P, Poynard T, Agut H.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=85438

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Hepatitis B Virus Biology. by Seeger C, Mason WS.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=98986

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Hepatitis B Virus Core Antigen Binds and Activates Naive Human B Cells In Vivo: Studies with a Human PBL-NOD/SCID Mouse Model. by Cao T, Lazdina U, Desombere I, Vanlandschoot P, Milich DR, Sallberg M, Leroux-Roels G.; 2001 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114358

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Hepatitis B Virus DNA in Blood Samples Positive for Antibodies to Core Antigen and Negative for Surface Antigen. by Gutierrez C, Leon G, Loureiro CL, Uzcategui N, Liprandi F, Pujol FH.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95771

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Hepatitis B Virus Genotype C Takes a More Aggressive Disease Course Than Hepatitis B Virus Genotype B in Hepatitis B e Antigen-Positive Patients. by Chan HL, Wong ML, Hui AY, Hung LC, Chan FK, Sung JJ.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=150268

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Hepatitis B virus HBx protein induces transcription factor AP-1 by activation of extracellular signal-regulated and c-Jun N-terminal mitogen-activated protein kinases. by Benn J, Su F, Doria M, Schneider RJ.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190451

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Hepatitis B virus HBx protein sensitizes cells to apoptotic killing by tumor necrosis factor [alpha]. by Su F, Schneider RJ.; 1997 Aug 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23107

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Hepatitis B Virus Surface Antigen (HBsAg) Mutants in Singapore Adults and Vaccinated Children with High Anti-Hepatitis B Virus Antibody Levels but Negative for HBsAg. by Chen WN.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87037

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Hepatitis C Virus Core Mutations Reduce the Sensitivity of a Fluorescence Enzyme Immunoassay. by Tokita H, Kaufmann GR, Matsubayashi M, Okuda I, Tanaka T, Harada H, Mukaide M, Suzuki K, Cooper DA.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87404

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Hepatitis C Virus Core Protein Leads to Immune Suppression and Liver Damage in a Transgenic Murine Model. by Soguero C, Joo M, Chianese-Bullock KA, Nguyen DT, Tung K, Hahn YS.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136450

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Hepatitis C virus genotypes in northern Italy: clinical and virological features. by Ravaggi A, Rossini A, Mazza C, Puoti M, Marin MG, Cariani E.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229411

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Hepatitis C Virus Genotyping Based on 5[prime prime or minute] Noncoding Sequence Analysis (Trugene). by Halfon P, Trimoulet P, Bourliere M, Khiri H, de

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Ledinghen V, Couzigou P, Feryn JM, Alcaraz P, Renou C, Fleury HJ, Ouzan D.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88023 ·

Hepatitis C Virus Genotyping: Interrogation of the 5[prime prime or minute] Untranslated Region Cannot Accurately Distinguish Genotypes 1a and 1b. by Chen Z, Weck KE.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130800

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Hepatitis C Virus Infection is Associated with the Development of Hepatocellular Carcinoma. by Saito I, Miyamura T, Ohbayashi A, Harada H, Katayama T, Kikuchi S, Watanabe Y, Koi S, Onji M, Ohta Y, Choo Q, Houghton M, Kuo G.; 1990 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54573

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Hepatitis C Virus Infections in Dialysis Centers in The Netherlands: a National Survey by Serological and Molecular Methods. by Schneeberger PM, Keur I, van der Vliet W, van Hoek K, Boswijk H, van Loon AM, van Dijk WC, Kauffmann RH, Quint W, van Doorn LJ.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104905

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Hepatitis C virus internal ribosome entry site RNA contains a tertiary structural element in a functional domain of stem --loop II. by Lyons AJ, Lytle JR, Gomez J, Robertson HD.; 2001 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=55737

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Hepatitis C Virus Nonstructural 5A Protein and Interferon Resistance: a New Model for Testing the Reliability of Mutational Analyses. by Sarrazin C, Herrmann E, Bruch K, Zeuzem S.; 2002 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136596

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Hepatitis C virus nonstructural region 5A protein is a potent transcriptional activator. by Kato N, Lan KH, Ono-Nita SK, Shiratori Y, Omata M.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=192353

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Hepatitis C Virus NS3 ATPases/Helicases from Different Genotypes Exhibit Variations in Enzymatic Properties. by Lam AM, Keeney D, Eckert PQ, Frick DN.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=150621

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Hepatitis C Virus Quantitation: Optimization of Strategies for Detecting Low-Level Viremia. by Hofgartner WT, Kant JA, Weck KE.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=86236

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Hepatitis C Virus RNA in Dried Serum Spotted onto Filter Paper Is Stable at Room Temperature. by Abe K, Konomi N.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105116

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Hepatitis C Virus RNA in Southern African Blacks with Hepatocellular Carcinoma. by Bukh J, Miller RH, Kew MC, Purcell RH.; 1993 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45977

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Hepatitis C Virus Serotype-Specific Core and NS4 Antibodies in Injecting Drug Users Participating in the Amsterdam Cohort Studies. by Beld M, Penning M, van Putten M, van den Hoek A, Lukashov V, McMorrow M, Goudsmit J.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105101

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Hepatitis C Virus Subtyping by a Core-Envelope 1-Based Reverse Transcriptase PCR Assay with Sequencing and Its Use in Determining Subtype Distribution among Danish Patients. by Corbet S, Bukh J, Heinsen A, Fomsgaard A.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=150254

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Hepatitis D Virus Genotypes in Intravenous Drug Users in Taiwan: Decreasing Prevalence and Lack of Correlation with Hepatitis B Virus Genotypes. by Kao JH, Chen PJ, Lai MY, Chen DS.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120675

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Hepatitis E Virus (HEV) Capsid Antigens Derived from Viruses of Human and Swine Origin Are Equally Efficient for Detecting Anti-HEV by Enzyme Immunoassay. by Engle RE, Yu C, Emerson SU, Meng XJ, Purcell RH.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=154628

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Hepatitis E Virus Immunoglobulin G Antibodies in Different Populations in Campinas, Brazil. by Goncales NS, Pinho JR, Moreira RC, Saraceni CP, Spina AM, Stucchi RB, Filho AD, Magna LA, Goncales Junior FL.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95961

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Hepatitis G Virus Infection in Amerindians and Other Venezuelan High-Risk Groups. by Pujol FH, Khudyakov YE, Devesa M, Cong ME, Loureiro CL, Blitz L, Capriles F, Beker S, Liprandi F, Fields HA.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104562

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Hepatitis Viruses: Changing Patterns of Human Disease. by Purcell RH.; 1994 Mar 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43379

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Heterogeneity and Seroprevalence of a Newly Identified Avian Hepatitis E Virus from Chickens in the United States. by Huang FF, Haqshenas G, Shivaprasad HL, Guenette DK, Woolcock PR, Larsen CT, Pierson FW, Elvinger F, Toth TE, Meng XJ.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=139663

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High incidence of hepatitis C virus infection in hemodialysis patients in units with high prevalence. by Pujol FH, Ponce JG, Lema MG, Capriles F, Devesa M, Sirit F, Salazar M, Vasquez G, Monsalve F, Blitz-Dorfman L.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229084

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High-level hepatitis B virus replication in transgenic mice. by Guidotti LG, Matzke B, Schaller H, Chisari FV.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189513

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Highly Sensitive Multiplex Assay for Detection of Human Immunodeficiency Virus Type 1 and Hepatitis C Virus RNA. by Giachetti C, Linnen JM, Kolk DP, Dockter J, Gillotte-Taylor K, Park M, Ho-Sing-Loy M, McCormick MK, Mimms LT, McDonough SH.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120571

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High-Throughput Real-Time Reverse Transcription-PCR Quantitation of Hepatitis C Virus RNA. by Martell M, Gomez J, Esteban JI, Sauleda S, Quer J, Cabot B, Esteban R, Guardia J.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=84298

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HLA Class I-Restricted Human Cytotoxic T Cells Recognize Endogenously Synthesized Hepatitis B Virus Nucleocapsid Antigen. by Bertoletti A, Ferrari C, Fiaccadori F, Penna A, Margolskee R, schlicht HJ, Fowler P, Guilhot S, Chisari FV.; 1991 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52945

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HLA-Cw*04 and Hepatitis C Virus Persistence. by Thio CL, Gao X, Goedert JJ, Vlahov D, Nelson KE, Hilgartner MW, O'Brien SJ, Karacki P, Astemborski J, Carrington M, Thomas DL.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136132

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Horizontal Transmission of a Hepatitis B Virus Surface Antigen Mutant. by Chen WN, Oon CJ, Koh S.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=86257

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Human CD4+ T-cell response to hepatitis delta virus: identification of multiple epitopes and characterization of T-helper cytokine profiles. by Nisini R, Paroli M, Accapezzato D, Bonino F, Rosina F, Santantonio T, Sallusto F, Amoroso A, Houghton M, Barnaba V.; 1997 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191332

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Human Immunodeficiency Virus (HIV) Type 1 Reverse Transcriptase Resistance Mutations in Hepatitis B Virus (HBV)-HIV-Coinfected Patients Treated for HBV Chronic Infection Once Daily with 10 Milligrams of Adefovir Dipivoxil Combined with Lamivudine. by Delaugerre C, Marcelin AG, Thibault V, Peytavin G, Bombled T, Bochet MV, Katlama C, Benhamou Y, Calvez V.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=127167

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Human Immunodeficiency Virus Seroconversion and Evolution of the Hepatitis C Virus Quasispecies. by Mao Q, Ray SC, Laeyendecker O, Ticehurst JR, Strathdee SA, Vlahov D, Thomas DL.; 2001 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114119

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Human Immunodeficiency Virus Type 1-Hepatitis C Virus Coinfection: Intraindividual Comparison of Cellular Immune Responses against Two Persistent Viruses. by Lauer GM, Nguyen TN, Day CL, Robbins GK, Flynn T, McGowan K, Rosenberg ES, Lucas M, Klenerman P, Chung RT, Walker BD.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=135971

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Human Monoclonal Antibodies That Inhibit Binding of Hepatitis C Virus E2 Protein to CD81 and Recognize Conserved Conformational Epitopes. by Hadlock KG, Lanford RE, Perkins S, Rowe J, Yang Q, Levy S, Pileri P, Abrignani S, Foung SK.; 2000 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=110915

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Hydrodynamic injection of viral DNA: A mouse model of acute hepatitis B virus infection. by Yang PL, Althage A, Chung J, Chisari FV.; 2002 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129782

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Identification by Phage Display and Characterization of Two Neutralizing Chimpanzee Monoclonal Antibodies to the Hepatitis E Virus Capsid Protein. by Schofield DJ, Glamann J, Emerson SU, Purcell RH.; 2000 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112041

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Identification of a Domain Containing B-Cell Epitopes in Hepatitis C Virus E2 Glycoprotein by Using Mouse Monoclonal Antibodies. by Lee JW, Kim KM, Jung SH, Lee KJ, Choi EC, Sung YC, Kang CY.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=103802

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Identification of a Hepatitis B Virus Genome in Wild Chimpanzees (Pan troglodytes schweinfurthi) from East Africa Indicates a Wide Geographical Dispersion among Equatorial African Primates. by Vartanian JP, Pineau P, Henry M, Hamilton WD, Muller MN, Wrangham RW, Wain-Hobson S.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136620

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Identification of Different States of Hepatitis B Virus Infection with a Quantitative PCR Assay. by Kessler HH, Preininger S, Stelzl E, Daghofer E, Santner BI, Marth E, Lackner H, Stauber RE.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95865

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Identification of Immunodominant and Conformational Epitopes in the Capsid Protein of Hepatitis E Virus by Using Monoclonal Antibodies. by Riddell MA, Li F, Anderson DA.; 2000 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112333

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Identification of numerous hepatitis C virus genotypes in Montreal, Canada. by Bernier L, Willems B, Delage G, Murphy DG.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229409

156 Hepatitis

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Identification of SRPK1 and SRPK2 as the Major Cellular Protein Kinases Phosphorylating Hepatitis B Virus Core Protein. by Daub H, Blencke S, Habenberger P, Kurtenbach A, Dennenmoser J, Wissing J, Ullrich A, Cotten M.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=155132

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Identification of Two Flavivirus-Like Genomes in the GB Hepatitis Agent. by Simons JN, Pilot-Matias TJ, Leary TP, Dawson GJ, Desai SM, Schlauder GG, Muerhoff AS, Erker JC, Buijk SL, Chalmers ML, Sant CL, Mushahwar IK.; 1995 Apr 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42174

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Identification of VP1/2A and 2C as Virulence Genes of Hepatitis A Virus and Demonstration of Genetic Instability of 2C. by Emerson SU, Huang YK, Nguyen H, Brockington A, Govindarajan S, St. Claire M, Shapiro M, Purcell RH.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136972

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Identity of a Novel Swine Hepatitis E Virus in Taiwan Forming a Monophyletic Group with Taiwan Isolates of Human Hepatitis E Virus. by Hsieh SY, Meng XJ, Wu YH, Liu ST, Tam AW, Lin DY, Liaw YF.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=85823

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Immunity in Chimpanzees Chronically Infected with Hepatitis C Virus: Role of Minor Quasispecies in Reinfection. by Wyatt CA, Andrus L, Brotman B, Huang F, Lee DH, Prince AM.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=109459

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Immunization with Surface Antigen Vaccine Alone and after Treatment with 1-(2Fluoro-5-Methyl-[beta]-l-Arabinofuranosyl)-Uracil (l-FMAU) Breaks Humoral and Cell-Mediated Immune Tolerance in Chronic Woodchuck Hepatitis Virus Infection. by Menne S, Roneker CA, Korba BE, Gerin JL, Tennant BC, Cote PJ.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=137055

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Immunogenicity and Tolerogenicity of Hepatitis B Virus Structural and Nonstructural Proteins: Implications for Immunotherapy of Persistent Viral Infections. by Kakimi K, Isogawa M, Chung J, Sette A, Chisari FV.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136410

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Impact of Hepatitis B and Hepatitis C Virus Infections in a Hematology-Oncology Unit at a Children's Hospital in Nicaragua, 1997 to 1999. by Visona K, Baez F, Taylor L, Berrios R, Leon B, Pacheco C, Jiron R, Luftig RB, Somarriba MM.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=119972

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Impact of universal preadolescent vaccination against hepatitis B on antenatal seroprevalence of hepatitis B markers in British Columbia women. by Dawar M, Patrick DM, Bigham M, Cook D, Krajden M, Ng H.; 2003 Mar 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154915

Studies 157

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Importance of Primer Selection for the Detection of Hepatitis C Virus RNA with the Polymerase Chain Reaction Assay. by Bukh J, Purcell RH, Miller RH.; 1992 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48201

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Improved Detection of Hepatitis B Virus Surface Antigen by a New Rapid Automated Assay. by Weber B, Bayer A, Kirch P, Schluter V, Schlieper D, Melchior W.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=85302

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Improved reactivity of hepatitis C virus core protein epitopes in a conformational antigen-presenting system. by Buratti E, Di Michele M, Song P, Monti-Bragadin C, Scodeller EA, Baralle FE, Tisminetzky SG.; 1997 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170488

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Improved Version 2.0 Qualitative and Quantitative AMPLICOR Reverse Transcription-PCR Tests for Hepatitis C Virus RNA: Calibration to International Units, Enhanced Genotype Reactivity, and Performance Characteristics. by Lee SC, Antony A, Lee N, Leibow J, Yang JQ, Soviero S, Gutekunst K, Rosenstraus M.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87559

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In Situ Distribution of Hepatitis C Virus Replicative-Intermediate RNA in Hepatic Tissue and Its Correlation with Liver Disease. by Chang M, Marquardt AP, Wood BL, Williams O, Cotler SJ, Taylor SL, Carithers RL Jr, Gretch DR.; 2000 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=111615

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In Vitro and In Vivo Infectivity and Pathogenicity of the Lymphoid Cell-Derived Woodchuck Hepatitis Virus. by Lew YY, Michalak TI.; 2001 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114086

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In vivo analysis of the 3[prime prime or minute] untranslated region of the hepatitis C virus after in vitro mutagenesis of an infectious cDNA clone. by Yanagi M, St. Claire M, Emerson SU, Purcell RH, Bukh J.; 1999 Mar 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26776

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In vivo antiviral activity and pharmacokinetics of (-)-cis-5-fluoro-1-[2(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine in woodchuck hepatitis virus-infected woodchucks. by Cullen JM, Smith SL, Davis MG, Dunn SE, Botteron C, Cecchi A, Linsey D, Linzey D, Frick L, Paff MT, Goulding A, Biron K.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=164073

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In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus. by Bordier BB, Ohkanda J, Liu P, Lee SY, Salazar FH, Marion PL, Ohashi K, Meuse L, Kay MA, Casey JL, Sebti SM, Hamilton AD, Glenn JS.; 2003 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166292

158 Hepatitis

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In Vivo Inhibition of Anti-Hepatitis B Virus Core Antigen (HBcAg) Immunoglobulin G Production by HBcAg-Specific CD4 + Th1-Type T-Cell Clones in a hu-PBLNOD/SCID Mouse Model. by Cao T, Meuleman P, Desombere I, Sallberg M, LerouxRoels G.; 2001 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114731

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Incidence and risk factors for hepatitis C among injection drug users in Baltimore, Maryland. by Villano SA, Vlahov D, Nelson KE, Lyles CM, Cohn S, Thomas DL.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230161

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Incidence of hepatitis C virus infection among injection drug users during an outbreak of HIV infection. by Patrick DM, Tyndall MW, Cornelisse PG, Li K, Sherlock CH, Rekart ML, Strathdee SA, Currie SL, Schechter MT, O'Shaughnessy MV.; 2001 Oct 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81496

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Incidence of seroconversion to positivity for hepatitis C antibody in repeat blood donors in England, 1993-5. by Soldan K, Barbara JA, Heptonstall J.; 1998 May 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28537

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Increased prevalence of genotype F hepatitis B virus isolates in Buenos Aires, Argentina. by Telenta PF, Poggio GP, Lopez JL, Gonzalez J, Lemberg A, Campos RH.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229861

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Indeterminate results of the second-generation hepatitis C virus (HCV) recombinant immunoblot assay: significance of high-level c22-3 reactivity and influence of HCV genotypes. by Zein NN, Germer JJ, Wendt NK, Schimek CM, Thorvilson JN, Mitchell PS, Persing DH.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229567

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Induction of macrophage procoagulant activity by murine hepatitis virus strain 3: role of tyrosine phosphorylation. by Dackiw AP, Zakrzewski K, Nathens AB, Cheung PY, Fingerote R, Levy GA, Rotstein OD.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189451

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Infection with HIV and hepatitis C virus among injecting drug users in a prevention setting: retrospective cohort study. by van Beek I, Dwyer R, Dore GJ, Luo K, Kaldor JM.; 1998 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28635

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Influence of hepatitis C virus (HCV) genotypes on HCV recombinant immunoblot assay patterns. by Pawlotsky JM, Roudot-Thoraval F, Pellet C, Aumont P, Darthuy F, Remire J, Duval J, Dhumeaux D.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228164

Studies 159

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Inhibition of duck hepatitis B virus replication by 2',3'-dideoxy-3'-fluoroguanosine in vitro and in vivo. by Hafkemeyer P, Keppler-Hafkemeyer A, al Haya MA, von JantaLipinski M, Matthes E, Lehmann C, Offensperger WB, Offensperger S, Gerok W, Blum HE.; 1996 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=163202

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Interferon alfa with or without ribavirin for chronic hepatitis C: systematic review of randomised trials. by Kjaergard LL, Krogsgaard K, Gluud C.; 2001 Nov 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59848

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Interferon Resistance of Hepatitis C Virus Genotype 1b: Relationship to Nonstructural 5A Gene Quasispecies Mutations. by Pawlotsky JM, Germanidis G, Neumann AU, Pellerin M, Frainais PO, Dhumeaux D.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=109724

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Intrahepatic Genetic Inoculation of Hepatitis C Virus RNA Confers Cross-Protective Immunity. by Weiner AJ, Paliard X, Selby MJ, Medina-Selby A, Coit D, Nguyen S, Kansopon J, Arian CL, Ng P, Tucker J, Lee CT, Polakos NK, Han J, Wong S, Lu HH, Rosenberg S, Brasky KM, Chien D, Kuo G, Houghton M.; 2001 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114443

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Introduction of a new hepatitis agent in retrospect: genetic studies of Swedish hepatitis D virus strains. by Zhang YY, Hansson BG.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229391

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Kinetics and Significance of Serum Hepatitis C Virus Core Antigen in Patients with Acute Hepatitis C. by Cividini A, Cerino A, Muzzi A, Furione M, Rebucci C, Segagni L, Gatti M, Barnaba V, Mondelli MU.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154695

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Kinetics of CD4 + and CD8 + Memory T-Cell Responses during Hepatitis C Virus Rechallenge of Previously Recovered Chimpanzees. by Nascimbeni M, Mizukoshi E, Bosmann M, Major ME, Mihalik K, Rice CM, Feinstone SM, Rehermann B.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=152131

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Labor and Cost Requirements of Two Commercial Assays for Qualitative Molecular Detection of Hepatitis C Virus. by Schrijver I, Baron EJ.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130744

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Laboratory Assays for Diagnosis and Management of Hepatitis C Virus Infection. by Richter SS.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=154655

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Lack of detection of negative-strand hepatitis C virus RNA in peripheral blood mononuclear cells and other extrahepatic tissues by the highly strand-specific rTth reverse transcriptase PCR. by Lanford RE, Chavez D, Chisari FV, Sureau C.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189758

160 Hepatitis

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Lack of evidence for hepatitis G virus replication in the livers of patients coinfected with hepatitis C and G viruses. by Laskus T, Radkowski M, Wang LF, Vargas H, Rakela J.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=192133

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Lack of Tumor Necrosis Factor Alpha Induces Impaired Proliferation of Hepatitis B Virus-Specific Cytotoxic T Lymphocytes. by Kasahara S, Ando K, Saito K, Sekikawa K, Ito H, Ishikawa T, Ohnishi H, Seishima M, Kakumu S, Moriwaki H.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=141095

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Lactoferrin Protects against Development of Hepatitis Caused by Sensitization of Kupffer Cells by Lipopolysaccharide. by Yamaguchi M, Matsuura M, Kobayashi K, Sasaki H, Yajima T, Kuwata T.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=96255

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Levels of hepatitis C virus (HCV) RNA in serum and their relationship to levels of immunoglobulin M and G antibodies against HCV core protein. by Chen M, Sonnerborg A, Sallberg M.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228037

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Line Probe Assay for Monitoring Drug Resistance in Hepatitis B Virus-Infected Patients during Antiviral Therapy. by Stuyver L, Van Geyt C, De Gendt S, Van Reybroeck G, Zoulim F, Leroux-Roels G, Rossau R.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=86181

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Liver-Specific Alpha 2 Interferon Gene Expression Results in Protection from Induced Hepatitis. by Aurisicchio L, Delmastro P, Salucci V, Paz OG, Rovere P, Ciliberto G, La Monica N, Palombo F.; 2000 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112004

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Longitudinal Evaluation of the Structure of Replicating and Circulating Hepatitis C Virus Quasispecies in Nonprogressive Chronic Hepatitis C Patients. by Cabot B, Martell M, Esteban JI, Piron M, Otero T, Esteban R, Guardia J, Gomez J.; 2001 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=116096

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Long-Term Evolution of the Hypervariable Region of Hepatitis C Virus in a Common-Source-Infected Cohort. by McAllister J, Casino C, Davidson F, Power J, Lawlor E, Yap PL, Simmonds P, Smith DB.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=110045

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Long-Term Follow-Up of Chimpanzees Inoculated with the First Infectious Clone for Hepatitis C Virus. by Major ME, Mihalik K, Fernandez J, Seidman J, Kleiner D, Kolykhalov AA, Rice CM, Feinstone SM.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104096

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Long-term serologic follow-up of hepatitis C virus-seropositive homosexual men. by Ndimbie OK, Nedjar S, Kingsley L, Riddle P, Rinaldo C.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170131

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Loss of resistance to murine hepatitis virus strain 3 infection after treatment with corticosteroids is associated with induction of macrophage procoagulant activity. by Fingerote RJ, Abecassis M, Phillips MJ, Rao YS, Cole EH, Leibowitz J, Levy GA.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190359

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Low frequency of mutations in the core promoter and precore regions of hepatitis B virus in anti-HBe positive Brazilian carriers. by Castro LD, Niel C, Gomes SA.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=35280

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Low prevalence of liver-kidney microsomal autoantibodies of type 1 (LKM1) in hepatitis C seropositive subjects on Crete, Greece. by Drygiannakis D, Lionis C, Drygiannakis I, Pappas G, Kouroumalis E.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33343

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Low-Level Viremia and Intracellular Expression of Hepatitis B Surface Antigen (HBsAg) in HBsAg Carriers with Concurrent Hepatitis C Virus Infection. by Chu CM, Yeh CT, Liaw YF.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104984

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Mapping B-Cell Epitopes of Hepatitis C Virus E2 Glycoprotein Using Human Monoclonal Antibodies from Phage Display Libraries. by Bugli F, Mancini N, Kang CY, Di Campli C, Grieco A, Manzin A, Gabrielli A, Gasbarrini A, Fadda G, Varaldo PE, Clementi M, Burioni R.; 2001 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114571

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Markedly Prolonged Incubation Period of Hepatitis B in a Chimpanzee Passively Immunized with a Human Monoclonal Antibody to the a Determinant of Hepatitis B Surface Antigen. by Ogata N, Ostberg L, Ehrlich PH, Wong DC, Miller RH, Purcell RH.; 1993 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46227

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Mechanism of Suppression of Hepatitis B Virus Precore RNA Transcription by a Frequent Double Mutation. by Li J, Buckwold VE, Hon MW, Ou JH.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=103946

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Metabolic Labeling of Woodchuck Hepatitis B Virus X Protein in Naturally Infected Hepatocytes Reveals a Bimodal Half-Life and Association with the Nuclear Framework. by Dandri M, Petersen J, Stockert RJ, Harris TM, Rogler CE.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=110361

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Mimicry of the immunodominant conformation-dependent antigenic site of hepatitis A virus by motifs selected from synthetic peptide libraries. by Mattioli S, Imberti L, Stellini R, Primi D.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189366

162 Hepatitis

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Molecular and Immunological Significance of Chimpanzee Major Histocompatibility Complex Haplotypes for Hepatitis C Virus Immune Response and Vaccination Studies. by Mizukoshi E, Nascimbeni M, Blaustein JB, Mihalik K, Rice CM, Liang TJ, Feinstone SM, Rehermann B.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136197

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Molecular Characteristic-Based Epidemiology of Hepatitis B, C, and E Viruses and GB Virus C/Hepatitis G Virus in Myanmar. by Nakai K, Win KM, Oo SS, Arakawa Y, Abe K.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87966

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Molecular Characterization of Hepatitis A Virus Isolates from a Transcontinental Shellfish-Borne Outbreak. by Sanchez G, Pinto RM, Vanaclocha H, Bosch A.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=139673

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Molecular Epidemiology of an Outbreak of Fulminant Hepatitis B. by Petrosillo N, Ippolito G, Solforosi L, Varaldo PE, Clementi M, Manzin A.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87163

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Molecular Epidemiology of Hepatitis B Virus Variants in Nonhuman Primates. by Grethe S, Heckel JO, Rietschel W, Hufert FT.; 2000 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=110896

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Molecular Epidemiology of Hepatitis C Virus Infection in an Area of Hyperendemicity in Southern Italy: a Population-Based Study. by Osella AR, Sonzogni L, Cavallini A, Foti L, Guerra V, Di Leo A, Mondelli MU, Misciagna G, Silini EM.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=85170

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Molecular Evidence of Male-to-Female Sexual Transmission of Hepatitis C Virus after Vaginal and Anal Intercourse. by Halfon P, Riflet H, Renou C, Quentin Y, Cacoub P.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87908

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Molecular Evolution of Hepatitis A Virus: a New Classification Based on the Complete VP1 Protein. by Costa-Mattioli M, Cristina J, Romero H, Perez-Bercof R, Casane D, Colina R, Garcia L, Vega I, Glikman G, Romanowsky V, Castello A, Nicand E, Gassin M, Billaudel S, Ferre V.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136434

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Monitoring Drug Resistance in Chronic Hepatitis B Virus (HBV)-Infected Patients during Lamivudine Therapy: Evaluation of Performance of INNO-LiPA HBV DR Assay. by Lok AS, Zoulim F, Locarnini S, Mangia A, Niro G, Decraemer H, Maertens G, Hulstaert F, De Vreese K, Sablon E.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130856

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Monitoring the Emergence of Hepatitis B Virus Polymerase Gene Variants during Lamivudine Therapy Using the LightCycler. by Whalley SA, Brown D, Teo CG, Dusheiko GM, Saunders NA.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87954

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Mother to child transmission of hepatitis C virus: prospective study of risk factors and timing of infection in children born to women seronegative for HIV-1. by Resti M, Azzari C, Mannelli F, Moriondo M, Novembre E, de Martino M, Vierucci A.; 1998 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28636

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Multigene Tracking of Hepatitis C Virus Quasispecies after Liver Transplantation: Correlation of Genetic Diversification in the Envelope Region with Asymptomatic or Mild Disease Patterns. by Sullivan DG, Wilson JJ, Carithers RL Jr, Perkins JD, Gretch DR.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=110527

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Murine Coronavirus Spike Protein Determines the Ability of the Virus To Replicate in the Liver and Cause Hepatitis. by Navas S, Seo SH, Chua MM, Sarma JD, Lavi E, Hingley ST, Weiss SR.; 2001 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114828

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Murine Coronavirus-Induced Hepatitis: JHM Genetic Background Eliminates A59 Spike-Determined Hepatotropism. by Navas S, Weiss SR.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=152168

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Nested Restriction Site-Specific PCR To Detect and Type Hepatitis C Virus (HCV): a Rapid Method To Distinguish HCV Subtype 1b from Other Genotypes. by Krekulova L, Rehak V, Wakil AE, Harris E, Riley LW.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88024

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New Enzyme Immunoassay for Detection of Hepatitis B Virus Core Antigen (HBcAg) and Relation between Levels of HBcAg and HBV DNA. by Kimura T, Rokuhara A, Matsumoto A, Yagi S, Tanaka E, Kiyosawa K, Maki N.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154683

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New, ultrasensitive enzyme immunoassay for detecting vaccine- and disease-induced hepatitis A virus-specific immunoglobulin G in saliva. by Ochnio JJ, Scheifele DW, Ho M, Mitchell LA.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229518

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Nondeletional T-Cell Receptor Transgenic Mice: Model for the CD4 + T-Cell Repertoire in Chronic Hepatitis B Virus Infection. by Chen M, Sallberg M, Thung SN, Hughes J, Jones J, Milich DR.; 2000 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112280

164 Hepatitis

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Nonenveloped Nucleocapsids of Hepatitis C Virus in the Serum of Infected Patients. by Maillard P, Krawczynski K, Nitkiewicz J, Bronnert C, Sidorkiewicz M, Gounon P, Dubuisson J, Faure G, Crainic R, Budkowska A.; 2001 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=115068

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Nonrandom Distribution of Hepatitis C Virus Quasispecies in Plasma and Peripheral Blood Mononuclear Cell Subsets. by Afonso AM, Jiang J, Penin F, Tareau C, Samuel D, Petit MA, Bismuth H, Dussaix E, Feray C.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112955

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Novel Approach To Reduce the Hepatitis C Virus (HCV) Window Period: Clinical Evaluation of a New Enzyme-Linked Immunosorbent Assay for HCV Core Antigen. by Icardi G, Ansaldi F, Bruzzone BM, Durando P, Lee S, de Luigi C, Crovari P.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88305

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Nuclear Covalently Closed Circular Viral Genomic DNA in the Liver of Hepatocyte Nuclear Factor 1[alpha]-Null Hepatitis B Virus Transgenic Mice. by Raney AK, Eggers CM, Kline EF, Guidotti LG, Pontoglio M, Yaniv M, McLachlan A.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=115916

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Nucleotide and Amino Acid Complexity of Hepatitis C Virus Quasispecies in Serum and Liver. by Cabot B, Martell M, Esteban JI, Sauleda S, Otero T, Esteban R, Guardia J, Gomez J.; 2000 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=111600

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Obesity increases sensitivity to endotoxin liver injury: Implications for the pathogenesis of steatohepatitis. by Yang SQ, Lin HZ, Lane MD, Clemens M, Diehl AM.; 1997 Mar 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20127

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Observational study of vaccine efficacy 14 years after trial of hepatitis B vaccination in Gambian children. by Whittle H, Jaffar S, Wansbrough M, Mendy M, Dumpis U, Collinson A, Hall A.; 2002 Sep 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124550

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Occult Hepatitis B Virus Infection and Clinical Outcomes of Patients with Chronic Hepatitis C. by Kao JH, Chen PJ, Lai MY, Chen DS.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=139665

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Opposing roles of STAT1 and STAT3 in T cell --mediated hepatitis: regulation by SOCS. by Hong F, Jaruga B, Kim WH, Radaeva S, El-Assal ON, Tian Z, Nguyen VA, Gao B.; 2002 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151811

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Outbreak of Nosocomial Hepatitis C Virus Infection Resolved by Genetic Analysis of HCV RNA. by Bruguera M, Saiz JC, Franco S, Gimenez-Barcons M, Sanchez-Tapias JM, Fabregas S, Vega R, Camps N, Dominguez A, Salleras L.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=139636

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Overestimation of the Hepatitis C Virus RNA Content of Reference Preparations by the AMPLICOR HCV Monitor Test, Version 2.0. by Pisani G, Cristiano K, Wirz M, Bisso GM, Gentili G.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=154603

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Partial nucleotide sequencing of six subtype 2c hepatitis C viruses detected in Italy. by Cammarota G, Maggi F, Vatteroni ML, Da Prato L, Barsanti L, Bendinelli M, Pistello M.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228577

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Past and Present Hepatitis G Virus Infections in Areas Where Hepatitis C is Highly Endemic and Those Where It Is Not Endemic. by Tanaka E, Tacke M, Kobayashi M, Nakatsuji Y, Kiyosawa K, Schmolke S, Engel AM, Hess G, Alter HJ.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=124818

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Past infection with hepatitis A virus among Vancouver street youth, injection drug users and men who have sex with men: implications for vaccination programs. by Ochnio JJ, Patrick D, Ho M, Talling DN, Dobson SR.; 2001 Aug 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81329

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Pattern of disease after murine hepatitis virus strain 3 infection correlates with macrophage activation and not viral replication. by Pope M, Rotstein O, Cole E, Sinclair S, Parr R, Cruz B, Fingerote R, Chung S, Gorczynski R, Fung L.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189358

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Performance of the COBAS AMPLICOR HCV MONITOR Test, Version 2.0, an Automated Reverse Transcription-PCR Quantitative System for Hepatitis C Virus Load Determination. by Gerken G, Rothaar T, Rumi MG, Soffredini R, Trippler M, Blunk MJ, Butcher A, Soviero S, Colucci G.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=86766

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Persistent hepatitis and enterocolitis in germfree mice infected with Helicobacter hepaticus. by Fox JG, Yan L, Shames B, Campbell J, Murphy JC, Li X.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174280

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Persistent Hepatitis C Virus Infection in a Chimpanzee is Associated with Emergence of a Cytotoxic T Lymphocyte Escape Variant. by Weiner A, Erickson AL, Kansopon J, Crawford K, Muchmore E, Hughes AL, Houghton M, Walker CM.; 1995 Mar 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42297

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Pharmacokinetics, Safety, and Antiviral Effects of Hypericin, a Derivative of St. John's Wort Plant, in Patients with Chronic Hepatitis C Virus Infection. by Jacobson JM, Feinman L, Liebes L, Ostrow N, Koslowski V, Tobia A, Cabana BE, Lee DH, Spritzler J, Prince AM.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90321

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Pharmacology of [beta]-l-Thymidine and [beta]-l-2[prime prime or minute]Deoxycytidine in HepG2 Cells and Primary Human Hepatocytes: Relevance to Chemotherapeutic Efficacy against Hepatitis B Virus. by Hernandez-Santiago B,

166 Hepatitis

Placidi L, Cretton-Scott E, Faraj A, Bridges EG, Bryant ML, Rodriguez-Orengo J, Imbach JL, Gosselin G, Pierra C, Dukhan D, Sommadossi JP.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=127241 ·

Phosphorylation of the hepatitis delta virus antigens. by Bichko V, Barik S, Taylor J.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191080

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Phylogenetic Origin of Hepatitis B Virus Strains with Precore C-1858 Variant. by Alestig E, Hannoun C, Horal P, Lindh M.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88319

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Physicians' preference values for hepatitis C health states and antiviral therapy: A survey. by Patil R, Cotler SJ, Banaad-Omiotek G, McNutt RA, Brown MD, Cotler S, Jensen DM.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=37537

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Polyphyletic Strains of Hepatitis E Virus Are Responsible for Sporadic Cases of Acute Hepatitis in Japan. by Mizuo H, Suzuki K, Takikawa Y, Sugai Y, Tokita H, Akahane Y, Itoh K, Gotanda Y, Takahashi M, Nishizawa T, Okamoto H.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130758

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Posttranscriptional Inhibition of Class I Major Histocompatibility Complex Presentation on Hepatocytes and Lymphoid Cells in Chronic Woodchuck Hepatitis Virus Infection. by Michalak TI, Hodgson PD, Churchill ND.; 2000 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=111969

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Preclinical evaluation of AMPLICOR hepatitis C virus test for detection of hepatitis C virus RNA. by Nolte FS, Thurmond C, Fried MW.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228267

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Precore mutant of hepatitis B virus prevails in acute and chronic infections in an area in which hepatitis B is endemic. by Chu CM, Yeh CT, Chiu CT, Sheen IS, Liaw YF.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229124

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Precore Stop Mutant in HBeAg-Positive Patients with Chronic Hepatitis B: Clinical Characteristics and Correlation with the Course of HBeAg-to-Anti-HBe Seroconversion. by Chu CM, Yeh CT, Lee CS, Sheen IS, Liaw YF.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120083

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Presence of Oligoclonal T Cells in Cerebrospinal Fluid of a Child with Multiphasic Disseminated Encephalomyelitis following Hepatitis A Virus Infection. by Oleszak EL, Lin WL, Legido A, Melvin J, Hardison H, Hoffman BE, Katsetos CD, Platsoucas CD.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=96183

Studies 167

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Prevalence of antibodies to hepatitis B, hepatitis C, and HIV and risk factors in entrants to Irish prisons: a national cross sectional survey. by Long J, Allwright S, Barry J, Reynolds SR, Thornton L, Bradley F, Parry JV.; 2001 Nov 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59992

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Prevalence of antibodies to hepatitis B, hepatitis C, and HIV and risk factors in Irish prisoners: results of a national cross sectional survey. by Allwright S, Bradley F, Long J, Barry J, Thornton L, Parry JV.; 2000 Jul 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27426

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Prevalence of Antibodies to Hepatitis E Virus in Veterinarians Working with Swine and in Normal Blood Donors in the United States and Other Countries. by Meng XJ, Wiseman B, Elvinger F, Guenette DK, Toth TE, Engle RE, Emerson SU, Purcell RH.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120098

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Prevalence of GB Virus C (Also Called Hepatitis G Virus) Markers in Norwegian Blood Donors. by Nordbo SA, Krokstad S, Winge P, Skjeldestad FE, Dalen AB.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=86975

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Prevalence of GB Virus C/Hepatitis G Virus Infection among Various Populations in Surabaya, Indonesia, and Identification of Novel Groups of Sequence Variants. by Handajani R, Soetjipto, Lusida MI, Suryohudoyo P, Adi P, Setiawan PB, Nidom CA, Soemarto R, Katayama Y, Fujii M, Hotta H.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=86171

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Prevalence of hepatitis B and C markers in high-risk hospitalised patients in Crete: a five-year observational study. by Koulentaki M, Ergazaki M, Moschandrea J, Spanoudakis S, Tzagarakis N, Drandakis PE, Spandidos DA, Kouroumalis EA.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64645

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Prevalence of Hepatitis E Virus Antibodies in Canadian Swine Herds and Identification of a Novel Variant of Swine Hepatitis E Virus. by Yoo D, Willson P, Pei Y, Hayes MA, Deckert A, Dewey CE, Friendship RM, Yoon Y, Gottschalk M, Yason C, Giulivi A.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=96251

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Prevalence of hepatitis G viremia among healthy subjects, individuals with liver disease, and persons at risk for parenteral transmission. by Feucht HH, Zollner B, Polywka S, Knodler B, Schroter M, Nolte H, Laufs R.; 1997 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229669

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Prevention of Hepatitis C Virus Infection in Chimpanzees After Antibody-Mediated in vitro Neutralization. by Farci P, Alter HJ, Wong DC, Miller RH, Govindarajan S, Engle R, Shapiro M, Purcell RH.; 1994 Aug 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44488

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Prevention of hepatitis C virus infection in chimpanzees by hyperimmune serum against the hypervariable region 1 of the envelope 2 protein. by Farci P, Shimoda A, Wong D, Cabezon T, De Gioannis D, Strazzera A, Shimizu Y, Shapiro M, Alter HJ, Purcell RH.; 1996 Dec 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26415

168 Hepatitis

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Previously Infected and Recovered Chimpanzees Exhibit Rapid Responses That Control Hepatitis C Virus Replication upon Rechallenge. by Major ME, Mihalik K, Puig M, Rehermann B, Nascimbeni M, Rice CM, Feinstone SM.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136282

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Production and Characterization of Monoclonal Antibodies Specific for a Conserved Epitope within Hepatitis C Virus Hypervariable Region 1. by Li C, Candotti D, Allain JP.; 2001 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=116137

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Prospective Characterization of Full-Length Hepatitis C Virus NS5A Quasispecies during Induction and Combination Antiviral Therapy. by Nousbaum JB, Polyak SJ, Ray SC, Sullivan DG, Larson AM, Carithers RL Jr, Gretch DR.; 2000 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=102099

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Prospective Comparison of Whole-Blood- and Plasma-Based Hepatitis C Virus RNA Detection Systems: Improved Detection Using Whole Blood as the Source of Viral RNA. by Stapleton JT, Klinzman D, Schmidt WN, Pfaller MA, Wu P, LaBrecque DR, Han JQ, Phillips MJ, Woolson R, Alden B.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=84440

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Prospective Multicenter Clinical Evaluation of AMPLICOR and COBAS AMPLICOR Hepatitis C Virus Tests. by Nolte FS, Fried MW, Shiffman ML, Ferreira-Gonzalez A, Garrett CT, Schiff ER, Polyak SJ, Gretch DR.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88479

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Protection against Woodchuck Hepatitis Virus (WHV) Infection by Gene Gun Coimmunization with WHV Core and Interleukin-12. by Garcia-Navarro R, BlancoUrgoiti B, Berraondo P, Sanchez de la Rosa R, Vales A, Hervas-Stubbs S, Lasarte JJ, Borras F, Ruiz J, Prieto J.; 2001 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114475

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Protective immunity against murine hepatitis virus (MHV) induced by intranasal or subcutaneous administration of hybrids of tobacco mosaic virus that carries an MHV epitope. by Koo M, Bendahmane M, Lettieri GA, Paoletti AD, Lane TE, Fitchen JH, Buchmeier MJ, Beachy RN.; 1999 Jul 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22137

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Purification of a baculovirus-expressed hepatitis E virus structural protein and utility in an enzyme-linked immunosorbent assay. by He J, Ching WM, Yarbough P, Wang H, Carl M.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228694

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Qualitative Detection of Hepatitis C Virus RNA: Comparison of Analytical Sensitivity, Clinical Performance, and Workflow of the Cobas Amplicor HCV Test Version 2.0 and the HCV RNA Transcription-Mediated Amplification Qualitative Assay. by Krajden M, Ziermann R, Khan A, Mak A, Leung K, Hendricks D, Comanor L.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120657

Studies 169

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Quantification of Hepatitis C Virus in Human Liver and Serum Samples by Using LightCycler Reverse Transcriptase PCR. by White PA, Pan Y, Freeman AJ, Marinos G, Ffrench RA, Lloyd AR, Rawlinson WD.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=139708

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Quantification of hepatitis C virus RNA by competitive amplification of RNA from denatured serum and hybridization on microtiter plates. by Ravaggi A, Zonaro A, Mazza C, Albertini A, Cariani E.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=227929

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Quantitation of Immunoglobulin to Hepatitis E Virus by Enzyme Immunoassay. by Innis BL, Seriwatana J, Robinson RA, Shrestha MP, Yarbough PO, Longer CF, Scott RM, Vaughn DW, Myint KS.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=120005

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Quantitative Detection of Hepatitis B Virus by Transcription-Mediated Amplification and Hybridization Protection Assay. by Kamisango K, Kamogawa C, Sumi M, Goto S, Hirao A, Gonzales F, Yasuda K, Iino S.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=84293

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Quantitative Detection of Hepatitis B Virus DNA by Real-Time Nucleic Acid Sequence-Based Amplification with Molecular Beacon Detection. by Yates S, Penning M, Goudsmit J, Frantzen I, van de Weijer B, van Strijp D, van Gemen B.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88403

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Quantitative Detection of Hepatitis C Virus RNA by Light Cycler PCR and Comparison with Two Different PCR Assays. by Schroter M, Zollner B, Schafer P, Laufs R, Feucht HH.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87816

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Rapid reverse transcription-PCR detection of hepatitis C virus RNA in serum by using the TaqMan fluorogenic detection system. by Morris T, Robertson B, Gallagher M.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229436

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Rate of Hepatitis B Virus Infection in Pregnant Women Determined by a Monoclonal Hepatitis B Surface Antigen Immunoassay. by Gotstein MG, Aide PM, Coleman PF, Sanborn MR.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130673

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Rebound of Hepatitis B Virus Replication in HepG2 Cells after Cessation of Antiviral Treatment. by Abdelhamed AM, Kelley CM, Miller TG, Furman PA, Isom HC.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=155168

170 Hepatitis

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Recent High Incidence of Fulminant Hepatitis in Samara, Russia: Molecular Analysis of Prevailing Hepatitis B and D Virus Strains. by Flodgren E, Bengtsson S, Knutsson M, Strebkova EA, Kidd AH, Alexeyev OA, Kidd-Ljunggren K.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87379

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Reciprocal Interaction of Human Immunodeficiency Virus and Hepatitis C Virus Infections. by Nelson KE, Thomas DL.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=96162

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Recognition of Multiple Classes of Hepatitis C Antibodies Increases Detection Sensitivity in Oral Fluid. by Zmuda JF, Wagoneer B, Liotta L, Whiteley G.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=96260

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Recombinant Hepatitis A Virus Antigen: Improved Production and Utility in Diagnostic Immunoassays. by LaBrecque FD, LaBrecque DR, Klinzman D, Perlman S, Cederna JB, Winokur PL, Han JQ, Stapleton JT.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104969

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Recombinant vaccinia viruses expressing hepatitis A virus structural polypeptides: detection of an anti-VP0 response in convalescent-phase sera. by Karayiannis P, O'Rourke S, Watts R, Waters J, Hill V, Carman WF, Thomas HC.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170226

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Reduced antibody reactivity to hepatitis C virus antigens in hemodialysis patients coinfected with hepatitis B virus. by Devesa M, Khudyakov YE, Capriles F, Blitz L, Fields HA, Liprandi F, Pujol FH.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170632

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Relative Sensitivity of Hepatitis B Virus and Other Hepatotropic Viruses to the Antiviral Effects of Cytokines. by McClary H, Koch R, Chisari FV, Guidotti LG.; 2000 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=111707

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Release of Virus from Lymphoid Tissue Affects Human Immunodeficiency Virus Type 1 and Hepatitis C Virus Kinetics in the Blood. by Muller V, Maree AF, De Boer RJ.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=115882

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Relevance of Reactivity in Commercially Available Hepatitis C Virus Antibody Assays. by Polywka S, Schroter M, Feucht HH, Zollner B, Laufs R.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87996

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Reliability of methods for hepatitis B virus DNA detection. by Quint WG, Heijtink RA, Schirm J, Gerlich WH, Niesters HG.; 1995 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=227915

Studies 171

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Replication Advantage and Host Factor-Independent Phenotypes Attributable to a Common Naturally Occurring Capsid Mutation (I97L) in Human Hepatitis B Virus. by Suk FM, Lin MH, Newman M, Pan S, Chen SH, Liu JD, Shih C.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136898

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Replication of GB Virus C (Hepatitis G Virus) in Interferon-Resistant Daudi Cells. by Shimizu YK, Hijikata M, Kiyohara T, Kitamura Y, Yoshikura H.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112859

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Replication of Naturally Occurring Woodchuck Hepatitis Virus Deletion Mutants in Primary Hepatocyte Cultures and after Transmission to Naive Woodchucks. by Lu M, Hilken G, Yang D, Kemper T, Roggendorf M.; 2001 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114872

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Reverse transcription-PCR detection of hepatitis G virus. by Schlueter V, Schmolke S, Stark K, Hess G, Ofenloch-Haehnle B, Engel AM.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229381

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Ribavirin Quantification in Combination Treatment of Chronic Hepatitis C. by Larrat S, Stanke-Labesque F, Plages A, Zarski JP, Bessard G, Souvignet C.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=149002

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Risk factors for hepatitis B virus infection in Rio de Janeiro, Brazil. by Lewis-Ximenez LL, do O KM, Ginuino CF, Silva JC, Schatzmayr HG, Stuver S, Yoshida CF.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140010

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Risk factors for hepatitis C virus infection among blood donors in southern Brazil: a case-control study. by Brandao AB, Costa Fuchs S.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122085

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Risk factors for hepatitis C virus infection among street youths. by Roy E, Haley N, Leclerc P, Boivin JF, Cedras L, Vincelette J.; 2001 Sep 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81413

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SCID/NCr Mice Naturally Infected with Helicobacter hepaticus Develop Progressive Hepatitis, Proliferative Typhlitis, and Colitis. by Li X, Fox JG, Whary MT, Yan L, Shames B, Zhao Z.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=108686

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Screening for Hepatitis C Virus in Human Immunodeficiency Virus-Infected Individuals. by Thio CL, Nolt KR, Astemborski J, Vlahov D, Nelson KE, Thomas DL.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=86151

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Search for Hepatitis C Virus Negative-Strand RNA Sequences and Analysis of Viral Sequences in the Central Nervous System: Evidence of Replication. by Radkowski M, Wilkinson J, Nowicki M, Adair D, Vargas H, Ingui C, Rakela J, Laskus T.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136845

172 Hepatitis

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Semiautomated Quantification of Hepatitis B Virus DNA in a Routine Diagnostic Laboratory. by Kessler HH, Stelzl E, Daghofer E, Santner BI, Marth E, Lackner H, Stauber RE.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95971

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Sensitive Enzyme Immunoassay for Hepatitis B Virus Core-Related Antigens and Their Correlation to Virus Load. by Kimura T, Rokuhara A, Sakamoto Y, Yagi S, Tanaka E, Kiyosawa K, Maki N.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=153363

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Sequence Analysis of the Core Gene of 14 Hepatitis C Virus Genotypes. by Bukh J, Purcell RH, Miller RH.; 1994 Aug 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44581

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Sequence variation within a nonstructural region of the hepatitis G virus genome. by Khudyakov YE, Cong ME, Bonafonte MT, Abdulmalek S, Nichols BL, Lambert S, Alter MJ, Fields HA.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191969

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Serodiagnosis of Hepatitis C Virus (HCV) Infection with an HCV Core Protein Molecularly Expressed by a Recombinant Baculovirus. by Chiba J, Ohba H, Matsuura Y, Watanabe Y, Katayama T, Kikuchi S, Saito I, Miyamura T.; 1991 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51721

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Seroepidemiology of Water-Borne Hepatitis in India and Evidence for a Third Enterically-Transmitted Hepatitis Agent. by Arankalle VA, Chadha MS, Tsarev SA, Emerson SU, Risbud AR, Banerjee K, Purcell RH.; 1994 Apr 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43590

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Serological determination of hepatitis C virus genotype: comparison with a standardized genotyping assay. by Pawlotsky JM, Prescott L, Simmonds P, Pellet C, Laurent-Puig P, Labonne C, Darthuy F, Remire J, Duval J, Buffet C, Etienne JP, Dhumeaux D, Dussaix E.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229831

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Serological Determination of Hepatitis C Virus Subtypes 1a, 1b, 2a, 2b, 3a, and 4a by a Recombinant Immunoblot Assay. by Schroter M, Feucht HH, Schafer P, Zollner B, Laufs R.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=85286

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Serological reactivity and viral genotypes in hepatitis C virus infection. by Maggi F, Vatteroni ML, Pistello M, Avio CM, Cecconi N, Panicucci F, Bendinelli M.; 1995 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=227910

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Seroreactivity to hepatitis E virus in areas where the disease is not endemic. by Thomas DL, Yarbough PO, Vlahov D, Tsarev SA, Nelson KE, Saah AJ, Purcell RH.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=232737

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Significance of indeterminate third-generation hepatitis C virus recombinant immunoblot assay. by Pawlotsky JM, Bastie A, Pellet C, Remire J, Darthuy F, Wolfe L, Sayada C, Duval J, Dhumeaux D.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228735

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Significant Closure of the Human Immunodeficiency Virus Type 1 and Hepatitis C Virus Preseroconversion Detection Windows with a Transcription-MediatedAmplification-Driven Assay. by Kolk DP, Dockter J, Linnen J, Ho-Sing-Loy M, GillotteTaylor K, McDonough SH, Mimms L, Giachetti C.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130666

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Simplified Hepatitis C Virus Genotyping by Heteroduplex Mobility Analysis. by White PA, Zhai X, Carter I, Zhao Y, Rawlinson WD.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=86128

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Simultaneous Detection of Multiplex-Amplified Human Immunodeficiency Virus Type 1 RNA, Hepatitis C Virus RNA, and Hepatitis B Virus DNA Using a Flow Cytometer Microsphere-Based Hybridization Assay. by Defoort JP, Martin M, Casano B, Prato S, Camilla C, Fert V.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=86341

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Single-step PCR in molecular diagnosis of hepatitis C virus infection. by Farma E, Boeri E, Bettini P, Repetto CM, McDermott J, Lillo FB, Varnier OE.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229477

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Strain from a Novel Subfamily of Hepatitis G Virus/Hepatitis GB Virus C Isolated from a Japanese Patient: Sequence Analysis of the Envelope 1 Region. by Tong JK, Masuko-Hongo K, Nishioka K, Kato T.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105216

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Structure of the 3' terminus of the hepatitis C virus genome. by Tanaka T, Kato N, Cho MJ, Sugiyama K, Shimotohno K.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190199

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Study of transmission routes of Helicobacter pylori in relation to seroprevalence of hepatitis A virus. by Furuta T, Kamata T, Takashima M, Futami H, Arai H, Hanai H, Kaneko E.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229866

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Study on reliability of commercially available hepatitis C virus antibody tests. by Feucht HH, Zollner B, Polywka S, Laufs R.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228001

174 Hepatitis

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Subcellular Localization, Stability, and trans-Cleavage Competence of the Hepatitis C Virus NS3-NS4A Complex Expressed in Tetracycline-Regulated Cell Lines. by Wolk B, Sansonno D, Krausslich HG, Dammacco F, Rice CM, Blum HE, Moradpour D.; 2000 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=111711

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Subtype 2c of hepatitis C virus is highly prevalent in Italy and is heterogeneous in the NS5A region. by Maggi F, Vatteroni ML, Fornai C, Morrica A, Giorgi M, Bendinelli M, Pistello M.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229530

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Subtype-Independent Immature Secretion and Subtype-Dependent Replication Deficiency of a Highly Frequent, Naturally Occurring Mutation of Human Hepatitis B Virus Core Antigen. by Yuan TT, Tai PC, Shih C.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=113064

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Subtyping of hepatitis C virus isolates by a line probe assay using hybridization. by Andonov A, Chaudhary RK.; 1995 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=227924

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Successful Passive and Active Immunization of Cynomolgus Monkeys Against Hepatitis E. by Tsarev SA, Tsareva TS, Emerson SU, Govindarajan S, Shapiro M, Gern JL, Purcell RH.; 1994 Oct 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44985

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Survey of type 6 group variants of hepatitis C virus in Southeast Asia by using a corebased genotyping assay. by Mellor J, Walsh EA, Prescott LE, Jarvis LM, Davidson F, Yap PL, Simmonds P.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228809

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Sustained Dysfunction of Antiviral CD8 + T Lymphocytes after Infection with Hepatitis C Virus. by Gruener NH, Lechner F, Jung MC, Diepolder H, Gerlach T, Lauer G, Walker B, Sullivan J, Phillips R, Pape GR, Klenerman P.; 2001 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114267

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Targeted Disruption of the Ceacam1 (MHVR) Gene Leads to Reduced Susceptibility of Mice to Mouse Hepatitis Virus Infection. by Blau DM, Turbide C, Tremblay M, Olson M, Letourneau S, Michaliszyn E, Jothy S, Holmes KV, Beauchemin N.; 2001 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=115062

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Targeted Recombination within the Spike Gene of Murine Coronavirus Mouse Hepatitis Virus-A59: Q159 Is a Determinant of Hepatotropism. by Leparc-Goffart I, Hingley ST, Chua MM, Phillips J, Lavi E, Weiss SR.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=110472

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T-Cell Response to Woodchuck Hepatitis Virus (WHV) Antigens during Acute SelfLimited WHV Infection and Convalescence and after Viral Challenge. by Menne S, Maschke J, Lu M, Grosse-Wilde H, Roggendorf M.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=110414

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Tear fluid of hepatitis C virus carriers could be infectious. by Feucht HH, Zollner B, Schroter M, Altrogge H, Laufs R.; 1995 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228367

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The Clearance of Hepatitis C Virus Infection in Chimpanzees May Not Necessarily Correlate with the Appearance of Acquired Immunity. by Thomson M, Nascimbeni M, Havert MB, Major M, Gonzales S, Alter H, Feinstone SM, Murthy KK, Rehermann B, Liang TJ.; 2003 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=140840

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The Conserved Serine 177 in the Delta Antigen of Hepatitis Delta Virus Is One Putative Phosphorylation Site and Is Required for Efficient Viral RNA Replication. by Mu JJ, Chen DS, Chen PJ.; 2001 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114477

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The degrees of hepatocyte nuclear but not cytoplasmic expression of hepatitis B core antigen reflect the level of viral replication in chronic hepatitis B virus infection. by Chu CM, Yeh CT, Chien RN, Sheen IS, Liaw YF.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229519

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The Dynamics of Hepatitis B Virus Infection. by Payne RJ, Nowak MA, Blumberg BS.; 1996 Jun 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39060

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The Enhancer I Core Region Contributes to the Replication Level of Hepatitis B Virus In Vivo and In Vitro. by Bock CT, Malek NP, Tillmann HL, Manns MP, Trautwein C.; 2000 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=111700

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The Fgl2/fibroleukin prothrombinase contributes to immunologically mediated thrombosis in experimental and human viral hepatitis. by Marsden PA, Ning Q, Fung LS, Luo X, Chen Y, Mendicino M, Ghanekar A, Scott JA, Miller T, Chan CW, Chan MW, He W, Gorczynski RM, Grant DR, Clark DA, Phillips MJ, Levy GA.; 2003 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=162293

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The frequency and significance of isolated hepatitis B core antibody and the suggested management of patients. by Al-Mekhaizeem KA, Miriello M, Sherker AH.; 2001 Oct 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=81543

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The In Vitro-Synthesized RNA from a cDNA Clone of Hepatitis E Virus Is Infectious. by Panda SK, Ansari IH, Durgapal H, Agrawal S, Jameel S.; 2000 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=111726

176 Hepatitis

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The Physical State of the Negative Strand of Hepatitis C Virus RNA in Serum of Patients with Chronic Hepatitis C. by Shindo M, Bisceglie AM, Akatsuka T, Fong T, Scaglione L, Donets M, Hoofnagle JH, Feinstone SM.; 1994 Aug 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44678

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The Ribavirin Analog ICN 17261 Demonstrates Reduced Toxicity and Antiviral Effects with Retention of both Immunomodulatory Activity and Reduction of Hepatitis-Induced Serum Alanine Aminotransferase Levels. by Tam RC, Ramasamy K, Bard J, Pai B, Lim C, Averett DR.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89855

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Three Cases of Infection with Hepatitis C Virus Genotype 5 among Brazilian Hepatitis Patients. by Levi JE, Takaoka DT, Garrini RH, Fachini RM, Focaccia R, de Bortholi Santos E, Mitre HP, de Mendonca JS, de Paula Cavalheiro N, Barone AA, Wendel S.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120608

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Thymus involution induced by mouse hepatitis virus A59 in BALB/c mice. by Godfraind C, Holmes KV, Coutelier JP.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189556

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Tracking hepatitis C virus quasispecies major and minor variants in symptomatic and asymptomatic liver transplant recipients. by Gretch DR, Polyak SJ, Wilson JJ, Carithers RL Jr, Perkins JD, Corey L.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190831

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Transcripts from a single full-length cDNA clone of hepatitis C virus are infectious when directly transfected into the liver of a chimpanzee. by Yanagi M, Purcell RH, Emerson SU, Bukh J.; 1997 Aug 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23104

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Transient Immunoglobulin M Antibody Response to Hepatitis C Virus Capsid Antigen in Posttransfusion Hepatitis C: Putative Serological Marker for Acute Viral Infection. by Chen P, Wang J, Hwang L, Yang Y, Hsieh C, Kao J, Sheu J, Lai M, Wang T, Chen D.; 1992 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49419

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Transmission of Hepatitis C Virus in a Gynecological Surgery Setting. by Massari M, Petrosillo N, Ippolito G, Solforosi L, Bonazzi L, Clementi M, Manzin A.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88251

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Tumor necrosis factor receptor p55 is essential for intrahepatic granuloma formation and hepatocellular apoptosis in a murine model of bacterium-induced fulminant hepatitis. by Tsuji H, Harada A, Mukaida N, Nakanuma Y, Bluethmann H, Kaneko S, Yamakawa K, Nakamura SI, Kobayashi KI, Matsushima K.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175237

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Two Successive Hepatitis C Virus Infections in an Intravenous Drug User. by Proust B, Dubois F, Bacq Y, Le Pogam S, Rogez S, Levillain R, Goudeau A.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87209

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Type, prevalence, and significance of core promoter/enhancer II mutations in hepatitis B viruses from immunosuppressed patients with severe liver disease. by Gunther S, Piwon N, Iwanska A, Schilling R, Meisel H, Will H.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190919

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Uneven Distribution of Hepatitis C Virus Quasispecies in Tissues from Subjects with End-Stage Liver Disease: Confounding Effect of Viral Adsorption and Mounting Evidence for the Presence of Low-Level Extrahepatic Replication. by Laskus T, Radkowski M, Wang LF, Nowicki M, Rakela J.; 2000 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=111624

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Update on Diagnosis, Management, and Prevention of Hepatitis B Virus Infection. by Mahoney FJ.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88921

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Use of Fluoroquinolones in Patients with Chronic Hepatitis C Virus-Induced Liver Failure. by Kojima H, Kaita KD, Hawkins K, Uhanova J, Minuk GY.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128783

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Use of Phylogenetic Analysis of Hepatitis C Virus (HCV) Hypervariable Region 1 Sequences To Trace an Outbreak of HCV in an Autodialysis Unit. by Halfon P, Roubicek C, Gerolami V, Quentin Y, Khiri H, Pepe G, Berland Y.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=140339

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Use of recombinant protein to identify a motif-negative human cytotoxic T-cell epitope presented by HLA-A2 in the hepatitis C virus NS3 region. by Kurokohchi K, Akatsuka T, Pendleton CD, Takamizawa A, Nishioka M, Battegay M, Feinstone SM, Berzofsky JA.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189809

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Utility of the Mayo End-Stage Liver Disease (MELD) score in assessing prognosis of patients with alcoholic hepatitis. by Sheth M, Riggs M, Patel T.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=65516

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Utilization of Chimeras between Human (HM-175) and Simian (AGM-27) Strains of Hepatitis A Virus To Study the Molecular Basis of Virulence. by Raychaudhuri G, Govindarajan S, Shapiro M, Purcell RH, Emerson AS.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=109981

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Viral Dynamics in Hepatitis B Virus Infection. by Nowak MA, Bonhoeffer S, Hill AM, Boehme R, Thomas HC, McDade H.; 1996 Apr 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39549

178 Hepatitis

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Viral Persistence, Antibody to E1 and E2, and Hypervariable Region 1 Sequence Stability in Hepatitis C Virus-Inoculated Chimpanzees. by Bassett SE, Thomas DL, Brasky KM, Lanford RE.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=103932

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Viral Superinfection in Previously Unrecognized Chronic Carriers of Hepatitis B Virus with Superimposed Acute Fulminant versus Nonfulminant Hepatitis. by Chu CM, Yeh CT, Liaw YF.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=84220

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Virus-Specific CD8 + Lymphocytes Share the Same Effector-Memory Phenotype but Exhibit Functional Differences in Acute Hepatitis B and C. by Urbani S, Boni C, Missale G, Elia G, Cavallo C, Massari M, Raimondo G, Ferrari C.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136708

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Vitamin B12 and hepatitis C: Molecular biology and human pathology. by Lott WB, Takyar SS, Tuppen J, Crawford DH, Harrison M, Sloots TP, Gowans EJ.; 2001 Apr 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33138

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Whole-Blood Hepatitis C Virus RNA Extraction Methods. by Schmidt W.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88445

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Wild-Type and e Antigen-Minus Hepatitis B Viruses and Course of Chronic Hepatitis. by Brunetto MR, Giarin MM, Oliveri F, Chiaberge E, Baldi M, Alfarano A, Serra A, Saracco G, Verme G, Will H, Bonino F.; 1991 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51623

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Woodchuck hepatitis virus X protein is present in chronically infected woodchuck liver and woodchuck hepatocellular carcinomas which are permissive for viral replication. by Dandri M, Schirmacher P, Rogler CE.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190481

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals.

6

PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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To generate your own bibliography of studies dealing with hepatitis, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “hepatitis” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for hepatitis (hyperlinks lead to article summaries): ·

A major CYP2D6 autoepitope in autoimmune hepatitis type 2 and chronic hepatitis C is a three-dimensional structure homologous to other cytochrome P450 autoantigens. Author(s): Sugimura T, Obermayer-Straub P, Kayser A, Braun S, Loges S, Alex B, Luttig B, Johnson EF, Manns MP, Strassburg CP. Source: Autoimmunity. 2002 December; 35(8): 501-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765476&dopt=Abstract

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A monoclonal antibody to the alpha2 domain of murine major histocompatibility complex class I that specifically kills activated lymphocytes and blocks liver damage in the concanavalin A hepatitis model. Author(s): Matsuoka S, Tsurui H, Abe M, Terashima K, Nakamura K, Hamano Y, Ohtsuji M, Honma N, Serizawa I, Ishii Y, Takiguchi M, Hirose S, Shirai T. Source: The Journal of Experimental Medicine. 2003 August 4; 198(3): 497-503. Epub 2003 July 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885869&dopt=Abstract

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A national survey of genitourinary medicine clinic attenders provides little evidence of sexual transmission of hepatitis C virus infection. Author(s): Balogun MA, Ramsay ME, Parry JV, Donovan L, Andrews NJ, Newham JA, McGarrigle C, Harris KA, Teo CG. Source: Sexually Transmitted Infections. 2003 August; 79(4): 301-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902580&dopt=Abstract

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A patient with acute hepatitis C and possible IFN toxicity. Author(s): Licata A, Di Marco V, Craxi A. Source: Dig Liver Dis. 2003 May; 35(5): 372-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846412&dopt=Abstract

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A patient with hepatitis C-related cirrhosis and hepatocellular carcinoma who was cured with an orthotopic liver transplantation and interferon therapy. Author(s): Shibata M, Yanaga K, Morizane T, Yanagawa T, Hirakawa M, Ueno Y, Esquivel CO, Mitamura K. Source: Journal of Gastroenterology. 2003; 38(6): 598-602. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858850&dopt=Abstract

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A prospect for pharmacogenomics in the interferon therapy of chronic viral hepatitis. Author(s): Yeh SH, Chen DS, Chen PJ. Source: The Journal of Antimicrobial Chemotherapy. 2003 August; 52(2): 149-51. Epub 2003 July 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12837727&dopt=Abstract

180 Hepatitis

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A real-time quantitative polymerase chain reaction method for hepatitis B virus in patients with chronic hepatitis B treated with lamivudine. Author(s): Ide T, Kumashiro R, Koga Y, Tanaka E, Hino T, Hisamochi A, Murashima S, Ogata K, Tanaka K, Kuwahara R, Sata M. Source: The American Journal of Gastroenterology. 2003 September; 98(9): 2048-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14499786&dopt=Abstract

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A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Author(s): Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, Lok AS. Source: Hepatology (Baltimore, Md.). 2003 August; 38(2): 518-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883497&dopt=Abstract

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A special risk group for hepatitis E infection: Turkish agricultural workers who use untreated waste water for irrigation. Author(s): Ceylan A, Ertem M, Ilcin E, Ozekinci T. Source: Epidemiology and Infection. 2003 August; 131(1): 753-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12948376&dopt=Abstract

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A study of serological markers of hepatitis B and C viruses in Istanbul, Turkey. Author(s): Erden S, Buyukozturk S, Calangu S, Yilmaz G, Palanduz S, Badur S. Source: Medical Principles and Practice : International Journal of the Kuwait University, Health Science Centre. 2003 July-September; 12(3): 184-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766338&dopt=Abstract

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Abrogation of hepatitis C virus NS3 helicase enzymatic activity by recombinant human antibodies. Author(s): Artsaenko O, Tessmann K, Sack M, Haussinger D, Heintges T. Source: The Journal of General Virology. 2003 September; 84(Pt 9): 2323-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917452&dopt=Abstract

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Acceptance of hepatitis B vaccine by workers in a Nigerian teaching hospital. Author(s): Fatusi AO, Fatusi OA, Esimai AO, Onayade AA, Ojo OS. Source: East Afr Med J. 2000 November; 77(11): 608-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12862107&dopt=Abstract

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Activation and inhibition of cellular calcium and tyrosine kinase signaling pathways identify targets of the HBx protein involved in hepatitis B virus replication. Author(s): Bouchard MJ, Puro RJ, Wang L, Schneider RJ. Source: Journal of Virology. 2003 July; 77(14): 7713-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829810&dopt=Abstract

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Acute exacerbation during interferon alfa treatment of chronic hepatitis B: frequency and relation to serum beta-2 microglobulin levels. Author(s): Akdogan M, Senturk H, Mert A, Tabak F, Ozbay G. Source: Journal of Gastroenterology. 2003; 38(5): 465-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768389&dopt=Abstract

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Acute hepatitis associated with Barakol. Author(s): Hongsirinirachorn M, Threeprasertsuk S, Chutaputti A. Source: J Med Assoc Thai. 2003 June; 86 Suppl 2: S484-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930029&dopt=Abstract

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Acute hepatitis B infection and hepatitis B surface antigen positivity reported in the Department of Veterans Affairs: occurrence in a population seeking medical assistance. Author(s): Kralovic SM, Danko LH, Simbartl LA, Roselle GA. Source: Military Medicine. 2003 June; 168(6): 493-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834144&dopt=Abstract

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Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance. Author(s): Gerlach JT, Diepolder HM, Zachoval R, Gruener NH, Jung MC, Ulsenheimer A, Schraut WW, Schirren CA, Waechtler M, Backmund M, Pape GR. Source: Gastroenterology. 2003 July; 125(1): 80-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851873&dopt=Abstract

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Acute hepatitis-like presentation of graft-versus-host disease following donor lymphocyte infusion. Author(s): Busca A, Locatelli F, Barbui A, Ghisetti V, Lovisone E, Aliberti S, Falda M. Source: Acta Haematologica. 2003; 110(1): 48-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12975560&dopt=Abstract

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Acute HIV seroconversion in a patient receiving pegylated interferon for treatment of hepatitis C. Author(s): Maser E, Dieterich DT. Source: Aids Read. 2003 June; 13(6): 279-80, 287. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846173&dopt=Abstract

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Adenovirus-mediated gene transfer of interferon alpha inhibits hepatitis C virus replication in hepatocytes. Author(s): Suzuki K, Aoki K, Ohnami S, Yoshida K, Kazui T, Kato N, Inoue K, Kohara M, Yoshida T. Source: Biochemical and Biophysical Research Communications. 2003 August 8; 307(4): 814-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878183&dopt=Abstract

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Advances in the diagnosis and management of human viral hepatitis. Author(s): Wisnom C, Siegel MA. Source: Dent Clin North Am. 2003 July; 47(3): 431-47. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848458&dopt=Abstract

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Adverse response to pegylated interferon therapy in two patients with chronic hepatitis C. Author(s): Thomas WL Jr, Ramos F, Hospenthal DR. Source: Hawaii Med J. 2003 August; 62(8): 163-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14533347&dopt=Abstract

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Aeromonas veronii biovar veronii septicaemia and acute suppurative cholangitis in a patient with hepatitis B. Author(s): Mencacci A, Cenci E, Mazzolla R, Farinelli S, D'Alo F, Vitali M, Bistoni F. Source: Journal of Medical Microbiology. 2003 August; 52(Pt 8): 727-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867570&dopt=Abstract

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Agents in clinical development for the treatment of chronic hepatitis B. Author(s): Raney AK, Hamatake RK, Hong Z. Source: Expert Opinion on Investigational Drugs. 2003 August; 12(8): 1281-95. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882617&dopt=Abstract

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Alcohol potentiates hepatitis C virus replicon expression. Author(s): Zhang T, Li Y, Lai JP, Douglas SD, Metzger DS, O'Brien CP, Ho WZ. Source: Hepatology (Baltimore, Md.). 2003 July; 38(1): 57-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829987&dopt=Abstract

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Alterations of RB1, p53 and Wnt pathways in hepatocellular carcinomas associated with hepatitis C, hepatitis B and alcoholic liver cirrhosis. Author(s): Edamoto Y, Hara A, Biernat W, Terracciano L, Cathomas G, Riehle HM, Matsuda M, Fujii H, Scoazec JY, Ohgaki H. Source: International Journal of Cancer. Journal International Du Cancer. 2003 September 1; 106(3): 334-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845670&dopt=Abstract

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An epidemiologic summary of the hepatitis C epidemic in Minnesota. Author(s): Fong F. Source: Minn Med. 2003 June; 86(6): 46-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834214&dopt=Abstract

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An infectious clone of woolly monkey hepatitis B virus. Author(s): Lanford RE, Chavez D, Barrera A, Brasky KM. Source: Journal of Virology. 2003 July; 77(14): 7814-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829821&dopt=Abstract

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An outbreak of hepatitis A associated with consumption of raw blueberries. Author(s): Calder L, Simmons G, Thornley C, Taylor P, Pritchard K, Greening G, Bishop J. Source: Epidemiology and Infection. 2003 August; 131(1): 745-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12948375&dopt=Abstract

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Analysis of complement-bound hepatitis B virus complexes by an immuno-capture polymerase chain reaction method. Author(s): Wang SY, Liu R, Zhang JY, Lian QZ, Peng XX. Source: Scandinavian Journal of Immunology. 2003 July; 58(1): 112-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828566&dopt=Abstract

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Antibody-selected mimics of hepatitis C virus hypervariable region 1 activate both primary and memory Th lymphocytes. Author(s): Frasca L, Scotta C, Del Porto P, Nicosia A, Pasquazzi C, Versace I, Masci AM, Racioppi L, Piccolella E. Source: Hepatology (Baltimore, Md.). 2003 September; 38(3): 653-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939592&dopt=Abstract

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Antiviral treatment down-regulates peripheral B-cell CD81 expression and CD5 expansion in chronic hepatitis C virus infection. Author(s): Zuckerman E, Kessel A, Slobodin G, Sabo E, Yeshurun D, Toubi E. Source: Journal of Virology. 2003 October; 77(19): 10432-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970428&dopt=Abstract

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Antiviral treatment in acute hepatitis C. Author(s): Macedo G, Correia A, Ribeiro T. Source: Hepatogastroenterology. 2003 July-August; 50(52): 1057-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845981&dopt=Abstract

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Apolipoprotein E and hepatitis C virus. Author(s): Itzhaki RF, Irving WL, Wozniak MA. Source: Hepatology (Baltimore, Md.). 2003 October; 38(4): 1060. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512896&dopt=Abstract

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Argentine and Latin American hepatitis A. Author(s): Ruttimann RW, Clemens RL. Source: Journal of Travel Medicine : Official Publication of the International Society of Travel Medicine and the Asia Pacific Travel Health Association. 2002 July-August; 9(4): 220. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12962620&dopt=Abstract

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Association of hepatitis B virus polymerase with promyelocytic leukemia nuclear bodies mediated by the S100 family protein p11. Author(s): Choi J, Chang JS, Song MS, Ahn BY, Park Y, Lim DS, Han YS. Source: Biochemical and Biophysical Research Communications. 2003 June 13; 305(4): 1049-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767936&dopt=Abstract

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Association of hepatitis C virus infection with sexual exposure in southern India. Author(s): Marx MA, Murugavel KG, Tarwater PM, SriKrishnan AK, Thomas DL, Solomon S, Celentano DD. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 August 15; 37(4): 514-20. Epub 2003 July 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12905135&dopt=Abstract

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Autoimmune hepatitis revealed by atorvastatin. Author(s): Pelli N, Setti M, Ceppa P, Toncini C, Indiveri F. Source: European Journal of Gastroenterology & Hepatology. 2003 August; 15(8): 921-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867804&dopt=Abstract

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Autoimmune hepatitis. Making sense of all those antibodies. Author(s): Luxon BA. Source: Postgraduate Medicine. 2003 July; 114(1): 79-82, 85-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875057&dopt=Abstract

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Bacterial virus phi29 pRNA as a hammerhead ribozyme escort to destroy hepatitis B virus. Author(s): Hoeprich S, Zhou Q, Guo S, Shu D, Qi G, Wang Y, Guo P. Source: Gene Therapy. 2003 August; 10(15): 1258-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858191&dopt=Abstract

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Baruch Blumberg--work on hepatitis B virus. Author(s): Shampo MA, Kyle RA. Source: Mayo Clinic Proceedings. 2003 September; 78(9): 1186. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12962173&dopt=Abstract

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Basal core promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers. Author(s): Kao JH, Chen PJ, Lai MY, Chen DS. Source: Gastroenterology. 2003 February; 124(2): 327-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12557138&dopt=Abstract

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Bilateral optic ischemic neuropathy related to chronic hepatitis C-associated anticardiolipin antibodies. Author(s): Sinnreich M, Rossillion B, Landis T, Burkhard PR, Sztajzel R. Source: European Neurology. 2003; 49(4): 243-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12736543&dopt=Abstract

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Bile acids for viral hepatitis. Author(s): Chen W, Liu J, Gluud C. Source: Cochrane Database Syst Rev. 2003; (2): Cd003181. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804455&dopt=Abstract

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Binding of the hepatitis C virus E2 glycoprotein to CD81 is strain specific and is modulated by a complex interplay between hypervariable regions 1 and 2. Author(s): Roccasecca R, Ansuini H, Vitelli A, Meola A, Scarselli E, Acali S, Pezzanera M, Ercole BB, McKeating J, Yagnik A, Lahm A, Tramontano A, Cortese R, Nicosia A. Source: Journal of Virology. 2003 February; 77(3): 1856-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12525620&dopt=Abstract

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Biochemical markers of fibrosis in patients with chronic hepatitis C: a comparison with prothrombin time, platelet count, and age-platelet index. Author(s): Myers RP, De Torres M, Imbert-Bismut F, Ratziu V, Charlotte F, Poynard T; MULTIVIRC Group. Source: Digestive Diseases and Sciences. 2003 January; 48(1): 146-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645802&dopt=Abstract

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Candida oesophagitis with hepatitis C virus: an uncommon association. Author(s): Yakoob J, Jafri W, Hussainy AS. Source: European Journal of Gastroenterology & Hepatology. 2003 June; 15(6): 701-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840684&dopt=Abstract

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Capillarization of hepatic sinusoid by liver endothelial cell-reactive autoantibodies in patients with cirrhosis and chronic hepatitis. Author(s): Xu B, Broome U, Uzunel M, Nava S, Ge X, Kumagai-Braesch M, Hultenby K, Christensson B, Ericzon BG, Holgersson J, Sumitran-Holgersson S. Source: American Journal of Pathology. 2003 October; 163(4): 1275-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14507637&dopt=Abstract

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Case fatality rate of acute viral hepatitis in Italy: 1995-2000. An update. Author(s): Bianco E, Stroffolini T, Spada E, Szklo A, Marzolini F, Ragni P, Gallo G, Balocchini E, Parlato A, Sangalli M, Lopalco PL, Zotti C; SEIEVA Collaborating Group. Source: Dig Liver Dis. 2003 June; 35(6): 404-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12868676&dopt=Abstract

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CD81-dependent binding of hepatitis C virus E1E2 heterodimers. Author(s): Cocquerel L, Kuo CC, Dubuisson J, Levy S. Source: Journal of Virology. 2003 October; 77(19): 10677-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970454&dopt=Abstract

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Cell cycle regulation of hepatitis C and encephalomyocarditis virus internal ribosome entry site-mediated translation in human embryonic kidney 293 cells. Author(s): Venkatesan A, Sharma R, Dasgupta A. Source: Virus Research. 2003 August; 94(2): 85-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902037&dopt=Abstract

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Cell surface expression of functional hepatitis C virus E1 and E2 glycoproteins. Author(s): Drummer HE, Maerz A, Poumbourios P. Source: Febs Letters. 2003 July 10; 546(2-3): 385-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832074&dopt=Abstract

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Changing epidemiology of hepatitis A: should we be doing more to vaccinate injecting drug users? Author(s): Perrett K, Granerod J, Crowcroft N, Carlisle R. Source: Commun Dis Public Health. 2003 June; 6(2): 97-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889286&dopt=Abstract

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Characterisation of the differences between hepatitis C virus genotype 3 and 1 glycoproteins. Author(s): Shaw ML, McLauchlan J, Mills PR, Patel AH, McCruden EA. Source: Journal of Medical Virology. 2003 July; 70(3): 361-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766998&dopt=Abstract

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Characterization of the structure and variability of an internal region of hepatitis C virus RNA for M1 RNA guide sequence ribozyme targeting. Author(s): Nadal A, Robertson HD, Guardia J, Gomez J. Source: The Journal of General Virology. 2003 June; 84(Pt 6): 1545-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771424&dopt=Abstract

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Chemiluminescence assay improves specificity of hepatitis C antibody detection. Author(s): Dufour DR, Talastas M, Fernandez MD, Harris B. Source: Clinical Chemistry. 2003 June; 49(6 Pt 1): 940-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765991&dopt=Abstract

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Cholesterol requirement of hepatitis B surface antigen (HBsAg) secretion. Author(s): Lin YL, Shiao MS, Mettling C, Chou CK. Source: Virology. 2003 September 15; 314(1): 253-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14517078&dopt=Abstract

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Chronic hepatitis associated with GB virus B persistence in a tamarin after intrahepatic inoculation of synthetic viral RNA. Author(s): Martin A, Bodola F, Sangar DV, Goettge K, Popov V, Rijnbrand R, Lanford RE, Lemon SM. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 August 19; 100(17): 9962-7. Epub 2003 Aug 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907703&dopt=Abstract

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Chronic hepatitis B with flare due to co-infection of hepatitis delta virus during lamivudine therapy. Author(s): Joh R, Hasegawa K, Tokushige K, Hashimoto E, Torii N, Yamashiro T, Enomoto N, Watanabe M, Hayashi N. Source: Intern Med. 2003 July; 42(7): 581-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879950&dopt=Abstract

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Chronic hepatitis C virus infection established and maintained in chimpanzees independent of dendritic cell impairment. Author(s): Rollier C, Drexhage JA, Verstrepen BE, Verschoor EJ, Bontrop RE, Koopman G, Heeney JL. Source: Hepatology (Baltimore, Md.). 2003 October; 38(4): 851-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512872&dopt=Abstract

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Chronic hepatitis C virus infection. Author(s): Kleinhaus RM. Source: Annals of Internal Medicine. 2003 September 2; 139(5 Pt 1): W67; Author Reply W68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12965959&dopt=Abstract

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Chronic hepatitis C with persistently normal aminotransferase levels: do we have an adequate definition? Author(s): Jamal MM, Abdelkarim BZ. Source: The American Journal of Gastroenterology. 2003 July; 98(7): 1455-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873562&dopt=Abstract

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Chronic hepatitis C. Treatment and side effect management. Author(s): Lee SP. Source: Adv Nurse Pract. 2003 July; 11(7): 73-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886741&dopt=Abstract

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Chronic hepatitis C: updated Swedish consensus. Author(s): Wejstal R, Alaeus A, Fischler B, Reichard O, Uhnoo I, Weiland O; Swedish National Expert Panel for the treatment of chronic hepatitis C. Source: Scandinavian Journal of Infectious Diseases. 2003; 35(8): 445-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14514142&dopt=Abstract

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Chronic hepatitis C--treatment results in northern India. Author(s): Sood A, Midha V, Sood N, Awasthi G. Source: Trop Gastroenterol. 2002 October-December; 23(4): 172-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12833703&dopt=Abstract

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Clinical aspects of chronic hepatitis C infection. Author(s): Schattner A, Knobler H. Source: Jama : the Journal of the American Medical Association. 2003 September 17; 290(11): 1453; Author Reply 1453-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13129978&dopt=Abstract

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Clinical aspects of chronic hepatitis C infection. Author(s): Leblebicioglu H. Source: Jama : the Journal of the American Medical Association. 2003 September 17; 290(11): 1453; Author Reply 1453-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13129977&dopt=Abstract

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Clinical aspects of chronic hepatitis C infection. Author(s): Kashyap AS, Anand KP, Kashyap S. Source: Jama : the Journal of the American Medical Association. 2003 September 17; 290(11): 1452; Author Reply 1453-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13129975&dopt=Abstract

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Clinical features and progression of perinatally acquired hepatitis C virus infection. Author(s): Resti M, Jara P, Hierro L, Azzari C, Giacchino R, Zuin G, Zancan L, Pedditzi S, Bortolotti F. Source: Journal of Medical Virology. 2003 July; 70(3): 373-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766999&dopt=Abstract

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Clinical features of hepatitis B virus genotype A in Japanese patients. Author(s): Kobayashi M, Arase Y, Ikeda K, Tsubota A, Suzuki Y, Hosaka T, Saitoh S, Kobayashi M, Suzuki F, Akuta N, Someya T, Matsuda M, Sato J, Kumada H. Source: Journal of Gastroenterology. 2003; 38(7): 656-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898358&dopt=Abstract

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Clinical observation of serum IL-18, IL-10 and sIL-2R levels in patients with chronic hepatitis C pre- and post antiviral treatment. Author(s): Jia H, Du J, Zhu S, Ma Y, Cai H. Source: Chin Med J (Engl). 2003 April; 116(4): 605-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875732&dopt=Abstract

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Clinical pharmacology consultations: consultation requests may be misleading -- an organized approach to drug-induced hepatitis. Author(s): Valois M, Cooper MA, Shear NH. Source: Can J Clin Pharmacol. 2003 Summer; 10(2): 59-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879142&dopt=Abstract

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Combination treatment of IFNalpha2b and ribavirin in patients with chronic hepatitis C and persistently normal ALTs. Author(s): Erhardt A, Behlen-Wilm U, Adams O, Donner A, Heintges T, Haussinger D. Source: Digestive Diseases and Sciences. 2003 May; 48(5): 921-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12772791&dopt=Abstract

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Comparative evaluation of the total hepatitis C virus core antigen, branched-DNA, and amplicor monitor assays in determining viremia for patients with chronic hepatitis C during interferon plus ribavirin combination therapy. Author(s): Veillon P, Payan C, Picchio G, Maniez-Montreuil M, Guntz P, Lunel F. Source: Journal of Clinical Microbiology. 2003 July; 41(7): 3212-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843066&dopt=Abstract

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Comparison of clinical features and survival of patients with hepatitis B- and hepatitis C-associated hepatocellular carcinoma in Thailand. Author(s): Tangkijvanich P, Suwangool P, Mahachai V. Source: J Med Assoc Thai. 2003 June; 86 Suppl 2: S250-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12929997&dopt=Abstract

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Correlation of single photon emission computed tomography parameters as a noninvasive alternative to liver biopsies in assessing liver involvement in the setting of HIV and hepatitis C virus coinfection: a multicenter trial of the Adult AIDS Clinical Trials Group. Author(s): Shiramizu B, Theodore D, Bassett R, Coel M, Sherman KE, Glesby MJ, Chow D, Alston B, Colquhoun D, Merigan TC Jr, Reichman RC, Berggren R, Burning WJ, Brobst S; Adult AIDS Clinical Trials Group 5096 Team. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 2003 July 1; 33(3): 329-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843743&dopt=Abstract

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Cost-effectiveness of treatment for chronic hepatitis C infection in an evolving patient population. Author(s): Salomon JA, Weinstein MC, Hammitt JK, Goldie SJ. Source: Jama : the Journal of the American Medical Association. 2003 July 9; 290(2): 22837. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851278&dopt=Abstract

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Cost-effectiveness of treatment for chronic hepatitis C infection. Author(s): Bernstein D. Source: Jama : the Journal of the American Medical Association. 2003 October 15; 290(15): 1993; Author Reply 1994. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14559948&dopt=Abstract

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Cost-effectiveness of treatment for chronic hepatitis C infection. Author(s): Dore GJ, Thein HH. Source: Jama : the Journal of the American Medical Association. 2003 October 15; 290(15): 1993; Author Reply 1994. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14559947&dopt=Abstract

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Cost-effectiveness of treatment of chronic hepatitis B with interferon-alpha. Author(s): Babu S. Source: Natl Med J India. 2003 May-June; 16(3): 175; Author Reply 175-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12929872&dopt=Abstract

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Cost-effectiveness of treatment of chronic hepatitis B with interferon-alpha. Author(s): Nagral A. Source: Natl Med J India. 2003 May-June; 16(3): 175; Author Reply 175-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12929871&dopt=Abstract

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Cost-effectiveness of treatment of chronic hepatitis B with interferon-alpha. Author(s): Desai HG. Source: Natl Med J India. 2003 May-June; 16(3): 175; Author Reply 175-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12929870&dopt=Abstract

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Cryoglobulins in chronic hepatitis C virus infection. Author(s): Trendelenburg M, Schifferli JA. Source: Clinical and Experimental Immunology. 2003 August; 133(2): 153-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869018&dopt=Abstract

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Current therapies for chronic hepatitis C. Drug combination achieves sustained response in more than half of patients. Author(s): Patel K, McHutchison JG. Source: Postgraduate Medicine. 2003 July; 114(1): 48-52, 57-9, 62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875055&dopt=Abstract

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Cytopathic and noncytopathic interferon responses in cells expressing hepatitis C virus subgenomic replicons. Author(s): Guo JT, Zhu Q, Seeger C. Source: Journal of Virology. 2003 October; 77(20): 10769-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512527&dopt=Abstract

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Cytotoxic T lymphocyte antigen-4 gene polymorphisms do not confer susceptibility to autoimmune hepatitis types 1 and 2 in Brazil. Author(s): Bittencourt PL, Palacios SA, Cancado EL, Porta G, Carrilho FJ, Laudanna AA, Kalil J, Goldberg AC. Source: The American Journal of Gastroenterology. 2003 July; 98(7): 1616-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873588&dopt=Abstract

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De novo autoimmune hepatitis affecting allograft but not the native liver in auxiliary partial orthotopic liver transplantation. Author(s): Miyagawa-Hayashino A, Haga H, Sakurai T, Shirase T, Manabe T, Egawa H. Source: Transplantation. 2003 July 15; 76(1): 271-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865828&dopt=Abstract

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De novo infection in a renal transplant recipient caused by novel mutants of hepatitis B virus despite the presence of protective anti-hepatitis B surface antibody. Author(s): Lu M, Lorentz T. Source: The Journal of Infectious Diseases. 2003 April 15; 187(8): 1323-6. Epub 2003 March 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12696014&dopt=Abstract

192 Hepatitis

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Decline of hepatitis B carrier rate in vaccinated and unvaccinated subjects: sixteen years after newborn vaccination program in Taiwan. Author(s): Lin HH, Wang LY, Hu CT, Huang SC, Huang LC, Lin SS, Chiang YM, Liu TT, Chen CL. Source: Journal of Medical Virology. 2003 April; 69(4): 471-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601753&dopt=Abstract

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Decompensated hepatitis B virus-related cirrhosis successfully treated with lamivudine allowing surgery for hepatocellular carcinoma. Author(s): Nakanishi S, Michitaka K, Miyake T, Hidaka S, Yoshino I, Konishi I, Iuchi H, Horiike N, Onji M. Source: Intern Med. 2003 May; 42(5): 416-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12793712&dopt=Abstract

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Dentistry as a possible route of hepatitis C transmission in Pakistan. Author(s): Butt AK, Khan AA, Khan SY, Sharea I. Source: Int Dent J. 2003 June; 53(3): 141-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873110&dopt=Abstract

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Depression and anxiety in chronic hepatitis B: effect of hepatitis B virus infection on psychological state in childhood. Author(s): Arslan N, Buyukgebiz B, Ozturk Y, Akay AP. Source: Turk J Pediatr. 2003 January-March; 45(1): 26-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12718367&dopt=Abstract

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Detection of functionally altered hepatitis C virus-specific CD4 T cells in acute and chronic hepatitis C. Author(s): Ulsenheimer A, Gerlach JT, Gruener NH, Jung MC, Schirren CA, Schraut W, Zachoval R, Pape GR, Diepolder HM. Source: Hepatology (Baltimore, Md.). 2003 May; 37(5): 1189-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12717401&dopt=Abstract

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Detection of hepatitis B virus DNA in sera from patients with chronic hepatitis B virus infection by DNA microarray method. Author(s): Kawaguchi K, Kaneko S, Honda M, Kawai HF, Shirota Y, Kobayashi K. Source: Journal of Clinical Microbiology. 2003 April; 41(4): 1701-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682163&dopt=Abstract

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Detection of hepatitis C virus antibody and RNA in hemostatic gauze used for dentistry. Author(s): Hasegawa H, Yamada T, Esumi M. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2003 February; 24(2): 137-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12602697&dopt=Abstract

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Detection of hepatitis C virus RNA in formalin-fixed, paraffin-embedded thin-needle liver biopsy specimens. Author(s): Vogt S, Schneider-Stock R, Klauck S, Roessner A, Rocken C. Source: American Journal of Clinical Pathology. 2003 October; 120(4): 536-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14560564&dopt=Abstract

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Detection of hepatitis C virus RNA in normal cervical smears. Author(s): Wang C, Polyak SJ, Corey L. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 July 15; 37(2): 314; Author Reply 314-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12856226&dopt=Abstract

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Detection of mutations in the hepatitis B virus polymerase gene. Author(s): Kessler HH, Stelzl E, Marth E, Stauber RE. Source: Clinical Chemistry. 2003 June; 49(6 Pt 1): 989-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766008&dopt=Abstract

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Detection of serologic responses to GB virus C/hepatitis G virus infection. Author(s): Lo SY, Ku CW, Ma HC, Li YH, Yu JH, Lin HH, Lua AC, Lee ML. Source: International Journal of Infectious Diseases : Ijid : Official Publication of the International Society for Infectious Diseases. 2002 September; 6(3): 223-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12718839&dopt=Abstract

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Determination of hepatitis C virus genotype by Pyrosequencing. Author(s): Elahi E, Pourmand N, Chaung R, Rofoogaran A, Boisver J, Samimi-Rad K, Davis RW, Ronaghi M. Source: Journal of Virological Methods. 2003 May; 109(2): 171-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711060&dopt=Abstract

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Determination of serum fibrosis indexes in patients with chronic hepatitis and its significance. Author(s): Zheng M, Cai W, Weng H, Liu R. Source: Chin Med J (Engl). 2003 March; 116(3): 346-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781034&dopt=Abstract

194 Hepatitis

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Determination of the fine epitope specificity of an anti-hepatitis B virus X protein monoclonal antibody using microanalytical and molecular biological methods. Author(s): Pal J, Czompoly T, Nyarady Z, Marczinovits I, Janaky T, Kele Z, Felici F, Nemeth P. Source: Molecular Immunology. 2003 September; 40(5): 241-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943796&dopt=Abstract

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Determination of the multimerization state of the hepatitis delta virus antigens in vivo. Author(s): Cornillez-Ty CT, Lazinski DW. Source: Journal of Virology. 2003 October; 77(19): 10314-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970416&dopt=Abstract

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Development of a candidate polyvalent live vaccine against human immunodeficiency, hepatitis B, and orthopox viruses. Author(s): Shchelkunov SN, Nesterov AE, Ryazankin IA, Ignat'ev GM, Sandakhchiev LS. Source: Doklady. Biochemistry and Biophysics. 2003 May-June; 390: 180-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12959074&dopt=Abstract

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Development of a hepatitis C virus vaccine. Author(s): Inchauspe G, Feinstone S. Source: Clinics in Liver Disease. 2003 February; 7(1): 243-59, Xi. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691469&dopt=Abstract

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Development of peptide nucleic acid mediated polymerase chain reaction clamping (PMPC)--direct sequencing method for detecting lamivudine-resistant hepatitis B virus (HBV) variants with high sensitivity and specificity. Author(s): Ogata N, Ichida T, Aoyagi Y, Kitajima I. Source: Rinsho Byori. 2003 April; 51(4): 313-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747252&dopt=Abstract

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Diabetes mellitus and viral hepatitis: the unsolved mystery. Author(s): Akbar DH. Source: Acta Diabetologica. 2003 June; 40(2): 77-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861404&dopt=Abstract

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Diagnosing fibrosis in hepatitis C: is the pendulum swinging from biopsy to blood tests? Author(s): Afdhal NH. Source: Hepatology (Baltimore, Md.). 2003 May; 37(5): 972-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12717376&dopt=Abstract

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Diagnosis of acute hepatitis C: anti-HCV or HCV-RNA? Author(s): Moller JM, Krarup HB. Source: Scandinavian Journal of Gastroenterology. 2003 May; 38(5): 556-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12795470&dopt=Abstract

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Didanosine, interferon-alfa and ribavirin: a highly synergistic combination with potential activity against HIV-1 and hepatitis C virus. Author(s): Klein MB, Campeol N, Lalonde RG, Brenner B, Wainberg MA. Source: Aids (London, England). 2003 May 2; 17(7): 1001-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12700449&dopt=Abstract

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Difference in prognosis between patients infected with hepatitis B virus with genotype B and those with genotype C in the Okinawa Islands: a prospective study. Author(s): Nakayoshi T, Maeshiro T, Nakayoshi T, Nakasone H, Sakugawa H, Kinjo F, Orito E, Mizokami M. Source: Journal of Medical Virology. 2003 July; 70(3): 350-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766996&dopt=Abstract

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Differential expression of perforin and granzyme B in the liver of patients with chronic hepatitis C. Author(s): Pham BN, Martinot-Peignoux M, Valla D, Dubois S, Degott C, Mosnier JF. Source: Human Pathology. 2003 August; 34(8): 770-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14506637&dopt=Abstract

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Differential inhibition of RNA editing in hepatitis delta virus genotype III by the short and long forms of hepatitis delta antigen. Author(s): Cheng Q, Jayan GC, Casey JL. Source: Journal of Virology. 2003 July; 77(14): 7786-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829818&dopt=Abstract

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Discussion on frequency of the HIV-protective CC chemokine receptor 5-Delta 32/Delta 32 genotype is increased in hepatitis C. Author(s): Klein RS. Source: Gastroenterology. 2003 May; 124(5): 1558; Author Reply 1560-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12744236&dopt=Abstract

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Distribution of hepatitis B virus (HBV) genotypes among HBV carriers in the Cote d'Ivoire: complete genome sequence and phylogenetic relatedness of HBV genotype E. Author(s): Suzuki S, Sugauchi F, Orito E, Kato H, Usuda S, Siransy L, Arita I, Sakamoto Y, Yoshihara N, El-Gohary A, Ueda R, Mizokami M. Source: Journal of Medical Virology. 2003 April; 69(4): 459-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601751&dopt=Abstract

196 Hepatitis

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Distribution of hepatitis B virus in the liver of chronic hepatitis C patients with occult hepatitis B virus infection. Author(s): Rodriguez-Inigo E, Mariscal L, Bartolome J, Castillo I, Navacerrada C, OrtizMovilla N, Pardo M, Carreno V. Source: Journal of Medical Virology. 2003 August; 70(4): 571-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794719&dopt=Abstract

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Diversification of hypervariable region 1 of hepatitis C virus after liver transplantation. Author(s): Fan X, Di Bisceglie AM. Source: Journal of Medical Virology. 2003 June; 70(2): 212-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12696107&dopt=Abstract

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Doctor allegedly infected patients with hepatitis C. Author(s): Siegel-Itzkovich J. Source: Bmj (Clinical Research Ed.). 2003 August 23; 327(7412): 414. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12933719&dopt=Abstract

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Does previous hepatitis A infection affect the clinicopathological status of chronic hepatitis C? Author(s): Chlabicz S, Grzeszczuk A, Panasiuk A, Prokopowicz D. Source: Hepatogastroenterology. 2003 July-August; 50(52): 1066-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845983&dopt=Abstract

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Dramatic reduction of the alpha-fetoprotein level after lamivudine treatment of patients with chronic hepatitis B virus infection and cirrhosis. Author(s): Yao FY. Source: Journal of Clinical Gastroenterology. 2003 May-June; 36(5): 440-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702990&dopt=Abstract

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Dual effects of hepatitis C virus Core protein on the transcription of cyclin-dependent kinase inhibitor p21 gene. Author(s): Kwun HJ, Jang KL. Source: Journal of Viral Hepatitis. 2003 July; 10(4): 249-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823590&dopt=Abstract

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Durable clearance of hepatitis B virus after allogeneic blood stem cell transplantation by adoptive immunity transfer and antiviral chemotherapy. Author(s): Groll AH, Baumann-Kohler M, Storkebaum B, Kuhn J, Jurgens H, Vormoor J. Source: The Pediatric Infectious Disease Journal. 2003 August; 22(8): 753-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12938680&dopt=Abstract

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Dynamics of alanine aminotransferase during hepatitis C virus treatment. Author(s): Ribeiro RM, Layden-Almer J, Powers KA, Layden TJ, Perelson AS. Source: Hepatology (Baltimore, Md.). 2003 August; 38(2): 509-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883496&dopt=Abstract

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Dynamics of hepatitis C virus replication in human liver. Author(s): Chang M, Williams O, Mittler J, Quintanilla A, Carithers RL Jr, Perkins J, Corey L, Gretch DR. Source: American Journal of Pathology. 2003 August; 163(2): 433-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875965&dopt=Abstract

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Dynamics of subgenomic hepatitis C virus replicon RNA levels in Huh-7 cells after exposure to nucleoside antimetabolites. Author(s): Stuyver LJ, McBrayer TR, Tharnish PM, Hassan AE, Chu CK, Pankiewicz KW, Watanabe KA, Schinazi RF, Otto MJ. Source: Journal of Virology. 2003 October; 77(19): 10689-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970456&dopt=Abstract

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Early HCV RNA changes in patients with chronic hepatitis C treated with peginterferon alfa 2b and ribavirin. Author(s): Gallegos-Orozco JF, Fuentes AP, Olivera-Martinez MA, Gutierrez-Reyes G, Cortina D, Oregel JA, Perez-Pruna C, Sixtos MS, Cruz-Castellanos S, Soto-Ramirez LE, Rodriguez-Diaz R, Fuentes-Romero L, Gutierrez-Ruiz MC, Kershenobich D. Source: Revista De Investigacion Clinica; Organo Del Hospital De Enfermedades De La Nutricion. 2003 March-April; 55(2): 138-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12827916&dopt=Abstract

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Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C. Author(s): Davis GL, Wong JB, McHutchison JG, Manns MP, Harvey J, Albrecht J. Source: Hepatology (Baltimore, Md.). 2003 September; 38(3): 645-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939591&dopt=Abstract

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Early, rapidly progressive cholestatic hepatitis C reinfection and graft loss after adult living donor liver transplantation. Author(s): Troppmann C, Rossaro L, Perez RV, McVicar JP. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2003 February; 3(2): 239-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603221&dopt=Abstract

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Early-onset acute transverse myelitis following hepatitis B vaccination and respiratory infection: case report. Author(s): Fonseca LF, Noce TR, Teixeira ML, Teixeira AL Jr, Lana-Peixoto MA. Source: Arquivos De Neuro-Psiquiatria. 2003 June; 61(2A): 265-8. Epub 2003 June 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12806509&dopt=Abstract

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Economic analysis of promotion of hepatitis B vaccinations among VietnameseAmerican children and adolescents in Houston and Dallas. Author(s): Zhou F, Euler GL, McPhee SJ, Nguyen T, Lam T, Wong C, Mock J. Source: Pediatrics. 2003 June; 111(6 Pt 1): 1289-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777543&dopt=Abstract

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Economic impact of a hepatitis A epidemic in a mid-sized urban community: the case of Spokane, Washington. Author(s): Bownds L, Lindekugel R, Stepak P. Source: Journal of Community Health. 2003 August; 28(4): 233-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12856793&dopt=Abstract

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Editorial comment: diagnosis of acute HIV infection in hepatitis C treatment nonresponders--is extra vigilance required? Author(s): Golia P, Talal A. Source: Aids Read. 2003 June; 13(6): 288-90. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846174&dopt=Abstract

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Editorial comment: drug-drug interactions, hepatitis C, and mitochondrial toxicity. Author(s): Glesby MJ, Gerber JG. Source: Aids Read. 2003 July; 13(7): 346-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889453&dopt=Abstract

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Effect of antiviral therapy on markers of fibrogenesis in patients with chronic hepatitis C. Author(s): Nojgaard C, Johansen JS, Krarup HB, Holten-Andersen M, Moller A, Bendtsen F; Danish Viral Hepatitis Study Group. Source: Scandinavian Journal of Gastroenterology. 2003 June; 38(6): 659-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825876&dopt=Abstract

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Effect of long-term lamivudine therapy on histological outcome in chronic hepatitis B. Author(s): De Ridder RJ, Stronkhorst A. Source: Gastroenterology. 2003 October; 125(4): 1286-7; Author Reply 1287. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14552322&dopt=Abstract

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Effect of ribavirin on hepatitis C viral kinetics in patients treated with pegylated interferon. Author(s): Herrmann E, Lee JH, Marinos G, Modi M, Zeuzem S. Source: Hepatology (Baltimore, Md.). 2003 June; 37(6): 1351-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12774014&dopt=Abstract

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Effect of treatment with peginterferon or interferon alfa-2b and ribavirin on steatosis in patients infected with hepatitis C. Author(s): Poynard T, Ratziu V, McHutchison J, Manns M, Goodman Z, Zeuzem S, Younossi Z, Albrecht J. Source: Hepatology (Baltimore, Md.). 2003 July; 38(1): 75-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829989&dopt=Abstract

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Effective interferon therapy for chronic hepatitis C patients with low viral loads. Author(s): Fujiyama S, Chikazawa H, Honda Y, Tomita K. Source: Hepatogastroenterology. 2003 May-June; 50(51): 817-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828092&dopt=Abstract

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Effects of marker for hepatic fibrosis and viral status on recurrence after resection of hepatitis B virus-related hepatocellular carcinoma. Author(s): Kubo S, Tsukamoto T, Kawai S, Hirohashi K, Tanaka H, Shuto T, Takemura S, Nishiguchi S, Kinoshita H. Source: Hepatogastroenterology. 2003 March-April; 50(50): 497-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749255&dopt=Abstract

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Efficacy of interferon alpha-2b and lamivudine therapy for chronic hepatitis B in children. Author(s): Bahar A, Iscan S, Karademir F, Gocmen I. Source: Chin Med J (Engl). 2003 April; 116(4): 593-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875729&dopt=Abstract

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Efficacy of lamivudine therapy and factors associated with emergence of resistance in chronic hepatitis B virus infection in Japan. Author(s): Suzuki F, Tsubota A, Arase Y, Suzuki Y, Akuta N, Hosaka T, Someya T, Kobayashi M, Saitoh S, Ikeda K, Kobayashi M, Matsuda M, Satoh J, Takagi K, Kumada H. Source: Intervirology. 2003; 46(3): 182-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867757&dopt=Abstract

200 Hepatitis

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Efficacy of selective antenatal screening for hepatitis B among pregnant women in Denmark: is selective screening still an acceptable strategy in a low-endemicity country? Author(s): Jensen L, Heilmann C, Smith E, Wantzin P, Peitersen B, Weber T, Krogsgaard K. Source: Scandinavian Journal of Infectious Diseases. 2003; 35(6-7): 378-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953948&dopt=Abstract

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Efficacy of virosome hepatitis A vaccine in young children in Nicaragua: randomized placebo-controlled trial. Author(s): Perez OM, Herzog C, Zellmeyer M, Loaisiga A, Frosner G, Egger M. Source: The Journal of Infectious Diseases. 2003 September 1; 188(5): 671-7. Epub 2003 August 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934183&dopt=Abstract

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Elimination of false-negative hepatitis C virus RNA results by removal of inhibitors in cadaver-organ donor blood specimens. Author(s): Padley DJ, Lucas SB, Saldanha J. Source: Transplantation. 2003 July 27; 76(2): 432-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883207&dopt=Abstract

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Endocytosis of hepatitis B immune globulin into hepatocytes inhibits the secretion of hepatitis B virus surface antigen and virions. Author(s): Schilling R, Ijaz S, Davidoff M, Lee JY, Locarnini S, Williams R, Naoumov NV. Source: Journal of Virology. 2003 August; 77(16): 8882-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885906&dopt=Abstract

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Endoscopic sonographic evaluation of the thickened gallbladder wall in patients with acute hepatitis. Author(s): Kim MY, Baik SK, Choi YJ, Park DH, Kim HS, Lee DK, Kwon SO. Source: Journal of Clinical Ultrasound : Jcu. 2003 June; 31(5): 245-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767019&dopt=Abstract

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Establishment of a hepatitis C virus subgenomic replicon derived from human hepatocytes infected in vitro. Author(s): Kato N, Sugiyama K, Namba K, Dansako H, Nakamura T, Takami M, Naka K, Nozaki A, Shimotohno K. Source: Biochemical and Biophysical Research Communications. 2003 July 4; 306(3): 75666. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810084&dopt=Abstract

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Etiology of endemic viral hepatitis in urban North India. Author(s): Kaur R, Gur R, Berry N, Kar P. Source: Southeast Asian J Trop Med Public Health. 2002 December; 33(4): 845-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12757236&dopt=Abstract

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Evaluation of a modified commercial assay in detecting antibody to hepatitis C virus in oral fluids and dried blood spots. Author(s): Judd A, Parry J, Hickman M, McDonald T, Jordan L, Lewis K, Contreras M, Dusheiko G, Foster G, Gill N, Kemp K, Main J, Murray-Lyon I, Nelson M. Source: Journal of Medical Virology. 2003 September; 71(1): 49-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858408&dopt=Abstract

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Evaluation of a new serotyping assay for detection of anti-hepatitis C virus typespecific antibodies in serum samples. Author(s): Gault E, Soussan P, Morice Y, Sanders L, Berrada A, Rogers B, Deny P. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 2084-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734252&dopt=Abstract

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Evaluation of the MagNA pure LC instrument for extraction of hepatitis C virus RNA for the COBAS AMPLICOR Hepatitis C Virus Test, version 2.0. Author(s): Germer JJ, Lins MM, Jensen ME, Harmsen WS, Ilstrup DM, Mitchell PS, Cockerill FR 3rd, Patel R. Source: Journal of Clinical Microbiology. 2003 August; 41(8): 3503-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904346&dopt=Abstract

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Evidence of patient-to-patient transmission of hepatitis C virus through contaminated intravenous anaesthetic ampoules. Author(s): Tallis GF, Ryan GM, Lambert SB, Bowden DS, McCaw R, Birch CJ, Moloney M, Carnie JA, Locarnini SA, Rouch GJ, Catton MG. Source: Journal of Viral Hepatitis. 2003 May; 10(3): 234-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753344&dopt=Abstract

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Evidence of recombination in natural populations of hepatitis A virus. Author(s): Costa-Mattioli M, Ferre V, Casane D, Perez-Bercoff R, Coste-Burel M, ImbertMarcille BM, Andre EC, Bressollette-Bodin C, Billaudel S, Cristina J. Source: Virology. 2003 June 20; 311(1): 51-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832202&dopt=Abstract

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Evidence of viral replication in circulating dendritic cells during hepatitis C virus infection. Author(s): Goutagny N, Fatmi A, De Ledinghen V, Penin F, Couzigou P, Inchauspe G, Bain C. Source: The Journal of Infectious Diseases. 2003 June 15; 187(12): 1951-8. Epub 2003 May 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792872&dopt=Abstract

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Evolution of hepatitis C virus quasispecies in renal transplant patients with de novo glomerulonephritis. Author(s): Kamar N, Rostaing L, Boulestin A, Sandres K, Dubois M, Ribes D, Modesto A, Durand D, Izopet J. Source: Journal of Medical Virology. 2003 April; 69(4): 482-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601755&dopt=Abstract

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Evolutionary history of Hepatitis B virus genotype F: an in-depth analysis of Argentine isolates. Author(s): Pineiro y Leone FG, Mbayed VA, Campos RH. Source: Virus Genes. 2003 August; 27(1): 103-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12913363&dopt=Abstract

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Ex vivo analysis of human memory CD4 T cells specific for hepatitis C virus using MHC class II tetramers. Author(s): Day CL, Seth NP, Lucas M, Appel H, Gauthier L, Lauer GM, Robbins GK, Szczepiorkowski ZM, Casson DR, Chung RT, Bell S, Harcourt G, Walker BD, Klenerman P, Wucherpfennig KW. Source: The Journal of Clinical Investigation. 2003 September; 112(6): 831-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12975468&dopt=Abstract

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Excellent outcome of Lamivudine treatment in patients with chronic renal failure and hepatitis B virus infection. Author(s): Schmilovitz-Weiss H, Melzer E, Tur-Kaspa R, Ben-Ari Z. Source: Journal of Clinical Gastroenterology. 2003 July; 37(1): 64-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811212&dopt=Abstract

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Exploiting hepatitis C virus activation of NFkappaB to deliver HCV-responsive expression of interferons alpha and gamma. Author(s): Matskevich AA, Strayer DS. Source: Gene Therapy. 2003 October; 10(22): 1861-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14502215&dopt=Abstract

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Expression and coordinated regulation of matrix metalloproteinases in chronic hepatitis C and hepatitis C virus-induced liver cirrhosis. Author(s): Lichtinghagen R, Bahr MJ, Wehmeier M, Michels D, Haberkorn CI, Arndt B, Flemming P, Manns MP, Boeker KH. Source: Clinical Science (London, England : 1979). 2003 September; 105(3): 373-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760742&dopt=Abstract

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Expression of bile duct-type cytokeratin in noncancerous hepatocytes in patients with hepatitis B virus-related hepatocellular carcinoma. Author(s): Uenishi T, Kubo S, Hirohashi K, Yamamoto T, Ogawa M, Tanaka H, Shuto T, Kinoshita H. Source: Hepatogastroenterology. 2003 July-August; 50(52): 1101-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845990&dopt=Abstract

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Expression of the chemokine IP-10 (CXCL10) by hepatocytes in chronic hepatitis C virus infection correlates with histological severity and lobular inflammation. Author(s): Harvey CE, Post JJ, Palladinetti P, Freeman AJ, Ffrench RA, Kumar RK, Marinos G, Lloyd AR. Source: Journal of Leukocyte Biology. 2003 September; 74(3): 360-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12949239&dopt=Abstract

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Expression of the chemokine IP-10 correlates with the accumulation of hepatic IFNgamma and IL-18 mRNA in chronic hepatitis C but not in hepatitis B. Author(s): Mihm S, Schweyer S, Ramadori G. Source: Journal of Medical Virology. 2003 August; 70(4): 562-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794718&dopt=Abstract

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Expression of the stromal cell-derived factor-1 receptor (CXCR4) on peripheral lymphocytes of patients with hepatitis-C-virus-associated mixed cryoglobulinaemia. Author(s): Porretti L, Lopa R, Maiocchi M, Di Cataldo D, Scalamogna M, Prati D. Source: Dig Liver Dis. 2003 May; 35(5): 370-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846411&dopt=Abstract

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Extrarespiratory Chlamydia pneumoniae infection associated with immune disorder, hepatitis and renal disease. Author(s): Kalambokis G, Ekonomou G, Kitsanou M, Kostoula A, Bobojianni C, Tsianos E. Source: Scandinavian Journal of Infectious Diseases. 2003; 35(6-7): 424-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953963&dopt=Abstract

204 Hepatitis

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Facilitating the WHO expanded program of immunization: the clinical profile of a combined diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae type b vaccine. Author(s): Aristegui J, Usonis V, Coovadia H, Riedemann S, Win KM, Gatchalian S, Bock HL. Source: International Journal of Infectious Diseases : Ijid : Official Publication of the International Society for Infectious Diseases. 2003 June; 7(2): 143-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839717&dopt=Abstract

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Factor V Leiden polymorphism and the rate of fibrosis development in chronic hepatitis C virus infection. Author(s): Wright M, Goldin R, Hellier S, Knapp S, Frodsham A, Hennig B, Hill A, Apple R, Cheng S, Thomas H, Thursz M. Source: Gut. 2003 August; 52(8): 1206-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865283&dopt=Abstract

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Factors affecting hepatitis vaccination refusal at a sexually transmitted disease clinic among men who have sex with men. Author(s): Rudy ET, Detels R, Douglas W, Greenland S. Source: Sexually Transmitted Diseases. 2003 May; 30(5): 411-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916132&dopt=Abstract

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Factors affecting the compliance of the antenatal hepatitis B screening programme in Italy. Author(s): Stroffolini T, Bianco E, Szklo A, Bernacchia R, Bove C, Colucci M, Cristina Coppola R, D'Argenio P, Lopalco P, Parlato A, Ragni P, Simonetti A, Zotti C, Mele A. Source: Vaccine. 2003 March 7; 21(11-12): 1246-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559805&dopt=Abstract

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Factors associated with hepatitis C virus infection in injection and noninjection drug users in Italy. Author(s): Quaglio G, Lugoboni F, Pajusco B, Sarti M, Talamini G, Lechi A, Mezzelani P, Des Jarlais DC. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 July 1; 37(1): 33-40. Epub 2003 June 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12830406&dopt=Abstract

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Factors influencing hepatitis B vaccine uptake in injecting drug users. Author(s): McGregor J, Marks PJ, Hayward A, Bell Y, Slack RC. Source: Journal of Public Health Medicine. 2003 June; 25(2): 165-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848409&dopt=Abstract

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Factors predisposing to the occurrence of cryoglobulinemia in two cohorts of Egyptian and Japanese patients with chronic hepatitis C infection: ethnic and genotypic influence. Author(s): Gad A, Tanaka E, Matsumoto A, el-Hamid Serwah A, Ali K, Makledy F, elGohary A, Orii K, Ijima A, Rokuhara A, Yoshizawa K, Nooman Z, Kiyosawa K. Source: Journal of Medical Virology. 2003 August; 70(4): 594-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794722&dopt=Abstract

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Factors that influence the severity of recurrent hepatitis C virus following liver transplantation. Author(s): Porter SB, Reddy KR. Source: Clinics in Liver Disease. 2003 August; 7(3): 603-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509529&dopt=Abstract

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Failure of therapeutic vaccination using hepatitis B surface antigen vaccine in the immunotolerant phase of children with chronic hepatitis B infection. Author(s): Dikici B, Bosnak M, Ucmak H, Dagli A, Ece A, Haspolat K. Source: Journal of Gastroenterology and Hepatology. 2003 February; 18(2): 218-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12542609&dopt=Abstract

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Familial clustering of hepatitis B infection: study of a family. Author(s): Verma G, Dalai P, Bapat M, Rathi P, Abraham P. Source: Indian J Gastroenterol. 2003 January-February; 22(1): 22-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12617448&dopt=Abstract

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Fas-mediated apoptosis in acute alcoholic hepatitis. Author(s): Tagami A, Ohnishi H, Moriwaki H, Phillips M, Hughes RD. Source: Hepatogastroenterology. 2003 March-April; 50(50): 443-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749243&dopt=Abstract

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Fatal hepatitis B virus reactivation by an escape mutant following rituximab therapy. Author(s): Westhoff TH, Jochimsen F, Schmittel A, Stoffler-Meilicke M, Schafer JH, Zidek W, Gerlich WH, Thiel E. Source: Blood. 2003 September 1; 102(5): 1930. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930732&dopt=Abstract

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Fatal outcome of SARS in a patient with reactivation of chronic hepatitis B. Author(s): Hui AY, Chan HL, Liew CT, Chan PK, To KF, Chan CP, Sung JJ. Source: The American Journal of Medicine. 2003 September; 115(4): 334-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12967706&dopt=Abstract

206 Hepatitis

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Fatigue is associated with high circulating leptin levels in chronic hepatitis C. Author(s): Romero-Gomez M, Sanchez-Munoz D, Cruz M. Source: Gut. 2003 June; 52(6): 915. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740359&dopt=Abstract

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Favorable prognosis of chronic hepatitis C after interferon therapy by long-term cohort study. Author(s): Imazeki F, Yokosuka O, Fukai K, Saisho H. Source: Hepatology (Baltimore, Md.). 2003 August; 38(2): 493-502. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883494&dopt=Abstract

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Feasibility of histological grading and staging of chronic viral hepatitis using specimens obtained by thin-needle biopsy. Author(s): Petz D, Klauck S, Rohl FW, Malfertheiner P, Roessner A, Rocken C. Source: Virchows Archiv : an International Journal of Pathology. 2003 March; 442(3): 238-44. Epub 2003 January 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12647213&dopt=Abstract

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Fibrosing cholestatic hepatitis developing after liver transplantation: case report of a patient with HCV-related cirrhosis. Author(s): Takahashi T, Ashizawa S, Matsumoto H, Furuta K, Omura T, Sato K, Kakita A. Source: Transplantation Proceedings. 2003 February; 35(1): 392-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591455&dopt=Abstract

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Fibrosing cholestatic hepatitis in a liver transplant recipient with hepatitis C virus infection: a case report. Author(s): Furuta K, Takahashi T, Aso K, Hoshino H, Sato K, Kakita A. Source: Transplantation Proceedings. 2003 February; 35(1): 389-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591454&dopt=Abstract

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Fibrosing cholestatic hepatitis-like syndrome in a hepatitis B virus and hepatitis C virus-negative renal transplant recipient: a case report with autopsy findings. Author(s): Duseja A, Nada R, Kalra N, Acharya SK, Minz M, Joshi K, Chawla Y. Source: Trop Gastroenterol. 2003 January-March; 24(1): 31-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974214&dopt=Abstract

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Fibrosis in chronic hepatitis C acquired in infancy: is it only a matter of time? Author(s): Guido M, Bortolotti F, Leandro G, Jara P, Hierro L, Larrauri J, Barbera C, Giacchino R, Zancan L, Balli F, Crivellaro C, Cristina E, Pucci A, Rugge M. Source: The American Journal of Gastroenterology. 2003 March; 98(3): 660-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650803&dopt=Abstract

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Fidelity of hepatitis B virus polymerase. Author(s): Park SG, Kim Y, Park E, Ryu HM, Jung G. Source: European Journal of Biochemistry / Febs. 2003 July; 270(14): 2929-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846825&dopt=Abstract

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First phase hepatitis c viral kinetics in previous nonresponders patients. Author(s): Cotler SJ, Layden JE, Neumann AU, Jensen DM. Source: Journal of Viral Hepatitis. 2003 January; 10(1): 43-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558911&dopt=Abstract

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First things first: balancing hepatitis C and human immunodeficiency virus. Author(s): Graham CS, Koziel MJ. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 February 1; 36(3): 368-9. Epub 2003 January 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12539080&dopt=Abstract

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Five-year survival predictive factors in patients with excessive alcohol intake and cirrhosis. Effect of alcoholic hepatitis, smoking and abstinence. Author(s): Pessione F, Ramond MJ, Peters L, Pham BN, Batel P, Rueff B, Valla DC. Source: Liver International : Official Journal of the International Association for the Study of the Liver. 2003 February; 23(1): 45-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640727&dopt=Abstract

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Frequency and phenotype of circulating Valpha24/Vbeta11 double-positive natural killer T cells during hepatitis C virus infection. Author(s): Lucas M, Gadola S, Meier U, Young NT, Harcourt G, Karadimitris A, Coumi N, Brown D, Dusheiko G, Cerundolo V, Klenerman P. Source: Journal of Virology. 2003 February; 77(3): 2251-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12525661&dopt=Abstract

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Frequency and significance of antibodies to chromatin in autoimmune hepatitis. Author(s): Czaja AJ, Shums Z, Binder WL, Lewis SJ, Nelson VJ, Norman GL. Source: Digestive Diseases and Sciences. 2003 August; 48(8): 1658-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924665&dopt=Abstract

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Frequency and significance of antibodies to soluble liver antigen/liver pancreas in variant autoimmune hepatitis. Author(s): Czaja AJ, Shums Z, Norman GL. Source: Autoimmunity. 2002 December; 35(8): 475-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765472&dopt=Abstract

208 Hepatitis

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Frequency of the 32-base pair deletion in the chemokine receptor CCR5 gene is not increased in hepatitis C patients. Author(s): Poljak M, Seme K, Marin IJ, Babic DZ, Matcic M, Meglic J. Source: Gastroenterology. 2003 May; 124(5): 1558-60; Author Reply 1560-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12744237&dopt=Abstract

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Frequent loss of p53 codon 72 Pro variant in hepatitis C virus-positive carriers with hepatocellular carcinoma. Author(s): Anzola M, Cuevas N, Lopez-Martinez M, Saiz A, Burgos JJ, de Pancorbo MM. Source: Cancer Letters. 2003 April 25; 193(2): 199-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706878&dopt=Abstract

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Frequent occult hepatitis B virus infection in patients infected with human immunodeficiency virus type 1. Author(s): Santos EA, Yoshida CF, Rolla VC, Mendes JM, Vieira IF, Arabe J, Gomes SA. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2003 February; 22(2): 92-8. Epub 2003 February 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627282&dopt=Abstract

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Frequent recovery and broad genotype 2 diversity characterize hepatitis C virus infection in Ghana, West Africa. Author(s): Candotti D, Temple J, Sarkodie F, Allain JP. Source: Journal of Virology. 2003 July; 77(14): 7914-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829831&dopt=Abstract

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Full-length genome of wild-type hepatitis A virus (DL3) isolated in China. Author(s): Liu GD, Hu NZ, Hu YZ. Source: World Journal of Gastroenterology : Wjg. 2003 March; 9(3): 499-504. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632505&dopt=Abstract

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Fulminant adenovirus hepatitis following bone marrow transplantation. A case report and brief review of the literature. Author(s): Wang WH, Wang HL. Source: Archives of Pathology & Laboratory Medicine. 2003 May; 127(5): E246-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708923&dopt=Abstract

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Fulminant hepatic failure caused by hepatitis B virus activation after chemotherapy for breast cancer treated with liver transplantation: a case report. Author(s): Hung CM, Jeng LB, Lee WC, Yu MC, Kuo LM, Chen MF. Source: Transplantation Proceedings. 2003 February; 35(1): 387-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591453&dopt=Abstract

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Fulminant hepatitis after grand mal seizures: mechanisms and role of liver transplantation. Author(s): Ichai P, Huguet E, Guettier C, Azoulay D, Gonzalez ME, Fromenty B, Masnou P, Saliba F, Roche B, Zeitoun F, Castaing D, Samuel D. Source: Hepatology (Baltimore, Md.). 2003 August; 38(2): 443-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883489&dopt=Abstract

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Fulminant hepatitis after infliximab in a patient with hepatitis B virus treated for an adult onset still's disease. Author(s): Michel M, Duvoux C, Hezode C, Cherqui D. Source: The Journal of Rheumatology. 2003 July; 30(7): 1624-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858469&dopt=Abstract

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GB virus C/hepatitis G virus infection among renal transplant recipients in Izmir, Turkey: Molecular analysis of phylogenetic groups. Author(s): Erensoy S, Zeytinoglu A, Goksel S, Ozacar T, Ozkahya M, Ok E, Tuumlrkoglu S, Bilgic A. Source: International Journal of Infectious Diseases : Ijid : Official Publication of the International Society for Infectious Diseases. 2002 September; 6(3): 242-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12718845&dopt=Abstract

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GB virus type C/Hepatitis G virus. Author(s): Stapleton JT. Source: Seminars in Liver Disease. 2003 May; 23(2): 137-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800067&dopt=Abstract

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Gender differences in hepatitis C infection and risks among persons with severe mental illness. Author(s): Butterfield MI, Bosworth HB, Meador KG, Stechuchak KM, Essock SM, Osher FC, Goodman LA, Swanson JW, Bastian LA, Horner RD; Five-Site Health and Risk Study Research Committee. Source: Psychiatric Services (Washington, D.C.). 2003 June; 54(6): 848-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773599&dopt=Abstract

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Gene expression profiling of the cellular transcriptional network regulated by alpha/beta interferon and its partial attenuation by the hepatitis C virus nonstructural 5A protein. Author(s): Geiss GK, Carter VS, He Y, Kwieciszewski BK, Holzman T, Korth MJ, Lazaro CA, Fausto N, Bumgarner RE, Katze MG. Source: Journal of Virology. 2003 June; 77(11): 6367-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743294&dopt=Abstract

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Generation of stable cell lines expressing Lamivudine-resistant hepatitis B virus for antiviral-compound screening. Author(s): Walters KA, Tipples GA, Allen MI, Condreay LD, Addison WR, Tyrrell L. Source: Antimicrobial Agents and Chemotherapy. 2003 June; 47(6): 1936-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760870&dopt=Abstract

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Genetic analysis of HAV strains recovered from patients with acute hepatitis from Southern Italy. Author(s): Chironna M, Grottola A, Lanave C, Villa E, Barbuti S, Quarto M. Source: Journal of Medical Virology. 2003 July; 70(3): 343-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766995&dopt=Abstract

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Genome replication, virion secretion, and e antigen expression of naturally occurring hepatitis B virus core promoter mutants. Author(s): Parekh S, Zoulim F, Ahn SH, Tsai A, Li J, Kawai S, Khan N, Trepo C, Wands J, Tong S. Source: Journal of Virology. 2003 June; 77(12): 6601-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767980&dopt=Abstract

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Genomic and antigenomic chains of hepatitis C virus and hepatitis G virus in serum, liver and peripheral blood mononuclear cells. Author(s): Torres C, Munoz de Rueda P, Ruiz-Extremera A, Quintero D, Palacios A, Salmeron J. Source: Rev Esp Enferm Dig. 2002 November; 94(11): 659-68. English, Spanish. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12690989&dopt=Abstract

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Genomic mutations with amino acid substitutions of circulating hepatitis B virus found in non-B, non-C patients with hepatocellular carcinoma. Author(s): Nakamoto N, Saito H, Ebinuma H, Tada S, Saito Y, Kurita S, Kitamura K, Ishii H. Source: Intern Med. 2003 April; 42(4): 322-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729320&dopt=Abstract

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Genotype analysis, using PCR with type-specific primers, of hepatitis B virus isolates from patients coinfected with hepatitis delta virus genotype II from Miyako Island, Japan. Author(s): Moriyama M, Taira M, Matsumura H, Aoki H, Mikuni M, Kaneko M, Shioda A, Iwaguchi K, Arai S, Ichijima S, Iwasaki H, Tanaka N, Abe K, Arakawa Y. Source: Intervirology. 2003; 46(2): 114-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684550&dopt=Abstract

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Genotype distribution of hepatitis C virus in the Hungarian population with chronic viral hepatitis C. Author(s): Gervain J, Simon Jr G, Simon J; Hungarian Viral Hepatitis Group. Source: European Journal of Gastroenterology & Hepatology. 2003 April; 15(4): 449-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655271&dopt=Abstract

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Genotypes and phylogenetic characterization of hepatitis B and delta viruses in Egypt. Author(s): Saudy N, Sugauchi F, Tanaka Y, Suzuki S, Aal AA, Zaid MA, Agha S, Mizokami M. Source: Journal of Medical Virology. 2003 August; 70(4): 529-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794714&dopt=Abstract

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Genotypes of hepatitis C virus circulating in Tunisia. Author(s): Djebbi A, Triki H, Bahri O, Cheikh I, Sadraoui A, Ben Ammar A, Dellagi K. Source: Epidemiology and Infection. 2003 June; 130(3): 501-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825736&dopt=Abstract

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Genotypic and phenotypic resistance: longitudinal and sequential analysis of hepatitis B virus polymerase mutations in patients with lamivudine resistance after liver transplantation. Author(s): Ben-Ari Z, Daudi N, Klein A, Sulkes J, Papo O, Mor E, Samra Z, Gadba R, Shouval D, Tur-Kaspa R. Source: The American Journal of Gastroenterology. 2003 January; 98(1): 151-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12526951&dopt=Abstract

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Geographic characterization of hepatitis virus infections, genotyping of hepatitis B virus, and p53 mutation in hepatocellular carcinoma analyzed by in situ detection of viral genomes from carcinoma tissues: comparison among six different countries. Author(s): Ding X, Park YN, Taltavull TC, Thung SN, Jin X, Jin Y, Trung NS, Edamoto Y, Sata T, Abe K. Source: Japanese Journal of Infectious Diseases. 2003 February; 56(1): 12-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711820&dopt=Abstract

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Global control of primary hepatocellular carcinoma with hepatitis B vaccine: the contributions of research in Taiwan. Author(s): Kane MA. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2003 January; 12(1): 2-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12540496&dopt=Abstract

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Global progress toward universal childhood hepatitis B vaccination, 2003. Author(s): Centers for Disease Control and Prevention (CDC). Source: Mmwr. Morbidity and Mortality Weekly Report. 2003 September 12; 52(36): 86870. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970620&dopt=Abstract

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Glucose intolerance in Chinese patients with chronic hepatitis C. Author(s): Chen LK, Hwang SJ, Tsai ST, Luo JC, Lee SD, Chang FY. Source: World Journal of Gastroenterology : Wjg. 2003 March; 9(3): 505-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632506&dopt=Abstract

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Guidelines for laboratory testing and result reporting of antibody to hepatitis C virus. Centers for Disease Control and Prevention. Author(s): Ann Intern Med. 2003 Feb 18;138(4):I52 Source: Mmwr. Recommendations and Reports : Morbidity and Mortality Weekly Report. Recommendations and Reports / Centers for Disease Control. 2003 February 7; 52(Rr-3): 1-13, 15; Quiz Ce1-4. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12585851

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HBe antigen loss during lamivudine therapy is not caused by mutations in precore and core promoter genes in patients with chronic hepatitis B. Author(s): Suzuki F, Tsubota A, Arase Y, Suzuki Y, Akuta N, Hosaka T, Someya T, Kobayashi M, Saitoh S, Ikeda K, Kobayashi M, Matsuda M, Satoh J, Takagi K, Kumada H. Source: Journal of Medical Virology. 2003 July; 70(3): 355-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766997&dopt=Abstract

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Hematologic disorders associated with hepatitis C virus infection and their management. Author(s): Dieterich DT, Spivak JL. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 August 15; 37(4): 533-41. Epub 2003 Aug 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12905138&dopt=Abstract

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Hepatitis A and B vaccination in a sexually transmitted disease clinic for men who have sex with men. Author(s): Sansom S, Rudy E, Strine T, Douglas W. Source: Sexually Transmitted Diseases. 2003 September; 30(9): 685-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12972790&dopt=Abstract

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Hepatitis A virus infections in injecting drug users. Author(s): Crowcroft NS. Source: Commun Dis Public Health. 2003 June; 6(2): 82-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889283&dopt=Abstract

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Hepatitis A: an unusual presentation. Author(s): Vaidya P, Kadam C. Source: Indian Pediatrics. 2003 September; 40(9): 910-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14530561&dopt=Abstract

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Hepatitis B and C in the hemodialysis unit of Tocantins, Brazil: serological and molecular profiles. Author(s): Souza KP, Luz JA, Teles SA, Carneiro MA, Oliveira LA, Gomes AS, Dias MA, Gomes SA, Yoshida CF, Martins RM. Source: Memorias Do Instituto Oswaldo Cruz. 2003 July; 98(5): 599-603. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13677340&dopt=Abstract

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Hepatitis B immune globulin preparations and use in liver transplantation. Author(s): Terrault NA, Vyas G. Source: Clinics in Liver Disease. 2003 August; 7(3): 537-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509525&dopt=Abstract

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Hepatitis B surface antigen (HbsAg) in the sera of medical, nursing and microbiology students in Ibadan, Nigeria. Author(s): Odemuyiwa SO, Oyedele OI, Forbi JC, Elemuwa CO, Ibeh MA, Kfutwah AK, Uche LN, Anibaba AA. Source: Afr J Med Med Sci. 2001 December; 30(4): 333-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14510114&dopt=Abstract

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Hepatitis B vaccination of incarcerated women: a pilot program. Author(s): Clarke J, Schwartzapfel B, Pomposelli J, Allen S, Spaulding A, Rich JD. Source: Journal of Health Care for the Poor and Underserved. 2003 August; 14(3): 31823. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12955912&dopt=Abstract

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Hepatitis B vaccination: myths and controversies. Author(s): Mittal SK. Source: Indian J Pediatr. 2003 June; 70(6): 499-502. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921320&dopt=Abstract

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Hepatitis B vaccine and risk of multiple sclerosis. Author(s): DeStefano F, Verstraeten T, Chen RT. Source: Expert Rev Vaccines. 2002 December; 1(4): 461-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901584&dopt=Abstract

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Hepatitis B virus genotypes in the United States: results of a nationwide study. Author(s): Chu CJ, Keeffe EB, Han SH, Perrillo RP, Min AD, Soldevila-Pico C, Carey W, Brown RS Jr, Luketic VA, Terrault N, Lok AS. Source: Gastroenterology. 2003 August; 125(2): 444-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891547&dopt=Abstract

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Hepatitis B virus immunization among young injection drug users in San Francisco, Calif: the UFO Study. Author(s): Lum PJ, Ochoa KC, Hahn JA, Page Shafer K, Evans JL, Moss AR; UFO Study. Source: American Journal of Public Health. 2003 June; 93(6): 919-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773355&dopt=Abstract

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Hepatitis B virus molecular diversity in Indonesia. Author(s): Handojo Muljono D, Soemohardjo S. Source: Advances in Experimental Medicine and Biology. 2003; 531: 163-76. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916788&dopt=Abstract

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Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United States. Author(s): Edlich RF, Diallo AO, Buchanan L, Martin ML. Source: Journal of Long-Term Effects of Medical Implants. 2003; 13(2): 117-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14510285&dopt=Abstract

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Hepatitis B: Implications for the oral health worker. Author(s): Naidoo S. Source: Sadj. 2003 June; 58(5): 196-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14596264&dopt=Abstract

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Hepatitis C among public safety workers-assessment of risk and strategies for prevention. Author(s): McCauley LA, Rischitelli DG, Salazar MK. Source: Aaohn Journal : Official Journal of the American Association of Occupational Health Nurses. 2003 August; 51(8): 333-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934859&dopt=Abstract

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Hepatitis C infection among dental personnel in the West of Scotland, UK. Author(s): Roy K, Kennedy C, Bagg J, Cameron S, Hunter I, Taylor M. Source: The Journal of Hospital Infection. 2003 September; 55(1): 73-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14505613&dopt=Abstract

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Hepatitis C seropositivity among chronic liver disease patients in Hazara, Pakistan. Author(s): Khan TS, Rizvi F, Rashid A. Source: J Ayub Med Coll Abbottabad. 2003 April-June; 15(2): 53-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14552251&dopt=Abstract

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Hepatitis C transmission and HIV post-exposure prophylaxis after needle- and syringe-sharing in Australian prisons. Author(s): O'Sullivan BG, Levy MH, Dolan KA, Post JJ, Barton SG, Dwyer DE, Kaldor JM, Grulich AE. Source: The Medical Journal of Australia. 2003 June 2; 178(11): 546-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765501&dopt=Abstract

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Hepatitis C virus clearance: the enigma of failure despite an impeccable survival strategy. Author(s): Isaguliants MG. Source: Current Pharmaceutical Biotechnology. 2003 June; 4(3): 169-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769761&dopt=Abstract

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Hepatitis C virus core protein expression leads to biphasic regulation of the p21 cdk inhibitor and modulation of hepatocyte cell cycle. Author(s): Nguyen H, Mudryj M, Guadalupe M, Dandekar S. Source: Virology. 2003 July 20; 312(1): 245-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890637&dopt=Abstract

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Hepatitis C virus infection among noninjecting drug users in New York City. Author(s): Koblin BA, Factor SH, Wu Y, Vlahov D. Source: Journal of Medical Virology. 2003 July; 70(3): 387-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767001&dopt=Abstract

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Hepatitis C virus infection: when silence is deception. Author(s): Racanelli V, Rehermann B. Source: Trends in Immunology. 2003 August; 24(8): 456-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12909460&dopt=Abstract

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Hepatitis C virus IRES efficiency is unaffected by the genomic RNA 3'NTR even in the presence of viral structural or non-structural proteins. Author(s): Imbert I, Dimitrova M, Kien F, Kieny MP, Schuster C. Source: The Journal of General Virology. 2003 June; 84(Pt 6): 1549-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771425&dopt=Abstract

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Hepatitis C virus NS5A as a potential viral Bcl-2 homologue interacts with Bax and inhibits apoptosis in hepatocellular carcinoma. Author(s): Chung YL, Sheu ML, Yen SH. Source: International Journal of Cancer. Journal International Du Cancer. 2003 October 20; 107(1): 65-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925958&dopt=Abstract

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Hepatitis C virus-specific cytolytic T cell responses after antiviral therapy. Author(s): Morishima C, Musey L, Elizaga M, Gaba K, Allison M, Carithers RL, Gretch DR, McElrath MJ. Source: Clinical Immunology (Orlando, Fla.). 2003 September; 108(3): 211-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14499244&dopt=Abstract

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Hepatitis C: a review of diagnosis, management, and ocular complications from treatment. Author(s): Tsolakos A, Zalatimo N. Source: Optometry. 2003 August; 74(8): 517-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926825&dopt=Abstract

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Hepatitis C: a review. Author(s): Yoho RA, Cruz LL, Mazaheri R, Cruz AT. Source: Plastic and Reconstructive Surgery. 2003 August; 112(2): 597-605. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12900622&dopt=Abstract

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Hepatitis C: Implications for the oral health worker. Author(s): Naidoo S. Source: Sadj. 2003 June; 58(5): 197-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14596266&dopt=Abstract

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Hepatitis C: nutrition care Canadian guidelines for health care providers. Author(s): Dietitians of Canada. Source: Can J Diet Pract Res. 2003 Fall; 64(3): 139-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12959661&dopt=Abstract

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Hepatitis C: the 'silent stalker'. Author(s): Harkness GA. Source: The American Journal of Nursing. 2003 September; 103(9): 24-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14506802&dopt=Abstract

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Hepatitis C-related hepatocellular carcinoma in the United States: influence of ethnic status. Author(s): Di Bisceglie AM, Lyra AC, Schwartz M, Reddy RK, Martin P, Gores G, Lok AS, Hussain KB, Gish R, Van Thiel DH, Younossi Z, Tong M, Hassanein T, Balart L, Fleckenstein J, Flamm S, Blei A, Befeler AS; Liver Cancer Network. Source: The American Journal of Gastroenterology. 2003 September; 98(9): 2060-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14499788&dopt=Abstract

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High body mass index is an independent risk factor for nonresponse to antiviral treatment in chronic hepatitis C. Author(s): Bressler BL, Guindi M, Tomlinson G, Heathcote J. Source: Hepatology (Baltimore, Md.). 2003 September; 38(3): 639-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939590&dopt=Abstract

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High prevalence of transfusion-transmitted virus infection in patients with chronic liver diseases in an endemic area of hepatitis B and C virus. Author(s): Savas MC, Guney C, Kadayifci A, Balkan A, Koruk M, Kubar A, Uygun A. Source: Medical Principles and Practice : International Journal of the Kuwait University, Health Science Centre. 2003 July-September; 12(3): 176-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766336&dopt=Abstract

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Hospitalization rates differ by hepatitis C satus in an urban HIV cohort. Author(s): Gebo KA, Diener-West M, Moore RD. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 2003 October 1; 34(2): 165-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14526205&dopt=Abstract

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Host background factors contributing to hepatitis C virus clearance. Author(s): Isaguliants MG, Ozeretskovskaya NN. Source: Current Pharmaceutical Biotechnology. 2003 June; 4(3): 185-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769762&dopt=Abstract

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Human immunodeficiency virus and hepatitis C virus: which is the cart, and which is the horse? Author(s): Jenny-Avital ER. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 September 1; 37(5): 739; Author Reply 740. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12942414&dopt=Abstract

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Hyperlipasemia associated with hepatitis C virus. Author(s): Yoffe B, Bagri AS, Tran T, Dural AT, Shtenberg KM, Khaoustov VI. Source: Digestive Diseases and Sciences. 2003 August; 48(8): 1648-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924663&dopt=Abstract

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Hyperpigmentation during interferon-alpha therapy for chronic hepatitis C virus infection. Author(s): Willems M, Munte K, Vrolijk JM, Den Hollander JC, Bohm M, Kemmeren MH, De Man RA, Brouwer JT. Source: The British Journal of Dermatology. 2003 August; 149(2): 390-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12932249&dopt=Abstract

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Identification of a ribavirin-resistant NS5B mutation of hepatitis C virus during ribavirin monotherapy. Author(s): Young KC, Lindsay KL, Lee KJ, Liu WC, He JW, Milstein SL, Lai MM. Source: Hepatology (Baltimore, Md.). 2003 October; 38(4): 869-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512874&dopt=Abstract

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Identification of hepatitis C virus (HCV) subtype 1b strains that are highly, or only weakly, associated with hepatocellular carcinoma on the basis of the secondary structure of an amino-terminal portion of the HCV NS3 protein. Author(s): Ogata S, Florese RH, Nagano-Fujii M, Hidajat R, Deng L, Ku Y, Yoon S, Saito T, Kawata S, Hotta H. Source: Journal of Clinical Microbiology. 2003 July; 41(7): 2835-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843009&dopt=Abstract

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Identification of swine hepatitis E virus (HEV) and prevalence of anti-HEV antibodies in swine and human populations in Korea. Author(s): Choi IS, Kwon HJ, Shin NR, Yoo HS. Source: Journal of Clinical Microbiology. 2003 August; 41(8): 3602-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904362&dopt=Abstract

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IgA class antineutrophil cytoplasmic antibodies in primary sclerosing cholangitis and autoimmune hepatitis. Author(s): Schwarze C, Terjung B, Lilienweiss P, Beuers U, Herzog V, Sauerbruch T, Spengler U. Source: Clinical and Experimental Immunology. 2003 August; 133(2): 283-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869036&dopt=Abstract

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Immunization and the decline of viral hepatitis as a cause of acute liver failure. Author(s): Sjogren M. Source: Hepatology (Baltimore, Md.). 2003 September; 38(3): 554-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939580&dopt=Abstract

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Immunization with an adjuvant hepatitis B vaccine after liver transplantation for hepatitis B-related disease. Author(s): Bienzle U, Gunther M, Neuhaus R, Vandepapeliere P, Vollmar J, Lun A, Neuhaus P. Source: Hepatology (Baltimore, Md.). 2003 October; 38(4): 811-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512868&dopt=Abstract

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Immunogenicity and reactogenicity of DTPw-HB/Hib vaccine administered to colombian infants after a birth dose of hepatitis B vaccine. Author(s): Lopez P, Rubiano L, del Pilar Rubio M, David MP, Safary A. Source: Expert Rev Vaccines. 2002 October; 1(3): 277-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901568&dopt=Abstract

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Immunology: hepatitis A virus link to atopic disease. Author(s): McIntire JJ, Umetsu SE, Macaubas C, Hoyte EG, Cinnioglu C, Cavalli-Sforza LL, Barsh GS, Hallmayer JF, Underhill PA, Risch NJ, Freeman GJ, DeKruyff RH, Umetsu DT. Source: Nature. 2003 October 9; 425(6958): 576. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14534576&dopt=Abstract

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Immunosuppression in hepatitis B virus and hepatitis C virus transplants: special considerations. Author(s): Samuel D, Kimmoun E. Source: Clinics in Liver Disease. 2003 August; 7(3): 667-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509533&dopt=Abstract

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Impact of hepatitis C virus (HCV) on morbidity and mortality rates among HIVinfected patients. Author(s): Nunez M, Martin-Carbonero L, Soriano V. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 August 1; 37(3): 460-1; Author Reply 461. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12884176&dopt=Abstract

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Impact of the introduction of a combined Haemophilus B conjugate vaccine and hepatitis B recombinant vaccine on vaccine coverage rats in a large West Coast health maintenance organization. Author(s): Davis RL, Coplan P, Mell L, Black S, Shinefield H, Lewis E. Source: The Pediatric Infectious Disease Journal. 2003 July; 22(7): 657-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886895&dopt=Abstract

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Implementation of universal antenatal screening for HIV and hepatitis B--lessons for future work. Author(s): Baird J, Hammond M, Barker M. Source: Journal of Public Health Medicine. 2003 June; 25(2): 171-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848410&dopt=Abstract

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Improved sensitivity for cell mapping of hepatitis C virus RNA sequences and cellular surface antigens in blood cells. Author(s): Gosalvez J, Ortiz-Movilla N, Gosalbez A, Rodriguez-Inigo E, Bartolome J, Carreno V. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2003 July; 83(7): 1089-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861048&dopt=Abstract

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In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus. Author(s): Bordier BB, Ohkanda J, Liu P, Lee SY, Salazar FH, Marion PL, Ohashi K, Meuse L, Kay MA, Casey JL, Sebti SM, Hamilton AD, Glenn JS. Source: The Journal of Clinical Investigation. 2003 August; 112(3): 407-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12897208&dopt=Abstract

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Inactivated hepatitis A vaccine: immunogenicity, efficacy, safety and review of official recommendations for use. Author(s): Andre F, Van Damme P, Safary A, Banatvala J. Source: Expert Rev Vaccines. 2002 June; 1(1): 9-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12908508&dopt=Abstract

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Inactivated parapoxvirus ovis (Orf virus) has antiviral activity against hepatitis B virus and herpes simplex virus. Author(s): Weber O, Siegling A, Friebe A, Limmer A, Schlapp T, Knolle P, Mercer A, Schaller H, Volk HD. Source: The Journal of General Virology. 2003 July; 84(Pt 7): 1843-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810878&dopt=Abstract

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Increased carbohydrate-deficient transferrin of unknown etiology in a 15-year-old male patient with autoimmune hepatitis type 1. Author(s): Arndt T, Kuhn D, Herbst H, Linnemann M, Nikolaidis N. Source: Clinical Chemistry. 2003 June; 49(6 Pt 1): 1025-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766022&dopt=Abstract

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Increased hepatitis C virus load among injection drug users infected with human immunodeficiency virus and human T lymphotropic virus type II. Author(s): Hisada M, Chatterjee N, Zhang M, Battjes RJ, Goedert JJ. Source: The Journal of Infectious Diseases. 2003 September 15; 188(6): 891-7. Epub 2003 Sep 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12964121&dopt=Abstract

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Infection with hepatitis B and C viruses and human retroviruses (HTLV-I and HIV) among high-risk Lebanese patients. Author(s): Ramia S, Klayme S, Naman R. Source: Annals of Tropical Medicine and Parasitology. 2003 March; 97(2): 187-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12803874&dopt=Abstract

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Infection with human herpesvirus-8 and its correlation with hepatitis B virus and hepatitis C virus markers among rural populations in Cambodia. Author(s): Sarmati L, Andreoni M, Suligoi B, Bugarini R, Uccella I, Pozio E, Rezza G. Source: The American Journal of Tropical Medicine and Hygiene. 2003 April; 68(4): 5012. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875304&dopt=Abstract

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Inhibition of hepatitis B virus by a novel L-nucleoside, beta-L-D4A and related analogues. Author(s): Wu JM, Lin JS, Xie N, Liang KH. Source: World Journal of Gastroenterology : Wjg. 2003 August; 9(8): 1840-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12918134&dopt=Abstract

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Inhibition of the protein kinase PKR by the internal ribosome entry site of hepatitis C virus genomic RNA. Author(s): Vyas J, Elia A, Clemens MJ. Source: Rna (New York, N.Y.). 2003 July; 9(7): 858-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810919&dopt=Abstract

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Injecting drug use in Australia: needle/syringe programs prove their worth, but hepatitis C still on the increase. Author(s): Copeman M. Source: The Medical Journal of Australia. 2003 July 21; 179(2): 119; Author Reply 119. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12864712&dopt=Abstract

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Integrating behavioral theory to understand hepatitis B vaccination among men who have sex with men. Author(s): Rhodes SD, Grimley DM, Hergenrather KC. Source: American Journal of Health Behavior. 2003 July-August; 27(4): 291-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882423&dopt=Abstract

222 Hepatitis

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Interferon for preventing and treating hepatocellular carcinoma associated with the hepatitis B and C viruses. Author(s): Tabor E. Source: Dig Liver Dis. 2003 May; 35(5): 297-305. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846400&dopt=Abstract

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Interferon monotherapy for dialysis patients with chronic hepatitis C: an analysis of the literature on efficacy and safety. Author(s): Russo MW, Goldsweig CD, Jacobson IM, Brown RS Jr. Source: The American Journal of Gastroenterology. 2003 July; 98(7): 1610-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873587&dopt=Abstract

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Interferon therapy in hepatitis B e antigen-negative chronic hepatitis B. Author(s): Colli A, Massironi S, Anreoletti M. Source: Hepatology (Baltimore, Md.). 2003 September; 38(3): 779-80; Author Reply 780. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939609&dopt=Abstract

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Interferon-alpha combined with ketoprofen as treatment of naive patients with chronic hepatitis C: a randomized controlled trial. Author(s): Andreone P, Gramenzi A, Cursaro C, Biselli M, Lorenzini S, Loggi E, Felline F, Fiorino S, Di Giammarino L, Porzio F, Galli S, Bernardi M. Source: Journal of Viral Hepatitis. 2003 July; 10(4): 306-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823598&dopt=Abstract

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Interferon-alpha for reinfection with hepatitis C virus in two patients with chronic hepatitis C who had responded to previous therapies. Author(s): Akuta N, Suzuki F, Tsubota A, Suzuki Y, Someya T, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Miyakawa Y, Kumada H. Source: Digestive Diseases and Sciences. 2003 August; 48(8): 1654-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924664&dopt=Abstract

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Interferon-alpha2b induction treatment with or without ribavirin in chronic hepatitis C: a multicenter, randomized, controlled trial. Author(s): Senturk H, Ersoz G, Ozaras R, Kaymakoglu S, Bozkaya H, Akdogan M, Mert A, Bozdayi M, Tabak F, Yenice N, Ozbay G. Source: Digestive Diseases and Sciences. 2003 June; 48(6): 1124-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822874&dopt=Abstract

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Interleukin 1beta gene polymorphism and hepatitis C virus-related hepatocellular carcinoma. Author(s): Yeo AE, Tanaka Y, Furuta T. Source: Hepatology (Baltimore, Md.). 2003 July; 38(1): 267-8; Author Reply 268-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12830011&dopt=Abstract

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Interleukin-10 promoter polymorphisms and the outcome of hepatitis C virus infection. Author(s): Knapp S, Hennig BJ, Frodsham AJ, Zhang L, Hellier S, Wright M, Goldin R, Hill AV, Thomas HC, Thursz MR. Source: Immunogenetics. 2003 September; 55(6): 362-9. Epub 2003 August 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12942209&dopt=Abstract

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Interleukin-2 has no additional therapeutic efficacy in the retreatment of patients with chronic hepatitis C that had not responded to interferon-alpha plus ribavirin. Author(s): Barreiros AP, Schlaak JF, Gerken G, Galle PR, Lohr HF. Source: European Journal of Clinical Investigation. 2003 July; 33(7): 628-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814401&dopt=Abstract

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Invasive and non-invasive monitoring of hepatitis C virus-induced liver fibrosis: alternatives or complements? Author(s): Olga OZ, Nikolai DY. Source: Current Pharmaceutical Biotechnology. 2003 June; 4(3): 195-209. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769763&dopt=Abstract

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Investigating hepatitis immunity. Author(s): Arya SC. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 June 24; 168(13): 1643; Author Reply 1643. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821607&dopt=Abstract

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Investigating the source of hepatitis C virus infection among individuals whose route of infection is undefined: a study of ten cases. Author(s): Roy KM, Goldberg D, Taylor A, Mills P. Source: Scandinavian Journal of Infectious Diseases. 2003; 35(5): 326-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875520&dopt=Abstract

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Investigation of infection control practices and knowledge of hepatitis C among body-piercing practitioners. Author(s): Hellard M, Aitken C, Mackintosh A, Ridge A, Bowden S. Source: American Journal of Infection Control. 2003 June; 31(4): 215-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12806358&dopt=Abstract

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Involvement of Crm1 in hepatitis B virus X protein-induced aberrant centriole replication and abnormal mitotic spindles. Author(s): Forgues M, Difilippantonio MJ, Linke SP, Ried T, Nagashima K, Feden J, Valerie K, Fukasawa K, Wang XW. Source: Molecular and Cellular Biology. 2003 August; 23(15): 5282-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861014&dopt=Abstract

224 Hepatitis

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Is liver biopsy necessary for hepatitis C virus carriers with persistently normal aminotransferase levels? Author(s): Pasquale G, Sagnelli E, Coppola N, Scarano F, Scolastico C, Bellomo PF, Lettieri A, Piccinino F. Source: European Journal of Gastroenterology & Hepatology. 2003 July; 15(7): 831-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811317&dopt=Abstract

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Isolated antibody to hepatitis B core antigen in human immunodeficiency virus type1-infected individuals. Author(s): Gandhi RT, Wurcel A, Lee H, McGovern B, Boczanowski M, Gerwin R, Corcoran CP, Szczepiorkowski Z, Toner S, Cohen DE, Sax PE, Ukomadu C. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 June 15; 36(12): 1602-5. Epub 2003 Jun 06. Erratum In: Clin Infect Dis. 2003 July 1; 37(1): 157. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802762&dopt=Abstract

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JAMA patient page. Hepatitis C. Author(s): Torpy JM, Lynm C, Glass RM. Source: Jama : the Journal of the American Medical Association. 2003 May 14; 289(18): 2450. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746370&dopt=Abstract

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Kawasaki disease presenting with hepatitis and prolonged fever: report of one case. Author(s): Chen WT, Huang SR, Wang JK. Source: Acta Paediatr Taiwan. 2003 May-June; 44(3): 174-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14521027&dopt=Abstract

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Kinetics and significance of serum hepatitis C virus core antigen in patients with acute hepatitis C. Author(s): Cividini A, Cerino A, Muzzi A, Furione M, Rebucci C, Segagni L, Gatti M, Barnaba V, Mondelli MU. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 2144-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734263&dopt=Abstract

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Kinetics of CD4+ and CD8+ memory T-cell responses during hepatitis C virus rechallenge of previously recovered chimpanzees. Author(s): Nascimbeni M, Mizukoshi E, Bosmann M, Major ME, Mihalik K, Rice CM, Feinstone SM, Rehermann B. Source: Journal of Virology. 2003 April; 77(8): 4781-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663785&dopt=Abstract

Studies 225

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Kinetics of HBV DNA and HBsAg in acute hepatitis B patients with and without coinfection by other hepatitis viruses. Author(s): Chulanov VP, Shipulin GA, Schaefer S, Gerlich WH. Source: Journal of Medical Virology. 2003 March; 69(3): 313-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12526040&dopt=Abstract

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Labeling may be an important cause of reduced quality of life in chronic hepatitis C. Author(s): Cordoba J, Reyes J, Esteban JI, Hernandez JM. Source: The American Journal of Gastroenterology. 2003 January; 98(1): 226-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12526976&dopt=Abstract

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Laboratory approach to acute and chronic hepatitis. Author(s): Dufour DR. Source: Mlo: Medical Laboratory Observer. 2003 September; 35(9): 10-2, 14, 16; Quiz 201. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14524144&dopt=Abstract

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Labour force participation among individuals with hepatitis C in the US. Author(s): Jacobs P, Ng YC, Stafinski T, Dodd R, Larke B, Wong W. Source: Pharmacoeconomics. 2003; 21(8): 565-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751914&dopt=Abstract

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Lack of association between hepatitis C virus and oral epithelial dysplasia in British patients. Author(s): Jaber MA, Porter SR, Bain L, Scully C. Source: International Journal of Oral and Maxillofacial Surgery. 2003 April; 32(2): 181-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729779&dopt=Abstract

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Lack of epidemiological evidence for a role of resolved hepatitis B virus infection in hepatocarcinogenesis in patients infected with hepatitis C virus in Japan. Author(s): Hiraoka T, Katayama K, Tanaka J, Ohno N, Joko K, Komiya Y, Kumagai J, Mizui M, Hino K, Miyakawa Y, Yoshizawa H. Source: Intervirology. 2003; 46(3): 171-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867755&dopt=Abstract

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Lack of hepatitis C transmission among institutionalized psychiatric patients. Author(s): Stroffolini T, Marchi L, Brunetti E, Filice C. Source: Journal of Hepatology. 2003 February; 38(2): 244. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12547417&dopt=Abstract

226 Hepatitis

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Lack of optimal T-cell reactivity against the hepatitis C virus is associated with the development of fibrosis/cirrhosis during chronic hepatitis. Author(s): Sreenarasimhaiah J, Jaramillo A, Crippin J, Lisker-Melman M, Chapman WC, Mohanakumar T. Source: Human Immunology. 2003 February; 64(2): 224-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559624&dopt=Abstract

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Lamivudine and Famciclovir resistant hepatitis B virus associated with fatal hepatic failure. Author(s): Ayres A, Bartholomeusz A, Lau G, Lam KC, Lee JY, Locarnini S. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2003 May; 27(1): 111-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727536&dopt=Abstract

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Lamivudine plasma levels in chronic hepatitis B patients. Author(s): Wolters LM, Geerlings CJ, van Dijk L, Niesters HG, Vulto AG, de Man RA. Source: The Netherlands Journal of Medicine. 2003 January; 61(1): 9-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12688563&dopt=Abstract

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Lamivudine therapy in renal allograft recipients with hepatitis B virus infection. Author(s): Tsang WK, Tong KL, Chan HW. Source: Transplantation Proceedings. 2003 February; 35(1): 278-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591398&dopt=Abstract

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Lamivudine treatment during pregnancy to prevent perinatal transmission of hepatitis B virus infection. Author(s): van Zonneveld M, van Nunen AB, Niesters HG, de Man RA, Schalm SW, Janssen HL. Source: Journal of Viral Hepatitis. 2003 July; 10(4): 294-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823596&dopt=Abstract

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Lamivudine treatment for chronic hepatitis B infection in children unresponsive to interferon. Author(s): Hartman C, Berkowitz D, Shouval D, Eshach-Adiv O, Hino B, Rimon N, Satinger I, Kra-Oz T, Daudi N, Shamir R. Source: The Pediatric Infectious Disease Journal. 2003 March; 22(3): 224-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634582&dopt=Abstract

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L-carnitine decreases severity and type of fatigue induced by interferon-alpha in the treatment of patients with hepatitis C. Author(s): Neri S, Pistone G, Saraceno B, Pennisi G, Luca S, Malaguarnera M. Source: Neuropsychobiology. 2003; 47(2): 94-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707492&dopt=Abstract

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Levels of plasma malondialdehyde and erythrocyte antioxidant enzyme activities in patients with chronic hepatitis B. Author(s): Demirdag K, Yilmaz S, Ozdarendeli A, Ozden M, Kalkan A, Kilic SS. Source: Hepatogastroenterology. 2003 May-June; 50(51): 766-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828081&dopt=Abstract

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Lichen planus and hepatitis C virus infection. Author(s): Gimenez-Garcia R, Perez-Castrillon JL. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2003 May; 17(3): 291-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702068&dopt=Abstract

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Lichen planus and leukocytoclastic vasculitis induced by interferon alpha-2b in a subject with HCV-related chronic active hepatitis. Author(s): Pinto JM, Marques MS, Correia TE. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2003 March; 17(2): 193-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705750&dopt=Abstract

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Life-threatening severe immune thrombocytopenia during alpha-interferon therapy for chronic hepatitis C. Author(s): Fujii H, Kitada T, Yamada T, Sakaguchi H, Seki S, Hino M. Source: Hepatogastroenterology. 2003 May-June; 50(51): 841-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828100&dopt=Abstract

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Limitations of TaqMan PCR for detecting divergent viral pathogens illustrated by hepatitis A, B, C, and E viruses and human immunodeficiency virus. Author(s): Gardner SN, Kuczmarski TA, Vitalis EA, Slezak TR. Source: Journal of Clinical Microbiology. 2003 June; 41(6): 2417-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791858&dopt=Abstract

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Limits of diagnostic accuracy of anti-hepatitis C virus antibodies detection by ELISA and immunoblot assay. Author(s): Suslov AP, Kuzin SN, Golosova TV, Shalunova NV, Malyshev NA, Sadikova NV, Vavilova LM, Somova AV, Musina EE, Ivanova MV, Kipor TT, Timonin IM, Kuzina LE, Godkov MA, Bajenov AI, Nesterenko VG. Source: Russ J Immunol. 2002 July; 7(2): 175-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687261&dopt=Abstract

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Liver disease and HIV. Hepatitis is an ongoing threat. Author(s): Johnson D, Cohen S, Bonacini M. Source: Adv Nurse Pract. 2003 June; 11(6): 63-6, 68, 70. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807059&dopt=Abstract

228 Hepatitis

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Liver histology and progression of fibrosis in individuals with chronic hepatitis C and persistently normal ALT. Author(s): Kyrlagkitsis I, Portmann B, Smith H, O'Grady J, Cramp ME. Source: The American Journal of Gastroenterology. 2003 July; 98(7): 1588-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873583&dopt=Abstract

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Liver p53 expression in patients with HCV-related chronic hepatitis. Author(s): Loguercio C, Cuomo A, Tuccillo C, Gazzerro P, Cioffi M, Molinari AM, Del Vecchio Blanco C. Source: Journal of Viral Hepatitis. 2003 July; 10(4): 266-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823592&dopt=Abstract

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Liver transplantation with hepatitis C virus-infected graft: interaction between donor and recipient viral strains. Author(s): Fan X, Lang DM, Xu Y, Lyra AC, Yusim K, Everhart JE, Korber BT, Perelson AS, Di Bisceglie AM. Source: Hepatology (Baltimore, Md.). 2003 July; 38(1): 25-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829983&dopt=Abstract

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Living donor liver transplantation and hepatitis C. Author(s): Baltz AC, Trotter JF. Source: Clinics in Liver Disease. 2003 August; 7(3): 651-65, Viii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509532&dopt=Abstract

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Local blistering reaction complicating subcutaneous injection of pegylated interferon in a patient with hepatitis C. Author(s): Gallina K, Brodell RT, Naffah F, Nedorost S. Source: J Drugs Dermatol. 2003 January; 2(1): 63-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12852384&dopt=Abstract

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Localization of hepatitis C virus in gastrointestinal mucosa: a possible reservoir for relapse. Author(s): Miglioresi L, Riva E, Antonelli G, Russo F, Ricci GL. Source: Hepatology (Baltimore, Md.). 2003 September; 38(3): 775. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939605&dopt=Abstract

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Long term antibody response to hepatitis B vaccination beginning at birth and to subsequent booster vaccination. Author(s): Williams IT, Goldstein ST, Tufa J, Tauillii S, Margolis HS, Mahoney FJ. Source: The Pediatric Infectious Disease Journal. 2003 February; 22(2): 157-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12586980&dopt=Abstract

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Long-range RNA-RNA interaction between the 5' nontranslated region and the corecoding sequences of hepatitis C virus modulates the IRES-dependent translation. Author(s): Kim YK, Lee SH, Kim CS, Seol SK, Jang SK. Source: Rna (New York, N.Y.). 2003 May; 9(5): 599-606. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702818&dopt=Abstract

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Long-term histologic and virologic outcomes of acute self-limited hepatitis B. Author(s): Yuki N, Nagaoka T, Yamashiro M, Mochizuki K, Kaneko A, Yamamoto K, Omura M, Hikiji K, Kato M. Source: Hepatology (Baltimore, Md.). 2003 May; 37(5): 1172-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12717399&dopt=Abstract

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Long-term interleukin 10 therapy in chronic hepatitis C patients has a proviral and anti-inflammatory effect. Author(s): Nelson DR, Tu Z, Soldevila-Pico C, Abdelmalek M, Zhu H, Xu YL, Cabrera R, Liu C, Davis GL. Source: Hepatology (Baltimore, Md.). 2003 October; 38(4): 859-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512873&dopt=Abstract

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Long-term outcome of kidney transplantation in patients with hepatitis B or C positive. Author(s): Lezaic V, Djukanovic Lj, Blagojevic R, Radivojevic D. Source: Clinical Transplantation. 2003 February; 17(1): 75-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588326&dopt=Abstract

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Long-term outcomes of cirrhosis in nonalcoholic steatohepatitis compared with hepatitis C. Author(s): Hui JM, Kench JG, Chitturi S, Sud A, Farrell GC, Byth K, Hall P, Khan M, George J. Source: Hepatology (Baltimore, Md.). 2003 August; 38(2): 420-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883486&dopt=Abstract

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Long-term suppression of hepatitis B e antigen-negative chronic hepatitis B by 24month interferon therapy. Author(s): Lampertico P, Del Ninno E, Vigano M, Romeo R, Donato MF, Sablon E, Morabito A, Colombo M. Source: Hepatology (Baltimore, Md.). 2003 April; 37(4): 756-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668967&dopt=Abstract

230 Hepatitis

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Long-term virological response and growth rate of children with chronic hepatitis C who received natural interferon-alpha. Author(s): Shiraki K, Morishima T, Terasawa S, Koike M, Fujisawa T, Tajiri H; OPC-18 Study Group. Source: European Journal of Pediatrics. 2002 November; 161(11): 629-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12532945&dopt=Abstract

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Low community seroprevalence of hepatitis C virus infection in the Gampaha district. Author(s): Gunasekera HA, Sunil-Chandra NP, de Silva HJ. Source: Ceylon Med J. 2002 December; 47(4): 122. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661342&dopt=Abstract

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Low prevalence of hepatitis C virus antibodies in HIV-endemic area of Zimbabwe support sexual transmission as the major route of HIV transmission in Africa. Author(s): Kallestrup P, Zinyama R, Gomo E, Dickmeiss E, Platz P, Gerstoft J, Ullum H. Source: Aids (London, England). 2003 June 13; 17(9): 1400-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799566&dopt=Abstract

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Lower expression of CD81 B-cell receptor in lymphoproliferative diseases associated with hepatitis C virus infection. Author(s): Cacoub P, Bourliere M, Hausfater P, Charlotte F, Khiri H, Toci S, Piette JC, Poynard T, Halfon P. Source: Journal of Viral Hepatitis. 2003 January; 10(1): 10-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558906&dopt=Abstract

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Low-positive anti-hepatitis C virus enzyme immunoassay results: an important predictor of low likelihood of hepatitis C infection. Author(s): Dufour DR, Talastas M, Fernandez MD, Harris B, Strader DB, Seeff LB. Source: Clinical Chemistry. 2003 March; 49(3): 479-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12600961&dopt=Abstract

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LPO and free-radical oxidation parameters in patients with acute viral hepatitis. Author(s): Nagoev BS, Abidov MT, Ivanova MR. Source: Bulletin of Experimental Biology and Medicine. 2002 December; 134(6): 557-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660837&dopt=Abstract

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L-SIGN (CD 209L) is a liver-specific capture receptor for hepatitis C virus. Author(s): Gardner JP, Durso RJ, Arrigale RR, Donovan GP, Maddon PJ, Dragic T, Olson WC. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 April 15; 100(8): 4498-503. Epub 2003 Apr 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12676990&dopt=Abstract

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Macrocyclic inhibitors of the NS3 protease as potential therapeutic agents of hepatitis C virus infection. Author(s): Tsantrizos YS, Bolger G, Bonneau P, Cameron DR, Goudreau N, Kukolj G, LaPlante SR, Llinas-Brunet M, Nar H, Lamarre D. Source: Angewandte Chemie (International Ed. in English). 2003 March 28; 42(12): 135660. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671967&dopt=Abstract

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Maintenance therapy with ribavirin in patients with chronic hepatitis C who fail to respond to combination therapy with interferon alfa and ribavirin. Author(s): Hoofnagle JH, Ghany MG, Kleiner DE, Doo E, Heller T, Promrat K, Ong J, Khokhar F, Soza A, Herion D, Park Y, Everhart JE, Liang TJ. Source: Hepatology (Baltimore, Md.). 2003 July; 38(1): 66-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829988&dopt=Abstract

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Management of healthcare workers after occupational exposure to hepatitis C virus. Author(s): Charles PG, Angus PW, Sasadeusz JJ, Grayson ML. Source: The Medical Journal of Australia. 2003 August 4; 179(3): 153-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885285&dopt=Abstract

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Management of hepatitis A in a food handler at a London secondary school. Author(s): Nicholls M, Bruce M, Thomas J. Source: Commun Dis Public Health. 2003 April; 6(1): 26-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12736968&dopt=Abstract

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Management of hepatitis B and C in HIV co-infected patients. Author(s): Rockstroh JK. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 2003 September; 34 Suppl 1: S59-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14562859&dopt=Abstract

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Management of hepatitis B and C in renal failure and renal transplant recipients. Author(s): Amarapurkar D, Das HS. Source: Trop Gastroenterol. 2002 April-June; 23(2): 49-53. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632966&dopt=Abstract

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Management of hepatitis C. Author(s): Smith C. Source: Minn Med. 2003 June; 86(6): 53-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834215&dopt=Abstract

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Management of HIV and hepatitis B or C co-infection in 15 HIV treatment centres. Disparity between protocols and practice. Author(s): Brook MG, Jones K, Dale AW, Miller RF. Source: International Journal of Std & Aids. 2003 July; 14(7): 469-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869227&dopt=Abstract

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Management of occupational exposure to hepatitis B, hepatitis C, and human immunodeficiency virus. Author(s): Bednarsh H, Eklund K. Source: Compend Contin Educ Dent. 2002 June; 23(6): 561-6, 568-9; Quiz 570. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789970&dopt=Abstract

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Managing occupational risks for hepatitis C transmission in the health care setting. Author(s): Henderson DK. Source: Clinical Microbiology Reviews. 2003 July; 16(3): 546-68. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12857782&dopt=Abstract

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Managing viral hepatitis. Author(s): Tang KH, Williams R. Source: The Practitioner. 2003 June; 247(1647): 537-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822322&dopt=Abstract

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Mannan-binding lectin and hepatitis C infection. Author(s): Kilpatrick DC, Delahooke TE, Koch C, Turner ML, Hayes PC. Source: Clinical and Experimental Immunology. 2003 April; 132(1): 92-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653842&dopt=Abstract

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Markers of disease activity in chronic hepatitis B virus infection. Author(s): Yalcin K, Degertekin H, Yildiz F, Celik Y. Source: Clinical and Investigative Medicine. Medecine Clinique Et Experimentale. 2003 February; 26(1): 27-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659467&dopt=Abstract

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Maternal viral load and hepatitis C virus vertical transmission. Author(s): Vincenzo ZG, Filippo S, Laura G, Marcello G. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 March; 36(3): 418-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604988&dopt=Abstract

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Mechanisms of antiviral treatment efficacy and failure in chronic hepatitis C. Author(s): Pawlotsky JM. Source: Antiviral Research. 2003 June; 59(1): 1-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834855&dopt=Abstract

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Memory CD8+ T cells are required for protection from persistent hepatitis C virus infection. Author(s): Shoukry NH, Grakoui A, Houghton M, Chien DY, Ghrayeb J, Reimann KA, Walker CM. Source: The Journal of Experimental Medicine. 2003 June 16; 197(12): 1645-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810686&dopt=Abstract

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Mimicry between the hepatitis C virus polyprotein and antigenic targets of nuclear and smooth muscle antibodies in chronic hepatitis C virus infection. Author(s): Gregorio GV, Choudhuri K, Ma Y, Pensati P, Iorio R, Grant P, Garson J, Bogdanos DP, Vegnente A, Mieli-Vergani G, Vergani D. Source: Clinical and Experimental Immunology. 2003 September; 133(3): 404-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930368&dopt=Abstract

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Minimal change disease in a patient receiving IFN-alpha therapy for chronic hepatitis C virus infection. Author(s): Dizer U, Beker CM, Yavuz I, Ortatatli M, Ozguven V, Pahsa A. Source: Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research. 2003 January; 23(1): 51-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639299&dopt=Abstract

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Mixed cryoglobulinemia secondary to interferon therapy for hepatitis C: case report & review of the literature. Author(s): Kimyai-Asadi A, Gohar K, Kang P, Usman A, Zenenberg R, Jih MH. Source: J Drugs Dermatol. 2002 July; 1(1): 72-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847761&dopt=Abstract

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Mix-infections with different genotypes of HCV and with HCV plus other hepatitis viruses in patients with hepatitis C in China. Author(s): Chen YD, Liu MY, Yu WL, Li JQ, Dai Q, Zhou ZQ, Tisminetzky SG. Source: World Journal of Gastroenterology : Wjg. 2003 May; 9(5): 984-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12717843&dopt=Abstract

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Moderate alcohol consumption increases oxidative stress in patients with chronic hepatitis C. Author(s): Rigamonti C, Mottaran E, Reale E, Rolla R, Cipriani V, Capelli F, Boldorini R, Vidali M, Sartori M, Albano E. Source: Hepatology (Baltimore, Md.). 2003 July; 38(1): 42-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829985&dopt=Abstract

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Modified protocol for hepatitis B virus DNA isolation and detection. Author(s): Khaja MN, Poduri CD, Habibullah CM. Source: Analytical Biochemistry. 2003 March 1; 314(1): 142-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12633613&dopt=Abstract

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Modulation of endothelial cell inflammatory integrins and stress markers with rhfactor VIIa in patients with advanced chronic hepatitis C. Author(s): Van Thiel DH, Anantharaju A, Mindikoglu AL, Shah N, Leone N, Bejna J, Tarasuk G, Todo A, Mobarhan S, George M. Source: Journal of Viral Hepatitis. 2003 July; 10(4): 310-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823599&dopt=Abstract

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Molecular diversity of hepatitis C virus in the Batam region. Author(s): Boland GJ, Cnossen N, van Bommel T, Rulos-van den Berg A, van den Berg JP, van Loon AM, van Hattum J. Source: Advances in Experimental Medicine and Biology. 2003; 531: 211-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916793&dopt=Abstract

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Molecular epidemiology and transmission of hepatitis B virus in close family contacts of HBV-related chronic liver disease patients. Author(s): Thakur V, Kazim SN, Guptan RC, Malhotra V, Sarin SK. Source: Journal of Medical Virology. 2003 August; 70(4): 520-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794713&dopt=Abstract

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Molecular epidemiology of hepatitis viruses and genotypic distribution of hepatitis B and C viruses in Harbin, China. Author(s): Ding X, Gu H, Zhong ZH, Zilong X, Tran HT, Iwaki Y, Li TC, Sata T, Abe K. Source: Japanese Journal of Infectious Diseases. 2003 February; 56(1): 19-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711821&dopt=Abstract

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Molecular investigation of hepatitis E virus infection in patients with acute hepatitis in Kathmandu, Nepal. Author(s): Shrestha SM, Shrestha S, Tsuda F, Nishizawa T, Gotanda Y, Takeda N, Okamoto H. Source: Journal of Medical Virology. 2003 February; 69(2): 207-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683409&dopt=Abstract

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Molecular pathogenesis of viral hepatitis. Author(s): Hayashi N, Kanto T, Housui A, Sugimoto K, Ohkawa K, Takehara T, Sasaki Y. Source: Intern Med. 2003 March; 42(3): 290-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705800&dopt=Abstract

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Monitoring response to antiviral therapy for patients with chronic hepatitis C virus infection by a core-antigen assay. Author(s): Rebucci C, Cerino A, Cividini A, Timo L, Furione M, Mondelli MU. Source: Journal of Clinical Microbiology. 2003 August; 41(8): 3881-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904409&dopt=Abstract

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Morphine enhances hepatitis C virus (HCV) replicon expression. Author(s): Li Y, Zhang T, Douglas SD, Lai JP, Xiao WD, Pleasure DE, Ho WZ. Source: American Journal of Pathology. 2003 September; 163(3): 1167-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937158&dopt=Abstract

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Mortality due to hepatitis C-related liver disease in HIV-infected patients in France (Mortavic 2001 study). Author(s): Rosenthal E, Poiree M, Pradier C, Perronne C, Salmon-Ceron D, Geffray L, Myers RP, Morlat P, Pialoux G, Pol S, Cacoub P; GERMIVIC Joint Study Group. Source: Aids (London, England). 2003 August 15; 17(12): 1803-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891066&dopt=Abstract

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Mortality of hepatitis B surface antigen-positive blood donors in England and Wales. Author(s): Crook PD, Jones ME, Hall AJ. Source: International Journal of Epidemiology. 2003 February; 32(1): 118-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12690022&dopt=Abstract

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Mortality rate during interferon alfa-ribavirin combination therapy of chronic hepatitis C. Author(s): Soza A, Hoofnagle JH. Source: Hepatology (Baltimore, Md.). 2003 July; 38(1): 267. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12830010&dopt=Abstract

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Motor-axonal polyneuropathy associated with hepatitis C virus. Author(s): Costa J, Resende C, de Carvalho M. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. 2003 March; 10(2): 183-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603295&dopt=Abstract

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Multicentre Italian Study Group (MISG) for the standardisation of hepatitis C virus (HCV) PCR. Author(s): Mancini C, Zerbini M, Azzi A, Piunno M. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2003 May; 27(1): 83-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727533&dopt=Abstract

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Mutagenic and inhibitory effects of ribavirin on hepatitis C virus RNA polymerase. Author(s): Vo NV, Young KC, Lai MM. Source: Biochemistry. 2003 September 9; 42(35): 10462-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950173&dopt=Abstract

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Mutations within the CD81-binding sites and hypervariable region 2 of the envelope 2 protein: correlation with treatment response in hepatitis C virus-infected patients. Author(s): Hofmann WP, Sarrazin C, Kronenberger B, Schonberger B, Bruch K, Zeuzem S. Source: The Journal of Infectious Diseases. 2003 March 15; 187(6): 982-7. Epub 2003 Mar 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660945&dopt=Abstract

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Mutations within the hepatitis B virus genome among chronic hepatitis B patients with hepatocellular carcinoma. Author(s): Blackberg J, Kidd-Ljunggren K. Source: Journal of Medical Virology. 2003 September; 71(1): 18-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858404&dopt=Abstract

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Natural beta interferon as an initial treatment for the elderly with chronic hepatitis C. Author(s): Komorizono Y, Sako K. Source: The American Journal of Gastroenterology. 2003 September; 98(9): 2103-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14499799&dopt=Abstract

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Natural course of acute hepatitis C: a long-term prospective study. Author(s): Santantonio T, Sinisi E, Guastadisegni A, Casalino C, Mazzola M, Gentile A, Leandro G, Pastore G. Source: Dig Liver Dis. 2003 February; 35(2): 104-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747629&dopt=Abstract

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Natural histories of hepatitis C virus infection in men and women simulated by the Markov model. Author(s): Tanaka J, Kumada H, Ikeda K, Chayama K, Mizui M, Hino K, Katayama K, Kumagai J, Komiya Y, Miyakawa Y, Yoshizawa H. Source: Journal of Medical Virology. 2003 July; 70(3): 378-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767000&dopt=Abstract

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Natural history and prognosis of hepatitis B. Author(s): Fattovich G. Source: Seminars in Liver Disease. 2003 February; 23(1): 47-58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12616450&dopt=Abstract

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Natural history of hepatitis B and outcomes after liver transplantation. Author(s): Huang MA, Lok AS. Source: Clinics in Liver Disease. 2003 August; 7(3): 521-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509524&dopt=Abstract

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Natural history of hepatitis C and outcomes following liver transplantation. Author(s): Charlton M. Source: Clinics in Liver Disease. 2003 August; 7(3): 585-602. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509528&dopt=Abstract

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Natural leukocyte interferon alfa for the treatment of chronic viral hepatitis in heart transplant recipients. Author(s): Fagiuoli S, Pevere S, Minniti F, Livi U, Caforio AL, Naccarato R, Chiaramonte M. Source: Transplantation. 2003 April 15; 75(7): 982-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698084&dopt=Abstract

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Neonatal cholestasis resulting from vertical transmission of hepatitis A infection. Author(s): Urganci N, Arapoglu M, Akyildiz B, Nuhoglu A. Source: The Pediatric Infectious Disease Journal. 2003 April; 22(4): 381-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712976&dopt=Abstract

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Neutralizing antibodies in hepatitis C virus infection: a review of immunological and clinical characteristics. Author(s): Kaplan M, Gawrieh S, Cotler SJ, Jensen DM. Source: Gastroenterology. 2003 August; 125(2): 597-604. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891562&dopt=Abstract

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Neutrophilic dermatosis of the hands (localized Sweet's syndrome) in association with chronic hepatitis C and sarcoidosis. Author(s): Baz K, Yazici AC, Kaya TI, Ikizoglu G, Ulubas B, Apa DD, Cinel L. Source: Clinical and Experimental Dermatology. 2003 July; 28(4): 377-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823297&dopt=Abstract

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New developments in the treatment of hepatitis C. Author(s): Rossi SJ, Wright TL. Source: Gut. 2003 May; 52(5): 756-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692065&dopt=Abstract

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New enzyme immunoassay for detection of hepatitis B virus core antigen (HBcAg) and relation between levels of HBcAg and HBV DNA. Author(s): Kimura T, Rokuhara A, Matsumoto A, Yagi S, Tanaka E, Kiyosawa K, Maki N. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 1901-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734224&dopt=Abstract

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New immunization initiatives and progress toward the global control of hepatitis B. Author(s): Kane MA, Brooks A. Source: Current Opinion in Infectious Diseases. 2002 October; 15(5): 465-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686877&dopt=Abstract

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New insights into acute hepatitis C. Author(s): Gordon SC. Source: Gastroenterology. 2003 July; 125(1): 253-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851890&dopt=Abstract

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New options in the treatment of chronic hepatitis. Author(s): Soemohardjo S. Source: Advances in Experimental Medicine and Biology. 2003; 531: 191-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916791&dopt=Abstract

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New targets and possible new therapeutic approaches in the chemotherapy of chronic hepatitis B. Author(s): Feld J, Lee JY, Locarnini S. Source: Hepatology (Baltimore, Md.). 2003 September; 38(3): 545-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939579&dopt=Abstract

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New therapies on the horizon for hepatitis C: are we close? Author(s): De Francesco R, Rice CM. Source: Clinics in Liver Disease. 2003 February; 7(1): 211-42, Xi. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691468&dopt=Abstract

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New treatment options for chronic hepatitis C. Author(s): van Soest H, van Hattum J. Source: Advances in Experimental Medicine and Biology. 2003; 531: 219-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916794&dopt=Abstract

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Non-A to E hepatitis. Author(s): Narayanan Menon KV. Source: Current Opinion in Infectious Diseases. 2002 October; 15(5): 529-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686888&dopt=Abstract

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Nonalcoholic fatty liver disease in patients with hepatitis C is associated with features of the metabolic syndrome. Author(s): Sanyal AJ, Contos MJ, Sterling RK, Luketic VA, Shiffman ML, Stravitz RT, Mills AS. Source: The American Journal of Gastroenterology. 2003 September; 98(9): 2064-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14499789&dopt=Abstract

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Non-alcoholic steato-hepatitis. Author(s): Chawla Y, Amrapurkar D. Source: Trop Gastroenterol. 2002 October-December; 23(4): 186-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12833707&dopt=Abstract

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Nonimmune complexed HCV RNA titer in serum as a predictor of interferon response in patients with chronic hepatitis C. Author(s): Fujita N, Kaito M, Takeo M, Iwasa M, Ikoma J, Watanabe S, Adachi Y. Source: The American Journal of Gastroenterology. 2003 March; 98(3): 645-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650801&dopt=Abstract

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Noninvasive prediction of fibrosis in patients with chronic hepatitis C. Author(s): Thabut D, Simon M, Myers RP, Messous D, Thibault V, Imbert-Bismut F, Poynard T. Source: Hepatology (Baltimore, Md.). 2003 May; 37(5): 1220-1; Author Reply 1221. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12717403&dopt=Abstract

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Non-responders to hepatitis B vaccination: a review. Author(s): Kubba AK, Taylor P, Graneek B, Strobel S. Source: Commun Dis Public Health. 2003 June; 6(2): 106-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889288&dopt=Abstract

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Nonresponse to interferon monotherapy in HCV-related chronic hepatitis: results of retreatment and prognostic factors. Author(s): Capra F, De Maria E, Franchini M, Marchiori L, Thalheimer U, Vantini I. Source: Digestive Diseases and Sciences. 2003 April; 48(4): 809-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741476&dopt=Abstract

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Nonstructural protein precursor NS4A/B from hepatitis C virus alters function and ultrastructure of host secretory apparatus. Author(s): Konan KV, Giddings TH Jr, Ikeda M, Li K, Lemon SM, Kirkegaard K. Source: Journal of Virology. 2003 July; 77(14): 7843-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829824&dopt=Abstract

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Normal erythropoietin response in chronic hepatitis C patients with ribavirininduced anaemia. Author(s): Durante Mangoni E, Marrone A, Saviano D, Del Vecchio C, Utili R, Ruggiero G. Source: Antivir Ther. 2003 February; 8(1): 57-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12713065&dopt=Abstract

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Nosocomial transmission of hepatitis C virus associated with the use of multidose saline vials. Author(s): Krause G, Trepka MJ, Whisenhunt RS, Katz D, Nainan O, Wiersma ST, Hopkins RS. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2003 February; 24(2): 122-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12602694&dopt=Abstract

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Novel assay of competitively differentiated polymerase chain reaction for screening point mutation of hepatitis B virus. Author(s): Peng XM, Chen XJ, Li JG, Gu L, Huang YS, Gao ZL. Source: World Journal of Gastroenterology : Wjg. 2003 August; 9(8): 1743-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12918112&dopt=Abstract

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Nuclear import of hepatitis B virus capsids and release of the viral genome. Author(s): Rabe B, Vlachou A, Pante N, Helenius A, Kann M. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 August 19; 100(17): 9849-54. Epub 2003 Aug 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12909718&dopt=Abstract

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Nucleoside analogues and other antivirals for treatment of hepatitis B in the peritransplant period. Author(s): Yu AS, Keeffe EB. Source: Clinics in Liver Disease. 2003 August; 7(3): 551-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509526&dopt=Abstract

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Nursing staff knowledge of the hepatitis B virus including attitudes and acceptance of hepatitis B vaccination: development of an effective program. Author(s): McGrane J, Staines A. Source: Aaohn Journal : Official Journal of the American Association of Occupational Health Nurses. 2003 August; 51(8): 347-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934862&dopt=Abstract

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Obesity and its nurturing effect on hepatitis C. Author(s): McCullough AJ. Source: Hepatology (Baltimore, Md.). 2003 September; 38(3): 557-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939581&dopt=Abstract

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Occult hepatitis B virus infection in HIV/hepatitis C virus co-infected patients. Author(s): Fabris P, Giordani MT, Tositti G, Rassu M, De Lalla F. Source: Aids (London, England). 2003 July 4; 17(10): 1581-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824807&dopt=Abstract

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Occupational hepatitis due to chronic inhalation of propane and butane gases. Author(s): Aydin Y, Ozcakar L. Source: Int J Clin Pract. 2003 July-August; 57(6): 546. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12918897&dopt=Abstract

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Occupational risk of infection by human immunodeficiency and hepatitis B viruses among health workers in south-eastern Nigeria. Author(s): Ansa VO, Udoma EJ, Umoh MS, Anah MU. Source: East Afr Med J. 2002 May; 79(5): 254-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12638809&dopt=Abstract

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Occurrence of false positives during testing for antibodies to hepatitis C virus among volunteer blood donors in India. Author(s): Raghuraman S, Subramaniam T, Daniel D, Sridharan G, Abraham P. Source: Journal of Clinical Microbiology. 2003 April; 41(4): 1788-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682189&dopt=Abstract

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Offering the vaccine and accepting it: an audit of hepatitis B vaccination in West Midlands region. Author(s): Jaleel H, Allan PS, Huengsberg M, Natin D; West Midlands Regional Audit Committee. Source: International Journal of Std & Aids. 2003 September; 14(9): 632-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14511502&dopt=Abstract

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Oral diseases possibly associated with hepatitis C virus. Author(s): Carrozzo M, Gandolfo S. Source: Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists. 2003; 14(2): 115-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12764074&dopt=Abstract

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Outbreak of hepatitis A among men who have sex with men: implications for hepatitis A vaccination strategies. Author(s): Cotter SM, Sansom S, Long T, Koch E, Kellerman S, Smith F, Averhoff F, Bell BP. Source: The Journal of Infectious Diseases. 2003 April 15; 187(8): 1235-40. Epub 2003 March 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12696002&dopt=Abstract

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Outbreak of hepatitis A in the injecting drug user and homeless populations in Bristol: control by a targeted vaccination programme and possible parenteral transmission. Author(s): Syed NA, Hearing SD, Shaw IS, Probert CS, Brooklyn TN, Caul EO, Barry RE, Sarangi J. Source: European Journal of Gastroenterology & Hepatology. 2003 August; 15(8): 901-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867801&dopt=Abstract

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Outbreak of hepatitis A infection among intravenous drug users in Suffolk and suspected risk factors. Author(s): Sundkvist T, Smith A, Mahgoub H, Kirkby A, Kent R, Wreghitt T, Davidkin I. Source: Commun Dis Public Health. 2003 June; 6(2): 101-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889287&dopt=Abstract

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Outcome and management of hepatitis C in liver transplant recipients. Author(s): Chan SE, Rosen HR. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 September 15; 37(6): 807-12. Epub 2003 August 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12955642&dopt=Abstract

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Outcome of patients with hepatitis C virus-related hepatocellular carcinoma occurring after interferon therapy. Author(s): Komorizono Y, Sako K, Yamasaki N, Hiwaki T, Sakurai K, Shibatou T, Maeda M, Kohara K, Shigenobu S, Hasegawa S, Arima T, Oketani M, Ishibashi K, Arima T. Source: Anticancer Res. 2002 November-December; 22(6B): 3573-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552958&dopt=Abstract

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Overexpression of a DEAD box/RNA helicase protein, rck/p54, in human hepatocytes from patients with hepatitis C virus-related chronic hepatitis and its implication in hepatocellular carcinogenesis. Author(s): Miyaji K, Nakagawa Y, Matsumoto K, Yoshida H, Morikawa H, Hongou Y, Arisaka Y, Kojima H, Inoue T, Hirata I, Katsu K, Akao Y. Source: Journal of Viral Hepatitis. 2003 July; 10(4): 241-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823589&dopt=Abstract

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Overexpression of thioredoxin prevents acute hepatitis caused by thioacetamide or lipopolysaccharide in mice. Author(s): Okuyama H, Nakamura H, Shimahara Y, Araya S, Kawada N, Yamaoka Y, Yodoi J. Source: Hepatology (Baltimore, Md.). 2003 May; 37(5): 1015-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12717382&dopt=Abstract

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Overlap syndromes of autoimmune hepatitis: what is known so far. Author(s): Durazzo M, Premoli A, Fagoonee S, Pellicano R. Source: Digestive Diseases and Sciences. 2003 March; 48(3): 423-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12757152&dopt=Abstract

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Overview: past and future of immunologic intervention in the pathogenesis, prophylaxis and therapeusis of hepatitis B. Author(s): Hilleman MR. Source: Journal of Gastroenterology and Hepatology. 2002 December; 17 Suppl: S449-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534776&dopt=Abstract

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Parental knowledge, attitudes, and practices associated with not receiving hepatitis A vaccine in a demonstration project in Butte County, California. Author(s): Bardenheier B, Gonzalez IM, Washington ML, Bell BP, Averhoff F, Massoudi MS, Hyams I, Simard EP, Yusuf H. Source: Pediatrics. 2003 October; 112(4): E269. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14523210&dopt=Abstract

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Pathogenicity of GB virus C on virus hepatitis and hemodialysis patients. Author(s): Zhu WF, Yin LM, Li P, Huang J, Zhuang H. Source: World Journal of Gastroenterology : Wjg. 2003 August; 9(8): 1739-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12918111&dopt=Abstract

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Pathologic quiz case: multiple foci of necrosis in the liver in a patient with T-cell lymphoma. Herpes simplex virus hepatitis. Author(s): Tan G, Frankel WL, Suster S. Source: Archives of Pathology & Laboratory Medicine. 2003 August; 127(8): 1049-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873187&dopt=Abstract

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Pattern of viral hepatitis infection in a selected population from Saudi Arabia. Author(s): Memish Z, Qasim L, Abed E, AlBasheer A, Aldraihim A, Knawy B, Hajeer AH. Source: Military Medicine. 2003 July; 168(7): 565-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901469&dopt=Abstract

244 Hepatitis

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Patterns of circulating hepatitis B virus serum nucleic acids during lamivudine therapy. Author(s): Zhang W, Hacker HJ, Tokus M, Bock T, Schroder CH. Source: Journal of Medical Virology. 2003 September; 71(1): 24-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858405&dopt=Abstract

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Peginterferon and ribavirin in a patient with acute hepatitis C. Author(s): Rodriguez-Gomez SJ, de la Serna-Higuera C, Perez-Villoria A, MartinezMoreno J, Betancourt-Gonzalez A, Martin-Arribas MI. Source: The American Journal of Gastroenterology. 2003 September; 98(9): 2102-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14499798&dopt=Abstract

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Pegylated interferons in the treatment of chronic hepatitis C. Author(s): Zhang F. Source: Chin Med J (Engl). 2003 April; 116(4): 495-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875709&dopt=Abstract

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Peripheral neurological symptoms after hepatitis B virus vaccination. Author(s): Bantz PM, Peiser C, Groneberg DA. Source: Qjm : Monthly Journal of the Association of Physicians. 2003 August; 96(8): 611. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12897348&dopt=Abstract

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Peripheral neuropathy in hepatitis C virus infection with and without cryoglobulinaemia. Author(s): Nemni R, Sanvito L, Quattrini A, Santuccio G, Camerlingo M, Canal N. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 September; 74(9): 1267-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12933932&dopt=Abstract

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Phenotypic and functional characterization of intrahepatic T lymphocytes during chronic hepatitis C. Author(s): Leroy V, Vigan I, Mosnier JF, Dufeu-Duchesne T, Pernollet M, Zarski JP, Marche PN, Jouvin-Marche E. Source: Hepatology (Baltimore, Md.). 2003 October; 38(4): 829-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512870&dopt=Abstract

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Phylogenetic analysis of hepatitis C virus isolates indicates a unique pattern of endemic infection in Cameroon. Author(s): Ndjomou J, Pybus OG, Matz B. Source: The Journal of General Virology. 2003 September; 84(Pt 9): 2333-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917453&dopt=Abstract

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Polymorphisms in XRCC1 and glutathione S-transferase genes and hepatitis B-related hepatocellular carcinoma. Author(s): Yu MW, Yang SY, Pan IJ, Lin CL, Liu CJ, Liaw YF, Lin SM, Chen PJ, Lee SD, Chen CJ. Source: Journal of the National Cancer Institute. 2003 October 1; 95(19): 1485-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14519756&dopt=Abstract

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Precore wild-type hepatitis B virus with G1896 in the resolution of persistent hepatitis B virus infection. Author(s): Kobayashi M, Arase Y, Ikeda K, Tsubota A, Suzuki Y, Saitoh S, Kobayashi M, Suzuki F, Akuta N, Hosaka T, Someya T, Matsuda M, Sato J, Takagi K, Miyakawa Y, Kumada H. Source: Intervirology. 2003; 46(3): 157-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867753&dopt=Abstract

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Predictive factors for the severity of liver fibrosis in patients with chronic hepatitis C and moderate alcohol consumption. Author(s): Vadan R, Gheorghe L, Becheanu G, Iacob R, Iacob S, Gheorghe C. Source: Rom J Gastroenterol. 2003 September; 12(3): 183-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14502317&dopt=Abstract

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Pre-s1 antigen-dependent infection of Tupaia hepatocyte cultures with human hepatitis B virus. Author(s): Glebe D, Aliakbari M, Krass P, Knoop EV, Valerius KP, Gerlich WH. Source: Journal of Virology. 2003 September; 77(17): 9511-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915565&dopt=Abstract

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Prevalence and characterization of lamivudine-resistant hepatitis B virus mutations in HIV-HBV co-infected individuals. Author(s): Cooley L, Ayres A, Bartholomeusz A, Lewin S, Crowe S, Mijch A, Locarnini S, Sasadeusz J. Source: Aids (London, England). 2003 July 25; 17(11): 1649-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853747&dopt=Abstract

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Prevalence of blood-borne viral hepatitis in different communities in Yemen. Author(s): Sallam TA, Tong CY, Cuevas LE, Raja'a YA, Othman AM, Al-Kharsa KR. Source: Epidemiology and Infection. 2003 August; 131(1): 771-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12948378&dopt=Abstract

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Prevalence of chronic hepatitis B and incidence of acute hepatitis B infection in human immunodeficiency virus-infected subjects. Author(s): Kellerman SE, Hanson DL, McNaghten AD, Fleming PL. Source: The Journal of Infectious Diseases. 2003 August 15; 188(4): 571-7. Epub 2003 Aug 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898445&dopt=Abstract

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Prevalence of hepatitis B virus markers in surgeons in Lagos, Nigeria. Author(s): Belo AC. Source: East Afr Med J. 2000 May; 77(5): 283-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858922&dopt=Abstract

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Prevalence of hepatitis C in psychiatric institutions. Author(s): Al Jurdi RK, Burruss JW. Source: Psychosomatics. 2003 September-October; 44(5): 439-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12954925&dopt=Abstract

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Prevalence of hepatitis C virus infection among haemodialysis patients in West Java, Indonesia. Author(s): Saketi JR, Boland GJ, van Loon AM, van Hattum J, Abdurachman SA, Sukandar E. Source: Advances in Experimental Medicine and Biology. 2003; 531: 201-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916792&dopt=Abstract

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Prevalence of Hepatitis C virus infection in a sample of homeless veterans. Author(s): Desai RA, Rosenheck RA, Agnello V. Source: Social Psychiatry and Psychiatric Epidemiology. 2003 July; 38(7): 396-401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861447&dopt=Abstract

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Prevalence of hepatitis C virus infection in urban children. Author(s): El-Kamary SS, Serwint JR, Joffe A, Santosham M, Duggan AK. Source: The Journal of Pediatrics. 2003 July; 143(1): 54-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915824&dopt=Abstract

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Prevalence of hepatitis viral infection in dental patients with impacted teeth or jaw deformities. Author(s): Takata Y, Tominaga K, Naito T, Kurokawa H, Sonoki K, Goto D, Wakisaka M, Fukuda J, Yokota M, Takahashi T. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2003 July; 96(1): 26-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847440&dopt=Abstract

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Production and release of infectious hepatitis C virus from human liver cell cultures in the three-dimensional radial-flow bioreactor. Author(s): Aizaki H, Nagamori S, Matsuda M, Kawakami H, Hashimoto O, Ishiko H, Kawada M, Matsuura T, Hasumura S, Matsuura Y, Suzuki T, Miyamura T. Source: Virology. 2003 September 15; 314(1): 16-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14517056&dopt=Abstract

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Promising candidates for the treatment of chronic hepatitis C. Author(s): Walker MP, Yao N, Hong Z. Source: Expert Opinion on Investigational Drugs. 2003 August; 12(8): 1269-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882616&dopt=Abstract

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Proteasome activator PA28gamma-dependent nuclear retention and degradation of hepatitis C virus core protein. Author(s): Moriishi K, Okabayashi T, Nakai K, Moriya K, Koike K, Murata S, Chiba T, Tanaka K, Suzuki R, Suzuki T, Miyamura T, Matsuura Y. Source: Journal of Virology. 2003 October; 77(19): 10237-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970408&dopt=Abstract

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Provision of hepatitis C education in a nationwide sample of drug treatment programs. Author(s): Astone J, Strauss SM, Vassilev ZP, Des Jarlais DC. Source: Journal of Drug Education. 2003; 33(1): 107-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773028&dopt=Abstract

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Psychosocial predictors of hepatitis B vaccination among young African-American gay men in the deep south. Author(s): Rhodes SD, Diclemente RJ. Source: Sexually Transmitted Diseases. 2003 May; 30(5): 449-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916138&dopt=Abstract

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Public health dispatch: multistate outbreak of hepatitis A among young adult concert attendees--United States, 2003. Author(s): Centers for Disease Control and Prevention (CDC). Source: Mmwr. Morbidity and Mortality Weekly Report. 2003 September 5; 52(35): 8445. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966361&dopt=Abstract

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Quantification of hepatitis C virus (HCV) in liver specimens and sera from patients with human immunodeficiency virus coinfection by using the Versant HCV RNA 3.0 (branched DNA-based) DNA assay. Author(s): Tedeschi R, Pivetta E, Zanussi S, Bidoli E, Ros M, di Gennaro G, Nasti G, De Paoli P. Source: Journal of Clinical Microbiology. 2003 July; 41(7): 3046-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843041&dopt=Abstract

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Quantitative assay of hepatitis C virus RNA using an automated extraction system for specific capture with probes and paramagnetic particle separation. Author(s): Miyachi H, Masukawa A, Asai S, Miura T, Tamatsukuri S, Hirose T, Ando Y. Source: Journal of Clinical Microbiology. 2003 February; 41(2): 572-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574248&dopt=Abstract

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Quinacrine-induced cytolytic hepatitis in sporadic Creutzfeldt-Jakob disease. Author(s): Scoazec JY, Krolak-Salmon P, Casez O, Besson G, Thobois S, Kopp N, PerretLiaudet A, Streichenberger N. Source: Annals of Neurology. 2003 April; 53(4): 546-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12666126&dopt=Abstract

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Rapid and sensitive assays for determination of hepatitis B virus (HBV) genotypes and detection of HBV precore and core promoter variants. Author(s): Hussain M, Chu CJ, Sablon E, Lok AS. Source: Journal of Clinical Microbiology. 2003 August; 41(8): 3699-705. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904378&dopt=Abstract

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Rapid quantification of hepatitis B virus DNA by real-time PCR using fluorescent hybridization probes. Author(s): Ho SK, Yam WC, Leung ET, Wong LP, Leung JK, Lai KN, Chan TM. Source: Journal of Medical Microbiology. 2003 May; 52(Pt 5): 397-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12721315&dopt=Abstract

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Recent advance on viral hepatitis A. Author(s): Lee SD. Source: J Chin Med Assoc. 2003 June; 66(6): 318-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889499&dopt=Abstract

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Recombinant hepatitis B triple antigen vaccine: Hepacare. Author(s): Zuckerman JN, Zuckerman AJ. Source: Expert Rev Vaccines. 2002 August; 1(2): 141-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901552&dopt=Abstract

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Regression of fibrosis in chronic hepatitis C after therapy with interferon and ribavirin. Author(s): Arif A, Levine RA, Sanderson SO, Bank L, Velu RP, Shah A, Mahl TC, Gregory DH. Source: Digestive Diseases and Sciences. 2003 July; 48(7): 1425-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870807&dopt=Abstract

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Regression of hepatic fibrosis and cirrhosis in patients with chronic hepatitis C treated with interferon-based therapy. Author(s): Metwally MA, Zein CO, Zein NN. Source: Gastroenterology. 2003 May; 124(5): 1561. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760398&dopt=Abstract

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Regular sources of medical care among persons with severe mental illness at risk of hepatitis C infection. Author(s): Swartz MS, Swanson JW, Hannon MJ, Bosworth HS, Osher FC, Essock SM, Rosenberg SD; Five-Site Health and Risk Study Research Committee. Source: Psychiatric Services (Washington, D.C.). 2003 June; 54(6): 854-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773600&dopt=Abstract

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Regulation of CC chemokine receptor 5 in hepatitis G virus infection. Author(s): Nattermann J, Nischalke HD, Kupfer B, Rockstroh J, Hess L, Sauerbruch T, Spengler U. Source: Aids (London, England). 2003 July 4; 17(10): 1457-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824783&dopt=Abstract

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Regulation of hepatitis B virus replication by the ras-mitogen-activated protein kinase signaling pathway. Author(s): Zheng Y, Li J, Johnson DL, Ou JH. Source: Journal of Virology. 2003 July; 77(14): 7707-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829809&dopt=Abstract

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Reinforced interferon alpha-2b and ribavirin is more effective than standard combination therapy in the retreatment of chronic hepatitis C previously nonresponsive to interferon: a randomized trial. Author(s): Poynard T, Marcellin P, Bissery A, Myers RP, Moussalli J, Degos F, Dhumeaux D, Riachi G, Bronowicki JP, Brissot P, Buffet C, Serfaty L, Naveau S, Sogni P, Beaugrand M, Gayno S, Larrey D, Samuel D, Eugene C, Pol S, Bedossa P, Daurat V, Chaumet-Riffaud P; GER-CYT-RIBANON group. Source: Journal of Viral Hepatitis. 2003 May; 10(3): 197-204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753338&dopt=Abstract

250 Hepatitis

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Relevance of hepatitis B core gene deletions in patients after kidney transplantation. Author(s): Bock CT, Buerke B, Tillmann HL, Tacke F, Kliem V, Manns MP, Trautwein C. Source: Gastroenterology. 2003 June; 124(7): 1809-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12806615&dopt=Abstract

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Remote abscess formation during interferon-alpha therapy for viral hepatitis. Author(s): Gogos CA, Starakis JK, Bassaris HP, Skoutelis AT. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2003 June; 9(6): 540-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848731&dopt=Abstract

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Renewed hope in the treatment of hepatitis C virus infection. Author(s): Vaamonde C, Boyle BA. Source: Aids Read. 1999 August; 9(5): 311-4. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737120&dopt=Abstract

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Replication of hepatitis C virus RNA occurs in a membrane-bound replication complex containing nonstructural viral proteins and RNA. Author(s): El-Hage N, Luo G. Source: The Journal of General Virology. 2003 October; 84(Pt 10): 2761-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13679611&dopt=Abstract

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Replication of hepatitis C virus subgenomes in nonhepatic epithelial and mouse hepatoma cells. Author(s): Zhu Q, Guo JT, Seeger C. Source: Journal of Virology. 2003 September; 77(17): 9204-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915536&dopt=Abstract

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Resolution of liver cirrhosis and prevention of hepatocellular carcinoma by interferon therapy against chronic hepatitis C. Author(s): Omata M, Yoshida H. Source: Scandinavian Journal of Gastroenterology. Supplement. 2003; (237): 47-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797682&dopt=Abstract

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Retreatment with interferon and ribavirin vs interferon alone according to viraemia in interferon responder-relapser hepatitis C patients: a prospective multicentre randomized controlled study. Author(s): Portal I, Bourliere M, Halfon P, De Ledinghen V, Couzigou P, Bernard PH, Blanc F, Caroli-Bosc F, Arpurt JP, Vetter D, Mathieu-Chandelier C, Chazouilleres O, Thiefin G, Pol S, Sogni P, Abergel A, Bailly F, Picon M, Debonne JM, Zamora C, Alleman I, Moreau X, Doll F, Eugene C, Ducloux S, Larrey D, Ouzan D, Grimaud JC, Gouvernet J, Botti G, Gerolami V, Khiri H, Gerolami A, Gauthier AP, Botta-Fridlund D. Source: Journal of Viral Hepatitis. 2003 May; 10(3): 215-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753341&dopt=Abstract

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Retrospective screening for hepatitis C in a tertiary paediatric referral centre. Author(s): McKeown C, Thaker U, Cubitt WD, Novelli V. Source: Commun Dis Public Health. 2003 April; 6(1): 40-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12736971&dopt=Abstract

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Rhabdomyolysis, hepatitis and multiple hematological disorders associated with alcohol abuse: a case report. Author(s): Yoshida Y, Take H, Kurabayashi H, Tamura K, Kubota K. Source: J Med. 2002; 33(1-4): 3-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939102&dopt=Abstract

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Rheumatic manifestations of hepatitis C infection. Author(s): Vassilopoulos D, Calabrese LH. Source: Curr Rheumatol Rep. 2003 June; 5(3): 200-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12744811&dopt=Abstract

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Ribavirin as maintenance therapy for hepatitis C patients: an interim peacekeeper? Author(s): Patel K, Dev A, Muir AJ, McHutchison JG. Source: Hepatology (Baltimore, Md.). 2003 July; 38(1): 21-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829982&dopt=Abstract

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Rising incidence of hepatocellular carcinoma: the role of hepatitis B and C; the impact on transplantation and outcomes. Author(s): Kaplan DE, Reddy KR. Source: Clinics in Liver Disease. 2003 August; 7(3): 683-714. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509534&dopt=Abstract

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Risk factors and seroprevalence of hepatitis C antibody in blood donors in Nigeria. Author(s): Halim NK, Ajayi OI. Source: East Afr Med J. 2000 August; 77(8): 410-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12862062&dopt=Abstract

252 Hepatitis

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Risk factors for HIV, hepatitis B, and hepatitis C among persons with severe mental illness. Author(s): Essock SM, Dowden S, Constantine NT, Katz L, Swartz MS, Meador KG, Osher FC, Rosenberg SD; Five-Site Health and Risk Study Research Committee. Source: Psychiatric Services (Washington, D.C.). 2003 June; 54(6): 836-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773597&dopt=Abstract

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Risk factors, clinical features and genotype distribution of diagnosed hepatitis C virus infections: a pilot for a sentinel laboratory-based surveillance. Author(s): Balogun MA, Laurichesse H, Ramsay ME, Sellwood J, Westmoreland D, Paver WK, Pugh SF, Zuckerman M, Pillay D, Wreghitt T. Source: Commun Dis Public Health. 2003 April; 6(1): 34-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12736970&dopt=Abstract

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Risk of hepatitis C virus transmission from patients to surgeons: model based on an unlinked anonymous study of hepatitis C virus prevalence in hospital patients in Glasgow. Author(s): Thorburn D, Roy K, Cameron SO, Johnston J, Hutchinson S, McCruden EA, Mills PR, Goldberg DJ. Source: Gut. 2003 September; 52(9): 1333-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12912867&dopt=Abstract

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Role of hepatitis B immunoglobulin in infants born to hepatitis B e antigen-negative carrier mothers in Taiwan. Author(s): Yang YJ, Liu CC, Chen TJ, Lee MF, Chen SH, Shih HH, Chang MH. Source: The Pediatric Infectious Disease Journal. 2003 July; 22(7): 584-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867831&dopt=Abstract

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Role of hepatitis B virus genotypes in chronic hepatitis B exacerbation. Author(s): Yuen MF, Sablon E, Wong DK, Yuan HJ, Wong BC, Chan AO, Lai CL. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 August 15; 37(4): 593-7. Epub 2003 July 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12905145&dopt=Abstract

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Role of liver biopsy in the management of liver dysfunction after hematopoietic stem-cell transplantation in a hepatitis B virus-prevalent patient population. Author(s): Ma SY, Au WY, Ng IO, Lie AK, Leung AY, Liang RH, Lau GK, Kwong YL. Source: Transplantation. 2003 July 15; 76(1): 169-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865805&dopt=Abstract

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Safety of immunisation and adverse events following vaccination against hepatitis B. Author(s): Duclos P. Source: Expert Opinion on Drug Safety. 2003 May; 2(3): 225-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904102&dopt=Abstract

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Sampling and repeatability in the evaluation of hepatitis C virus genetic variability. Author(s): Torres-Puente M, Bracho MA, Jimenez N, Garcia-Robles I, Moya A, Gonzalez-Candelas F. Source: The Journal of General Virology. 2003 September; 84(Pt 9): 2343-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917454&dopt=Abstract

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Selection of a secretion-incompetent mutant in the serum of a patient with severe hepatitis B. Author(s): Kalinina T, Riu A, Fischer L, Santantonio T, Will H, Sterneck M. Source: Gastroenterology. 2003 October; 125(4): 1077-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14517791&dopt=Abstract

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Selective inhibition of hepatitis B virus replication by RNA interference. Author(s): Ying C, De Clercq E, Neyts J. Source: Biochemical and Biophysical Research Communications. 2003 September 19; 309(2): 482-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12951075&dopt=Abstract

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Sequence elements correlating with circulating viral load in genotype 1b hepatitis C virus infection. Author(s): Watanabe H, Nagayama K, Enomoto N, Itakura J, Tanabe Y, Hamano K, Izumi N, Sato C, Watanabe M. Source: Virology. 2003 July 5; 311(2): 376-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842626&dopt=Abstract

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Seroepidemiology of hepatitis B virus in Addis Ababa, Ethiopia: transmission patterns and vaccine control. Author(s): Abebe A, Nokes DJ, Dejene A, Enquselassie F, Messele T, Cutts FT. Source: Epidemiology and Infection. 2003 August; 131(1): 757-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12948377&dopt=Abstract

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Seroprevalence of hepatitis B in pregnant women in Mexico. Author(s): Vazquez-Martinez JL, Coreno-Juarez MO, Montano-Estrada LF, Attlan M, Gomez-Dantes H. Source: Salud P'ublica De M'exico. 2003 May-June; 45(3): 165-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870417&dopt=Abstract

254 Hepatitis

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Severe acute pancreatitis associated with acute hepatitis A: a case report. Author(s): Batra Y, Chakravarty S, Bhatt G. Source: Trop Gastroenterol. 2003 January-March; 24(1): 27-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974212&dopt=Abstract

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Severe acute pancreatitis due to hepatitis A virus infection in a patient of acute viral hepatitis. Author(s): Khanna S, Vij JC. Source: Trop Gastroenterol. 2003 January-March; 24(1): 25-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974211&dopt=Abstract

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Severe hepatitis E virus infection after ingestion of uncooked liver from a wild boar. Author(s): Matsuda H, Okada K, Takahashi K, Mishiro S. Source: The Journal of Infectious Diseases. 2003 September 15; 188(6): 944. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12964128&dopt=Abstract

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Sexual transmission of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus type 1 infections among male transvestite comercial sex workers in Montevideo, Uruguay. Author(s): Russi JC, Serra M, Vinoles J, Perez MT, Ruchansky D, Alonso G, Sanchez JL, Russell KL, Montano SM, Negrete M, Weissenbacher M. Source: The American Journal of Tropical Medicine and Hygiene. 2003 June; 68(6): 71620. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12887033&dopt=Abstract

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Sexual transmission of hepatitis C virus from a patient with chronic disease to his sex partner after removal of an intrauterine device. Author(s): Quer J, Murillo P, Esteban JI, Martell M, Esteban R, Guardia J. Source: Sexually Transmitted Diseases. 2003 May; 30(5): 470-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916140&dopt=Abstract

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Should treatment of hepatitis C in HIV-seropositive and HIV-seronegative patients with hemophilia include induction doses of interferon? Author(s): McGovern B, Bica I. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 August 1; 37(3): 463-4; Author Reply 464-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12884180&dopt=Abstract

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Significance of pretreatment analysis of hepatitis C virus genotype 1b hypervariable region 1 sequences to predict antiviral outcome. Author(s): Gaudy C, Moreau A, Veillon P, Temoin S, Lunel F, Goudeau A. Source: Journal of Clinical Microbiology. 2003 August; 41(8): 3615-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904364&dopt=Abstract

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Significance of prior hepatitis B virus infection in the development of hepatocellular carcinoma in patients with chronic hepatitis C. Author(s): Imazeki F, Yokosuka O, Fukai K, Hiraide A, Saisho H. Source: Digestive Diseases and Sciences. 2003 September; 48(9): 1786-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14561002&dopt=Abstract

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Slowing the progression of chronic hepatitis B. Early antiviral therapy can help minimize complications. Author(s): Purow DB, Jacobson IM. Source: Postgraduate Medicine. 2003 July; 114(1): 65-8, 73-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875056&dopt=Abstract

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Small molecule inhibition of hepatitis C virus E2 binding to CD81. Author(s): VanCompernolle SE, Wiznycia AV, Rush JR, Dhanasekaran M, Baures PW, Todd SC. Source: Virology. 2003 September 15; 314(1): 371-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14517089&dopt=Abstract

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Smooth muscle antibodies and type 1 autoimmune hepatitis. Author(s): Muratori P, Muratori L, Agostinelli D, Pappas G, Veronesi L, Granito A, Cassani F, Terlizzi P, Lenzi M, Bianchi FB. Source: Autoimmunity. 2002 December; 35(8): 497-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765475&dopt=Abstract

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Some hepatitis C patients -- especially women -- don't really benefit from early therapy. Author(s): Levenson D. Source: Rep Med Guidel Outcomes Res. 2003 July 25; 14(14): 9-10, 12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12931703&dopt=Abstract

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Spectrum of acute viral hepatitis and its clinical outcome--a study from Ludhiana, Punjab. Author(s): Kaur H, John M, Pawar G, Ninan J, Verma V. Source: Indian Journal of Medical Sciences. 2003 February; 57(2): 71-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14514273&dopt=Abstract

256 Hepatitis

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Spontaneous elimination of serum hepatitis C virus (HCV) RNA in chronic HCV carriers: a population-based cohort study. Author(s): Watanabe H, Saito T, Shinzawa H, Okumoto K, Hattori E, Adachi T, Takeda T, Sugahara K, Ito JI, Saito K, Togashi H, Suzuki R, Hayashi M, Miyamura T, Matsuura Y, Kawata S. Source: Journal of Medical Virology. 2003 September; 71(1): 56-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858409&dopt=Abstract

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Sporadic acute or fulminant hepatitis E in Hokkaido, Japan, may be food-borne, as suggested by the presence of hepatitis E virus in pig liver as food. Author(s): Yazaki Y, Mizuo H, Takahashi M, Nishizawa T, Sasaki N, Gotanda Y, Okamoto H. Source: The Journal of General Virology. 2003 September; 84(Pt 9): 2351-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917455&dopt=Abstract

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Student leadership in public health advocacy: lessons learned from the hepatitis B initiative. Author(s): Hsu LD, DeJong W, Hsia R, Chang M, Ryou M, Yeh E. Source: American Journal of Public Health. 2003 August; 93(8): 1250-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893606&dopt=Abstract

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Substance abuse and the transmission of hepatitis C among persons with severe mental illness. Author(s): Osher FC, Goldberg RW, McNary SW, Swartz MS, Essock SM, Butterfield MI, Rosenberg SD; Five-Site Health and Risk Study Research Committee. Source: Psychiatric Services (Washington, D.C.). 2003 June; 54(6): 842-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773598&dopt=Abstract

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Successful bone marrow plus cord blood stem cell transplantation in a girl who developed myelodysplastic syndrome from hepatitis-associated aplastic anemia treated with long-term immunosuppressants and growth factors. Author(s): Shibuya A, Ishii S, Obinata K. Source: Hematology (Amsterdam, Netherlands). 2002 October; 7(5): 301-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850817&dopt=Abstract

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Successful clearance of hepatitis B virus after allogeneic stem cell transplantation: beneficial combination of adoptive immunity transfer and lamivudine. Author(s): Chiba T, Yokosuka O, Goto S, Fukai K, Imazeki F, Shishido H, Narita M, Saisho H. Source: European Journal of Haematology. 2003 September; 71(3): 220-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930325&dopt=Abstract

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Successful treatment with cyclosporin in adult-onset Still disease manifesting as acute hepatitis with marked hyperferritinemia. Author(s): Omagari K, Matsunaga Y, Yamashita H, Nishiyama H, Hazama H, Oda H, Isomoto H, Mizuta Y, Murase K, Kohno S. Source: The American Journal of the Medical Sciences. 2003 September; 326(3): 148-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14501232&dopt=Abstract

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Susceptibility of human hepatitis delta virus RNAs to small interfering RNA action. Author(s): Chang J, Taylor JM. Source: Journal of Virology. 2003 September; 77(17): 9728-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915586&dopt=Abstract

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Swine hepatitis E virus: cross-species infection and risk in xenotransplantation. Author(s): Meng XJ. Source: Curr Top Microbiol Immunol. 2003; 278: 185-216. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934945&dopt=Abstract

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Synergistic effect of hepatitis virus infection and occupational exposures to vinyl chloride monomer and ethylene dichloride on serum aminotransferase activity. Author(s): Hsieh HI, Wang JD, Chen PC, Cheng TJ. Source: Occupational and Environmental Medicine. 2003 October; 60(10): 774-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14504367&dopt=Abstract

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Targeted cleavage of hepatitis E virus 3' end RNA mediated by hammerhead ribozymes inhibits viral RNA replication. Author(s): Sriram B, Thakral D, Panda SK. Source: Virology. 2003 August 1; 312(2): 350-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12919740&dopt=Abstract

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The association of hepatitis C prevalence, activity, and genotype with HIV infection in a cohort of New York City drug users. Author(s): Strasfeld L, Lo Y, Netski D, Thomas DL, Klein RS. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 2003 July 1; 33(3): 356-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843747&dopt=Abstract

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The chemokine CCL21 modulates lymphocyte recruitment and fibrosis in chronic hepatitis C. Author(s): Bonacchi A, Petrai I, Defranco RM, Lazzeri E, Annunziato F, Efsen E, Cosmi L, Romagnani P, Milani S, Failli P, Batignani G, Liotta F, Laffi G, Pinzani M, Gentilini P, Marra F. Source: Gastroenterology. 2003 October; 125(4): 1060-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14517790&dopt=Abstract

258 Hepatitis

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The cost effectiveness of hepatitis immunization for US college students. Author(s): Jacobs RJ, Saab S, Meyerhoff AS. Source: Journal of American College Health : J of Ach. 2003 May; 51(6): 227-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14510025&dopt=Abstract

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The costs of not treating hepatitis C virus infection in injecting drug users in New Zealand. Author(s): Sheerin IG, Green FT, Sellman JD. Source: Drug and Alcohol Review. 2003 June; 22(2): 159-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850902&dopt=Abstract

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The C-terminal region of hepatitis C core protein is required for Fas-ligand independent apoptosis in Jurkat cells by facilitating Fas oligomerization. Author(s): Moorman JP, Prayther D, McVay D, Hahn YS, Hahn CS. Source: Virology. 2003 August 1; 312(2): 320-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12919737&dopt=Abstract

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The Delta 32 mutation of the chemokine-receptor 5 gene neither is correlated with chronic hepatitis C nor does it predict response to therapy with interferon-alpha and ribavirin. Author(s): Glas J, Torok HP, Simperl C, Konig A, Martin K, Schmidt F, Schaefer M, Schiemann U, Folwaczny C. Source: Clinical Immunology (Orlando, Fla.). 2003 July; 108(1): 46-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865070&dopt=Abstract

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The effect of phenobarbital on the accuracy of technetium-99m diisopropyl iminodiacetic acid hepatobiliary scintigraphy in differentiating biliary atresia from neonatal hepatitis syndrome. Author(s): Charearnrad P, Chongsrisawat V, Tepmongkol S, Poovorawan Y. Source: J Med Assoc Thai. 2003 June; 86 Suppl 2: S189-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12929988&dopt=Abstract

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The efficacy of a two-dose hepatitis B vaccination scheme. Author(s): Boland GJ, van Bommel T, Rulos-van den Berg A, van den Berg JP, van Loon AM, van Hattum J. Source: Advances in Experimental Medicine and Biology. 2003; 531: 185-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916790&dopt=Abstract

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The epidemiology and control of hepatitis C infection. Author(s): Gungabissoon U. Source: Nurs Times. 2003 August 5-11; 99(31): 24-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13677115&dopt=Abstract

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The Fgl2/fibroleukin prothrombinase contributes to immunologically mediated thrombosis in experimental and human viral hepatitis. Author(s): Marsden PA, Ning Q, Fung LS, Luo X, Chen Y, Mendicino M, Ghanekar A, Scott JA, Miller T, Chan CW, Chan MW, He W, Gorczynski RM, Grant DR, Clark DA, Phillips MJ, Levy GA. Source: The Journal of Clinical Investigation. 2003 July; 112(1): 58-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840059&dopt=Abstract

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The German network of excellence for viral hepatitis (Hep-Net). Author(s): Manns MP, Meyer S, Wedemeyer H. Source: Hepatology (Baltimore, Md.). 2003 September; 38(3): 543-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939578&dopt=Abstract

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The impact of hepatitis C status on postoperative outcome. Author(s): Cheung RC, Hsieh F, Wang Y, Pollard JB. Source: Anesthesia and Analgesia. 2003 August; 97(2): 550-4, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873952&dopt=Abstract

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The impact of hepatitis C virus coinfection on HIV progression before and after highly active antiretroviral therapy. Author(s): Klein MB, Lalonde RG, Suissa S. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 2003 July 1; 33(3): 365-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843748&dopt=Abstract

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The influence of viral genotypes and rejection episodes on the recurrence of hepatitis C after liver transplantation. Author(s): Sugo H, Balderson GA, Crawford DH, Fawcett J, Lynch SV, Strong RW, Futagawa S. Source: Surgery Today. 2003; 33(6): 421-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768367&dopt=Abstract

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The prevalence of hepatitis G virus in cancer patients. Author(s): Buyukberber N, Buyukberber S, Kadayifci A, Guney C, Camci C, Balkan A, Kubar A, Turk HM, Sevinc A. Source: New Microbiol. 2003 July; 26(3): 243-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901419&dopt=Abstract

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The T(1858) variant predisposing to the precore stop mutation correlates with one of two major genotype F hepatitis B virus clades. Author(s): Norder H, Arauz-Ruiz P, Blitz L, Pujol FH, Echevarria JM, Magnius LO. Source: The Journal of General Virology. 2003 August; 84(Pt 8): 2083-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867638&dopt=Abstract

260 Hepatitis

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Therapeutic antibodies against viral hepatitis. Author(s): Dagan S, Eren R. Source: Curr Opin Mol Ther. 2003 April; 5(2): 148-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12772504&dopt=Abstract

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Tissue-specific replicating capacity of a chimeric poliovirus that carries the internal ribosome entry site of hepatitis C virus in a new mouse model transgenic for the human poliovirus receptor. Author(s): Yanagiya A, Ohka S, Hashida N, Okamura M, Taya C, Kamoshita N, Iwasaki K, Sasaki Y, Yonekawa H, Nomoto A. Source: Journal of Virology. 2003 October; 77(19): 10479-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970433&dopt=Abstract

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To transplant or not to transplant recurrent hepatitis C and liver failure. Author(s): Forman LM. Source: Clinics in Liver Disease. 2003 August; 7(3): 615-29. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509530&dopt=Abstract

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Transmission of hepatitis B and C viruses in outpatient settings--New York, Oklahoma, and Nebraska, 2000-2002. Author(s): Centers for Disease Control and Prevention (CDC). Source: Mmwr. Morbidity and Mortality Weekly Report. 2003 September 26; 52(38): 9016. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14508437&dopt=Abstract

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Transmission profile of hepatitis B virus infection in the Batam region, Indonesia. Evidence for a predominantly horizontal transmission profile. Author(s): van Hattum J, Boland GJ, Jansen KG, Kleinpenning AS, van Bommel T, van Loon AM, Abdurachman SA, Yusuf H, Rulos-van den Berg A, van den Berg J. Source: Advances in Experimental Medicine and Biology. 2003; 531: 177-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916789&dopt=Abstract

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Treatment of chronic hepatitis B in 2002. Author(s): Husa P, Husova L. Source: Bratisl Lek Listy. 2003; 104(2): 59-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839213&dopt=Abstract

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Treatment of interferon-induced psychosis in patients with comorbid hepatitis C and HIV. Author(s): Hoffman RG, Cohen MA, Alfonso CA, Weiss JJ, Jones S, Keller M, Condemarin JR, Chiu NM, Jacobson JM. Source: Psychosomatics. 2003 September-October; 44(5): 417-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12954918&dopt=Abstract

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Treatment strategies for hepatitis C: intervention prior to liver transplant, preemptively or after established disease. Author(s): Berenguer M, Wright TL. Source: Clinics in Liver Disease. 2003 August; 7(3): 631-50, Vii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509531&dopt=Abstract

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Tumor necrosis factor alpha promoter polymorphisms at position -308 in Taiwanese chronic hepatitis C patients treated with interferon-alpha. Author(s): Yu ML, Dai CY, Chiu CC, Lee LP, Lin ZY, Chen SC, Hsieh MY, Wang LY, Chen CJ, Chuang WL, Chang WY. Source: Antiviral Research. 2003 June; 59(1): 35-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834858&dopt=Abstract

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Tumour necrosis factor alpha is an important mediator of portal and systemic haemodynamic derangements in alcoholic hepatitis. Author(s): Mookerjee RP, Sen S, Davies NA, Hodges SJ, Williams R, Jalan R. Source: Gut. 2003 August; 52(8): 1182-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865279&dopt=Abstract

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Twenty-year survey of the epidemiology of hepatitis B in Denmark: effect of immigration. Author(s): Gjorup IE, Smith E, Borgwardt L, Skinhoj P. Source: Scandinavian Journal of Infectious Diseases. 2003; 35(4): 260-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839156&dopt=Abstract

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Type 1 diabetes mellitus in patients with chronic hepatitis C before and after interferon therapy. Author(s): Fabris P, Floreani A, Tositti G, Vergani D, De Lalla F, Betterle C. Source: Alimentary Pharmacology & Therapeutics. 2003 September 15; 18(6): 549-58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12969081&dopt=Abstract

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Type C-chronic hepatitis patients who had autoimmune phenomenon and developed jaundice during interferon therapy. Author(s): Sezaki H, Arase Y, Tsubota A, Suzuki Y, Kobayashi M, Saitoh S, Suzuki F, Akuta N, Someya T, Ikeda K, Kumada H. Source: Journal of Gastroenterology. 2003; 38(5): 493-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768394&dopt=Abstract

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Ultrasonography in malarial hepatitis. Author(s): Kachawaha S, Pokharana R, Rawat N, Garg P, Badjatiya H, Kochar DK. Source: Indian J Gastroenterol. 2003 May-June; 22(3): 110. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839391&dopt=Abstract

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Unexpected distribution of hepatitis C virus genotypes in patients on hemodialysis and kidney transplant recipients. Author(s): Perez RM, Ferraz ML, Figueiredo MS, Contado D, Koide S, Ferreira AP, Cendoroglo Neto M, Medina Pestana JO, Silva AE. Source: Journal of Medical Virology. 2003 April; 69(4): 489-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601756&dopt=Abstract

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Universal hepatitis B vaccination of UK adolescents: a feasibility and acceptability study. Author(s): Bramley JC, Wallace LA, Ahmed S, Duff R, Carman WF, Cameron SO, Kitchin NR, Watson MW, Goldberg DJ. Source: Commun Dis Public Health. 2002 December; 5(4): 318-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12564249&dopt=Abstract

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Upregulation of endogenous intrahepatic interferon stimulated genes during chronic hepatitis C virus infection. Author(s): MacQuillan GC, Mamotte C, Reed WD, Jeffrey GP, Allan JE. Source: Journal of Medical Virology. 2003 June; 70(2): 219-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12696108&dopt=Abstract

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Upregulation of lymphotoxin beta expression in liver progenitor (oval) cells in chronic hepatitis C. Author(s): Lowes KN, Croager EJ, Abraham LJ, Olynyk JK, Yeoh GC. Source: Gut. 2003 September; 52(9): 1327-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12912866&dopt=Abstract

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Upregulation of major histocompatibility complex class I on liver cells by hepatitis C virus core protein via p53 and TAP1 impairs natural killer cell cytotoxicity. Author(s): Herzer K, Falk CS, Encke J, Eichhorst ST, Ulsenheimer A, Seliger B, Krammer PH. Source: Journal of Virology. 2003 August; 77(15): 8299-309. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12857899&dopt=Abstract

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Use and interpretation of hepatitis C virus diagnostic assays. Author(s): Pawlotsky JM. Source: Clinics in Liver Disease. 2003 February; 7(1): 127-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691462&dopt=Abstract

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Use of liver grafts from donors positive for antihepatitis B-core antibody (anti-HBc) in the era of prophylaxis with hepatitis-B immunoglobulin and lamivudine. Author(s): Nery JR, Nery-Avila C, Reddy KR, Cirocco R, Weppler D, Levi DM, Nishida S, Madariaga J, Kato T, Ruiz P, Schiff E, Tzakis AG. Source: Transplantation. 2003 April 27; 75(8): 1179-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12717200&dopt=Abstract

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Use of the organ donor with prior hepatitis B infection: a safe option? Author(s): Fabrizi F, Bunnapradist S, Martin P. Source: Int J Artif Organs. 2003 January; 26(1): 6-11. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12602463&dopt=Abstract

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Vaccination against hepatitis B in patients on chronic haemodialysis. Author(s): Kovacic V. Source: Int J Clin Pract. 2003 April; 57(3): 161-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723714&dopt=Abstract

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Vaccine induced protection against hepatitis B. Author(s): Van Damme P, Banatvala JE. Source: Bmj (Clinical Research Ed.). 2003 January 11; 326(7380): 105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521983&dopt=Abstract

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Vacuolization in hepatitis B virus-infected hepatocytes. Author(s): Roingeard P. Source: Hepatology (Baltimore, Md.). 2003 May; 37(5): 1223-4; Author Reply 1224. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12717405&dopt=Abstract

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Validation of a simple predictive model for the identification of mild hepatic fibrosis in chronic hepatitis C patients. Author(s): Patel K, Muir AJ, McHutchison JG. Source: Hepatology (Baltimore, Md.). 2003 May; 37(5): 1222; Author Reply 1222-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12717404&dopt=Abstract

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Validation of an in vitro potency test for the Cuban hepatitis B vaccine. Author(s): Landys Chovel Cuervo M, Reyes Huerta N. Source: Dev Biol (Basel). 2002; 111: 305-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678254&dopt=Abstract

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Validation of the FibroTest biochemical markers score in assessing liver fibrosis in hepatitis C patients. Author(s): Rossi E, Adams L, Prins A, Bulsara M, de Boer B, Garas G, MacQuillan G, Speers D, Jeffrey G. Source: Clinical Chemistry. 2003 March; 49(3): 450-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12600957&dopt=Abstract

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Validity and clinical utility of the aspartate aminotransferase-alanine aminotransferase ratio in assessing disease severity and prognosis in patients with hepatitis C virus-related chronic liver disease. Author(s): Giannini E, Risso D, Botta F, Chiarbonello B, Fasoli A, Malfatti F, Romagnoli P, Testa E, Ceppa P, Testa R. Source: Archives of Internal Medicine. 2003 January 27; 163(2): 218-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546613&dopt=Abstract

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Validity of injecting drug users' self report of hepatitis A, B, and C. Author(s): Schlicting EG, Johnson ME, Brems C, Wells RS, Fisher DG, Reynolds G. Source: Clin Lab Sci. 2003 Spring; 16(2): 99-106. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12757189&dopt=Abstract

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Variability in the incidence of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus infection among young injecting drug users in New York City. Author(s): Des Jarlais DC, Diaz T, Perlis T, Vlahov D, Maslow C, Latka M, Rockwell R, Edwards V, Friedman SR, Monterroso E, Williams I, Garfein RS. Source: American Journal of Epidemiology. 2003 March 1; 157(5): 467-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615611&dopt=Abstract

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Vertical transmission of the hepatitis C virus to infants of anti-human immunodeficiency virus-negative mothers: molecular evolution of hypervariable region 1 in prenatal and perinatal or postnatal infections. Author(s): Caudai C, Battiata M, Riccardi MP, Toti M, Bonazza P, Padula MG, Pianese M, Valensin PE. Source: Journal of Clinical Microbiology. 2003 August; 41(8): 3955-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904428&dopt=Abstract

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Very rapid evolution of infection with hepatitis C virus transmitted by an accidental needlestick. Author(s): Garcia JM, Serrano PL, Terron Sdel C, Marugan RB, Garcia GM, Grande LG, Miquel J, Plaza AG. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 June 15; 36(12): 1632-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802777&dopt=Abstract

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Viraemia, cryoglobulins and autoantibodies in haemodialysis patients infected with hepatitis C virus. Author(s): Siagris D, Labropoulou-Karatza C, Christofidou M, Goumenos D, Thomopoulos K, Lekkou A, Gogos CA, Vlachojannis J. Source: European Journal of Gastroenterology & Hepatology. 2003 February; 15(2): 1337. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560756&dopt=Abstract

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Viral and cellular determinants of hepatitis C virus RNA replication in cell culture. Author(s): Lohmann V, Hoffmann S, Herian U, Penin F, Bartenschlager R. Source: Journal of Virology. 2003 March; 77(5): 3007-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584326&dopt=Abstract

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Viral and clinical factors associated with the fulminant course of hepatitis A infection. Author(s): Rezende G, Roque-Afonso AM, Samuel D, Gigou M, Nicand E, Ferre V, Dussaix E, Bismuth H, Feray C. Source: Hepatology (Baltimore, Md.). 2003 September; 38(3): 613-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939587&dopt=Abstract

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Viral escape and T cell exhaustion in hepatitis C virus infection analysed using Class I peptide tetramers. Author(s): Kantzanou M, Lucas M, Barnes E, Komatsu H, Dusheiko G, Ward S, Harcourt G, Klenerman P. Source: Immunology Letters. 2003 January 22; 85(2): 165-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527224&dopt=Abstract

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Viral etiopathogenesis of Sjogren's syndrome: role of the hepatitis C virus. Author(s): Ramos-Casals M, Garcia-Carrasco M, Brito Zeron MP, Cervera R, Font J. Source: Autoimmunity Reviews. 2002 August; 1(4): 238-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849002&dopt=Abstract

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Viral hepatitis (Part-I). Author(s): Banker DD. Source: Indian Journal of Medical Sciences. 2003 August; 57(8): 363-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12944695&dopt=Abstract

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Viral hepatitis among young men who have sex with men: prevalence of infection, risk behaviors, and vaccination. Author(s): Diamond C, Thiede H, Perdue T, Secura GM, Valleroy L, Mackellar D, Corey L; Seattle Young Men's Survey Team. Source: Sexually Transmitted Diseases. 2003 May; 30(5): 425-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916134&dopt=Abstract

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Viral hepatitis in health service workers in the Province of Wielkopolska. Author(s): Bilski B, Wysocki J, Hemerling M. Source: International Journal of Occupational Medicine and Environmental Health. 2002; 15(4): 347-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608622&dopt=Abstract

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Viral hepatitis-related acute liver failure. Author(s): Schiodt FV, Davern TJ, Shakil AO, McGuire B, Samuel G, Lee WM. Source: The American Journal of Gastroenterology. 2003 February; 98(2): 448-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591067&dopt=Abstract

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Viral kinetics in hepatitis C. Author(s): Lutchman G, Hoofnagle JH. Source: Hepatology (Baltimore, Md.). 2003 June; 37(6): 1257-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12774002&dopt=Abstract

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Virological and histological outcome of a patient with chronic hepatitis B transplanted with liver from hepatitis C virus-positive donor. Author(s): Chan HL, Chui AK, Chan FK, Rao AR, Wong J, Lau WY. Source: Transplantation Proceedings. 2003 February; 35(1): 423-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591470&dopt=Abstract

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Vitamin K and hepatitis B vaccine. Author(s): O'Bryant C. Source: Midwifery Today Int Midwife. 2001 Spring; (57): 66; Author Reply 66-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12596416&dopt=Abstract

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Week 48 resistance surveillance in two phase 3 clinical studies of adefovir dipivoxil for chronic hepatitis B. Author(s): Westland CE, Yang H, Delaney WE 4th, Gibbs CS, Miller MD, Wulfsohn M, Fry J, Brosgart CL, Xiong S; 437 and 438 Study Teams. Source: Hepatology (Baltimore, Md.). 2003 July; 38(1): 96-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829991&dopt=Abstract

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What is the real prevalence of the D virus infection in chronic hepatitis and liver cirrhosis in Romania? Author(s): Grigorescu M, Pascu O, Acalovschi M, Radu C. Source: Rom J Gastroenterol. 2003 September; 12(3): 179-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14502316&dopt=Abstract

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What should be done about hepatitis-B-infected health-care workers? Author(s): Carman WF, Cameron SO. Source: Journal of Medical Microbiology. 2003 May; 52(Pt 5): 371-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12721310&dopt=Abstract

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What surgeons should know about viral hepatitis and hepatocellular carcinoma. Author(s): Hassoun Z, Gores GJ. Source: Surg Oncol Clin N Am. 2003 January; 12(1): 1-11, Vii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735125&dopt=Abstract

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Who should receive hepatitis A vaccine? Author(s): Arankalle VA, Chadha MS. Source: Journal of Viral Hepatitis. 2003 May; 10(3): 157-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753332&dopt=Abstract

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Woodchuck hepatitis virus post-transcriptional regulation element enhances transgene expression from adenovirus vectors. Author(s): Xu ZL, Mizuguchi H, Mayumi T, Hayakawa T. Source: Biochimica Et Biophysica Acta. 2003 June 11; 1621(3): 266-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12787924&dopt=Abstract

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Worsening of steatosis is an independent factor of fibrosis progression in untreated patients with chronic hepatitis C and paired liver biopsies. Author(s): Castera L, Hezode C, Roudot-Thoraval F, Bastie A, Zafrani ES, Pawlotsky JM, Dhumeaux D. Source: Gut. 2003 February; 52(2): 288-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12524415&dopt=Abstract

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Zoonotic transmission of hepatitis E virus from deer to human beings. Author(s): Tei S, Kitajima N, Takahashi K, Mishiro S. Source: Lancet. 2003 August 2; 362(9381): 371-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907011&dopt=Abstract

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CHAPTER 2. NUTRITION AND HEPATITIS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and hepatitis.

Finding Nutrition Studies on Hepatitis The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “hepatitis” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7

Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following is a typical result when searching for recently indexed consumer information on hepatitis: ·

A case of polymyositis with dilated cardiomyopathy associated with interferon alpha treatment for hepatitis B. Author(s): The Hospital for Rheumatic Diseases, Hanyang University, 17 Haengdongdong, Seongdong-gu, Seoul 133-792, Korea. Source: Lee, Seung Won Kim, Ki Chan Oh, Dong Ho Jung, Sung Soo Yoo, Dae Hyun Kim, Seong Yoon Choe, Gheeyoung Kim, Tae Hwan J-Korean-Med-Sci. 2002 February; 17(1): 141-3 1011-8934

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A prenylation inhibitor prevents production of infectious hepatitis delta virus particles. Author(s): Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 269 Campus Drive, Palo Alto, CA 94305-5187, USA. Source: Bordier, B B Marion, P L Ohashi, K Kay, M A Greenberg, H B Casey, J L Glenn, J S J-Virol. 2002 October; 76(20): 10465-72 0022-538X

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A randomized controlled clinical trial on the treatment of Thymosin a1 versus interferon-alpha in patients with hepatitis B. Author(s): Department of Infectious Diseases, The First Affiliated Hospital of Kunming Medical College, 153# Xi Chang Road, Kunming 650032, Yunnan Province, China. Source: You, J Zhuang, L Tang, B Z Yang, W B Ding, S Y Li, W Wu, R X Zhang, H L Zhang, Y M Yan, S M Zhang, L World-J-Gastroenterol. 2001 June; 7(3): 411-4 1007-9327

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Altered DNA mutation spectrum in aflatoxin b1-treated transgenic mice that express the hepatitis B virus x protein. Author(s): Department of Molecular Virology and Microbiology. Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA. Source: Madden, C R Finegold, M J Slagle, B L J-Virol. 2002 November; 76(22): 11770-4 0022-538X

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Biological and clinical significance of endotoxemia in the course of hepatitis C virus infection. Author(s): Laboratories of Immunopathology, Scientific Institute for Digestive Diseases, Castellana Grotte, Bari, Italy. Source: Caradonna, L Mastronardi, M L Magrone, T Cozzolongo, R Cuppone, R Manghisi, O G Caccavo, D Pellegrino, N M Amoroso, A Jirillo, E Amati, L Curr-PharmDes. 2002; 8(11): 995-1005 1381-6128

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Chemical synthesis of NS-1 region of hepatitis C-viral polyprotein fragments: a comparison of PS-BDODMA resin and merrifield resin. Author(s): School of Chemical Sciences, Mahatma Gandhi University, Priyadarsini Hills, Kottayam, Kerala, India. [email protected] Source: Roice, M KuMarch, K S Pillai, V N Protein-Pept-Lett. 2002 June; 9(3): 245-52 0929-8665

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Clinical and biochemical features and therapy responses in primary biliary cirrhosis and primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. Author(s): Department of Gastroenterology, Ege University Hospital Izmir, Turkey. [email protected] Source: Gunsar, F Akarca, U S Ersoz, G Karasu, Z Yuce, G Batur, Y Hepatogastroenterology. 2002 Sep-October; 49(47): 1195-200 0172-6390

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Clinical observation of salvianolic acid B in treatment of liver fibrosis in chronic hepatitis B. Author(s): Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. [email protected] Source: Liu, P Hu, Y Y Liu, C Zhu, D Y Xue, H M Xu, Z Q Xu, L M Liu, C H Gu, H T Zhang, Z Q World-J-Gastroenterol. 2002 August; 8(4): 679-85 1007-9327

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Combination thymosin-alpha 1 and interferon-alpha 2b in the treatment of anti-HBepositive chronic hepatitis B in Turkey. Author(s): Department of Gastroenterology, Celal Bayar University, School of Medicine, Manisa, Turkey. [email protected] Source: Saruc, M Yuceyar, H Kucukmetin, N Demir, M A Kandiloglu, A R Hepatogastroenterology. 2002 May-June; 49(45): 798-802 0172-6390

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Critical roles of nuclear receptor response elements in replication of hepatitis B virus. Author(s): McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, Wisconsin 53706-1599, USA. Source: Yu, X Mertz, J E J-Virol. 2001 December; 75(23): 11354-64 0022-538X

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Detecting the replication of the hepatitis B virus using the ImmunoMax technique following treatment with interferon-alpha in children with chronic hepatitis. Author(s): Department of Histology and Embryology, Medical University of Poznan, Poland. [email protected] Source: Kasprzak, Aldona Wysocki, Jacek Zabel, Maciej Surdyk Zasada, Joanna MedSci-Monit. 2002 January; 8(1): PR1-7 1234-1010

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Dietary iron restriction improves aminotransferase levels in chronic hepatitis C patients. Author(s): Third Department of Internal Medicine, Mie University School of Medicine, Edobashi 2-174, Tsu City, Mie 514-8507, Japan. [email protected] Source: Iwasa, M Kaito, M Ikoma, J Kobayashi, Y Tanaka, Y Higuchi, K Takeuchi, K Iwata, K Watanabe, S Adachi, Y Hepatogastroenterology. 2002 Mar-April; 49(44): 529-31 0172-6390

·

Does ascorbic acid prevent retinopathy during interferon therapy in patients with chronic hepatitis C? Author(s): Third Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan. Source: Nishiguchi, S Shiomi, S Enomoto, M Lee, C Jomura, H Tamori, A Habu, D Takeda, T Yanagihara, N Shiraki, K J-Gastroenterol. 2001 July; 36(7): 486-91 0944-1174

·

Drugs and steatohepatitis. Author(s): Storr Liver Unit, Westmead Millennium Institute, University of Sydney at Westmead Hospital, Westmead, NSW, Australia. [email protected] Source: Farrell, Geoffrey C Semin-Liver-Dis. 2002; 22(2): 185-94 0272-8087

·

Evolving new therapies of autoimmune hepatitis. Author(s): Center for Liver Diseases and Transplantation and Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, and UCLA School of Medicine, CA 90048, USA. [email protected] Source: Vierling, J M Flores, P A Clin-Liver-Dis. 2002 August; 6(3): 537-62, ix 1089-3261

·

Further in vitro characterization of mouse hepatitis virus papain-like proteinase 1: cleavage sequence requirements within pp1a. Author(s): Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia 19104-6076, USA.

272 Hepatitis

Source: Teng, Henry Weiss, Susan R J-Neurovirol. 2002 April; 8(2): 143-9 1355-0284 ·

Hepatitis B virus surface antigen suppresses the activation of monocytes through interaction with a serum protein and a monocyte-specific receptor. Author(s): Center for Vaccinology, Department of Clinical Biology, Microbiology and Immunology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium. [email protected] Source: Vanlandschoot, Peter Van Houtte, Freya Roobrouck, Annelies Farhoudi, Ali Leroux Roels, Geert J-Gen-Virol. 2002 June; 83(Pt 6): 1281-9 0022-1317

·

Hepatitis C virus RNA synthesis in a cell-free system isolated from repliconcontaining hepatoma cells. Author(s): Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, USA. Source: Hardy, R W Marcotrigiano, J Blight, K J Majors, J E Rice, C M J-Virol. 2003 February; 77(3): 2029-37 0022-538X

·

Hepatoprotective action of abhrak bhasma, an ayurvedic drug in albino rats against hepatitis induced by CCl4. Author(s): Department of Zoology, Shivaji University, Kolhapur, India. Source: Buwa, S Patil, S Kulkarni P, H Kanase, A Indian-J-Exp-Biol. 2001 October; 39(10): 1022-7 0019-5189

·

HIV and hepatitis virus infections among injecting drug users in a medically controlled heroin prescription programme. Author(s): Addiction Research Institute, Zurich, Switzerland. [email protected] Source: Steffen, T Blattler, R Gutzwiller, F Zwahlen, M Eur-J-Public-Health. 2001 December; 11(4): 425-30 1101-1262

·

Impact of immunosuppressive therapy on recurrence of hepatitis C. Author(s): Hepatology, University of Colorado School of Medicine, Denver, CO 80262, USA. [email protected] Source: Everson, G T Liver-Transpl. 2002 October; 8(10 Suppl 1): S19-27 1527-6465

·

In vitro RNA replication directed by replicase complexes isolated from the subgenomic replicon cells of hepatitis C virus. Author(s): Department of Drug Discovery, Research and Development, Ribapharm, Inc., Costa Mesa, California 92626, USA. [email protected] Source: Lai, V C Dempsey, S Lau, J Y Hong, Z Zhong, W J-Virol. 2003 February; 77(3): 2295-300 0022-538X

·

Incidence of side effects during therapy with different types of alpha interferon: a randomised controlled trial comparing recombinant alpha 2b versus leukocyte interferon in the therapy of naive patients with chronic hepatitis C. Author(s): Dept. of Gastroenterology, Liver and Pancreatic Unit, Cardarelli Hospital, Naples, Italy. [email protected] Source: Ascione, A De Luca, M Di Costanzo, G G Picciotto, F P Lanza, A G Canestrini, C Morisco, F Tuccillo, C Caporaso, N Curr-Pharm-Des. 2002; 8(11): 977-80 1381-6128

·

Increased risk of chronic hepatitis in children with cancer. Author(s): Department of Pediatric Oncology, Uludag University, Faculty of Medicine, Gorukle, Bursa, Turkey. [email protected] Source: Sevinir, B Meral, A Gunay, U Ozkan, T Ozuysal, S Sinirtas, M Med-PediatrOncol. 2003 February; 40(2): 104-10 0098-1532

Nutrition

27 3

·

Inhibition of hepatitis B virus by oxymatrine in vivo. Author(s): Department of Cell Biology, the Second Military Medical University, Shanghai 200433,China. [email protected] Source: Chen, X S Wang, G J Cai, X Yu, H Y Hu, Y P World-J-Gastroenterol. 2001 February; 7(1): 49-52 1007-9327

·

Interaction of hepatitis C virus-like particles and cells: a model system for studying viral binding and entry. Author(s): Liver Diseases Section, National Institute of Diabetes and DigestiveKidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Source: Triyatni, M Saunier, B Maruvada, P Davis, A R Ulianich, L Heller, T Patel, A Kohn, L D Liang, T J J-Virol. 2002 September; 76(18): 9335-44 0022-538X

·

Interferon versus interferon and UDCA combined therapy in chronic hepatitis C. Author(s): Department of Internal Medicine, Medical University of Silesia, St. Barbara's District Hospital, Plac Medykow 1, 41-200 Sosnowiec, Poland. Source: Mazur, W Machniak, M Mazurek, U Jurzak, M Wilczok, T Gonciarz, Z Med-SciMonit. 2001 May; 7 Suppl 1: 157-64 1234-1010

·

Interstitial pneumonitis during combination therapy with interferon-alpha and ribavirin in a patient with chronic Hepatitis C. Author(s): Zentrum fur Innere Medizin I, Abteilung fur Gastroenterologie und Hepatologie, Robert-Bosch-Krankenhaus, Germany. [email protected] Source: Rothfuss, K S Bode, J C Z-Gastroenterol. 2002 September; 40(9): 807-10 0044-2771

·

L-Homoserine: a novel excreted metabolic marker of hepatitis B abnormally produced in liver from methionine. Author(s): Department of Molecular Biology and Biotechnology, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico D. F., Mexico. [email protected] Source: Gazarian, K G Gening, L V Gazarian, T G Med-Hypotheses. 2002 April; 58(4): 279-83 0306-9877

·

Management of chronic hepatitis C and prevention of hepatocellular carcinoma. Author(s): Department of Gastroenterology, Toranomon Hospital, Okinaka, Memorial Institute for Medical Research, Tokyo, Japan. Source: Chayama, K J-Gastroenterol. 2002; 37 Suppl 13: 69-73 0944-1174

·

Mechanism of de novo initiation by the hepatitis C virus RNA-dependent RNA polymerase: role of divalent metals. Author(s): Department of Biology, Indiana University, 1001 E. Third Street, Bloomington, IN 47405, USA. Source: Ranjith KuMarch, C T Kim, Y C Gutshall, L Silverman, C Khandekar, S Sarisky, R T Kao, C C J-Virol. 2002 December; 76(24): 12513-25 0022-538X

·

Misuse of randomization: a review of Chinese randomized trials of herbal medicines for chronic hepatitis B. Author(s): The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, H:S Rigshospitalet, Denmark. Source: Liu, J Kjaergard, L L Gluud, C Am-J-Chin-Med. 2002; 30(1): 173-6 0192-415X

·

Nitrofurantoin-induced chronic active hepatitis. Author(s): Department of Medicine, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel. Source: Amit, Guy Cohen, Patrizia Ackerman, Zvi Isr-Med-Assoc-J. 2002 March; 4(3): 184-6 1565-1088

274 Hepatitis

·

Preliminary results of Thymosin-a1 versus interferon-alpha-treatment in patients with HBeAg negative and serum HBV DNA positive chronic hepatitis B. Author(s): Department of Hepatology, Kunming Third Municipal People's Hospital, 319 Wu Jin Road, Kunming 650041,Yunnan Province, China. Source: Zhuang, L You, J Tang, B Z Ding, S Y Yan, K H Peng, D Zhang, Y M Zhang, L World-J-Gastroenterol. 2001 June; 7(3): 407-10 1007-9327

·

Proliferative suppression and class I insufficiency on peripheral blood cells from hepatitis C patients overcome by exogenous cytokines or high-dose mitogen. Author(s): Department of Surgery and Hepatology, Virginia Commonwealth University, Medical College of Virginia Campus, Richmond, Virginia, USA. Source: Kimball, Pam Verbeke, Scott Shiffman, Mitchell Clin-Immunol. 2002 June; 103(3 Pt 1): 317-23 1521-6616

·

Quantitative method of intracellular hepatitis C virus RNA using LightCycler PCR. Author(s): Department of Molecular Biology, Okayama University Graduate School of Medicine and Dentistry, Japan. Source: Nozaki, A Kato, N Acta-Med-Okayama. 2002 April; 56(2): 107-10 0386-300X

·

Role of the asialoglycoprotein receptor in binding and entry of hepatitis C virus structural proteins in cultured human hepatocytes. Author(s): Edison Biotechnology Institute and College of Osteopathic Medicine, Ohio University, Athens 45701, USA. [email protected] Source: Saunier, B Triyatni, M Ulianich, L Maruvada, P Yen, P Kohn, L D J-Virol. 2003 January; 77(1): 546-59 0022-538X

·

Sequential combination of glucocorticosteroids and alfa interferon versus alfa interferon alone for HBeAg-positive chronic hepatitis B. Author(s): The Copenhagen Trial Unit, Copenhagen University Hospital, H:S Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark, DK-2100. [email protected] Source: Mellerup, M T Krogsgaard, K Mathurin, P Gluud, C Poynard, T CochraneDatabase-Syst-Revolume 2002; (2): CD000345 1469-493X

·

The efficacy of a herbal medicine (Mao-to) in combination with intravenous natural interferon-beta for patients with chronic hepatitis C, genotype 1b and high viral load: a pilot study. Author(s): Department of Japanese Oriental Medicine, Toyama Medical and Pharmaceutical University, Sugitani. [email protected] Source: Kainuma, M Ogata, N Kogure, T Kohta, K Hattori, N Mitsuma, T Terasawa, K Phytomedicine. 2002 July; 9(5): 365-72 0944-7113

·

The use of alternative medicine in the treatment of hepatitis C. Author(s): Rogers Memorial Hospital, Oconomowac, WI, USA. [email protected] Source: Bean, P Am-Clin-Lab. 2002 May; 21(4): 19-21 1041-3235

·

Therapeutic efficacy of transcatheter arterial chemoembolization as compared with hepatic resection in hepatocellular carcinoma patients with compensated liver function in a hepatitis B virus-endemic area: a prospective cohort study. Author(s): Department of Internal Medicine, Liver Research Institute, Seoul National University Hospital, Chongno-gu, Korea. [email protected] Source: Lee, H S Kim, K M Yoon, J H Lee, T R Suh, K S Lee, K U Chung, J W Park, J H Kim, C Y J-Clin-Oncol. 2002 November 15; 20(22): 4459-65 0732-183X

Nutrition

27 5

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Thymosin-alpha1 and famciclovir combination therapy activates T-cell response in patients with chronic hepatitis B virus infection in immune-tolerant phase. Author(s): Departments of Medicine and Pathology, Queen Mary Hospital Clinical Trials Centre, The Institute of Molecular Biology, The University of Hong Kong, Hong Kong SAR, China. [email protected] Source: Lau, G K Nanji, A Hou, J Fong, D Y Au, W S Yuen, S T Lin, M Kung, H F Lam, S K J-Viral-Hepat. 2002 July; 9(4): 280-7 1352-0504

·

Transmission of hepatitis C in a pharmacologic study. Author(s): Division of Infectious Diseases, Ottawa Hospital and the University of Ottawa, Ontario, Canada. Source: Saginur, R Nixon, J Devries, B Bruce, N Carruthers, C Scully, L Berger, R Leech, J Nicolle, L Mackenzie, A Infect-Control-Hosp-Epidemiol. 2001 November; 22(11): 697700 0899-823X

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Treatment strategies in autoimmune hepatitis. Author(s): Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. [email protected] Source: Czaja, A J Clin-Liver-Dis. 2002 August; 6(3): 511-36 1089-3261

·

Viral genotypes and response to interferon in patients with acute prolonged hepatitis B virus infection of adulthood in Japan. Author(s): Research Institute for Hepatology, Toranomon Hospital, Tokyo, Japan. [email protected] Source: Kobayashi, M Arase, Y Ikeda, K Tsubota, A Suzuki, Y Saitoh, S Kobayashi, M Suzuki, F Akuta, N Someya, T Matsuda, M Sato, J Takagi, K Miyakawa, Y Kumada, H JMed-Virol. 2002 December; 68(4): 522-8 0146-6615

·

Vitamin B12 stalls the 80 S ribosomal complex on the hepatitis C internal ribosome entry site. Author(s): Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, Herston, Qld 4029, Australia. Source: Takyar, Seyedtaghi S Gowans, Eric J Lott, William B J-Mol-Biol. 2002 May 24; 319(1): 1-8 0022-2836

The following information is typical of that found when using the “Full IBIDS Database” to search for “hepatitis” (or a synonym): ·

A case of polymyositis with dilated cardiomyopathy associated with interferon alpha treatment for hepatitis B. Author(s): The Hospital for Rheumatic Diseases, Hanyang University, 17 Haengdongdong, Seongdong-gu, Seoul 133-792, Korea. Source: Lee, Seung Won Kim, Ki Chan Oh, Dong Ho Jung, Sung Soo Yoo, Dae Hyun Kim, Seong Yoon Choe, Gheeyoung Kim, Tae Hwan J-Korean-Med-Sci. 2002 February; 17(1): 141-3 1011-8934

·

A prenylation inhibitor prevents production of infectious hepatitis delta virus particles. Author(s): Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 269 Campus Drive, Palo Alto, CA 94305-5187, USA. Source: Bordier, B B Marion, P L Ohashi, K Kay, M A Greenberg, H B Casey, J L Glenn, J S J-Virol. 2002 October; 76(20): 10465-72 0022-538X

276 Hepatitis

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A randomized controlled clinical trial on the treatment of Thymosin a1 versus interferon-alpha in patients with hepatitis B. Author(s): Department of Infectious Diseases, The First Affiliated Hospital of Kunming Medical College, 153# Xi Chang Road, Kunming 650032, Yunnan Province, China. Source: You, J Zhuang, L Tang, B Z Yang, W B Ding, S Y Li, W Wu, R X Zhang, H L Zhang, Y M Yan, S M Zhang, L World-J-Gastroenterol. 2001 June; 7(3): 411-4 1007-9327

·

Altered DNA mutation spectrum in aflatoxin b1-treated transgenic mice that express the hepatitis B virus x protein. Author(s): Department of Molecular Virology and Microbiology. Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA. Source: Madden, C R Finegold, M J Slagle, B L J-Virol. 2002 November; 76(22): 11770-4 0022-538X

·

Biological and clinical significance of endotoxemia in the course of hepatitis C virus infection. Author(s): Laboratories of Immunopathology, Scientific Institute for Digestive Diseases, Castellana Grotte, Bari, Italy. Source: Caradonna, L Mastronardi, M L Magrone, T Cozzolongo, R Cuppone, R Manghisi, O G Caccavo, D Pellegrino, N M Amoroso, A Jirillo, E Amati, L Curr-PharmDes. 2002; 8(11): 995-1005 1381-6128

·

Chemical synthesis of NS-1 region of hepatitis C-viral polyprotein fragments: a comparison of PS-BDODMA resin and merrifield resin. Author(s): School of Chemical Sciences, Mahatma Gandhi University, Priyadarsini Hills, Kottayam, Kerala, India. [email protected] Source: Roice, M KuMarch, K S Pillai, V N Protein-Pept-Lett. 2002 June; 9(3): 245-52 0929-8665

·

Clinical and biochemical features and therapy responses in primary biliary cirrhosis and primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. Author(s): Department of Gastroenterology, Ege University Hospital Izmir, Turkey. [email protected] Source: Gunsar, F Akarca, U S Ersoz, G Karasu, Z Yuce, G Batur, Y Hepatogastroenterology. 2002 Sep-October; 49(47): 1195-200 0172-6390

·

Clinical observation of salvianolic acid B in treatment of liver fibrosis in chronic hepatitis B. Author(s): Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. [email protected] Source: Liu, P Hu, Y Y Liu, C Zhu, D Y Xue, H M Xu, Z Q Xu, L M Liu, C H Gu, H T Zhang, Z Q World-J-Gastroenterol. 2002 August; 8(4): 679-85 1007-9327

·

Combination thymosin-alpha 1 and interferon-alpha 2b in the treatment of anti-HBepositive chronic hepatitis B in Turkey. Author(s): Department of Gastroenterology, Celal Bayar University, School of Medicine, Manisa, Turkey. [email protected] Source: Saruc, M Yuceyar, H Kucukmetin, N Demir, M A Kandiloglu, A R Hepatogastroenterology. 2002 May-June; 49(45): 798-802 0172-6390

·

Critical roles of nuclear receptor response elements in replication of hepatitis B virus. Author(s): McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, Wisconsin 53706-1599, USA. Source: Yu, X Mertz, J E J-Virol. 2001 December; 75(23): 11354-64 0022-538X

Nutrition

27 7

·

Detecting the replication of the hepatitis B virus using the ImmunoMax technique following treatment with interferon-alpha in children with chronic hepatitis. Author(s): Department of Histology and Embryology, Medical University of Poznan, Poland. [email protected] Source: Kasprzak, Aldona Wysocki, Jacek Zabel, Maciej Surdyk Zasada, Joanna MedSci-Monit. 2002 January; 8(1): PR1-7 1234-1010

·

Dietary iron restriction improves aminotransferase levels in chronic hepatitis C patients. Author(s): Third Department of Internal Medicine, Mie University School of Medicine, Edobashi 2-174, Tsu City, Mie 514-8507, Japan. [email protected] Source: Iwasa, M Kaito, M Ikoma, J Kobayashi, Y Tanaka, Y Higuchi, K Takeuchi, K Iwata, K Watanabe, S Adachi, Y Hepatogastroenterology. 2002 Mar-April; 49(44): 529-31 0172-6390

·

Does ascorbic acid prevent retinopathy during interferon therapy in patients with chronic hepatitis C? Author(s): Third Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan. Source: Nishiguchi, S Shiomi, S Enomoto, M Lee, C Jomura, H Tamori, A Habu, D Takeda, T Yanagihara, N Shiraki, K J-Gastroenterol. 2001 July; 36(7): 486-91 0944-1174

·

Drugs and steatohepatitis. Author(s): Storr Liver Unit, Westmead Millennium Institute, University of Sydney at Westmead Hospital, Westmead, NSW, Australia. [email protected] Source: Farrell, Geoffrey C Semin-Liver-Dis. 2002; 22(2): 185-94 0272-8087

·

Evolving new therapies of autoimmune hepatitis. Author(s): Center for Liver Diseases and Transplantation and Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, and UCLA School of Medicine, CA 90048, USA. [email protected] Source: Vierling, J M Flores, P A Clin-Liver-Dis. 2002 August; 6(3): 537-62, ix 1089-3261

·

Further in vitro characterization of mouse hepatitis virus papain-like proteinase 1: cleavage sequence requirements within pp1a. Author(s): Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia 19104-6076, USA. Source: Teng, Henry Weiss, Susan R J-Neurovirol. 2002 April; 8(2): 143-9 1355-0284

·

Hepatitis B virus surface antigen suppresses the activation of monocytes through interaction with a serum protein and a monocyte-specific receptor. Author(s): Center for Vaccinology, Department of Clinical Biology, Microbiology and Immunology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium. [email protected] Source: Vanlandschoot, Peter Van Houtte, Freya Roobrouck, Annelies Farhoudi, Ali Leroux Roels, Geert J-Gen-Virol. 2002 June; 83(Pt 6): 1281-9 0022-1317

·

Hepatitis C virus RNA synthesis in a cell-free system isolated from repliconcontaining hepatoma cells. Author(s): Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, USA. Source: Hardy, R W Marcotrigiano, J Blight, K J Majors, J E Rice, C M J-Virol. 2003 February; 77(3): 2029-37 0022-538X

278 Hepatitis

·

Hepatoprotective action of abhrak bhasma, an ayurvedic drug in albino rats against hepatitis induced by CCl4. Author(s): Department of Zoology, Shivaji University, Kolhapur, India. Source: Buwa, S Patil, S Kulkarni P, H Kanase, A Indian-J-Exp-Biol. 2001 October; 39(10): 1022-7 0019-5189

·

HIV and hepatitis virus infections among injecting drug users in a medically controlled heroin prescription programme. Author(s): Addiction Research Institute, Zurich, Switzerland. [email protected] Source: Steffen, T Blattler, R Gutzwiller, F Zwahlen, M Eur-J-Public-Health. 2001 December; 11(4): 425-30 1101-1262

·

Impact of immunosuppressive therapy on recurrence of hepatitis C. Author(s): Hepatology, University of Colorado School of Medicine, Denver, CO 80262, USA. [email protected] Source: Everson, G T Liver-Transpl. 2002 October; 8(10 Suppl 1): S19-27 1527-6465

·

In vitro RNA replication directed by replicase complexes isolated from the subgenomic replicon cells of hepatitis C virus. Author(s): Department of Drug Discovery, Research and Development, Ribapharm, Inc., Costa Mesa, California 92626, USA. [email protected] Source: Lai, V C Dempsey, S Lau, J Y Hong, Z Zhong, W J-Virol. 2003 February; 77(3): 2295-300 0022-538X

·

Incidence of side effects during therapy with different types of alpha interferon: a randomised controlled trial comparing recombinant alpha 2b versus leukocyte interferon in the therapy of naive patients with chronic hepatitis C. Author(s): Dept. of Gastroenterology, Liver and Pancreatic Unit, Cardarelli Hospital, Naples, Italy. [email protected] Source: Ascione, A De Luca, M Di Costanzo, G G Picciotto, F P Lanza, A G Canestrini, C Morisco, F Tuccillo, C Caporaso, N Curr-Pharm-Des. 2002; 8(11): 977-80 1381-6128

·

Increased risk of chronic hepatitis in children with cancer. Author(s): Department of Pediatric Oncology, Uludag University, Faculty of Medicine, Gorukle, Bursa, Turkey. [email protected] Source: Sevinir, B Meral, A Gunay, U Ozkan, T Ozuysal, S Sinirtas, M Med-PediatrOncol. 2003 February; 40(2): 104-10 0098-1532

·

Inhibition of hepatitis B virus by oxymatrine in vivo. Author(s): Department of Cell Biology, the Second Military Medical University, Shanghai 200433,China. [email protected] Source: Chen, X S Wang, G J Cai, X Yu, H Y Hu, Y P World-J-Gastroenterol. 2001 February; 7(1): 49-52 1007-9327

·

Interaction of hepatitis C virus-like particles and cells: a model system for studying viral binding and entry. Author(s): Liver Diseases Section, National Institute of Diabetes and DigestiveKidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Source: Triyatni, M Saunier, B Maruvada, P Davis, A R Ulianich, L Heller, T Patel, A Kohn, L D Liang, T J J-Virol. 2002 September; 76(18): 9335-44 0022-538X

·

Interferon versus interferon and UDCA combined therapy in chronic hepatitis C. Author(s): Department of Internal Medicine, Medical University of Silesia, St. Barbara's District Hospital, Plac Medykow 1, 41-200 Sosnowiec, Poland.

Nutrition

27 9

Source: Mazur, W Machniak, M Mazurek, U Jurzak, M Wilczok, T Gonciarz, Z Med-SciMonit. 2001 May; 7 Suppl 1: 157-64 1234-1010 ·

Interstitial pneumonitis during combination therapy with interferon-alpha and ribavirin in a patient with chronic Hepatitis C. Author(s): Zentrum fur Innere Medizin I, Abteilung fur Gastroenterologie und Hepatologie, Robert-Bosch-Krankenhaus, Germany. [email protected] Source: Rothfuss, K S Bode, J C Z-Gastroenterol. 2002 September; 40(9): 807-10 0044-2771

·

L-Homoserine: a novel excreted metabolic marker of hepatitis B abnormally produced in liver from methionine. Author(s): Department of Molecular Biology and Biotechnology, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico D. F., Mexico. [email protected] Source: Gazarian, K G Gening, L V Gazarian, T G Med-Hypotheses. 2002 April; 58(4): 279-83 0306-9877

·

Management of chronic hepatitis C and prevention of hepatocellular carcinoma. Author(s): Department of Gastroenterology, Toranomon Hospital, Okinaka, Memorial Institute for Medical Research, Tokyo, Japan. Source: Chayama, K J-Gastroenterol. 2002; 37 Suppl 13: 69-73 0944-1174

·

Mechanism of de novo initiation by the hepatitis C virus RNA-dependent RNA polymerase: role of divalent metals. Author(s): Department of Biology, Indiana University, 1001 E. Third Street, Bloomington, IN 47405, USA. Source: Ranjith KuMarch, C T Kim, Y C Gutshall, L Silverman, C Khandekar, S Sarisky, R T Kao, C C J-Virol. 2002 December; 76(24): 12513-25 0022-538X

·

Misuse of randomization: a review of Chinese randomized trials of herbal medicines for chronic hepatitis B. Author(s): The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, H:S Rigshospitalet, Denmark. Source: Liu, J Kjaergard, L L Gluud, C Am-J-Chin-Med. 2002; 30(1): 173-6 0192-415X

·

Nitrofurantoin-induced chronic active hepatitis. Author(s): Department of Medicine, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel. Source: Amit, Guy Cohen, Patrizia Ackerman, Zvi Isr-Med-Assoc-J. 2002 March; 4(3): 184-6 1565-1088

·

Preliminary results of Thymosin-a1 versus interferon-alpha-treatment in patients with HBeAg negative and serum HBV DNA positive chronic hepatitis B. Author(s): Department of Hepatology, Kunming Third Municipal People's Hospital, 319 Wu Jin Road, Kunming 650041,Yunnan Province, China. Source: Zhuang, L You, J Tang, B Z Ding, S Y Yan, K H Peng, D Zhang, Y M Zhang, L World-J-Gastroenterol. 2001 June; 7(3): 407-10 1007-9327

·

Proliferative suppression and class I insufficiency on peripheral blood cells from hepatitis C patients overcome by exogenous cytokines or high-dose mitogen. Author(s): Department of Surgery and Hepatology, Virginia Commonwealth University, Medical College of Virginia Campus, Richmond, Virginia, USA. Source: Kimball, Pam Verbeke, Scott Shiffman, Mitchell Clin-Immunol. 2002 June; 103(3 Pt 1): 317-23 1521-6616

280 Hepatitis

·

Quantitative method of intracellular hepatitis C virus RNA using LightCycler PCR. Author(s): Department of Molecular Biology, Okayama University Graduate School of Medicine and Dentistry, Japan. Source: Nozaki, A Kato, N Acta-Med-Okayama. 2002 April; 56(2): 107-10 0386-300X

·

Role of the asialoglycoprotein receptor in binding and entry of hepatitis C virus structural proteins in cultured human hepatocytes. Author(s): Edison Biotechnology Institute and College of Osteopathic Medicine, Ohio University, Athens 45701, USA. [email protected] Source: Saunier, B Triyatni, M Ulianich, L Maruvada, P Yen, P Kohn, L D J-Virol. 2003 January; 77(1): 546-59 0022-538X

·

Sequential combination of glucocorticosteroids and alfa interferon versus alfa interferon alone for HBeAg-positive chronic hepatitis B. Author(s): The Copenhagen Trial Unit, Copenhagen University Hospital, H:S Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark, DK-2100. [email protected] Source: Mellerup, M T Krogsgaard, K Mathurin, P Gluud, C Poynard, T CochraneDatabase-Syst-Revolume 2002; (2): CD000345 1469-493X

·

The efficacy of a herbal medicine (Mao-to) in combination with intravenous natural interferon-beta for patients with chronic hepatitis C, genotype 1b and high viral load: a pilot study. Author(s): Department of Japanese Oriental Medicine, Toyama Medical and Pharmaceutical University, Sugitani. [email protected] Source: Kainuma, M Ogata, N Kogure, T Kohta, K Hattori, N Mitsuma, T Terasawa, K Phytomedicine. 2002 July; 9(5): 365-72 0944-7113

·

The use of alternative medicine in the treatment of hepatitis C. Author(s): Rogers Memorial Hospital, Oconomowac, WI, USA. [email protected] Source: Bean, P Am-Clin-Lab. 2002 May; 21(4): 19-21 1041-3235

·

Therapeutic efficacy of transcatheter arterial chemoembolization as compared with hepatic resection in hepatocellular carcinoma patients with compensated liver function in a hepatitis B virus-endemic area: a prospective cohort study. Author(s): Department of Internal Medicine, Liver Research Institute, Seoul National University Hospital, Chongno-gu, Korea. [email protected] Source: Lee, H S Kim, K M Yoon, J H Lee, T R Suh, K S Lee, K U Chung, J W Park, J H Kim, C Y J-Clin-Oncol. 2002 November 15; 20(22): 4459-65 0732-183X

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Thymosin-alpha1 and famciclovir combination therapy activates T-cell response in patients with chronic hepatitis B virus infection in immune-tolerant phase. Author(s): Departments of Medicine and Pathology, Queen Mary Hospital Clinical Trials Centre, The Institute of Molecular Biology, The University of Hong Kong, Hong Kong SAR, China. [email protected] Source: Lau, G K Nanji, A Hou, J Fong, D Y Au, W S Yuen, S T Lin, M Kung, H F Lam, S K J-Viral-Hepat. 2002 July; 9(4): 280-7 1352-0504

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Transmission of hepatitis C in a pharmacologic study. Author(s): Division of Infectious Diseases, Ottawa Hospital and the University of Ottawa, Ontario, Canada. Source: Saginur, R Nixon, J Devries, B Bruce, N Carruthers, C Scully, L Berger, R Leech, J Nicolle, L Mackenzie, A Infect-Control-Hosp-Epidemiol. 2001 November; 22(11): 697700 0899-823X

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Treatment strategies in autoimmune hepatitis. Author(s): Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. [email protected] Source: Czaja, A J Clin-Liver-Dis. 2002 August; 6(3): 511-36 1089-3261

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Viral genotypes and response to interferon in patients with acute prolonged hepatitis B virus infection of adulthood in Japan. Author(s): Research Institute for Hepatology, Toranomon Hospital, Tokyo, Japan. [email protected] Source: Kobayashi, M Arase, Y Ikeda, K Tsubota, A Suzuki, Y Saitoh, S Kobayashi, M Suzuki, F Akuta, N Someya, T Matsuda, M Sato, J Takagi, K Miyakawa, Y Kumada, H JMed-Virol. 2002 December; 68(4): 522-8 0146-6615

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Vitamin B12 stalls the 80 S ribosomal complex on the hepatitis C internal ribosome entry site. Author(s): Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, Herston, Qld 4029, Australia. Source: Takyar, Seyedtaghi S Gowans, Eric J Lott, William B J-Mol-Biol. 2002 May 24; 319(1): 1-8 0022-2836

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: ·

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

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Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: ·

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDÒHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

The following is a specific Web list relating to hepatitis; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: ·

Vitamins Vitamin B12 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin C Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,904,00.html Vitamin E Source: Healthnotes, Inc.; www.healthnotes.com Vitamin E Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin E Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,906,00.html

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Minerals Copper Source: Integrative Medicine Communications; www.drkoop.com Iron Source: Healthnotes, Inc.; www.healthnotes.com Lecithin and Choline Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10040,00.html Lecithin/phosphatidylcholine/choline Source: Healthnotes, Inc.; www.healthnotes.com Selenium Source: Healthnotes, Inc.; www.healthnotes.com Selenium Source: Prima Communications, Inc.www.personalhealthzone.com

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Food and Diet Shiitake Mushrooms Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,308,00.html

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CHAPTER 3. ALTERNATIVE MEDICINE AND HEPATITIS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to hepatitis. At the conclusion of this chapter, we will provide additional sources.

The Combined Health Information Database The Combined Health Information Database (CHID) is a bibliographic database produced by health-related agencies of the U.S. federal government (mostly from the National Institutes of Health) that can offer concise information for a targeted search. The CHID database is updated four times a year at the end of January, April, July, and October. Check the titles, summaries, and availability of CAM-related information by using the “Simple Search” option at the following Web site: http://chid.nih.gov/simple/simple.html. In the drop box at the top, select “Complementary and Alternative Medicine.” Then type “hepatitis” (or synonyms) in the second search box. We recommend that you select 100 “documents per page” and to check the “whole records” options. The following was extracted using this technique: ·

Ginkgo: A Practical Guide Source: Garden City Park, NY: Avery Publishing Group. 1998. 172 p. Contact: Avery Publishing Group. 120 Old Broadway, Garden City Park, NY 11040. (800) 548-5757; INTERNATIONAL: (516) 741-2155; FAX: (516) 742-1892. PRICE: $9.95. ISBN: 0895298120. Summary: This book is designed to help consumers use 'Ginkgo biloba' safely and effectively to promote health, prevent illness, and treat disease. Chapter 1 reviews the history of Ginkgo in herbal medicine; and Chapter 2 examines the attitudes toward herbal medicines in Chinese, Indian, and Western cultures. Chapter 3 discusses the science of Ginkgo, including its key active components and its actions in the body. Chapters 4 through 7 focus on specific applications of Ginkgo and its effects in disorders of the brain, the heart and circulatory system, the senses, and sexuality. Chapter 8 discusses the use of Ginkgo in other conditions such as radiation exposure, sun damage,

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allergies, asthma, and hepatitis; and offers advice to consumers about the reasons for taking Ginkgo, methods of taking it, and how much to take. Chapter 9 summarizes the health benefits of using Ginkgo. The book includes a glossary and an index. ·

Milk Thistle: Effects on Liver Disease and Cirrhosis and Clinical Adverse Effects Source: Gaithersburg, MD: National Center for Complementary and Alternative Medicine. 2000. 12 p. Contact: Available from National Center for Complementary and Alternative Medicine Clearinghouse. P.O. Box 7923, Gaithersburg, MD 20898. (888) 644-6226; INTERNATIONAL PHONE: (301) 519-3153; TTY: (866) 464-3615; FAX: (866) 464-3616; EMAIL: [email protected]. PRICE: Free. Publication Number: D029. Summary: This evidence report details a systematic review summarizing clinical studies of milk thistle in humans. The report addresses two areas: (1) the effects of milk thistle on liver disease of alcohol, viral, toxin, cholestatic, and primary malignancy etiologies, and (2) the clinical adverse effects associated with milk thistle ingestion or contact. It addresses ten questions regarding whether milk thistle supplements (when compared with no supplement, placebo, other oral supplements, or drugs): (1) alter the physiologic markers of liver function, or (2) reduce mortality or morbidity, or improve the quality of life in adults with alcohol-related, toxin-induced, or drug-induced liver disease, viral hepatitis, cholestasis, or primary hepatic malignancy. One question addresses the constituents of commonly available milk thistle preparations, and three questions address the common and uncommon symptomatic adverse effects of milk thistle. The report explains the methodology, followed by a summary of its findings, including mechanisms of action, preparations of milk thistle, benefit of milk thistle for liver disease, and adverse effects. It summarizes conclusions and discusses areas for future research. The addendum includes evidence-based practice centers, topics, available evidence reports, and contact information.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to hepatitis and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “hepatitis” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to hepatitis: ·

A comparative study of Phyllanthus amarus compound and interferon in the treatment of chronic viral hepatitis B. Author(s): Xin-Hua W, Chang-Qing L, Xing-Bo G, Lin-Chun F. Source: Southeast Asian J Trop Med Public Health. 2001 March; 32(1): 140-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11485076&dopt=Abstract

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A survey on community perceptions of jaundice in east Delhi: implications for the prevention and control of viral hepatitis.

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Author(s): Singh J, Shakya N, Jain DC, Bhatia R, Bora D, Pattanayak PK, Gupta S, Datta KK, Sokhey J. Source: Trans R Soc Trop Med Hyg. 2000 May-June; 94(3): 243-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10974987&dopt=Abstract ·

Acute cholestatic hepatitis associated with celecoxib. Author(s): Grieco A, Miele L, Giorgi A, Civello IM, Gasbarrini G. Source: The Annals of Pharmacotherapy. 2002 December; 36(12): 1887-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452750&dopt=Abstract

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Acute cholestatic hepatitis caused by Teucrium polium (golden germander) with transient appearance of antimitochondrial antibody. Author(s): Polymeros D, Kamberoglou D, Tzias V. Source: Journal of Clinical Gastroenterology. 2002 January; 34(1): 100-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11743258&dopt=Abstract

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Acute hepatitis associated with herb (Teucrium capitatum L.) administration. Author(s): Dourakis SP, Papanikolaou IS, Tzemanakis EN, Hadziyannis SJ. Source: European Journal of Gastroenterology & Hepatology. 2002 June; 14(6): 693-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12072605&dopt=Abstract

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Acute hepatitis induced by Greater Celandine (Chelidonium majus). Author(s): Stickel F, Poschl G, Seitz HK, Waldherr R, Hahn EG, Schuppan D. Source: Scandinavian Journal of Gastroenterology. 2003 May; 38(5): 565-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12795472&dopt=Abstract

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Acute hepatitis induced by kava kava. Author(s): Humberston CL, Akhtar J, Krenzelok EP. Source: Journal of Toxicology. Clinical Toxicology. 2003; 41(2): 109-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12733846&dopt=Abstract

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Acute hepatitis induced by Shou-Wu-Pian, a herbal product derived from Polygonum multiflorum. Author(s): Park GJ, Mann SP, Ngu MC. Source: Journal of Gastroenterology and Hepatology. 2001 January; 16(1): 115-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11206309&dopt=Abstract

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Acute hepatitis induced by traditional Chinese herbs used in the treatment of psoriasis. Author(s): Verucchi G, Calza L, Attard L, Chiodo F.

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Source: Journal of Gastroenterology and Hepatology. 2002 December; 17(12): 1342-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12423285&dopt=Abstract ·

Acute thrombocytopenic purpura after ingestion of Sho-saiko-to for hepatitis. Author(s): Kiguchi T, Kimura F, Niiya K, Katayama Y, Harada M. Source: Liver. 2000 December; 20(6): 491. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11169065&dopt=Abstract

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Adult syncytial giant cell chronic hepatitis due to herbal remedy. Author(s): Fraquelli M, Colli A, Cocciolo M, Conte D. Source: Journal of Hepatology. 2000 September; 33(3): 505-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11020009&dopt=Abstract

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AM3 (Inmunoferon) as an adjuvant to hepatitis B vaccination in hemodialysis patients. Author(s): Perez-Garcia R, Perez-Garcia A, Verbeelen D, Bernstein ED, Villarrubia VG, Alvarez-Mon M. Source: Kidney International. 2002 May; 61(5): 1845-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11967036&dopt=Abstract

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An in vitro system combined with an in-house quantitation assay for screening hepatitis C virus inhibitors. Author(s): Ho TY, Wu SL, Lai IL, Cheng KS, Kao ST, Hsiang CY. Source: Antiviral Research. 2003 May; 58(3): 199-208. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767467&dopt=Abstract

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Analyzing the mechanisms of interferon-induced apoptosis using CrmA and hepatitis C virus NS5A. Author(s): Ezelle HJ, Balachandran S, Sicheri F, Polyak SJ, Barber GN. Source: Virology. 2001 March 1; 281(1): 124-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11222103&dopt=Abstract

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Anti-hepatitis B virus effects of wogonin isolated from Scutellaria baicalensis. Author(s): Huang RL, Chen CC, Huang HL, Chang CG, Chen CF, Chang C, Hsieh MT. Source: Planta Medica. 2000 December; 66(8): 694-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11199123&dopt=Abstract

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Antiviral activities of extracts isolated from Terminalis chebula Retz., Sanguisorba officinalis L., Rubus coreanus Miq. and Rheum palmatum L. against hepatitis B virus. Author(s): Kim TG, Kang SY, Jung KK, Kang JH, Lee E, Han HM, Kim SH.

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Source: Phytotherapy Research : Ptr. 2001 December; 15(8): 718-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11746867&dopt=Abstract ·

Approach to the patient with chronic hepatitis C virus infection. Author(s): Herrine SK. Source: Annals of Internal Medicine. 2002 May 21; 136(10): 747-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020143&dopt=Abstract

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Autoimmune hepatitis triggered by Brucella infection or doxycycline or both. Author(s): Selimoglu MA, Ertekin V. Source: Int J Clin Pract. 2003 September; 57(7): 639-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14529072&dopt=Abstract

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Black cohosh and other herbal remedies associated with acute hepatitis. Author(s): Vitetta L, Thomsen M, Sali A. Source: The Medical Journal of Australia. 2003 April 21; 178(8): 411-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697018&dopt=Abstract

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Black cohosh and other herbal remedies associated with acute hepatitis. Author(s): Whiting PW, Clouston A, Kerlin P. Source: The Medical Journal of Australia. 2002 October 21; 177(8): 440-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12381254&dopt=Abstract

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Can science meet the challenges of the HCV pandemic: new treatment options for chronic hepatitis C. Author(s): Roehr B. Source: J Int Assoc Physicians Aids Care. 1998 July; 4(7): 24-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11365638&dopt=Abstract

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Chinese herbal medicine and interferon in the treatment of chronic hepatitis B: a meta-analysis of randomized, controlled trials. Author(s): McCulloch M, Broffman M, Gao J, Colford JM Jr. Source: American Journal of Public Health. 2002 October; 92(10): 1619-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356611&dopt=Abstract

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Chinese medicinal herbs for asymptomatic carriers of hepatitis B virus infection. Author(s): Liu JP, McIntosh H, Lin H. Source: Cochrane Database Syst Rev. 2001; (2): Cd002231. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11406038&dopt=Abstract

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Chinese medicinal herbs for chronic hepatitis B. Author(s): Liu JP, McIntosh H, Lin H.

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Source: Cochrane Database Syst Rev. 2001; (1): Cd001940. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11279742&dopt=Abstract ·

Chinese medicinal herbs for chronic hepatitis B: a systematic review. Author(s): Liu J, McIntosh H, Lin H. Source: Liver. 2001 August; 21(4): 280-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11454192&dopt=Abstract

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Chromium-induced toxic hepatitis. Author(s): Lanca S, Alves A, Vieira AI, Barata J, de Freitas J, de Carvalho A. Source: European Journal of Internal Medicine. 2002 December; 13(8): 518-520. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12446198&dopt=Abstract

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Clinical observation of salvianolic acid B in treatment of liver fibrosis in chronic hepatitis B. Author(s): Liu P, Hu YY, Liu C, Zhu DY, Xue HM, Xu ZQ, Xu LM, Liu CH, Gu HT, Zhang ZQ. Source: World Journal of Gastroenterology : Wjg. 2002 August; 8(4): 679-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12174378&dopt=Abstract

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Clinical pathological study of treatment of chronic hepatitis with hyperbaric oxygenation. Author(s): Liu W, Zhao W, Lu X, Zheng X, Luo C. Source: Chin Med J (Engl). 2002 August; 115(8): 1153-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215281&dopt=Abstract

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Clinical study on the treatment of liver fibrosis due to hepatitis B by IFN-alpha(1) and traditional medicine preparation. Author(s): Cheng ML, Wu YY, Huang KF, Luo TY, Ding YS, Lu YY, Liu RC, Wu J. Source: World Journal of Gastroenterology : Wjg. 1999 June; 5(3): 267-269. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11819444&dopt=Abstract

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Combined lamivudine and interferon-alpha therapy for chemotherapy-induced reactivation of hepatitis B virus. Author(s): Ohmoto K, Tsuduki M, Yamamoto S. Source: The American Journal of Gastroenterology. 2003 May; 98(5): 1215-6; Author Reply 1217. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809863&dopt=Abstract

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Commercial tattooing as a potentially important source of hepatitis C infection. Clinical epidemiology of 626 consecutive patients unaware of their hepatitis C serologic status. Author(s): Haley RW, Fischer RP.

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Source: Medicine; Analytical Reviews of General Medicine, Neurology, Psychiatry, Dermatology, and Pediatrics. 2001 March; 80(2): 134-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11307589&dopt=Abstract ·

Cytotoxicity and anti-hepatitis B virus activities of saikosaponins from Bupleurum species. Author(s): Chiang LC, Ng LT, Liu LT, Shieh DE, Lin CC. Source: Planta Medica. 2003 August; 69(8): 705-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14531019&dopt=Abstract

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Differential effects of dietary casein and soybean protein isolate on lipopolysaccharide-induced hepatitis in D-galactosamine-sensitized rats. Author(s): Sugiyama K, Shimada Y, Iwai K, Morita T. Source: Bioscience, Biotechnology, and Biochemistry. 2002 October; 66(10): 2232-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450139&dopt=Abstract

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Does the control of alanine aminotransferase levels lead to a regression of liver fibrosis in chronic hepatitis C patients? Author(s): Yagura M, Murai S, Kojima H, Tokita H, Kamitsukasa H, Harada H. Source: Hepatology Research : the Official Journal of the Japan Society of Hepatology. 2001 February; 19(2): 144-157. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11164739&dopt=Abstract

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Double-blinded placebo-controlled study of Phyllanthus urinaris for the treatment of chronic hepatitis B. Author(s): Chan HL, Sung JJ, Fong WF, Chim AM, Yung PP, Hui AY, Fung KP, Leung PC. Source: Alimentary Pharmacology & Therapeutics. 2003 August 1; 18(3): 339-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12895219&dopt=Abstract

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Downregulation of hepatitis B surface antigen expression in human hepatocellular carcinoma cell lines by HD-03, a polyherbal formulation. Author(s): Yeh SF, Gupta M, Sarma DN, Mitra SK. Source: Phytotherapy Research : Ptr. 2003 January; 17(1): 89-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12557256&dopt=Abstract

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Drug development with hints from traditional Indian Ayurveda medicine: hepatitis and rheumatoid as an example. Author(s): Okamoto T, Hino O. Source: International Journal of Molecular Medicine. 2000 December; 6(6): 613-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11078818&dopt=Abstract

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Effects of a mistletoe preparation with defined lectin content on chronic hepatitis C: an individually controlled cohort study. Author(s): Huber R, Ludtke R, Klassen M, Muller-Buscher G, Wolff-Vorbeck G, Scheer R. Source: European Journal of Medical Research. 2001 September 28; 6(9): 399-405. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11669085&dopt=Abstract

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Effects of homeopathic preparations on the liver in rats with acute and chronic toxic hepatitis. Author(s): Vetoshkina TV, Fomina TI. Source: Bulletin of Experimental Biology and Medicine. 2003; 135 Suppl 1: 85-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12949661&dopt=Abstract

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Effects of storage and type of blood collection tubes on hepatitis C virus level in whole blood samples. Author(s): Kessler HH, Stelzl E, Raggam RB, Haas J, Kirchmeir F, Hegenbarth K, Daghofer E, Santner BI, Marth E, Stauber RE. Source: Journal of Clinical Microbiology. 2001 May; 39(5): 1788-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11325991&dopt=Abstract

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Effects of the Japanese herbal medicine 'Inchinko-to' (TJ-135) on concanavalin Ainduced hepatitis in mice. Author(s): Yamashiki M, Mase A, Arai I, Huang XX, Nobori T, Nishimura A, Sakaguchi S, Inoue K. Source: Clinical Science (London, England : 1979). 2000 November; 99(5): 421-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11052923&dopt=Abstract

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Establishment of a simple assay in vitro for hepatitis C virus NS3 serine protease based on recombinant substrate and single-chain protease. Author(s): Du GX, Hou LH, Guan RB, Tong YG, Wang HT. Source: World Journal of Gastroenterology : Wjg. 2002 December; 8(6): 1088-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439931&dopt=Abstract

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Fatal herpes simplex virus hepatitis complicating chemotherapy with weekly docetaxel. Author(s): Hofer S, Hunziker S, Tornillo L, Ludwig CU. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 February; 14(2): 340. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562665&dopt=Abstract

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Fully automated detection of hepatitis C virus RNA in serum and whole-blood samples. Author(s): Kessler HH, Clarici AM, Stelzl E, Muhlbauer G, Daghofer E, Santner BI, Marth E, Stauber RE.

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Source: Clinical and Diagnostic Laboratory Immunology. 2002 November; 9(6): 1385-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414781&dopt=Abstract ·

Fulminant exacerbation of autoimmune hepatitis after the use of ma huang. Author(s): Borum ML. Source: The American Journal of Gastroenterology. 2001 May; 96(5): 1654-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11374728&dopt=Abstract

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Functional proteomics of nonalcoholic steatohepatitis: mitochondrial proteins as targets of S-adenosylmethionine. Author(s): Santamaria E, Avila MA, Latasa MU, Rubio A, Martin-Duce A, Lu SC, Mato JM, Corrales FJ. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 March 18; 100(6): 3065-70. Epub 2003 Mar 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631701&dopt=Abstract

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Genus Phyllanthus for chronic hepatitis B virus infection: a systematic review. Author(s): Liu J, Lin H, McIntosh H. Source: Journal of Viral Hepatitis. 2001 September; 8(5): 358-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11555193&dopt=Abstract

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Glycyrrhizin inhibits the lytic pathway of complement--possible mechanism of its anti-inflammatory effect on liver cells in viral hepatitis. Author(s): Fujisawa Y, Sakamoto M, Matsushita M, Fujita T, Nishioka K. Source: Microbiol Immunol. 2000; 44(9): 799-804. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11092245&dopt=Abstract

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Hepatitis associated with Chinese herbs. Author(s): McRae CA, Agarwal K, Mutimer D, Bassendine MF. Source: European Journal of Gastroenterology & Hepatology. 2002 May; 14(5): 559-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11984156&dopt=Abstract

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Hepatitis associated with Kava, a herbal remedy for anxiety. Author(s): Escher M, Desmeules J, Giostra E, Mentha G. Source: Bmj (Clinical Research Ed.). 2001 January 20; 322(7279): 139. Erratum In: Bmj 2001 May 5; 322(7294): 1097. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11159570&dopt=Abstract

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Hepatitis B and C virus prevalence in a rural area of South Korea: the role of acupuncture. Author(s): Shin HR, Kim JY, Kim JI, Lee DH, Yoo KY, Lee DS, Franceschi S.

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Source: British Journal of Cancer. 2002 July 29; 87(3): 314-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12177801&dopt=Abstract ·

Hepatitis B infection in China. Author(s): Lau GK. Source: Clinics in Liver Disease. 2001 May; 5(2): 361-79. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11385968&dopt=Abstract

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Hepatitis C in Peru: risk factors for infection, potential iatrogenic transmission, and genotype distribution. Author(s): Sanchez JL, Sjogren MH, Callahan JD, Watts DM, Lucas C, Abdel-Hamid M, Constantine NT, Hyams KC, Hinostroza S, Figueroa-Barrios R, Cuthie JC. Source: The American Journal of Tropical Medicine and Hygiene. 2000 NovemberDecember; 63(5-6): 242-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11421371&dopt=Abstract

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Hepatitis C practice routines among Connecticut's naturopathic physicians. Author(s): Jacoby D, St Louis T, Navarro V. Source: The American Journal of Gastroenterology. 2001 September; 96(9): 2801-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11570394&dopt=Abstract

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Hepatitis c virus infection in employees of a large university hospital in Israel. Author(s): Sermoneta-Gertel S, Donchin M, Adler R, Baras M, Perlstein T, Manny N, Shouval D, Galun E. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2001 December; 22(12): 754-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11876453&dopt=Abstract

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Hepatitis C virus-polymerase chain reaction minipool testing: 3 years in the largest Swiss blood transfusion service. Author(s): Stolz M, Gilgen M, Niederhauser C. Source: Vox Sanguinis. 2003 February; 84(2): 105-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609016&dopt=Abstract

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Hepatitis C; a retrospective study, literature review, and naturopathic protocol. Author(s): Milliman WB, Lamson DW, Brignall MS. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 2000 August; 5(4): 355-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10956381&dopt=Abstract

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Hepatitis induced by Kava (Piper methysticum rhizoma). Author(s): Stickel F, Baumuller HM, Seitz K, Vasilakis D, Seitz G, Seitz HK, Schuppan D.

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Source: Journal of Hepatology. 2003 July; 39(1): 62-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821045&dopt=Abstract ·

Hepatitis treatment update: new approvals, not much news. Author(s): Learned J. Source: Notes Undergr. 1998-99 Winter; (No 38): 7-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11366197&dopt=Abstract

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Hepatocellular carcinoma associated with hepatitis C virus infection in Japan: projection to other countries in the foreseeable future. Author(s): Yoshizawa H. Source: Oncology. 2002; 62 Suppl 1: 8-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11868791&dopt=Abstract

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Hepatoprotective action of abhrak bhasma, an ayurvedic drug in albino rats against hepatitis induced by CCl4. Author(s): Buwa S, Patil S, Kulkarni PH, Kanase A. Source: Indian J Exp Biol. 2001 October; 39(10): 1022-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11883510&dopt=Abstract

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Hepatoprotective properties of aqueous extract from Pentaphylloides fruticosa during chronic toxic hepatitis. Author(s): Kolpakov MA, Grek OR, Bashkirova YV, Lyubarskii MS, Ravilova YR. Source: Bulletin of Experimental Biology and Medicine. 2001 May; 131(5): 470-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11550056&dopt=Abstract

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Herbal and complementary and alternative medicine therapies for liver disease. A focus on Chinese traditional medicine in hepatitis C virus. Author(s): Cohen MR. Source: Clinics in Liver Disease. 2001 May; 5(2): 461-78, Vii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11385972&dopt=Abstract

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Impaired response to high-dose interferon treatment in African-Americans with chronic hepatitis C. Author(s): De Maria N, Colantoni A, Idilman R, Friedlander L, Harig J, Van Thiel DH. Source: Hepatogastroenterology. 2002 May-June; 49(45): 788-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12063991&dopt=Abstract

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In vitro cold activation of complement shown by an overestimation of total complement 4: a study in patients with hepatitis C virus infection. Author(s): Maguire OC, Curry MP, O'Gorman P, Parfrey N, Hegarty J, Cunningham SK.

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Source: Annals of Clinical Biochemistry. 2001 November; 38(Pt 6): 687-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11732652&dopt=Abstract ·

Increased risk of chronic hepatitis in children with cancer. Author(s): Sevinir B, Meral A, Gunay U, Ozkan T, Ozuysal S, Sinirtas M. Source: Medical and Pediatric Oncology. 2003 February; 40(2): 104-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12461794&dopt=Abstract

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Information from teachers on viral hepatitis transmission and prevention in Brazil. Author(s): Gaze R, de Carvalho DM, Rangel-Tura LF. Source: Salud P'ublica De M'exico. 2003 July-August; 45(4): 245-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974041&dopt=Abstract

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Inhibitory effect of M50054, a novel inhibitor of apoptosis, on anti-Fas-antibodyinduced hepatitis and chemotherapy-induced alopecia. Author(s): Tsuda T, Ohmori Y, Muramatsu H, Hosaka Y, Takiguchi K, Saitoh F, Kato K, Nakayama K, Nakamura N, Nagata S, Mochizuki H. Source: European Journal of Pharmacology. 2001 December 14; 433(1): 37-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11755132&dopt=Abstract

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Inhibitory effects of sudanese medicinal plant extracts on hepatitis C virus (HCV) protease. Author(s): Hussein G, Miyashiro H, Nakamura N, Hattori M, Kakiuchi N, Shimotohno K. Source: Phytotherapy Research : Ptr. 2000 November; 14(7): 510-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11054840&dopt=Abstract

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Interstitial pneumonitis during combination therapy with interferon-alpha and ribavirin in a patient with chronic Hepatitis C. Author(s): Rothfuss KS, Bode JC. Source: Zeitschrift Fur Gastroenterologie. 2002 September; 40(9): 807-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215950&dopt=Abstract

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Introduction to therapy of hepatitis C. Author(s): Lindsay KL. Source: Hepatology (Baltimore, Md.). 2002 November; 36(5 Suppl 1): S114-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12407584&dopt=Abstract

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Is acupuncture a risk factor for hepatitis? Systematic review of epidemiological studies. Author(s): Ernst E, Sherman K.

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Source: Journal of Gastroenterology and Hepatology. 2003 November; 18(11): 1231-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14535978&dopt=Abstract ·

Iscador Qu for chronic hepatitis C: an exploratory study. Author(s): Tusenius KJ, Spoek JM, Kramers CW. Source: Complementary Therapies in Medicine. 2001 March; 9(1): 12-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11264964&dopt=Abstract

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Lamivudine and rapid regeneration of the atrophic liver in decompensated cirrhosis due to hepatitis B. Author(s): Saito T, Shinzawa H, Watanabe H, Sugahara K, Okumoto K, Togashi H, Kawata S. Source: The American Journal of Gastroenterology. 2002 February; 97(2): 493-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11866301&dopt=Abstract

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Licorice for hepatitis C: yum-yum or just ho-hum? Author(s): Lewis JH. Source: The American Journal of Gastroenterology. 2001 August; 96(8): 2291-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11513162&dopt=Abstract

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Making a diagnosis of herbal-related toxic hepatitis. Author(s): Haller CA, Dyer JE, Ko R, Olson KR. Source: The Western Journal of Medicine. 2002 January; 176(1): 39-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11788538&dopt=Abstract

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Management of nonalcoholic steatohepatitis: an analytic review. Author(s): Agrawal S, Bonkovsky HL. Source: Journal of Clinical Gastroenterology. 2002 September; 35(3): 253-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192203&dopt=Abstract

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Management of viral hepatitis C. Author(s): Leung NW. Source: Journal of Gastroenterology and Hepatology. 2002 February; 17 Suppl: S146-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12000600&dopt=Abstract

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Medicinal herbs for hepatitis C virus infection. Author(s): Liu JP, Manheimer E, Tsutani K, Gluud C. Source: Cochrane Database Syst Rev. 2001; (4): Cd003183. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11687177&dopt=Abstract

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Medicinal herbs for hepatitis C virus infection: a Cochrane hepatobiliary systematic review of randomized trials. Author(s): Liu J, Manheimer E, Tsutani K, Gluud C. Source: The American Journal of Gastroenterology. 2003 March; 98(3): 538-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650784&dopt=Abstract

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Milk thistle and the treatment of hepatitis. Author(s): Giese LA. Source: Gastroenterology Nursing : the Official Journal of the Society of Gastroenterology Nurses and Associates. 2001 March-April; 24(2): 95-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11847735&dopt=Abstract

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Misuse of randomization: a review of Chinese randomized trials of herbal medicines for chronic hepatitis B. Author(s): Liu J, Kjaergard LL, Gluud C. Source: The American Journal of Chinese Medicine. 2002; 30(1): 173-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12067091&dopt=Abstract

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Mitral valve vegetation and cerebral emboli in a primary antiphospholipid syndrome patient who had hepatitis C virus infection: report of a case and review of the literature. Author(s): Pamuk ON, Cakir N, Soy M, Aktoz M, Celik Y, Akdemir O. Source: Clinical Rheumatology. 2003 May; 22(2): 136-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740679&dopt=Abstract

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Molecular epidemiology of a large outbreak of hepatitis B linked to autohaemotherapy. Author(s): Webster GJ, Hallett R, Whalley SA, Meltzer M, Balogun K, Brown D, Farrington CP, Sharma S, Hamilton G, Farrow SC, Ramsay ME, Teo CG, Dusheiko GM. Source: Lancet. 2000 July 29; 356(9227): 379-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10972370&dopt=Abstract

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Mycophenolate mofetil for maintenance of remission in autoimmune hepatitis in patients resistant to or intolerant of azathioprine. Author(s): Richardson PD, James PD, Ryder SD. Source: Journal of Hepatology. 2000 September; 33(3): 371-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11019991&dopt=Abstract

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Natural history and treatment of Hepatitis C. Author(s): Highleyman L. Source: Beta. 1999; 12(4): 16-29. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11367245&dopt=Abstract

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New treatments for hepatitis B and C [antigen-specific transfer for A, B & C (chisolm biologicals) and thymate]. Author(s): Konlee M. Source: Posit Health News. 1998 Fall; (No 17): 19-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11366548&dopt=Abstract

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Nodular vasculitis associated with chronic hepatitis C. Author(s): Ural I, Erel A, Ozenirler S, Tekin NS, Gurert MA. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2002 May; 16(3): 298-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12195584&dopt=Abstract

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Osthole prevents anti-Fas antibody-induced hepatitis in mice by affecting the caspase-3-mediated apoptotic pathway. Author(s): Okamoto T, Kawasaki T, Hino O. Source: Biochemical Pharmacology. 2003 February 15; 65(4): 677-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566097&dopt=Abstract

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Parenteral and mucosal prime-boost immunization strategies in mice with hepatitis B surface antigen and CpG DNA. Author(s): McCluskie MJ, Weeratna RD, Payette PJ, Davis HL. Source: Fems Immunology and Medical Microbiology. 2002 February 18; 32(3): 179-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11934561&dopt=Abstract

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Pharmacokinetics, safety, and antiviral effects of hypericin, a derivative of St. John's wort plant, in patients with chronic hepatitis C virus infection. Author(s): Jacobson JM, Feinman L, Liebes L, Ostrow N, Koslowski V, Tobia A, Cabana BE, Lee D, Spritzler J, Prince AM. Source: Antimicrobial Agents and Chemotherapy. 2001 February; 45(2): 517-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11158749&dopt=Abstract

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Preliminary results of individual therapy of chronic hepatitis C by Ukrain and interferon-alpha. Author(s): Voltchek I, Sologub T, Nowicky JW, Grigoryeva T, Belozyorova L, Belopolskaya M, Semenyako N, Lamanova E. Source: Drugs Exp Clin Res. 2000; 26(5-6): 261-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11345036&dopt=Abstract

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Pretreatment of whole blood for use in immunochromatographic assays for hepatitis B virus surface antigen. Author(s): Shin HS, Kim CK, Shin KS, Chung HK, Heo TR.

300 Hepatitis

Source: Clinical and Diagnostic Laboratory Immunology. 2001 January; 8(1): 9-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11139189&dopt=Abstract ·

Prevention and therapy of hepatitis B. Author(s): Tao Q, Feng B. Source: Chin Med J (Engl). 1999 October; 112(10): 942-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11717982&dopt=Abstract

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Primary prophylaxis with lamivudine of hepatitis B virus reactivation in chronic HbsAg carriers with lymphoid malignancies treated with chemotherapy. Author(s): Rossi G, Pelizzari A, Motta M, Puoti M. Source: British Journal of Haematology. 2001 October; 115(1): 58-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11722410&dopt=Abstract

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Prophylactic effect of interferon-alpha for exacerbation of hepatitis B after high-dose chemotherapy. Author(s): Matano S, Kobayashi K, Ohta H, Minouchi K, Sanada T, Sugimoto T. Source: Acta Haematologica. 2001; 106(3): 138-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11713383&dopt=Abstract

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Prophylaxis against chemotherapy-induced reactivation of hepatitis B virus infection with Lamivudine. Author(s): Simpson ND, Simpson PW, Ahmed AM, Nguyen MH, Garcia G, Keeffe EB, Ahmed A. Source: Journal of Clinical Gastroenterology. 2003 July; 37(1): 68-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811213&dopt=Abstract

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Prospective multicenter clinical evaluation of AMPLICOR and COBAS AMPLICOR hepatitis C virus tests. Author(s): Nolte FS, Fried MW, Shiffman ML, Ferreira-Gonzalez A, Garrett CT, Schiff ER, Polyak SJ, Gretch DR. Source: Journal of Clinical Microbiology. 2001 November; 39(11): 4005-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11682522&dopt=Abstract

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Radix Sophorae flavescentis for chronic hepatitis B: a systematic review of randomized trials. Author(s): Liu J, Zhu M, Shi R, Yang M. Source: The American Journal of Chinese Medicine. 2003; 31(3): 337-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943166&dopt=Abstract

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Recent developments in the treatment of alcoholic hepatitis. Author(s): Madhotra R, Gilmore IT.

Alternative Medicine 301

Source: Qjm : Monthly Journal of the Association of Physicians. 2003 June; 96(6): 391400. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788957&dopt=Abstract ·

Review article: immunopathogenetic and therapeutic aspects of autoimmune hepatitis. Author(s): Medina J, Garcia-Buey L, Moreno-Otero R. Source: Alimentary Pharmacology & Therapeutics. 2003 January; 17(1): 1-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492728&dopt=Abstract

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Screening of 25 compounds isolated from Phyllanthus species for anti-human hepatitis B virus in vitro. Author(s): Huang RL, Huang YL, Ou JC, Chen CC, Hsu FL, Chang C. Source: Phytotherapy Research : Ptr. 2003 May; 17(5): 449-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12748977&dopt=Abstract

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Steroid-free chemotherapy decreases risk of hepatitis B virus (HBV) reactivation in HBV-carriers with lymphoma. Author(s): Cheng AL, Hsiung CA, Su IJ, Chen PJ, Chang MC, Tsao CJ, Kao WY, Uen WC, Hsu CH, Tien HF, Chao TY, Chen LT, Whang-Peng J; Lymphoma Committee of Taiwan Cooperative Oncology Group. Source: Hepatology (Baltimore, Md.). 2003 June; 37(6): 1320-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12774010&dopt=Abstract

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Suppressive effect of coffee on lipopolysaccharide-induced hepatitis in Dgalactosamine-sensitized rats. Author(s): He P, Noda Y, Sugiyama K. Source: Bioscience, Biotechnology, and Biochemistry. 2001 August; 65(8): 1924-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11577746&dopt=Abstract

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Thalidomide-associated hepatitis: a case report. Author(s): Fowler R, Imrie K. Source: American Journal of Hematology. 2001 April; 66(4): 300-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11279644&dopt=Abstract

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The efficacy of a herbal medicine (Mao-to) in combination with intravenous natural interferon-beta for patients with chronic hepatitis C, genotype 1b and high viral load: a pilot study. Author(s): Kainuma M, Ogata N, Kogure T, Kohta K, Hattori N, Mitsuma T, Terasawa K.

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Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2002 July; 9(5): 365-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12222653&dopt=Abstract ·

The efficacy of herbal medicine (kampo) in reducing the adverse effects of IFN-beta in chronic hepatitis C. Author(s): Kainuma M, Hayashi J, Sakai S, Imai K, Mantani N, Kohta K, Mitsuma T, Shimada Y, Kashiwagi S, Terasawa K. Source: The American Journal of Chinese Medicine. 2002; 30(2-3): 355-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12230024&dopt=Abstract

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The hepatitis B virus-X protein activates a phosphatidylinositol 3-kinase-dependent survival signaling cascade. Author(s): Lee YI, Kang-Park S, Do SI, Lee YI. Source: The Journal of Biological Chemistry. 2001 May 18; 276(20): 16969-77. Epub 2001 March 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11278872&dopt=Abstract

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The use of alternative medicine in the treatment of hepatitis C. Author(s): Bean P. Source: Am Clin Lab. 2002 May; 21(4): 19-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12087634&dopt=Abstract

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Toxic hepatitis caused by herbal medicine. Author(s): Okpara RA. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 2000 July-August; 13(4): 321. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10933302&dopt=Abstract

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Treatment of chronic hepatitis B: case selection and duration of therapy. Author(s): Leung N. Source: Journal of Gastroenterology and Hepatology. 2002 April; 17(4): 409-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11982721&dopt=Abstract

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Treatment of chronic hepatitis C virus infection. Author(s): Malnick SD, Beergabel M, Lurie Y. Source: The Annals of Pharmacotherapy. 2000 October; 34(10): 1156-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11054985&dopt=Abstract

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Treatment of hepatitis caused by cytomegalovirus with allitridin injection--an experimental study. Author(s): Fang F, Li H, Cui W, Dong Y.

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Source: J Tongji Med Univ. 1999; 19(4): 271-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12938515&dopt=Abstract ·

Zafirlukast-induced acute hepatitis. Author(s): Su CW, Wu JC, Huang YH, Huang YS, Chang FY, Lee SD. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2002 November; 65(11): 553-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12583521&dopt=Abstract

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Zinc supplementation enhances the response to interferon therapy in patients with chronic hepatitis C. Author(s): Takagi H, Nagamine T, Abe T, Takayama H, Sato K, Otsuka T, Kakizaki S, Hashimoto Y, Matsumoto T, Kojima A, Takezawa J, Suzuki K, Sato S, Mori M. Source: Journal of Viral Hepatitis. 2001 September; 8(5): 367-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11555194&dopt=Abstract

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: ·

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.comÒ: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMDÒHealth: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to hepatitis; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation:

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·

General Overview Alcoholism Source: Integrative Medicine Communications; www.drkoop.com Bladder Infection Alternative names: Urinary Tract Infection [UTI] Source: Prima Communications, Inc.www.personalhealthzone.com Cancer Prevention and Diet Source: Healthnotes, Inc.; www.healthnotes.com Cirrhosis Source: Integrative Medicine Communications; www.drkoop.com Colon Cancer Source: Healthnotes, Inc.; www.healthnotes.com Depression (mild to Moderate) Source: Prima Communications, Inc.www.personalhealthzone.com Erythema Source: Integrative Medicine Communications; www.drkoop.com Hemophilia Source: Integrative Medicine Communications; www.drkoop.com Hepatitis Source: Healthnotes, Inc.; www.healthnotes.com High Cholesterol Source: Integrative Medicine Communications; www.drkoop.com Hives Source: Healthnotes, Inc.; www.healthnotes.com Hypercholesterolemia Source: Integrative Medicine Communications; www.drkoop.com Immune Function Source: Healthnotes, Inc.; www.healthnotes.com Insomnia Source: Integrative Medicine Communications; www.drkoop.com Liver Cirrhosis Source: Healthnotes, Inc.; www.healthnotes.com Liver Disease Source: Integrative Medicine Communications; www.drkoop.com

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Lung Cancer Source: Healthnotes, Inc.; www.healthnotes.com Malabsorption Source: Healthnotes, Inc.; www.healthnotes.com Osteoarthritis Source: Healthnotes, Inc.; www.healthnotes.com Pancreatitis Source: Integrative Medicine Communications; www.drkoop.com Peptic Ulcer Source: Integrative Medicine Communications; www.drkoop.com Rheumatoid Arthritis Source: Healthnotes, Inc.; www.healthnotes.com Sleeplessness Source: Integrative Medicine Communications; www.drkoop.com Viral Hepatitis Source: Prima Communications, Inc.www.personalhealthzone.com ·

Alternative Therapy Acupuncture Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,663,00.html

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Chinese Medicine Chuipencao Alternative names: Stringy Stonecrop Herb; Herba Sedi Source: Chinese Materia Medica Ershiwuwei Songshi Wan Alternative names: Ershiwuwei Songshi Pills (Used by Tibetan Nationality); Ershiwuwei Songshi Wan (Er Shi Wu Wei Song Shi Wan) Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Hyperlink: http://www.newcenturynutrition.com/cgilocal/patent_herbs_db/db.cgi?db=default&Chinese=Ershiwuwei%20Songshi%20W an&mh=10&sb=---&view_records=View+Records Gonglaomu Alternative names: Chinese Mahonia Stem; Caulis Mahoniae Source: Chinese Materia Medica

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Hugan Pian Alternative names: Hugan Tablets Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Hyperlink: http://www.newcenturynutrition.com/cgilocal/patent_herbs_db/db.cgi?db=default&Chinese=Hugan%20Pian&mh=10&sb=--&view_records=View+Records Jigucao Alternative names: Canton Love-pea Vine; Herba Abri Source: Chinese Materia Medica Shisanwei Bangga San Alternative names: Shisanwei Bangga Powder; Shisanwei Bangga San; (Shi San Wei Banq Qa San) Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Hyperlink: http://www.newcenturynutrition.com/cgilocal/patent_herbs_db/db.cgi?db=default&Chinese=Shisanwei%20Bangga%20San &mh=10&sb=---&view_records=View+Records Yinchen Alternative names: Virgate Wormwood Herb; Herba Artemisiae Scopariae Source: Chinese Materia Medica ·

Herbs and Supplements Alpha Lipoic Acid Source: Healthnotes, Inc.; www.healthnotes.com Alpha-lipoic Acid Source: Integrative Medicine Communications; www.drkoop.com Alpha-lipoic Acid Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10002,00.html Andrographis Alternative names: Andrographis paniculata Source: Healthnotes, Inc.; www.healthnotes.com Aristolochia Alternative names: Snakeroot, Guaco; Aristolochia sp Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Astragalus Alternative names: Astragalus membranaceus Source: Healthnotes, Inc.; www.healthnotes.com

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Astragalus Alternative names: Astragalus membranaceus, Astragalus membranaceus var. mongholicus, Huang-qi, Milk-Vetch Root Source: Integrative Medicine Communications; www.drkoop.com Astragalus Source: Prima Communications, Inc.www.personalhealthzone.com Astragalus Mem Alternative names: Huang-Qi; Astragalus membranaceus Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Astragalus Membranaceus Source: Integrative Medicine Communications; www.drkoop.com Astragalus Mongholicus Alternative names: Astragalus membranaceus, Astragalus membranaceus var. mongholicus, Huang-qi, Milk-Vetch Root Source: Integrative Medicine Communications; www.drkoop.com Ava Source: Integrative Medicine Communications; www.drkoop.com Blue Flag Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Boswellia Alternative names: Frankincense; Boswellia serrata Roxb. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Bupleurum Alternative names: Bupleurum chinense, Bupleurum falcatum Source: Healthnotes, Inc.; www.healthnotes.com Chinese Scullcap Alternative names: Scutellaria baicalensis Source: Healthnotes, Inc.; www.healthnotes.com Corydalis Alternative names: Corydalis turtschaninovii, Corydalis yanhusuo Source: Healthnotes, Inc.; www.healthnotes.com Culver's Root Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Cynara Artichoke Alternative names: Artichoke; Cynara scolymus L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

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Cysteine Source: Integrative Medicine Communications; www.drkoop.com Dandelion Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10021,00.html Flavonoids Source: Healthnotes, Inc.; www.healthnotes.com Glycyrrhiza Glabra Source: Integrative Medicine Communications; www.drkoop.com Glycyrrhiza1 Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Greater Celandine Alternative names: Chelidonium majus Source: Healthnotes, Inc.; www.healthnotes.com Green Tea Source: Prima Communications, Inc.www.personalhealthzone.com Green-lipped Mussel Source: Healthnotes, Inc.; www.healthnotes.com Huang-qi Source: Integrative Medicine Communications; www.drkoop.com Interferon Source: Healthnotes, Inc.; www.healthnotes.com Kava Kava Alternative names: Piper methysticum, Ava Source: Integrative Medicine Communications; www.drkoop.com Lecithin Source: Prima Communications, Inc.www.personalhealthzone.com Licorice Alternative names: Glycyrrhiza glabra, Glycyrrhiza uralensis Source: Healthnotes, Inc.; www.healthnotes.com Licorice Alternative names: Glycyrrhiza glabra, Spanish Licorice Source: Integrative Medicine Communications; www.drkoop.com Licorice Source: Prima Communications, Inc.www.personalhealthzone.com

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Licorice Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,801,00.html Lipotropic Combination Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,861,00.html Liquorice Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Liver Extracts Source: Healthnotes, Inc.; www.healthnotes.com Lobelia Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Mad-dog Skullcap Source: Integrative Medicine Communications; www.drkoop.com Milk Thistle Alternative names: Silybum marianum, Carduus marianus Source: Healthnotes, Inc.; www.healthnotes.com Milk Thistle Alternative names: Silybum marianum, St. Mary's Thistle Source: Integrative Medicine Communications; www.drkoop.com Milk Thistle Source: Prima Communications, Inc.www.personalhealthzone.com Milk Thistle Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Milk Thistle Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10044,00.html Milk-vetch Root Source: Integrative Medicine Communications; www.drkoop.com N-acetyl Cysteine Source: Healthnotes, Inc.; www.healthnotes.com Paba Source: Healthnotes, Inc.; www.healthnotes.com

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Phyllanthus Alternative names: Phyllanthus niruri Source: Healthnotes, Inc.; www.healthnotes.com Phyllanthus/ayurvedic Liver Support Combination Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10050,00.html Picrorhiza Alternative names: Picrorhiza kurroa Source: Healthnotes, Inc.; www.healthnotes.com Piper Methysticum Source: Integrative Medicine Communications; www.drkoop.com Plantago Psyllium Alternative names: Psyllium, Ispaghula; Plantago psyllium/ovata Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Reishi Alternative names: Ganoderma lucidum Source: Healthnotes, Inc.; www.healthnotes.com Reishi Source: Prima Communications, Inc.www.personalhealthzone.com Same Source: Healthnotes, Inc.; www.healthnotes.com Same (s-adenosylmethionine) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,818,00.html Schisandra Alternative names: Schisandra chinensis Source: Healthnotes, Inc.; www.healthnotes.com Scutellaria Lateriflora Source: Integrative Medicine Communications; www.drkoop.com Shiitake Alternative names: Lentinus edodes Source: Healthnotes, Inc.; www.healthnotes.com Silybum Alternative names: Milk Thistle; Silybum marianum (L.) Gaertn. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

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Silybum Marianum Source: Integrative Medicine Communications; www.drkoop.com Skullcap Alternative names: Scutellaria lateriflora, Mad-dog Skullcap Source: Integrative Medicine Communications; www.drkoop.com Smilax Alternative names: Sarsaparilla; Smilax glabra Roxb. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Spanish Licorice Source: Integrative Medicine Communications; www.drkoop.com St. John's Wort Source: Prima Communications, Inc.www.personalhealthzone.com St. Mary's Thistle Source: Integrative Medicine Communications; www.drkoop.com Swertia Alternative names: Swertia sp Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tanacetum V Alternative names: Tansy; Tanacetum vulgare (L.) Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Taraxacum Alternative names: Dandelion; Taraxacum officinale (Dhudhal) Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Taurine Source: Prima Communications, Inc.www.personalhealthzone.com Terminalia Alternative names: Myrobalans; Terminalia arjuna Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Thymus Extracts Source: Healthnotes, Inc.; www.healthnotes.com Uva Ursi Source: Prima Communications, Inc.www.personalhealthzone.com Zizyphus Alternative names: Jujube; Ziziphus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

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General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS ON HEPATITIS Overview In this chapter, we will give you a bibliography on recent dissertations relating to hepatitis. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “hepatitis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on hepatitis, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Hepatitis ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to hepatitis. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: ·

A Case-control Study of Hepatitis C Virus Infection and Non-hodgkin's Lymphoma in Egypt by Cowgill, Karen Deirdre; Phd from The Johns Hopkins University, 2002, 209 pages http://wwwlib.umi.com/dissertations/fullcit/3046437

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A Mechanistic Investigation of the Ns3 Helicase Encoded by the Hepatitis C Virus: a Comparison Study with the Dda Helicase from Bacteriophage T4 by Tackett, Alan Jackson; Phd from University of Arkansas for Medical Sciences, 2002, 188 pages http://wwwlib.umi.com/dissertations/fullcit/3049609

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An Assessment of Support Group Participation on Depression and Adherence in Veterans with Hepatitis C by Chun, Doris Sohyun; Phd from New York University, 2002, 154 pages http://wwwlib.umi.com/dissertations/fullcit/3045705

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An Educational Needs Assessment of Adult Chronic Type Hepatitis C Patients Undergoing Anti-viral Therapy by Cirillo, Jane Marie; Edd from Columbia University Teachers College, 2002, 313 pages http://wwwlib.umi.com/dissertations/fullcit/3052870

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Analysis of Antihepadnaviral Activity of Nucleoside Analogs Using Hepatitis B Virus Recombinant Baculovirus-hepg2 System by Abdelhamed, Ayman Mohamed Osman; Phd from The Pennsylvania State University, 2002, 314 pages http://wwwlib.umi.com/dissertations/fullcit/3051612

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Blood, Blame, and Belonging: Hiv, Hepatitis C, and Emergence of 'tainted-blood Activism' in Canada, 1985--2000 by Orsini, Michael; Phd from Carleton University (canada), 2002, 343 pages http://wwwlib.umi.com/dissertations/fullcit/NQ67055

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Cd4+ T-helper Cell Responses in Hepatitis C Virus Infection by Day, Cheryl Liane; Phd from Harvard University, 2003, 219 pages http://wwwlib.umi.com/dissertations/fullcit/3091540

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Characterization Antiviral Activity of Adefovir Dipivoxil in Transgenic Mice Expressing Hepatitis B Virus by Julander, Justin G.; Ms from Utah State University, 2002, 63 pages http://wwwlib.umi.com/dissertations/fullcit/1409343

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Characterization of the Hepatitis C Viral Helicase, And, a Sequence Analysis Algorithm That Predicts Functional Interactions by Pang, Phillip Soon-ho; Phd from Columbia University, 2002, 190 pages http://wwwlib.umi.com/dissertations/fullcit/3066886

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Chronic Active Hepatitis: Discriminant Function Analysis As a Method for Validating Hypothesized Classification Systems. by Durall, Wilma Colleen, Phd from Southern Illinois University at Carbondale, 1979, 86 pages http://wwwlib.umi.com/dissertations/fullcit/7916073

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Cultural Factors Related to the Epidemiology of Viral Hepatitis in a Southwestern United States County (infectious Disease, Socioeconomic, Public Health, Behavior, Communicable) by Mccombie, Susan Carole, Phd from The University of Arizona, 1986, 184 pages http://wwwlib.umi.com/dissertations/fullcit/8613437

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Design and Synthesis of Hepatitis C Virus Ns3 Protease Inhibitors by Johansson, Anja; Phd from Uppsala Universitet (sweden), 2003, 79 pages http://wwwlib.umi.com/dissertations/fullcit/f57697

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Design, Synthesis and Testing of Hepatitis a Virus 3c Proteinase Inhibitors by Ramtohul, Yeeman Koomar; Phd from University of Alberta (canada), 2002, 228 pages http://wwwlib.umi.com/dissertations/fullcit/NQ68616

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Determinants of the Sex Ratio at Birth (hepatitis B) by Chahnazarian, Anouch, Phd from Princeton University, 1986, 195 pages http://wwwlib.umi.com/dissertations/fullcit/8621187

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Development and Clinical Applications of Improved Assays for Detection and Quantitation of Hepatitis C Virus by Hadfield, Stephen James; Phd from University of Southampton (united Kingdom), 2002 http://wwwlib.umi.com/dissertations/fullcit/f335953

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Development of Disinfectant Efficacy Assay for Duck Hepatitis B Virus Using Pcr and Real-time Quantitative Pcr by Wang, Chi-young John; Phd from Auburn University, 2002, 129 pages http://wwwlib.umi.com/dissertations/fullcit/3057174

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Differentiation and Other Factors Influencing the Replication of Murine Hepatitis Viruses in Cells from the Rat Central Nervous System by Beushausen, Sven A; Phd from The University of Western Ontario (canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL36094

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Dna Unwinding Mechanism of the Helicase from Hepatitis C Virus by Levin, Mikhail Konstantinovich; Phd from The Ohio State University, 2002, 152 pages http://wwwlib.umi.com/dissertations/fullcit/3056976

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Economic Evaluation of Vaccination Programmes in Humans: a Methodological Exploration with Applications to Hepatitis B, Varicella-zoster, Measles, Pertussis, Hepatitis a and Pneumococcal Vaccination by Beutels, Philippe; Phd from Universitaire Instelling Antwerpen (belgium), 2002, 523 pages http://wwwlib.umi.com/dissertations/fullcit/3045453

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Epidemiology of Hepatitis C Virus Infection among Blood Donors in Northern Thailand by Thaikruea, Lakkana; Phd from The Johns Hopkins University, 2003, 152 pages http://wwwlib.umi.com/dissertations/fullcit/3080779

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Evaluation of the Cognitive Functioning of Patients Undergoing Combination Therapy for the Treatment of Chronic Hepatitis C by Williams, Karren R.; Phd from State University of New York at Binghamton, 2002, 56 pages http://wwwlib.umi.com/dissertations/fullcit/3059839

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Family Behavior and the Transmission of Hepatitis B Virus in Malo, New Hebrides. Ethology, Ethnography and Epidemiology in the Study of the Natural History of Disease by Dickie, Elizabeth Reed, Phd from University of Pennsylvania, 1979, 321 pages http://wwwlib.umi.com/dissertations/fullcit/8009393

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Hepatitis B Surface Antigen Expression in Plant Cell Culture: Characterization of the Production System, the Antigen and Its Stabilization upon Extraction by Smith, Mark Lionel; Phd from Cornell University, 2002, 360 pages http://wwwlib.umi.com/dissertations/fullcit/3050394

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Hepatitis C and E Virus in Rural Egyptian Women and Children by Stoszek, Sonia Karolina; Phd from The Johns Hopkins University, 2003, 212 pages http://wwwlib.umi.com/dissertations/fullcit/3068217

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Host-cell Mediation of Murine Hepatitis Virus (mhv) Persistence by Mizzen, Lee A; Phd from The University of Western Ontario (canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL33046

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Identification and Characterization of Mouse Hepatitis Virus Papain-like Proteinase 2 Activity by Kanjanahaluethai, Amornrat; Phd from Loyola University of Chicago, 2002, 180 pages http://wwwlib.umi.com/dissertations/fullcit/3056425

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Immunological Studies in Hepatitis B by Jutcovich, Morris; Phd from University of Ottawa (canada), 1981 http://wwwlib.umi.com/dissertations/fullcit/NK60211

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Impact of Highly Active Antiretroviral Therapy on Hepatitis C Virus Rna Levels over One Year in Hiv-hcv Co-infected Individuals by Cooper, Curtis; Msc from University of Ottawa (canada), 2002, 150 pages http://wwwlib.umi.com/dissertations/fullcit/MQ76570

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Improvement of Hepatitis B Surface Antigen Expression in Plant Cell Culture System with Plant Signal Peptide, Endoplasmic Reticulum Retention Signal, and 3-prime Untranslated Region by Sojikul, Punchapat; Phd from Cornell University, 2003, 189 pages http://wwwlib.umi.com/dissertations/fullcit/3075865

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In Vitro and in Vivo Investigations into Idiosyncratic Drug Reactions: the Role of Reactive Metabolites Produced by the Target Tissue in Terbinafine-induced Cholestatic Hepatitis and Antipsychotic-induced Agranulocytosis by Iverson, Suzanne Leah; Phd from University of Toronto (canada), 2002, 309 pages http://wwwlib.umi.com/dissertations/fullcit/NQ74756

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Mapping Disasters: the Application of a Disaster-sociological 'theoretical Superstructure' and Methodology in a Prima Facie Case for Investigating the Role of Hepatitis B Vaccines in the Contamination of the Canadian Blood Supply with Human Immunodeficien by Krassnitzky, Olaf; Phd from Carleton University (canada), 2000, 483 pages http://wwwlib.umi.com/dissertations/fullcit/NQ52326

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Mechanisms of the Pathogenesis of Cell Injury and Viral Persistence in the Woodchuck Model of Hepatitis B by Hodgson, Paul Douglas; Phd from Memorial University of Newfoundland (canada), 2002, 269 pages http://wwwlib.umi.com/dissertations/fullcit/NQ73549

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Modulation of Murine Hepatitis Virus Infection by the Host Cell Membrane by Daya, Maleki; Phd from University of Calgary (canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL54204

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Modulation of the Host Cell Signaling Pathways and Protein Synthesis by Hepatitis C Virus Nonstructural 5a Protein by He, Yupeng; Phd from University of Washington, 2002, 254 pages http://wwwlib.umi.com/dissertations/fullcit/3053511

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Mucosal Immune Responses to Hepatitis C Virus by Samoff, Erika; Phd from Yale University, 2003, 142 pages http://wwwlib.umi.com/dissertations/fullcit/3084363

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Murine Hepatitis Virus (mhv) Replication a Molecular Study by Cheley, Stephen B; Phd from The University of Western Ontario (canada), 1984 http://wwwlib.umi.com/dissertations/fullcit/NK61764

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Optimizing the Scid/upa Mouse Model for Hepatitis C by Schiller, Daniel Eric; Msc from University of Alberta (canada), 2002, 137 pages http://wwwlib.umi.com/dissertations/fullcit/MQ69756

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Pathogenesis of Hepatitis B Virus Infection: the Effect of the Hbx Protein from Hbv on Cell Survival and Death by Diao, Jingyu; Phd from University of Toronto (canada), 2002, 232 pages http://wwwlib.umi.com/dissertations/fullcit/NQ75593

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Personal and Social Effects of Being a Carrier of Hepatitis B (chronicity, Interactionalism) by Foley, Maryann Brichler, Phd from Case Western Reserve University, 1984, 227 pages http://wwwlib.umi.com/dissertations/fullcit/8425584

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Quantitative Analysis of Hepatitis C Virus in Peripheral Leukocytes and Phenotypic Analysis of Liver-infiltrating Lymphocytes in Hcv Infection by Boisvert, Judith Esther; Phd from Stanford University, 2002, 149 pages http://wwwlib.umi.com/dissertations/fullcit/3038067

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Regulation of the Fgl2 Gene in Viral Hepatitis by Lakatoo, Sophia Julie; Msc from University of Toronto (canada), 2002, 88 pages http://wwwlib.umi.com/dissertations/fullcit/MQ74007

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Ribosomal Binding Domains in the Hepatitis C Virus Internal Ribosome Entry Site by Lytle, Jennifer Robin; Phd from Cornell University Medical College, 2002, 143 pages http://wwwlib.umi.com/dissertations/fullcit/3057642

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Structural and Functional Studies of the 3' Untranslated Region of Mouse Hepatitis Virus Strain Jhm Genomic Rna by Liu, Qi; Phd from Texas A&m University, 2002, 156 pages http://wwwlib.umi.com/dissertations/fullcit/3049987

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The Association between Hepatitis C Virus Infection and Type 2 Diabetes Mellitus by Mehta, Shruti Hemendra; Phd from The Johns Hopkins University, 2002, 166 pages http://wwwlib.umi.com/dissertations/fullcit/3046513

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The Effect of Therapeutic Interventions on Cytokine Profile in Hepatitis C Infection by Ibrahim, Asma; Msc from University of Toronto (canada), 2002, 98 pages http://wwwlib.umi.com/dissertations/fullcit/MQ74131

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The Politics of Scientific Practice in Taiwan: the Hepatitis B Control Program (china) by Lin, Chung-hsi, Phd from Virginia Polytechnic Institute and State University, 1994, 393 pages http://wwwlib.umi.com/dissertations/fullcit/9426267

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The Reduction of Hepatitis a Virus and Other Model Viruses by Coagulation, Flocculation, Sedimentation, Rapid Sand Filtration, Chlorine Disinfection and High Ph Lime Softening by Battigelli, David Albert; Phd from The University of North Carolina at Chapel Hill, 2002, 162 pages http://wwwlib.umi.com/dissertations/fullcit/3046962

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The Role of Cyclooxygenase-2 in Chronic Hepatitis B by Cheng, Sze-lok Alfred; Phd from Chinese University of Hong Kong (people's Republic of China), 2002, 211 pages http://wwwlib.umi.com/dissertations/fullcit/3052118

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The Roles Offgl2 in Innate and Acquired Immunity: Implications in Chronic Hepatitis B Infection by Chan, Camie Wing Yan; Phd from University of Toronto (canada), 2003, 263 pages http://wwwlib.umi.com/dissertations/fullcit/NQ78414

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Vaccine Safety: a Review and a Study of Newborn Hepatitis B Vaccine Coverage during a Period of Changing Recommendations by Biroscak, Brian Joseph; Ms from Michigan State University, 2002, 72 pages http://wwwlib.umi.com/dissertations/fullcit/1411911

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Value-based Pricing of Pharmaceutical Innovations: the Case of Genetically Engineered Hepatitis B Vaccines by Maes, Edith Louise; Dba from Maastricht School of Management (the Netherlands), 2002, 342 pages http://wwwlib.umi.com/dissertations/fullcit/3056609

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What Are the Life Patterns of People with Hepatitis C? by Thomas, Judy Ann; Ms from University of Nevada, Reno, 2002, 100 pages http://wwwlib.umi.com/dissertations/fullcit/1410214

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. CLINICAL TRIALS AND HEPATITIS Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning hepatitis.

Recent Trials on Hepatitis The following is a list of recent trials dedicated to hepatitis.8 Further information on a trial is available at the Web site indicated. ·

12 Week Study of Anti-Viral Effect of Oral UT-231B in Non-cirrhotic Hepatitis C Patients who have Failed Interferon-based Therapy. Condition(s): Hepatitis C Study Status: This study is currently recruiting patients. Sponsor(s): United Therapeutics Purpose - Excerpt: This is a multi-center study. Neither the study subjects nor the physicians will know what treatment an individual subject is receiving. Subjects will be randomly assigned (like flipping a coin) to one of five treatment groups. The treatment groups include four different dosing groups of active study drug and one group of subjects who will receive placebo. A 12 week follow up period occurs after the 12 weeks of dosing. There will be pharmacokinetic sampling at the beginning and end of the treatment period requiring an overnight stay in the hospital. Subjects will receive compensation for the overnight stays. The study endpoint is a reduction in Hepatitis C viral load. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00069511

8

These are listed at www.ClinicalTrials.gov.

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A Comparison Study of the Efficacy of Adefovir and Tenofovir for the Treatment of Lamivudine-Resistant Hepatitis B Virus Condition(s): HIV Infections; Hepatitis B Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to find out if adding adefovir dipivoxil (ADV) or tenofovir disoproxil fumarate (TDF) with lamivudine (3TC) has an effect on hepatitis B virus (HBV) infection, and to study the tolerability and safety of the drugs. HBV infection that lasts for a long time is an important cause of death, occurrence of disease, and a source of potential new infections around the world. Treatment with nucleoside analogue drugs such as 3TC can help inhibit HBV, but these drugs cannot always control the infection for a long period of time. Failure of 3TC to suppress HBV is particularly common in people who are also being treated for human immunodeficiency virus (HIV). To help people whose HBV infections cannot be controlled with 3TC, researchers need to identify and study other anti-HBV drugs. Both ADV and TDF are drugs that can inhibit HBV. This study will compare the combination of ADV and 3TC with the combination of TDF and 3TC to determine which drug combination is most effective in people who are infected with both HBV and HIV. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033163

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An Open-Label Program of Adefovir Dipivoxil in the Treatment of Patients with Lamivudine-Resistant Chronic Hepatitis B With Limited Treatment Options Condition(s): Chronic Hepatitis B Study Status: This study is currently recruiting patients. Sponsor(s): Gilead Sciences Purpose - Excerpt: The purpose of this early access protocol is to provide access to adefovir dipivoxil prior to its commercial availability to people with lamivudineresistant chronic hepatitis B who have limited treatment options. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00042393

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Epidemiology, Infectivity and Natural History of Hepatitis C Virus Infection Condition(s): Hepatitis C Study Status: This study is currently recruiting patients. Sponsor(s): Warren G Magnuson Clinical Center (CC) Purpose - Excerpt: This study will evaluate hepatitis C virus (HCV) infection in blood donors who test positive for antibodies to this virus. Most HCV-infected people do not become ill and are not aware that they have hepatitis or have had it in the past. Some infected people recover completely, whereas others remain chronically infected. The

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study will try to define infectivity of anti-HCV positive individuals, routes of transmission of the virus, and the number of HCV-infected persons who have evidence of liver disease. Blood donors at the NIH Clinical Center or the Central Maryland Chapter of the American Red Cross who test positive for HCV may be eligible for this study. Participants will have a physical examination and history, including questions about socioeconomic status and current sexual practices. They will have 100 milliliters (ml) (6 tablespoons) of blood drawn at the first visit and 50 ml (3 tablespoons) drawn 3, 6, 9 and 12 months after the initial visit. Some participants may undergo plasmapheresis, a procedure for collecting additional plasma (the liquid portion of the blood). For this procedure, whole blood is collected through a needle placed in an arm vein. The blood circulates through a machine that separates it into its components. The plasma is then removed, and the red and white cells and platelets are returned to the body, either through the same needle used to draw the blood or through a second needle placed in the other arm. In some individuals, other body fluids (saliva, urine or semen) may also be collected. Participants may be asked to bring their household contacts and sexual partners to NIH for interview and blood testing for evidence of HCV infection and liver disease. Although this is not required for participation in the study, it would provide additional valuable information. Participants found to have chronic viral infection will be seen more often and will provide additional blood samples for routine medical care. Further medical evaluation may include X-rays or liver scans and referral to a specialist for additional tests or therapy. Ten people in this study will be recruited to participate in a secondary investigation to analyze changes in the level of HCV and the immune response to it, and to relate these changes to the degree of liver damage. In addition to blood collected for the primary study, participants in this investigation will have an additional 50 ml (3 tablespoons) of blood drawn from an arm vein every week for 10 weeks to measure levels of virus, ALT (a liver enzyme), and immune response. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004850 ·

Evaluate Efficacy, Safety and PK of Adefovir Dipivoxil Liquid Suspension in Patients with Chronic Hepatitis B Condition(s): Chronic Hepatitis B Study Status: This study is currently recruiting patients. Sponsor(s): Gilead Sciences Purpose - Excerpt: This is a multi-center phase 3, open-label, parallel-group study designed to evaluate the efficacy, safety and pharmacokinetics of adefovir dipivoxil liquid suspension in patients with chronic hepatitis B and varying degrees of renal impairment. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00071201

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Gamma Interferon Therapy for Chronic Hepatitis C Condition(s): Chronic Hepatitis C

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Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: This study will test whether gamma interferon is effective in treating chronic hepatitis C infection-a long-lasting viral infection affecting the liver. One-third of patients with hepatitis C infection develop cirrhosis of the liver, which can lead to liver failure or liver cancer. The current treatment for hepatitis C infection is pegylated alpha interferon (peginterferon) plus ribavirin; however, this treatment is successful in only about half of patients. Gamma interferon works similarly to alpha interferon, but through different pathways, and therefore might be helpful in patients who do not respond to alpha interferon. Patients 18 years of age and older with chronic hepatitis C infection, genotype 1, who did not respond to alpha interferon and ribavirin therapy may be eligible for this study. (Genotype 1 is a strain of hepatitis C virus that has a lower treatment success rate.) Potential participants will be admitted to the NIH Clinical Center for 2 to 3 days for a medical evaluation to determine eligibility for the study and, if enrolled, to begin gamma interferon therapy. Screening will include a medical history and physical examination, blood and urine tests, and possibly chest X-ray, abdominal ultrasound, and psychiatric evaluation. Participants will receive injections of gamma interferon under the skin 3 times a week for 4 weeks (a total of 12 injections). They will be randomly assigned to receive either 100 or 200 micrograms of drug per injection. Blood will be drawn just before the first injection and then 6, 12, 24 and 48 hours later to monitor changes in the levels of hepatitis C virus and immune responses to treatment. The amount and rapidity of decrease in virus will be compared with what occurs with alpha interferon treatment to define the relative effectiveness of gamma interferon. (Patients may leave the hospital at any time after the first day, but must return in time for the final blood test.) Patients will be seen in the clinic each week during treatment to report symptoms and drug side effects and to have blood drawn for routine tests and viral levels. After the 4-week treatment is completed, patients will return for follow-up visits at weeks 6 and 8 for routine blood tests. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00028275 ·

Genetics of Hepatitis C Virus Infection Condition(s): Hepatitis C; Liver Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: The course of hepatitis C varies among people infected with the virus. Some people respond to treatment while many do not; some recover completely while others remain chronically infected; and among those who remain infected, some have mild symptoms while others' symptoms are severe. This study will look for genetic factors that may contribute to these differences. Children over 2 years of age and adults with hepatitis C virus infection or with other kinds of liver disease (such as hepatitis B virus infection, primary biliary cirrhosis, Wilson's disease and others), and normal volunteers may be eligible for this study. Participants will provide 40 to 60 centiliters (1 to 2 ounces) of blood. DNA will be isolated from the white blood cells for analysis of genes involved in certain immune functions. The genetic findings from patients with hepatitis C, patients with other forms of liver disease, and normal volunteers will be

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compared to try to learn how the differences may influence the symptoms and course of hepatitis C and to understand how the virus causes disease. The results of this study may provide information useful for developing a vaccine and better treatments for hepatitis C. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005657 ·

Hepatitis C Antiviral Resistance in African-Americans Condition(s): Hepatitis C Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: This study is designed to test the hypothesis that African-Americans respond less well to combination pegylated interferon and ribavirin therapy than Caucasian-Americans who have chronic hepatitis C genotype 1 and who were not previously treated with either interferon or ribavirin. Reasons for differences in response, regardless of race, will be studied. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00038974

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Hepatitis C: Grading and Staging by MR Condition(s): Hepatitis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: To compare MR imaging findings with biopsy for grading and staging early hepatitis C. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00059397

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Immune Response to Hepatitis C Virus Condition(s): Hepatitis C Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: This study will identify and characterize immune factors involved in hepatitis C infection and elimination of the virus. Individual responses to hepatitis C infection vary; some people are able to eliminate the virus, whereas others remain chronically infected. This study may identify factors important in preventing infection that may be of help in developing a vaccine or more effective treatments. People over 18 years old who have been exposed to hepatitis C virus may participate in this study. Subjects will be recruited from the National Institutes of Health, Inova Fairfax Hospital,

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Occupational Medical Services-IDP P.C., Washington Hospital Center and Holy Cross Hospital, all in the Washington, D.C. metropolitan area. Individual patients from other centers will also be recruited on a case by case basis. Participants will have 40 to 60 cc (1 to 2 ounces) of blood drawn at seven intervals. The first collection will be as soon as possible after exposure to hepatitis C virus and then again at 2, 4, 6, 12, 24, and 48 weeks after exposure. The white blood cells will be studied for their response to the virus, and markers for infection will be followed. If infection develops, additional samples of blood may be requested, and patients will be offered evaluation for treatment. Test results will be kept confidential and will not be entered into any medical records. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006301 ·

Lamivudine and Adefovir to Treat Chronic Hepatitis B Condition(s): HBV; Hepatitis B; Hepatitis; Liver Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: This study will evaluate the safety and effectiveness of lamivudine plus adefovir versus adefovir alone to treat chronic hepatitis B infection. The Food and Drug Administration has approved lamivudine for the treatment of hepatitis B. However, the drug is not effective in all patients, and many of those in whom it initially works develop resistance after 1 to 3 years. Adefovir is an experimental drug that inhibits replication of the hepatitis B virus (HBV). Adefovir used alone may be adequate to provide sustained suppression of the virus and improvement in liver disease. However combining two anti-viral agents may be superior to using one alone, similar to the strategy employed for the treatment of AIDS. This study will test whether the combination of lamivudine and adefovir is better than adefovir alone for the treatment of chronic hepatitis B. Patients 18 years of age and older, who have been infected with HBV for at least 6 months, may be eligible for this study. Candidates may not have received lamivudine treatment in the past 6 months or prior treatment with adefovir and must not be taking other anti-viral treatments for their hepatitis. They will have a blood test to confirm HBV infection. Participants will be admitted to the NIH Clinical Center for 2 to 3 days for a medical evaluation, including a history and physical examination, blood and urine tests, 24-hour urine collection, chest X-ray, electrocardiogram (EKG), abdominal ultrasound and a liver biopsy if one has not been done within the last year. This procedure involves obtaining a small sample of liver tissue through a needle placed in the liver. One to 2 weeks after the evaluation, patients will be randomized to begin taking 100 milligrams/day of lamivudine and 10 mg/day of adefovir, both in pill form or 10 mg of adefovir alone. Therapy will continue for at least 12 months. Follow-up clinic visits will be scheduled weekly for the first month, then every 4 to 8 weeks for the rest of the treatment period. The visits will involve a history and physical examination and blood tests. At the end of 1 year, patients will be evaluated in the Clinical Center with the same tests done at the beginning of the study. Patients who have not improved with treatment will stop taking the treatment and will be evaluated in the clinic once every 4 weeks for another 6 months. Patients who show an improvement in their liver injury may continue taking lamivudine and adefovir or adefovir alone for 4 more years, as long as they continue to improve with the medication. Progress will be evaluated with blood tests for HBV levels and liver enzymes. If the test results show no continued improvement or are negative for hepatitis

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B antigens, therapy will be stopped. Patients who continue treatment for 5 years will be readmitted at year 4 to the Clinical Center for another medical evaluation and liver biopsy to assess the effects of treatment at that time. After the 5 years all patients will stop therapy at and be followed with regular clinic visits for at least 6 months. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00023309 ·

Long-Term Therapy with Ribavirin for Chronic Hepatitis C Condition(s): Chronic Hepatitis C Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Chronic hepatitis C is a disease of the liver caused by the hepatitis C virus. The disease can be serious and even fatal. Approximately 25% of patients with chronic hepatitis C will develop cirrhosis and some of these patients will develop cancer of the liver or liver failure. Presently the disease is treated with a combination of alpha interferon or peginterferon (antiviral and immune stimulating drugs) and ribavirin (an antiviral drug). Alpha interferon is given by injection three times a week whereas peginterferon is given by injection only once a week. Ribavirin is given as a tablet by mouth twice a day. The combination therapy is given for 6 to months. About half of the patients given these medications will receive a lasting benefit and many patients do not respond well to the combination therapy. This study will select up to 50 patients will chronic hepatitis C who have not responded to combination therapy or who could not stand the side effects associated with interferon or peginterferon therapy. These subjects will be evaluated and undergo liver biopsy to determine their present liver condition. If selected as subjects they will be started on single drug therapy with ribavirin. The drug will be given orally twice a day at a dose based on the patient's body weight. The patients will be followed on an out-patient basis. They will we asked to return for regular check-ups and blood tests every 2 to 8 weeks for the duration of the study. After 6 months, the medication will be stopped or adjusted based on the results of the subject's blood tests (liver enzymes). A response is considered if a decrease of 50% or more of the initial liver enzyme (alanine aminotransferase, ALT) is noted. A complete response will be considered if liver enzymes return to normal levels. Therapy will be discontinued after 6 months if patients do not respond. However, patients that respond to the single drug therapy will continue to receive the medication at a decreased dose. The patients will remain on an appropriate dose for up to 8 years with repeat liver biopsies at 2, 4 and 8 years to assess progress. This study will determine if long-term therapy with ribavirin is safe and effective. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001854

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Low-Dose Peginterferon and Ribavirin to Treat Chronic Hepatitis C in Patients Infected with HCV Genotype 2 or 3 Condition(s): Hepatitis C Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: This study will examine the effectiveness of low-dose peginterferon and ribavirin therapy for certain patients with chronic hepatitis C-a liver disease that, in some patients, can progress to cirrhosis of the liver, liver cancer, and liver failure. This disease is caused by the hepatitis C virus (HCV). There are six major strains, or genotypes, of HCV. Patients infected with genotypes 2 and 3 respond better and more quickly to the standard treatment for this disease-high-dose peginterferon and ribavirin for 24 to 48 weeks-than do patients with other genotypes. Although the side effects of these medications are more severe at higher doses, patients with all genotypes, including genotypes 2 and 3, currently receive the same standard treatment. This study will examine whether patients infected with HCV genotypes 2 and 3 will respond equally well, and with fewer side effects, to lower doses of peginterferon and ribavirin given for a shorter period of time. Patients 18 years of age and older with chronic hepatitis C genotype 2 or 3 may be eligible for this study. Each candidate will be screened with a medical history, physical examination, blood tests, and liver ultrasound. Patients who have not had a chest x-ray or electrocardiogram within a year of entering the study will have those tests as well. Additional tests, such as eye examination, hearing test, stress test, or others, will be done if deemed necessary because of the individual's particular medical condition or risk factors for side effects of therapy. Participants will be admitted to the NIH Clinical Center for 1 day for supervised administration of the first doses of peginterferon and ribavirin and 24-hour observation. The treatment regimen consists of two capsules of ribavirin twice a day every day and an injection of peginterferon under the skin once a week. Patients will return to the clinic at 2, 4, 8, 12, 16, 20 and 24 weeks after the first dose of therapy for a brief medical history and physical examination, blood test, and check on hepatitis symptoms and treatment side effects. Women capable of becoming pregnant will also have a pregnancy test at each visit. Patients will be tested for HCV levels after 12 weeks of therapy. Those who are negative for the virus at that time will continue therapy for another 12 weeks to insure that the response lasts. They will be monitored during that time and re-tested for the virus at the end of that period. Patients who do not respond to treatment after 12 weeks will stop low-dose therapy and be offered the higher-dose standard treatment for 48 weeks. Patients who responded after 12 weeks and completed 24 weeks of therapy but subsequently became positive after stopping treatment will also be offered standard high-dose treatment for the full 48-week regimen. Patients on high-dose therapy will return to the clinic every 4 weeks during the 48-week course for evaluation and blood tests. Patients who remain positive for HCV after 24 weeks of high-dose therapy will stop treatment, as a response is unlikely to occur beyond that time. After treatment, patients will return to the clinic at 4- to 8-week intervals for evaluations until 6 months. At 6 months, they will have a series of blood and urine tests and ultrasound of the liver. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056862

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Peginterferon alpha-2b And Ribavirin to Treat Hepatitis C in HIV-Infected Patients Condition(s): Hepatitis C; HIV Infections Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will evaluate the safety and effectiveness of combination therapy with peginterferon alpha-2b and ribavirin for treating hepatitis C virus (HCV) infection in HIV-infected patients. In studies of patients with hepatitis C alone, interferon alpha-2b plus ribavirin treatment eradicated the HCV in almost half the patients. Peginterferon alpha-2b is a compound that results from attaching a polyethylene glycol molecule to interferon alpha-2b. This compound stays in the blood longer than unmodified interferon alpha-2b, causing a higher blood concentration and thus maintaining activity against the hepatitis C virus. HIV-infected patients 21 years of age and older with chronic hepatitis C infection and a viral load greater than 2000 copies/mL may be eligible for this 2 1/2-year study. Candidates will be screened with blood and urine tests and possibly a liver biopsy, if a recent one is not available. The liver biopsy is done to determine the severity of liver disease. For this test, patients are admitted to the NIH Clinical Center for 1 to 2 days. A sedative is injected into an arm vein, the skin in the area over the biopsy site is numbed with a local anesthetic, and a needle is inserted rapidly into and out of the liver to obtain a small tissue sample. The patient remains in the hospital overnight for monitoring. A chest X-ray, electrocardiogram (EKG) and liver ultrasound are also done. Within 4 weeks of the screening tests, candidates who appear eligible for the study will have a physical examination, medical history and repeat blood tests. Women who can become pregnant will have serial pregnancy tests throughout the study. Patients who meet the study criteria and decide to participate will begin treatment with weekly injections under the skin of peginterferon alpha-2b and take ribavirin pills twice a day by mouth. In addition, patients will continue to take all other medications prescribed by their doctor. Clinic visits will be scheduled as follows: - Days 1, 3, 5, 7, 10 and 21 - Blood will be drawn for safety tests and to measure blood levels of HIV and HCV. - Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 52, 56 and 64 - Blood and urine tests will be done to determine the side effects of treatment and its effect on the HCV infection. - Week 48 or end of treatment - Treatment will stop after 48 weeks. At this time, or earlier for those who do not complete the 48 weeks, patients will return to the clinic for a routine clinic visit, blood tests (including tests for hepatitis B and D) and abdominal ultrasound. Patients will be hospitalized for 2 days for a repeat liver biopsy. - Week 72 and extended follow-up visits - At week 72, patients will return for blood tests and a routine clinic visit. HCV viral load will be measured. Follow-up visits every 3 months for an additional year will include a blood test to measure HCV viral load and a complete physical examination. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018031

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Peg-Intron for Prevention of Disease Progression in Chronic Hepatitis C Patients with Cirrhosis who failed with a Interferon plus Ribavirin Therapy Condition(s): Chronic Hepatitis C; Cirrhosis Study Status: This study is currently recruiting patients.

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Sponsor(s): Schering-Plough Purpose - Excerpt: The objective of the study is to evaluate the safety and efficacy of PEG-Intron vs. no treatment for the prevention of disease progression in adult subjects with compensated cirrhosis secondary to chronic hepatitis C, who failed to respond to therapy with an a interferon plus ribavirin. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00048724 ·

PEG-Intron for Prevention of Disease Progression in Chronic Hepatitis C Patients with Significant Liver Fibrosis who failed PEG-Intron plus Rebetol in Protocol P02370 Condition(s): Chronic Hepatitis C; Liver Fibrosis Study Status: This study is currently recruiting patients. Sponsor(s): Schering-Plough Purpose - Excerpt: The objective of the study is to evaluate the safety and efficacy of PEG-Intron vs. no treatment for the prevention of fibrosis progression in adult subjects with moderate to severe liver fibrosis secondary to chronic hepatitis, who failed PEGIntron plus Rebetol treatment in protocol P02370. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049842

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Pegylated Interferon to Treat Chronic Hepatitis D Condition(s): Hepatitis D Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: This study will evaluate the safety and effectiveness of a long-acting form of alpha interferon called pegylated interferon in treating hepatitis D virus (HDV) infection. HDV only infects people who already have hepatitis B infection. HDV is often severe and progressive. Alpha interferon is the standard treatment for HDV, given by injection once a day or three times a week for up to 12 months. However, this treatment does not work for everyone, and those who respond usually relapse when the drug is stopped. The sustained-release form of the drug, pegylated interferon, is given just once a week. Pegylated interferon is more effective than standard interferon in hepatitis C patients, with patients experiencing longer-term improvement. This study will evaluate the effects of pegylated interferon on hepatitis D and hepatitis B. It will determine whether long-term therapy with this drug improves inflammation and scarring of the liver, thereby delaying or reversing cirrhosis, and whether the improvement can be maintained. Patients with chronic hepatitis D over 6 years old may be eligible for this study. Participants will have a medical evaluation, including a history and physical examination, blood tests, routine urinalysis and 24-hour urine collection. Chest X-ray, electrocardiogram, abdominal ultrasound and liver biopsy will be done if these tests

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have not been done within the last year. In addition, depending on their age and individual health status, some patients may have exercise stress testing, an eye examination, hearing test, and psychiatric consultation. All patients will fill out a healthrelated quality of life questionnaire. Patients will receive pegylated interferon by injection once a week and have blood tests to measure the effects of treatment on the liver and on HBV and HDV levels. The medical examination and liver biopsy will be repeated at the end of 12 months. Patients who improved with treatment may continue therapy long-term. Medical evaluations and liver biopsies will be repeated at 3 years and at 5 years. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00023322 ·

Rituximab to Treat Hepatitis C-Associated Cryoglobulinemic Vasculitis Condition(s): Hepatitis C; Vasculitis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will examine the safety and effectiveness of the drug Rituximab in treating hepatitis C-associated cryoglobulinemic vasculitis. About 5 percent of patients with hepatitis C develop cryoglobulinemic vasculitis. This syndrome, characterized by inflammation of blood vessels (vasculitis), may involve the skin, joints, kidneys, nerves and other sites, and cause skin rashes, joint pain, weakness, fatigue, and numbness. About 10 to 30 percent of patients develop kidney disease, which, in some cases, can lead to kidney failure. Although the cause of cryoglobulinemic vasculitis is not known, a critical component is the presence of cryoglobulins-abnormal proteins that white blood cells called B lymphocytes produce in response to the chronic hepatitis C infection. Rituximab decreases the number of B cells. The Food and Drug Administration approved Rituximab in 1997 for the treatment of B-cell non-Hodgkin's lymphoma. Patients between 18 and 75 years of age with hepatitis C and signs and symptoms of cryoglobulinemic vasculitis may be eligible for this study. They must have failed, or been unable to tolerate, treatment with IFN-a and ribavirin. Candidates will be screened with a history and physical examination, electrocardiogram (ECG), blood and urine tests, 24-hour urine collection and chest X-ray, if clinically indicated. Participants will be randomly assigned to receive Rituximab upon entering the study or 6 months after entering the study. Those whose treatment is delayed 6 months will be followed once a month at NIH for disease evaluation and blood tests during that time. Patients will be given Rituximab intravenously (through a vein) once a week for 4 weeks. For the first dose, patients will be admitted to the hospital for at least 24 hours after the infusion for monitoring. Subsequent infusions will be given on an inpatient or outpatient basis, depending on how the infusion is tolerated. The day before each infusion they will have a history and physical examination, blood work, and other tests, such as X-rays, as clinically indicated. After the four infusions, patients will be followed for drug side effects and response to treatment. They will have blood tests every week for 4 weeks and will then return to NIH for 1 day every month for 12 months for a physical examination, blood tests, and X-rays, if medically indicated. Visits may be more frequent, if necessary, and patients may be asked to stay longer than a day if test findings require further investigation. Patients whose cryoglobulinemic vasculitis

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improves and remains inactive for 12 months after completing Rituximab therapy will have completed the study. Those who benefit from treatment but have a later worsening of disease may receive a second course of four infusions, with follow-up for 12 months after the last infusion. Patients who do not respond to treatment and whose disease worsens will be advised of other treatment options, but will be asked to return to NIH monthly for 12 months for follow-up. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00029107 ·

Study of FK788 in Subjects with Chronic Hepatitis C Virus Infection Condition(s): Hepatitis C Study Status: This study is currently recruiting patients. Sponsor(s): Fujisawa Healthcare, Inc. Purpose - Excerpt: The purpose of this study is to assess the safety, tolerability and pharmacokinetics of 4 weeks therapy with FK788 in subjects with chronic hepatitis C virus (HCV) infection. Also, to assess the effect of FK788 on serum ALT concentration and hepatitis C viral level during therapy and for four weeks following therapy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00047814

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The Impact of HAART on Response to Hepatitis C Treatment in Patients Taking Peginterferon alpha-2b and Ribavirin Condition(s): HIV Infections; Hepatitis C Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will evaluate how controlling HIV infection with HAART (highly active antiretroviral therapy) affects the response to hepatitis C treatment with peginterferon alpha-2b and ribavirin in HIV-infected patients with chronic hepatitis C. HIV worsens liver disease caused by hepatitis C. Since treatment of HIV infection with HAART improves immune function, it may be beneficial to start HAART before treating HCV. HIV-infected patients 18 years of age and older with chronic hepatitis C infection may be eligible for this study. Patients must have an HCV viral load greater than 2000 copies/mL and a CD4 count that is either more than 500 cells/mm3, or more than 350 cells/mm3 with an HIV viral load no greater than 40,000 particles/mL. Candidates will be screened for current or previous diseases, conditions or treatments that may exclude them from this study. Screening includes a medical history and physical examination, eye examination, blood and urine tests, chest X-ray, electrocardiogram (EKG), liver ultrasound, and, possibly, a liver biopsy, if a recent one is not available. The liver biopsy is optional and is done to determine the severity of liver disease. Patients will be sedated for this test. The skin in the area over the biopsy site is numbed with a local anesthetic, and a needle is inserted rapidly into and out of the liver to obtain a small tissue sample.

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Patients remain in the hospital overnight for monitoring. Women of childbearing age will have a pregnancy test. Patients enrolled in the study will be randomly assigned to one of the following treatment groups: 1) pegylated interferon and ribavirin for 48 weeks (control group); or 2) HAART for 6 months, followed by 48 weeks of pegylated interferon and ribavirin. HAART group - Patients taking HAART will be followed in the clinic every 2 weeks for the first month and then monthly for the next 5 months. After 6 months of HAART they will begin taking pegylated interferon and ribavirin and will follow the dosing and follow-up schedule outlined below for patients in the control group. Control group - Patients will have weekly injections under the skin of peginterferon alpha-2b and ribavirin pills daily by mouth. Clinic visits will be scheduled as follows: - Days 1, 3, 7, and 21 - Blood will be drawn for safety tests and to measure blood levels of HIV and HCV. HCV medications will be injected on days 7 and 21. Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 52, 56, and 64 - Blood and urine tests will be done to determine the side effects of pegylated interferon and ribavirin treatment and its effect on the HCV infection. Eye examinations will be done every 3 months. - Week 48 or end of treatment - Treatment with pegylated interferon and ribavirin will stop after 48 weeks. At this time (or earlier for those who do not complete the 48 weeks of treatment), patients will return to the clinic for a routine visit, blood tests (including a test for hepatitis B) and abdominal ultrasound. Patients may also be hospitalized for 2 days for a repeat optional liver biopsy. - Week 72 and extended follow-up visits - At week 72, patients will return for blood tests and a routine clinic visit. HCV viral load will be measured. Follow-up visits every 3 months for an additional year will include a blood test to measure HCV viral load and a complete physical examination. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00031343 ·

Thymosin Plus PEG-Interferon in Hepatitis C Patients with Cirrhosis Who Did Not Respond to Interferon or Interferon Plus Ribavirin Condition(s): Hepatitis C; Hepatitis C, Chronic Study Status: This study is currently recruiting patients. Sponsor(s): SciClone Pharmaceuticals Purpose - Excerpt: Chronic hepatitis C infection is one of the leading causes of chronic liver disease in the United States. Approximately one-third of patients with hepatitis C infection develop cirrhosis of the liver, which can lead to liver failure or liver cancer. The current treatment for hepatitis C infection in previously untreated patients is successful in only about half of patients. There is no established therapy for non-responders. This is a randomized, double-blinded, multicenter trial to determine the effectiveness of thymosin alpha 1 (thymalfasin) 1.6 mg twice weekly plus PEGinterferon alfa-2a 180 ug/wk compared to placebo plus PEGinterferon alfa-2a in adults with chronic hepatitis C with early cirrhosis or progression to cirrhosis who are non-responders to previous treatment with interferon or interferon plus ribavirin. The definition of non-response requires a positive HCV RNA test at the end of a course of at least 12 weeks of therapy. Patients will receive treatment for 12 months, and will be followed-up for a further 6 months after the end of therapy Phase(s): Phase III Study Type: Interventional

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00039962 ·

Treatment of Hepatitis B Virus (HBV) Before Beginning Anti-HIV Drugs in Patients with Both HBV and HIV Condition(s): HIV Infections; Hepatitis B Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will evaluate the drug telbivudine (LdT) for treatment of hepatitis B virus (HBV) in HIV infected patients. Patients will take telbivudine alone for 24 weeks, add anti-HIV drugs for 24 weeks, then stop taking telbivudine while continuing their anti-HIV drug regimen. To enroll in this study, patients must not be taking any anti-HIV drugs and cannot have taken more than 31 days of treatment with lamivudine (3TC), protease inhibitors (PIs), or nonnucleoside reverse transcriptase inhibitors (NNRTIs). Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00051090

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A Comparison of the Effectiveness, Safety, and Tolerability of Two Different Hepatitis C Treatments in Patients Infected with Both HIV and Hepatitis C Virus (HCV) Condition(s): HIV Infections; Hepatitis C Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to see if treatment with PEG-interferonalfa-2a (PEG-IFN) plus ribavirin is a more effective treatment for hepatitis C virus (HCV) than interferon-alfa-2a (IFN) plus ribavirin for patients infected with both HCV and HIV. The study will also compare the 2 regimens to see which has fewer side effects. HCV infection is common in patients infected with HIV. Patients infected with both HIV and HCV viruses seem to have more severe hepatitis C. A combination of IFN and ribavirin has been shown to lessen the severity of HCV. PEG-IFN is a modified form of IFN that stays in the blood longer, which means that patients would not have to take the treatment as often. This study will compare the safety and effectiveness of PEG-IFN to IFN when each is combined with ribavirin. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00008463

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A Phase III Study of Entecavir vs Lamivudine in Adults with Chronic Hepatitis B Infection and negative for Hepatitis B e Antigen Condition(s): Chronic Hepatitis B Study Status: This study is no longer recruiting patients.

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Sponsor(s): Bristol-Myers Squibb Purpose - Excerpt: The purpose of this clinical research study is to assess the safety and effectiveness of entecavir, as compared to lamivudine, in the treatment of adults with chronic hepatitis B infection who are hepatitis B e antigen negative. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00035789 ·

A Phase III Study of Entecavir vs Lamivudine in Adults with Chronic Hepatitis B Infection and Positive for Hepatitis B E Antigen Condition(s): Chronic Hepatitis B Study Status: This study is no longer recruiting patients. Sponsor(s): Bristol-Myers Squibb Purpose - Excerpt: The purpose of this clinical research study is to assess the safety effectiveness of entecavir, as compared to lamivudine, in the treatment of adults with chronic hepatitis B infection who are hepatitis B e antigen positive. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00035633

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A Safety Study to Evaluate 12 Weeks of Treatment with Clevudine in Patients Infected with Hepatitis B Virus. Condition(s): Hepatitis B Study Status: This study is no longer recruiting patients. Sponsor(s): Triangle Pharmaceuticals Purpose - Excerpt: The purpose of the study is to evaluate the safety and effectiveness of 12 weeks of treatment with clevudine, at one of three doses, in patients chronically infected with hepatitis B virus. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00044135

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Adefovir Dipivoxil to Treat Hepatitis B in HIV-Infected Patients Condition(s): Hepatitis B; HIV Infection Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will evaluate the safety and effectiveness of adding the experimental drug adefovir dipivoxil to lamivudine for treating hepatitis B virus (HBV) infection in HIV-infected patients with liver cirrhosis. Adefovir inhibits HBV by

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interfering with replication of the virus's genetic material. In some people, the drug has been active against strains of HBV that are resistant to lamivudine; it may also have some activity against HIV. HIV-infected patients 21 years of age and older with chronic hepatitis B infection and liver cirrhosis who have received lamivudine treatment for at least 1 year may be eligible for this 48-week study. Candidates will be screened with a complete medical history, blood tests and a 24-hour urine collection. Blood tests include HLA typing (a test of genetic markers on white blood cells that permit specialized immunology studies). Within 4 weeks, candidates who appear eligible for the study will have a physical examination and medical history, an abdominal ultrasound (imaging test using sound waves) to check for cancer of the liver, chest X-ray and electrocardiogram (EKG). Blood and urine tests will also be done, and women who can become pregnant will have a pregnancy test. Patients who meet the study criteria and decide to participate will then start treatment with one 10-mg adefovir pill per day by mouth. In addition, patients will continue to take all other medications prescribed by their doctor. Follow-up clinic visits will be scheduled as follows: - Days 1, 3, 5, 7, 10 and 21 - Blood will be drawn for specialized immunology tests and to measure blood levels of HIV and HBV. - Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 - Blood and urine (single sample) tests will be done to determine the side effects of adefovir and its effect on the HBV infection. - Week 48 or early termination (end of study) - Blood tests (including tests for hepatitis C and D), abdominal ultrasound and a 24-hour urine collection to evaluate kidney function will be done. - Monthly visits beyond week 48 - Based on the HBV response to treatment and the availability of the drug from the sponsor, patients may be offered to extend their treatment with adefovir. Those who continue will have monthly follow-up visits for blood and urine (single sample) tests. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00013702 ·

Interleukin-2 (IL-2), Pegylated Interferon (PEG-IFN alfa-2b), and Ribavirin (RBV) Treatment in Patients with Hepatitis C and HIV Coinfection Condition(s): HIV Infections; Hepatitis C Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will test the safety and effectiveness of a new treatment for hepatitis C (HCV) in patients who also have HIV. The usual treatment for HCV in people who are not HIV-infected is interferon-alfa (IFN) with ribavirin (RBV), an approved treatment by the Food and Drug Administration (FDA). This study will use a new, longer acting form of IFN called PEG-IFN alfa-2b. PEG-IFN alfa-2b is approved by the FDA for use in treating HCV but has not yet been approved for use with RBV. This study also will use IL-2, which is a substance that the body naturally produces. People with HIV infection usually do not make enough IL-2. IL-2 is being tested in this study to see if it will "boost" the immune system's response to HCV. The FDA has approved IL-2 for the treatment of some cancers. (The name PEG-IFN alfa-2b was changed from PEGINTRON.) Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00015652

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Lamivudine and Adefovir to Treat Chronic Hepatitis B Infection in People With and Without HIV Infection Condition(s): HIV Infections; Chronic Hepatitis B Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will evaluate the safety and effectiveness of adefovir plus lamivudine for chronic hepatitis B infection in people with and without HIV infection. Lamuvidine, an FDA-approved treatment for hepatitis B infection, also works against HIV. In some patients, the hepatitis B virus (HBV) continues to reproduce despite lamivudine treatment. Adefovir is an experimental drug that inhibits HBV replication and may work against some strains of the virus that have become resistant to lamivudine. Patients 21 years of age or older with active hepatitis B infection despite treatment with lamivudine for at least 1 year may be eligible for this 48-week study. Patients both with or without HIV infection may participate. Candidates will be screened with a medical history, blood and urine tests, liver ultrasound exam, electrocardiogram (EKG) and chest X-ray. Participants will have a physical examination, review of their medical history, blood tests, and a 24-hour urine collection. They will be admitted to the hospital for a liver biopsy to determine if they can receive the study drug. For this procedure, the patient is given a sedative for relaxation. The skin over the biopsy is numbed with an anesthetic and the biopsy needle is passed rapidly into and out of the liver to collect a tissue specimen. Patients are monitored in the hospital overnight for possible complications. After discharge, they return home and begin taking the study medications. Patients will be randomized to two treatment groups. One group will take 10 milligrams/day of adefovir by mouth, and the other will take a placebo-a lookalike pill with no active ingredient. Both groups will also take 150 mg lamivudine by mouth and L-carnitine pills or liquid. Patients with HIV infection will continue to take antiretroviral therapy as well. Patients will be followed in the clinic at study weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44 for blood and urine tests to determine the safety of the drug and to evaluate the response to treatment. On week 48, a repeat 24-hour urine test and repeat liver biopsy will be done. At the end of the 48 weeks, patients may continue to receive adefovir for another 48 weeks and possibly longer. All those who participate in this extension phase will receive active adefovir, regardless of whether they had previously taken adefovir or placebo. All patients will have the option to enroll in a separate study to examine the levels of HBV (and levels of HIV in HIV-infected patients) in the blood immediately after starting treatment and to determine if these initial levels can predict later outcome. This involves seven additional visits, for which participants will be compensated. At these visits, blood will be drawn on study days 0 (before starting drug treatment), 1, 3, 5, 7, 10 and 21 for HIV and HBV viral loads and specialized immunology tests. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00023153

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Lamivudine for Chronic Hepatitis B Condition(s): Chronic Polyarteritis Nodosa

Hepatitis

B;

Chronic

Hepatitis

Study Status: This study is no longer recruiting patients.

D;

Glomerulonephritis;

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Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Chronic hepatitis B is a disease of the liver caused by the hepatitis B virus. It affects nearly 1 million Americans. Approximately 25% of patients with chronic hepatitis B will develop liver cirrhosis and 5% of patients will develop liver cancer. Presently, two medications have been shown effective in the treatment of hepatitis B: lamivudine and alpha interferon. Alpha interferon (an antiviral drug that acts through the immune system) is given by injection once daily or three times a week for four to six months. Lamivudine (also known as 3-thiacytidine: 3TC) is an antiviral medication given as a pill once a day for twelve months. These treatments have been known to provide long-term improvement in one third of patients receiving them. In previous research, the drug lamivudine was shown to stop the growth of the hepatitis B virus and to lead marked decreases in the levels of hepatitis B virus and to improvements in the disease in 50 to 70% of patients. However, once lamivudine therapy was discontinued the virus returned to levels noted before the therapy began. In those studies lamivudine was given for 3 to 12 months then discontinued. This study will investigate the safety and effectiveness of long-term therapy with lamivudine. This study will select 60 patients diagnosed with hepatitis B. After a thorough medical examination and liver biopsy, subjects will be given lamivudine. The drug will be taken by mouth in tablet form (100 mg) once a day for up to 5 years. Subjects will undergo regular check-ups and after 1 year of therapy be admitted to the Clinical Center for another medical examination and liver biopsy to assess progress. Patients who have benefitted from the therapy will continue taking the medication for up to 5 years. A third liver biopsy will be done during the last year of treatment. The effectiveness of lamivudine will be determined by whether levels of hepatitis B virus decrease in the blood, whether liver enzymes improve, and whether inflammation and scarring decreases in the liver biopsies. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001457 ·

Long Term Interferon for Patients Who Did Not Clear Hepatitis C Virus with Standard Treatment Condition(s): Chronic Hepatitis C; Cirrhosis, Liver; Fibrosis, Liver; Hepatic Cirrhosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institute of Allergy and Infectious Diseases (NIAID); National Center on Minority Health and Health Disparities (NCMHD); National Cancer Institute (NCI); Hoffmann-La Roche Purpose - Excerpt: The HALT-C Trial is a National Institute of Diabetes and Digestive and Kidney Diseases sponsored, randomized clinical trial of long-term use of Peginterferon alfa-2a (pegylated interferon) in patients who failed to respond to prior interferon treatment. All patients who enter the trial will be treated for 6 months with Peginterferon alfa-2a and Ribavirin. Patients who respond to this 6 month treatment will continue to be treated for an additional 6 months. Patients who do not respond to this treatment will be eligible for the long-term maintenance phase of this study where patients will be randomly selected to be treated with Peginterferon alfa-2a or to discontinue treatment for 3.5 years. Patients in both arms of this study will be followed

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closely with quarterly study visits. The combination of peginterferon plus ribavirin has recently been approved by the FDA for treatment of chronic HCV. Patients who remain HCV-RNA positive after being treated for at least 6 months with peginterferon and ribavirin outside of this study may be eligible to directly enter the randomized portion of the HALT-C Trial. The HALT-C study is designed to determine if continuing interferon long-term over several years will suppress Hepatitis C virus, prevent progression to cirrhosis, prevent liver cancer and reduce the need for liver transplantation. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006164 ·

Pegylated Interferon and Ribavarin to Treat Chronic Hepatitis C with and without Kidney Disease Condition(s): Hepatitis C Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: This study will examine the effectiveness of pegylated interferon, or peginterferon (a long-acting form of alpha interferon) plus ribavirin in treating hepatitis C (genotype 1) infection with and without kidney disease. (Genotype 1 is a strain of hepatitis C virus that has a lower success rate of therapy.) Combination therapy with alpha interferon and ribavirin is the recommended treatment for hepatitis C infection in patients without kidney disease. However, it is not successful in all patients. An early predictor of who is or is not likely to respond to therapy would allow treatment to be stopped in non-responders within 2 to 4 weeks rather than 6 or 12 months. This study will determine whether early changes in viral levels with treatment predict the ultimate outcome. It will also compare responses in patients without and with kidney disease to better evaluate problems of therapy in the latter group. Ribavirin is not given to people with kidney disease because of possible severe drug side effects. However, because patients with kidney disease are poor treatment responders and because ribavirin increases the success of therapy in patients without kidney disease 2- to 3-fold, however, this study will look for a dose of the drug that can safely be given to patients with kidney disease. Patients 18 years of age and older with hepatitis C, genotype 1, with or without kidney disease may be eligible for this study. Candidates will be screened with a medical history and physical evaluation, blood tests, symptom questionnaires, 24-hour urine collection, chest X-ray, electrocardiogram, and liver ultrasound. A liver biopsy (removal of a small piece of liver tissue) will be done in patients who have not had one within the last year. Additional procedures, such as eye examination, treadmill stress test, hearing test, or others may be required depending on the individual's medical condition. Patients without kidney disease will be randomly assigned to one of two treatment groups: Group A will take both peginterferon (by injection under the skin once a week) and ribavirin (capsules by mouth) from the start of therapy; Group B will start treatment with peginterferon alone and add ribavirin after 4 weeks. Patients with kidney disease (Group C) will start with peginterferon alone and add ribavirin 4 weeks later. All patients will be admitted to the NIH Clinical Center for a few days when treatment starts in order to draw blood at precise intervals (6, 12, 24, 48, and 72 hours after the first peginterferon injection) for measurements of viral levels. Blood will then be drawn once a week for 4 weeks (just before each injection) to determine how rapidly

338 Hepatitis

viral levels decrease with treatment and to measure blood levels of interferon and ribavirin. After 4 weeks of therapy, patients will have a blood test and check of symptoms and side effects every 4 weeks for 24 weeks (every 2 weeks for Group C patients until the optimum ribavirin dose is found) and then every 8 weeks for the remainder of the study. They will have a physical examination and urine test every 12 weeks. Patients will be tested for hepatitis virus RNA after 24 weeks of therapy to determine if they are a responder or non-responder. Responders will be advised to continue therapy for a full 48 weeks to ensure a continued response when treatment stops. Non-responders-whose chances for a lasting response are estimated at only 2%will be offered the option to continue treatment, to stop treatment and continue being followed without treatment, or to enroll in other studies of non-responders. At the end of the 72-week treatment and follow-up, patients will have the same blood and urine tests as were done at the beginning of the study and a repeat liver ultrasound. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00028093 ·

Pneumococcal Vaccine and Routine Pediatric Immunizations in HIV-Infected Children Receiving Anti-HIV Drugs Condition(s): HIV Infections; Hepatitis B; Measles; Pneumococcal Infections; Pertussis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID); National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: The purpose of this study is to determine if 2 doses of Pneumococcal Conjugate Vaccine (PCV) followed by 1 dose of Pneumococcal Polysaccharide Vaccine (PPV) in HIV-infected children on anti-HIV therapy is helpful and safe in fighting pneumococcal infections in this group of children. This study will also look at the protection provided by childhood vaccination against measles, pertussis, and hepatitis B virus. Pneumococcal infections are the most common AIDS-related infection in HIVinfected children. PCV may help reduce the chances of HIV-infected children getting pneumococcal infections. This study will look at whether pneumococcal vaccines are safe and effective in HIV-infected children receiving HAART. It will look at whether HIV-infected children are protected by childhood vaccines received previously and if more doses are safe and improve protection. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00013871

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Prevalence of Hepatitis C Virus Infection in HIV-Infected Children Condition(s): HIV Infections; Hepatitis C Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID); National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: The purpose of this study is to find out how many children who are infected with HIV are also infected with hepatitis C virus (HCV). HCV infection is a

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major health concern. HIV-infected adults who are co-infected with HCV appear to have more rapid HIV disease progression. There is little data on how widespread HCV is among children who are HIV-infected. Information from this study will help determine the need for future HCV studies. This study also will obtain blood samples for future testing for other hepatitis viruses such as hepatitis G virus (HGV or GB virus C). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00037076 ·

Safety and antiviral activity study of ACH-126,443 (beta-L-Fd4C) in treatment naive adults with chronic Hepatitis B Virus infection Condition(s): Hepatitis B, Chronic Study Status: This study is no longer recruiting patients. Sponsor(s): Achillion Pharmaceuticals Purpose - Excerpt: The purpose of this study is to determine the safety and anti-HBV activity of ACH-126, 443 (beta-L-Fd4C) in comparison to lamivudine or placebo in treatment naive adults with chronic Hepatitis B infection. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00034359

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Safety and antiviral study of ACH126, 433 (b-L-Fd4C) in adults with lamivudineresistant chronic hepatitis B Condition(s): Chronic Hepatitis B Study Status: This study is no longer recruiting patients. Sponsor(s): Achillion Pharmaceuticals Purpose - Excerpt: The purpose of this study is to determine the safety and antiviral HBV activity of ACH126, 433 (b-L-Fd4C) in the treatment of adults with lamivudineresistant chronic Hepatitis B. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00040144

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Safety and antiviral study of ACH-126, 443 (beta-L-Fd4C) in the treatment of adults with chronic Hepatitis B infection. Condition(s): Chronic Hepatitis B Study Status: This study is no longer recruiting patients. Sponsor(s): Achillion Pharmaceuticals Purpose - Excerpt: The purpose of this study is to determine the safety and antiviral HBV activity of ACH-126,443 (beta-L-Fd4C) in the treatment of Subjects of Previous Achillion-Sponsored Phase 1 and 2 Studies in Chronic Hepatitis B Infection.

340 Hepatitis

Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00037622 ·

Thymosin Plus PEG-Interferon in Non-Cirrhotic Hepatitis C Patients Who Did Not Respond to Interferon or Interferon Plus Ribavirin Condition(s): Hepatitis C; Hepatitis C, Chronic Study Status: This study is no longer recruiting patients. Sponsor(s): SciClone Pharmaceuticals Purpose - Excerpt: Chronic hepatitis C infection is one of the leading causes of chronic liver disease in the United States. Approximately one-third of patients with hepatitis C infection develop cirrhosis of the liver, which can lead to liver failure or liver cancer. The current treatment for hepatitis C infection in previously untreated patients is successful in only about half of patients. There is no established therapy for non-responders. This is a randomized, double-blinded, multicenter trial to determine the effectiveness of thymosin alpha 1 (thymalfasin) 1.6 mg twice weekly plus PEGinterferon alfa-2a 180 ug/wk compared to placebo plus PEGinterferon alfa-2a in adults with chronic hepatitis C without cirrhosis who are non-responders to previous treatment with interferon or interferon plus ribavirin. The definition of non-response requires a positive HCV RNA test at the end of a course of at least 12 weeks of therapy. Patients will receive treatment for 12 months, and will be followed-up for a further 6 months after the end of therapy. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00040027

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Treatment of Hepatitis C in Hemophilic Patients with HIV Condition(s): HIV Infections; Hepatitis C; Hemophilia Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: Pegylated interferon (PEG-interferon) and ribavirin are accepted treatments for hepatitis C virus (HCV) infection. However, HCV infection progresses differently in patients who are coinfected with HIV and in hemophiliacs. This study will evaluate the effectiveness of PEG-interferon and ribavirin for treating HCV in HIV infected hemophiliacs. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055341

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Treatment of Hepatitis in Patients who are Triple-Infected with HIV, Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV) Condition(s): HIV Infections; Hepatitis B; Hepatitis C Study Status: This study is no longer recruiting patients.

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Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will investigate the safety and effectiveness of using adefovir dipivoxil (ADV), pegylated interferon (PEG-INF), and ribavirin (RBV) in patients triple-infected with hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV. Patients in this study must be taking lamivudine (3TC). Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00051077 ·

A Controlled Prospective Study of Transfusion-Associated Hepatitis Condition(s): Hepatitis Study Status: This study is completed. Sponsor(s): Warren G Magnuson Clinical Center (CC) Purpose - Excerpt: This protocol represents a continuation of a series of prospective studies to define the incidence and etiology of transfusion-associated hepatitis (TAH) and to examine the impact on TAH of various modifications in the selection of blood donors. The primary goal of the study will be to determine TAH incidence after the institution of a variety of interventive measures to exclude hepatitis and AIDS virus carriers: including surrogate assays (ALT, anti-HBc), a specific assay for the hepatitis C virus (HCV), a specific assay for the human immunodeficiency virus (HIV) and intensified donor questioning for high-risk behavior patterns. There is high probability that the exclusion of donors at high risk for AIDS transmission will also exclude donors at high risk for hepatitis transmission. Incidence data obtained in the study will be enhanced by the simultaneous follow-up of a control population undergoing identical surgical procedures, but receiving no blood or only autologous blood. This control population, made possible by the recent dramatic increase in the amount of autologous blood utilized, will allow for a clear distinction between transfusion-associated hepatitis and that due to nosocomial transmission or other background causes of hepatocellular inflammation in cardiac surgery patients. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004848

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A Study to Evaluate the Effects of Anti-HIV Drugs in HIV-Positive Patients Who Also Have Hepatitis C Infection Condition(s): HIV Infections; Hepatitis C Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study evaluates patients infected with both HIV and Hepatitis C virus (HCV) who are receiving anti-HIV drugs. The purpose of this study is to learn more about HCV infection in patients whose HIV blood level decreases to less than 500 copies/ml. Phase(s): Phase II Study Type: Observational

342 Hepatitis

Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001117 ·

Combination Drug Therapy for Patients with Hepatitis C Condition(s): Chronic Hepatitis C; Fibrosis; Hemolytic Anemia Study Status: This study is completed. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Hepatitis C is a major cause of liver disease in the United States and leads to cirrhosis of the liver in approximately one-third of patients some of whom will ultimately suffer from liver failure or liver cancer. At present, the recommended therapy of hepatitis C is the combination of alpha interferon and ribavirin given for 6 to 12 months. Ribavirin is a antiviral drug that is given by mouth. Interferon is both an antiviral and an immune medication which must be given by injections (three times a week) and has many difficult side effects. The purpose of this study is to determine whether the combination of ribavirin and interferon improve the liver disease of hepatitis C and whether improvements can be maintained by continuing ribavirin therapy long-term. This study will take 100 to 120 patients suffering from hepatitis C and place them under combination drug therapy with alpha interferon and ribavirin. The course of drug therapy is scheduled to last 6 to 12 months. Patients will be selected after appropriate screening for hepatitis C virus and elevated liver enzymes are conducted and liver biopsy shows chronic hepatitis with some degree of injury and scarring. During the first 6 months of the study, subjects will be asked to return to the outpatient clinic for routine check-ups and blood tests every 2 to 4 weeks. Blood tests will include tests for hepatitis C virus. If the virus test becomes negative on treatment, the therapy will be considered successful and will be continued for a full 6 or 12 months (depending upon the strain of virus). If the virus test does not become negative during the first six months of treatment, subjects will be considered "non-responders" and will stop taking interferon but will continue on ribavirin alone or an identically appearing placebo tablet. These non-responsive subjects will continue this therapy for an additional 12 months. (A year-and-a-half total). Upon completion of the drug therapies, subjects will be requested to submit blood samples and undergo a liver biopsy to determine if the therapy was successful. Test results that reveal a loss of hepatitis C antibodies or normal levels of liver enzymes will be deemed successful. Patients that have successful laboratory test results will be considered for continuation of ribavirin therapy. Patients that received placebo for a year will be eligible to receive ribavirin long-term at the end of the study. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001729

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Comparing Single Photon Emission Computed Tomography (SPECT) and Liver Biopsy to Evaluate the Liver in Patients with HIV and Hepatitis C Virus Condition(s): HIV Infections; Hepatitis C Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID)

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Purpose - Excerpt: The purpose of this study is to find if the Single Photon Emission Computed Tomography (SPECT) scan is as effective as a liver biopsy (using a special needle to remove tissue from the liver) in examining liver damage in patients with HIV and hepatitis C virus (HCV). A standard way to examine the liver for disease has been to perform a liver biopsy. The SPECT scan, which takes a picture of the liver, has been found to be effective in determining liver damage but studies need to be done in patients with hepatitis. This study will compare the effectiveness of the liver biopsy and SPECT scan in determining liver disease in patients with HIV and HCV. The SPECT scan might be a good replacement for the liver biopsy if it is found to be as good as or better than liver biopsies. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006643 ·

Hepatitis B Vaccine Clinical Trial Condition(s): Hepatitis B; Hepatitis, Viral, Human; Liver Diseases Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the efficacy of a hepatitis vaccine in preventing hepatitis B. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000583

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History of Hepatitis C in Volunteer Blood Donors Condition(s): Hepatitis C Study Status: This study is completed. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Hepatitis C is a disease of the liver caused by the Hepatitis C Virus (HCV). Patients with hepatitis C may feel well and show no signs or symptoms of being ill. However, researchers would like to study the long-term effects of this disease. Volunteer blood donors diagnosed with chronic hepatitis C viral (HCV) and various levels of liver enzyme activity will be offered a complete medical evaluation and liver biopsy. The tests will enable researchers to provide the patients with an idea of how severe their liver disease is. The virus and patient will be studied in order to understand why patients with hepatitis C develop different levels of liver damage. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001982

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Interruption of Maternal-to-Infant Transmission of Hepatitis B by Means of Hepatitis B Immune Globulin Condition(s): Hepatitis B; Hepatitis, Viral, Human; Liver Diseases

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Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To evaluate whether hepatitis B immune globulin with a high level of antibody against the hepatitis B antigen would be capable of interrupting maternal-fetal transmission of hepatitis B virus, the single most important route of hepatitis spread in the entire Third World. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000580 ·

Phase III Randomized Study of High vs Standard Dose of Interferon alfa for Chronic Hepatitis C Condition(s): Hepatitis C Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); Tulane University School of Medicine Purpose - Excerpt: Objectives: I. Determine whether the initial response to interferon alfa (IFN-A) can be increased by starting at a dose of 5 MU three times a week in patients with chronic hepatitis C. II. Determine whether patients who had normalized alanine aminotransferase (ALT) levels can maintain normal ALT during stepwise dose reduction from 5 MU to 3 MU to 1.5 MU. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004804

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Siliphos Treatment for Hepatitis C Disease Condition(s): Hepatitis C, Chronic Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: This study will measure the safety and tolerability of three different doses of IdB 1016 (Siliphos) in patients with hepatitis C disease who have not responded to or are poor candidates for interferon-based therapies. NOTE: THE STUDY WILL ONLY RECRUIT STUDY PARTICIPANTS AT UNIVERSITY OF WASHINGTON MEDICAL CENTER IN SEATTLE Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055445

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The Safety and Effectiveness of a Two-Drug Combination in the Treatment of Patients with Hepatitis C Plus Advanced HIV Infections Condition(s): HIV Infections; Hepatitis C Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID); ScheringPlough Purpose - Excerpt: To investigate the toxicity of interferon alfa-2b ( IFN alfa-2b ) in combination with nucleoside analog therapy in HIV-positive patients with chronic hepatitis C. To determine the efficacy of treatment with IFN alfa-2b for chronic hepatitis C in patients with advanced HIV infections treated with nucleoside analog therapy. IFN alfa-2b has HIV inhibitory properties and has also been approved for treatment of chronic hepatitis C. Studies have shown that IFN alfa-2b is effective in asymptomatic HIV-positive patients with chronic hepatitis C, but the drug's benefit against hepatitis C in patients with advanced HIV infection has not been determined. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001035

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “hepatitis” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: ·

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 6. PATENTS ON HEPATITIS Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “hepatitis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on hepatitis, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Hepatitis By performing a patent search focusing on hepatitis, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We

9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on hepatitis: ·

[1,8] naphthyridine derivatives having antiviral activity Inventor(s): Levesque; Sophie (Mirabel, CA), Siddiqui; Arshad (Dollard Des Ormeaux, CA), Bachand; Benoit (Montreal, CA), Nguyen-Ba; Nghe (Laprairie, CA) Assignee(s): BioChem Pharma Inc. (Quebec, CA) Patent Number: 6,605,614 Date filed: December 27, 2001 Abstract: The present invention is concerned with novel [1,8] naphthyridine derivatives useful for the inhibition of the hepatitis virus, more specifically the hepatitis C virus. Excerpt(s): The present invention relates to heterocyclic compounds, more specifically derivatives of [1,8] naphthyridine, useful for the inhibition of viral infections. The main sources of contamination with HCV is blood. The magnitude of the HCV infection as a health problem is illustrated by the prevalence among high-risk groups. For example, 60% to 90% of hemophiliacs and more than 80% of intravenous drug abusers in western countries are chronically infected with HCV. For intravenous drug abusers, the prevalence varies from about 28% to 70% depending on the population studied. The proportion of new HCV infections associated with post-transfusion has been markedly reduced lately due to advances in diagnostic tools used to screen blood donors. The only treatment currently available for HCV infection is interferon-.alpha. (IFN-.alpha.), either as monotherapy and in combination with ribavirin. However, according to different clinical studies, only 70% of treated patients normalize alanine aminotransferase (ALT) levels in the serum and after discontinuation of IFN, 35t to 45% of these responders relapse. In general, only 40% of patients have long-term responses to IFN/ribavirin combination therapy. On the other hand, pilot studies suggest that combination treatment with IFN plus Ribavirin (RIBA) results in sustained response in the majority of patients. Different genotypes of HCV respond differently to IFN therapy, genotype 1b is more resistant to IFN therapy than type 2 and 3. Web site: http://www.delphion.com/details?pn=US06605614__

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6-methylnicotinamide derivatives as antiviral agents Inventor(s): Park; Sang-Jin (Seoul, KR), Yoon; Sung-June (Seoul, KR), Lee; Jin-Soo (Anyang-si, KR), Lee; Sang-Wook (Anyang-si, KR), Lee; Hak-Dong (Anyang-si, KR), Kim; Nam-Doo (Inchon-si, KR), Park; Hee-Jeong (Anyang-si, KR), Kim; Jong-Woo (Anyang-si, KR), Lee; Geun-Hyung (Anyang-si, KR) Assignee(s): Dong Wha Pharm. Ind. Co., Ltd. (Seoul, KR) Patent Number: 6,608,058 Date filed: October 10, 2002 Abstract: The present invention relates to novel 6-methylnicotinamide derivatives and their pharmaceutically acceptable salts, the process for preparing them, and the pharmaceutical compositions containing said compounds as active ingredients. The 6methylnicotinamide derivatives of the present invention exhibit their inhibitory activity against the proliferation of human immunodeficiency virus (HIV) as well as hepatitis B

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virus (HBV) and hepatitis C virus (HCV), such that they can be used for hepatitis B, hepatitis C and acquired immune deficiency syndrome (AIDS). Excerpt(s): This patent application claims a benefit of priority from Korean Patent Application No. 2000/20137 filed Apr. 17, 2000 and Korean Patent Application No. 2000/31926 filed Jun. 10, 2000 through PCT Application Serial No. PCT/KRO1/00613 filed Apr. 13, 2001, the contents of each of which are incorporated herein by reference. Hepatitis B virus (HBV; referred as "HBV" hereinafter) causes acute or chronic hepatitis, which may progress to liver cirrhosis and liver cancer. It is estimated that three hundred million people are infected with HBV in the world (Tiollais & Buendia, Sci. Am., 264, 48, 1991). There has been much research about the molecular biological characteristics of HBV and their relationship to liver diseases in order to find ways to prevent and treat hepatitis B. Various vaccines and diagnostic drugs have been developed and much effort is being channeled into research to find treatment for hepatitis B. The gene for HBV polymerase comprises 80% of the whole virus genome and produces a protein of 94 kD size with 845 amino acids, which has several functions in the replication of virus genome. This polypeptide includes sequences responsible for activities of protein primer, RNA dependent DNA polymerase, DNA dependent DNA polymerase, and RNase H. Kaplan and his coworkers first discovered reverse transcriptase activities of polymerase, which led to much research in replicating mechanism of HBV. Web site: http://www.delphion.com/details?pn=US06608058__ ·

Adsorbent for eliminating hepatitis C virus, adsorber, and adsorption method Inventor(s): Kaneko; Shuichi (Kanazawa, JP), Asahi; Takashi (Kobe, JP), Ogino; Eiji (Kobe, JP), Sakai; Akito (Kanazawa, JP), Nomura; Michio (Kakogawa, JP) Assignee(s): Kaneka Corporation (Osaka, JP) Patent Number: 6,600,014 Date filed: November 9, 1999 Abstract: An adsorbent for removing hepatitis C virus which has the ability to adsorb HCV particles, particularly immune-complex HCV particles, from a patient's body blood safely and with high efficiency and high selectivity for enhancing the efficacy of interferon therapy, an HCV adsorption apparatus including said adsorbent, and a adsorbing method for removing HCV are provided.An adsorbent for removing hepatitis C virus which comprises a compound capable of adsorbing hepatitis C virus as immobilized on a water-insoluble carrier, an adsorption apparatus including said adsorbent, and an adsorbing method for removing HCV. Excerpt(s): The present invention relates to an adsorbent for removing hepatitis C virus which is capable of selectively adsorbing hepatitis C virus from body fluids such as blood, plasma, etc. to thereby expedite the cure for hepatitis C, an adsorption apparatus including said adsorbent, and an adsorbing method for removing hepatitis C virus. With the successful cloning of the RNA virus genome of hepatitis C virus in 1989 (Q. L. Choo et al.: Science, 244, 359, 1989), it became possible to assay anti-hepatitis C virus antibody using a recombinant protein. As a result, most of the hepatitis termed non-A, non-B hepatitis in the past were found to be hepatitis C. Thus, it is estimated that in Japan today there are about 2,000,000 HCV carriers and, of them, 1,400,000 have chronic hepatitis and 300,000 have cirrhosis (Shiro Iino: Medical Practice in Gastroenterology-2, Hepatitis C, 11-17, 1993). According to the Ministry of Health and welfare demographic statistics, the number of deaths due to primary liver cancer in 1992 was 27 thousand

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(1992 Demographic Statistics, Minister of Health and Welfare Statistical Information Bureau, Vol. 1, 1993) and approximately 70% of the casualties were due to hepatocellular carcinoma associated with hepatitis C virus infection and it is by now considered that this cancer ensues following the progression of chronic hepatitis to cirrhosis (S. Kaneko et al.: Intervirology, 37, 108, 1994; Eiki Matsushita et al.: Japanese Journal of Clinics, 53, 727, 1995 Special Issue). Therefore, hepatitis C can be said to be a refractory disease which progresses to cirrhosis to hepatocellular carcinoma. Web site: http://www.delphion.com/details?pn=US06600014__ ·

Antigenic structural peptide, antigenic and immunogenic compounds, and uses for detecting, preventing and treating an HCV infection Inventor(s): Jolivet; Michel (Bron, FR), Penin; Fran.cedilla.ois (Decines, FR), Dalbon; Pascal (Lyons, FR), Lacoux; Xavier (Lyons, FR), Ladaviere; Laurent (Villeurbanne, FR) Assignee(s): Bio Merieux (Marcy l'Etoile, FR) Patent Number: 6,576,240 Date filed: September 7, 1999 Abstract: The invention concerns a structural peptide, identified by antibodies directed against a polypeptide, comprising the 2-45 amino acid sequence of the N-terminal end of the Core or nucleocapsid (p21) protein of the hepatitis C virus (HCV), excluding any protein or peptide compound comprising or consisting of the N-terminal end. The invention is characterized in that it comprises a tertiary structure consisting of at least a first peptide fragment having a secondary structure in.alpha. helix, a second peptide fragment having secondary structure in.alpha. helix and a third peptide bond fragment linking the two.alpha. helices, these two.alpha. helices being substantially perpendicular to each other in space. This peptide can be used for detecting antibodies directed against the p21 protein of HCV, for detecting all of part of the RNA of HCV and for preparing a diagnostic, prophylactic or therapeutic composition for detecting, preventing or treating an HCV infection. Excerpt(s): The present invention relates to the characterization of an antigenic site belonging to an immuno-dominant multiepitope region located in the N-terminal end of the Core or nucleocapsid protein (or p21 protein) of the hepatitis C virus (HCV), [B. Hosein et al., Proc. Natl. Acad. Sci. USA, 88, 3647-51 (1991)] as well as to the applications resulting therefrom, in particular in the diagnosis, treatment or prevention of an HCV infection. In accordance with the document EP-A-0 569 309, in the name of the Applicant, a peptide is known which extends from the amino acid at position 2 to the amino acid at position 45 of the N-terminal end of the HCV nucleocapsid protein, and whose sequence is identified by SEQ ID NO: 1. This peptide determines an immunodominant region which is sufficient, on its own, for obtaining the same sensitivity and specificity, in terms of detection of antibodies directed against HCV, as with the nucleocapsid protein in its entirety. this immunodominant epitope is of conformational type, and corresponds to a three-dimensional unit of helix-loop or elbow-helix type, in which the two helices are arranged substantially perpendicularly to each other. Web site: http://www.delphion.com/details?pn=US06576240__

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Boraadamantane compounds for the treatment of pathogenic viruses and other medical applications Inventor(s): Chang; Yu-An (3631 Hamilton St., Irvine, CA 92614) Assignee(s): Chang; Yu-An (Irvine, CA) Patent Number: 6,613,507 Date filed: March 21, 2001 Abstract: Methods for treating patients with viral infections and Parkinson's disease with pharmaceutical agents are disclosed. In one embodiment, the viruses are Hepatitis C, Influenza A and B. The Pharmaceutical agents are 1-boraadamantane and the conjugate amines described in this patent application. Excerpt(s): Hepatitis C infection is associated with advanced liver disease (Liang, et al. Hepatology 18:1326-1333, (1993) and Tsukuma, et. al. The New England Journal of Medicine 328:1797-1801 (1993)), and liver failure due to hepatitis C infection is the most common indication for liver transplantation. Currently, the approved treatment for hepatitis C infection is.alpha.-interferon with or without combination of another pharmaceutical agents, e.g. ribavirin. However, many of those responding to these treatments will relapse upon discontinuation of the therapies (Davis, et al. The New England Journal of Medicine 321:1501-1506 (1989) and Di Bisceglie, et al. The New England Journal of Medicine 321:1506-1510 (1989)). Most of the patients who are retreated will again relapse if these drugs were withdrawed (Tine et al. Journal of Hepatology 13:192-199 (1991)). For those patients who do not respond to the initial interferon therapies, heavier dose treatments only produced little positive results. Significant increase of side effects has been observed on those patients treated with high dose regiments (Poynard et al. New England Journal of Medicine 332:1457-1462 (1995)). The low response rate and significant positive synergistic effect of combination of.alpha.-interferon with other pharmaceutical agent such as ribavirin have prompt investigators to search for other drugs which may be active against hepatitis C virus. Smith J P (Digestive Diseases Sciences 1997 August; 42(8):1681-7) of Pennsylvania State University performed an open-labeled prospective pilot study to test the safety and efficacy of the antiviral drug, amantadine, in patients with chronic hepatitis C infection who had previously failed therapy with interferon-alpha 2b. Their clinical results indicated that amantadine improved both biochemical and virological markers in patients with hepatitis C who had previously not responded to treatment with interferon. Amantadine Hydrochloride, N. F. (Orth R. E. in "Principels of Medicinal Chemistry, 2.sup.nd edition, page 866-867. Ed. Foye, W. O. (1981)) has been approved by the FDA for the treatment of influenza A2 infection. It is active against influenza A, A1 and A2, Sendai and rubella viruses. Amantadine (Neumeyer J. L. in Principles of Medicinal Chemistry, 2.sup.nd edition, page 248-249. Ed. Foye W. O. (1981)) also has clinically significant anti-parkinsonian effects. It appears to increase the release of dopamine and enhance accumulation of brain dopamine with fewer side effects than levodopa or the anticholinergic drugs. Web site: http://www.delphion.com/details?pn=US06613507__

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Composition and method for diagnosing auto-immune hepatitis Inventor(s): Lohse; Ansgar W. (Georg-Buchner-Strasse 8, 55129 Mainz, DE) Assignee(s): none reported Patent Number: 6,638,771 Date filed: September 25, 2000 Abstract: A composition and method for the diagnosis of autoimmune hepatitis. The composition, which contains SLA antigens detects soluble liver antigen (SLA) autoantibodies, which occur in sera of patients suffering from chronic hepatitis. Excerpt(s): The present invention relates to a composition and method for diagnosing auto-immune hepatitis, which use an immune reaction to detect soluble liver antigen ("SLA") auto-antibodies. Auto-immune hepatitis (AIH) is a chronic inflammation of the liver that when left untreated leads to cirrhosis, but when treated has a very good prognosis. For this reason, a timely diagnosis is important. It is estimated that 5% of all patients in Western countries who have chronic hepatitis have AIH. At the present time, there is no specific diagnostic test for AIH. Rather the diagnosis for AIH is undertaken by a plurality of diagnosis, such as excluding viral hepatitis, recognizing [hyper] immunoglobulinaemia, recognizing the tissue type (HLA type), and detecting autoantibodies. Auto-antibodies are found in about 90% of patients with chronic hepatitis, and most of the detectable auto-antibodies are also present, at least in low titers, in other inflammations of the liver as well. In particular, these auto-antibodies are antibodies to nuclear antigens (ANA) and unstriated muscles (SMA), as well as the very rare antibodies to cytochrome p450 (LKM). SLA auto-antibodies were described for the first time in 1987 (Manns M. et al., Lancet 1987;1:292-4). Tests have shown that SLA autoantibodies occur in about 25 to 30% of patients having AIH, but hardly ever occur in patients having other diseases, including other auto-immune diseases (Lohse A. W. et al., Z. Gastroenterol 1995;33:527-33)Detecting SLA auto-antibodies therefore provides a significant diagnostic procedure for recognizing AIH. The present invention is directed to use and detection of SLA antigens, which are a prerequisite for developing a specific immuunoassay for detecting SLA auto-antibodies in patients' sera. Previous methods known in the art could not detect such SLA auto-antibodies in patients' sera. Liver cytokeratins 8 and 18 were described in 1990 as target antigens of the SLA autoantibodies (Journal of Repatology, 1990; 11: 232 to 239), however, these findings were never confirmed, and were even refuted (Wies I. et al., Z. Gastroenterol. 1998;36:93). Web site: http://www.delphion.com/details?pn=US06638771__

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Composition for the treatment of hepatitis including HCV Inventor(s): Pruthi; Som C. (25675 Meadowview Ct., Salinas, CA 93908) Assignee(s): none reported Patent Number: 6,582,733 Date filed: May 15, 2002 Abstract: A composition for use in treating hepatitis includes: 4%-28% Gulancha by weight; 20%-7% Sodium Biborate by weight; 5%-47% Horseradish by weight; and 3%14% Mysore Gamboge be weight. Excerpt(s): The present invention relates to a composition comprising all natural ingredients and, more particularly, to an all natural composition for the treatment of

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inflammation of the liver such as, but not limited to, Hepatitis including HCV. Hepatitis is an inflammation of the liver primarily caused by a virus and, less commonly, by certain medications or toxins (e.g. alcohol). The viral infection is often acquired through exposure to contaminated blood. Those most likely to contract the virus are intravenous drug users who share contaminated needles, although sexual contact with a person who has a form of Hepatitis can also spread the disease. In some instances, healthcare workers exposed to contaminated blood and persons who need repeated transfusions of blood have acquired a form of Hepatitis. Three main types of viral Hepatitis have been identified, namely Hepatitis A, Hepatitis B and Hepatitis C. Hepatitis A is a highly infectious form of Hepatitis and is the most common form of the disease. Hepatitis A is usually transmitted by contaminated food or water. The symptoms of Hepatitis A often are similar to those of intestinal flu and a vast majority of persons with Hepatitis A recover completely. Web site: http://www.delphion.com/details?pn=US06582733__ ·

Compositions and methods for treatment of hepatitis C virus-associated diseases Inventor(s): Nozaki; Chikateru (Kumamoto, JP), Hanecak; Ronnie C. (San Clemente, CA), Anderson; Kevin P. (Carlsbad, CA) Assignee(s): ISIS Pharmaceuticals, Inc. (Carlsbad, CA) Patent Number: 6,608,191 Date filed: October 18, 2000 Abstract: Antisense oligonucleotides are provided which are complementary to and hybridizable with at least a portion of HCV RNA and which are capable of inhibiting the function of the HCV RNA. These oligonucleotides can be administered to inhibit the activity of Hepatitis C virus in vivo or in vitro. These compounds can be used either prophylactically or therapeutically to reduce the severity of diseases associated with Hepatitis C virus, and for diagnosis and detection of HCV and HCV-associated diseases. Methods of using these compounds are also disclosed. Excerpt(s): This invention relates to the design and synthesis of antisense oligonucleotides which can be administered to inhibit the activity of Hepatitis C virus in vivo or in vitro and to prevent or treat Hepatitis C virus-associated disease. These compounds can be used either prophylactically or therapeutically to reduce the severity of diseases associated with Hepatitis C virus. These compounds can also be used for detection of Hepatitis C virus and diagnosis of Hepatitis C virus-associated diseases. Oligonucleotides which are specifically hybridizable with Hepatitis C virus RNA targets and are capable of inhibiting the function of these RNA targets are disclosed. Methods of using these compounds are also disclosed. The predominant form of hepatitis currently resulting from transfusions is not related to the previously characterized Hepatitis A virus or Hepatitis B virus and has, consequently, been referred to as Non-A, Non-B Hepatitis (NANBH). NANBH currently accounts for over 90% of cases of posttransfusion hepatitis. Estimates of the frequency of NANBH in transfusion recipients range from 5%-13% for those receiving volunteer blood, or 25-54% for those receiving blood from commercial sources. Acute NANBH, while often less severe than acute disease caused by Hepatitis A or Hepatitis B viruses, can lead to severe or fulminant hepatitis. Of greater concern, progression to chronic hepatitis is much more common after NANBH than after either Hepatitis A or Hepatitis B infection. Chronic NANBH has been reported in 10%-70% of infected individuals. This form of hepatitis can be transmitted even by asymptomatic patients, and frequently progresses to malignant

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disease such as cirrhosis and hepatocellular carcinoma. Chronic active hepatitis, with or without cirrhosis, is seen in 44%-90% of posttransfusion hepatitis cases. Of those patients who developed cirrhosis, approximately one-fourth died of liver failure. Web site: http://www.delphion.com/details?pn=US06608191__ ·

Delivery of nucleic acids by porphyrins Inventor(s): Takle; Garry B. (New York, NY), George; Shaji T. (New York, NY) Assignee(s): Sirna Therapeutics, Inc. (Boulder, CO), Yale University (New Haven, CT) Patent Number: 6,620,805 Date filed: March 14, 1996 Abstract: Efficient methods and compositions are provided for the targeted delivery of effective concentrations of compounds, including nucleic acid molecules and oligonucleotides such as EGSs, ribozymes and antisense, proteins, peptides, carbohydrate, and synthetic organic and inorganic molecules, or combinations thereof, to cells, especially hepatocytes. In the preferred embodiment, the compound is an negatively charged oligonucleotide which binds in a stoichiometric ratio to a water soluble, positively charged macrocycle such as a porphyrin, which targets and protects the oligonucleotide. The porphyrin protects the compound to be delivered and delivers the compound preferentially to certain cells and tissue types. In another embodiment, the porphyrin has anti-human hepatitis virus activity, when administered alone, which is significantly enhanced when in combination with an antiviral compound, especially an oligonucleotide. Excerpt(s): The present invention relates generally to delivery of compounds with a net negative charge, especially oligonucleotides, to specific cell types, and is in particular a means of using positively-charged porphyrins and other macrocyclic compounds with positive charges that can stack along oligonucleic acid backbones to stabilize and promote uptake into cells of the oligonucleotides or other negatively charged compounds. The present invention is also a method for treating viral diseases, especially hepatitis B and C. Targeted drug delivery improves the therapeutic index of numerous drugs, reduces potential drug cost and may increase tissue half life. Although drugs can be encapsulated in tablets or capsules for oral delivery, encapsulation into more sophisticated vehicles is required for targeted delivery and for delivery of molecules such as therapeutic oligonucleotides and gene therapy reagents, which are extremely sensitive to the presence of nucleases in the body. Many different systems have been proposed for targeted drug delivery. The most commonly used method has been to covalently attach antibodies to the surface of microparticulate carriers. Web site: http://www.delphion.com/details?pn=US06620805__

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Diagnosis method of inflammatory, fibrotic or cancerous disease using biochemical markers Inventor(s): Poynard; Thierry (Paris, FR) Assignee(s): Assistance Publique-Hopitaux de Paris (AP-HP) (Paris, FR) Patent Number: 6,631,330 Date filed: October 13, 2000

Patents 355

Abstract: The present invention is drawn to a new diagnosis method for detecting the extend of a inflammatory, fibrotic or cancerous disease in a patient, in particular liver fibrosis, in particular in a patient infected with hepatitis C virus, by using the serum concentration of easily detectable biological markers. The invention is also drawn to diagnosis kits for the implementation of the method. Excerpt(s): The present invention is drawn to a new diagnosis method for detecting the extend of a inflammatory, fibrotic or cancerous disease in a patient, in particular liver fibrosis, in particular in a patient-infected with hepatitis C virus, by using the serum concentration of easily detectable biological markers. The invention is also drawn to diagnosis kits for the implementation of the method. Liver biopsy is considered as mandatory for the management of patients infected by the hepatitis C virus (HCV), particularly for the staging of fibrosis (1-4). For patients and general practitioner it can be considered as an aggressive procedure (5-6). Numerous studies have shown significant predictive values of several markers for the diagnosis of cirrhosis (6-15) but none for the diagnosis of earlier stage as few septa (beginning of bridging fibrosis), prospectively in a large population infected only by HCV virus. It is nevertheless important to be able to detect these early stages in the development of liver pathology, in order to improve the patient treatment, and the follow-up of the disease. As liver biopsy is still an invasive procedure, it could be advantageous to have a fast and easy to perform test that would give a good predictive value of the level of fibrosis in the patient. Web site: http://www.delphion.com/details?pn=US06631330__ ·

Fas ligand-like protein, its production and use Inventor(s): Nishi; Kazunori (Tsukuba, JP), Hikichi; Yukiko (Tsukuba, JP), Shintani; Yasushi (Tsukuba, JP) Assignee(s): Takeda Chemical Industries, Ltd. (Osaka, JP) Patent Number: 6,590,090 Date filed: August 31, 2000 Abstract: This invention relates to a Fas ligand-like protein having an apotosis-inducing actibvity, etc. or its salt, a partial peptide of the protein or its salt; a DNA coding for the protein; a recombinant vector; a transformant; a method for producing the protein, a pharmaceutical composition comprising the protein, the partial peptide or its salt; and an antibody to the protein or the partial peptide. The protein, the partial peptide or its salt, and the DNA are useful as a prophylactic or therapeutic agent for cancer, viral infection, Helicobacter pylori infection, invasive staphylococcia, hepatitis, nephritis, bone disease, atherosclerosis or pain. The antibody can be used in assay of the protein, the partial peptide or its salt. The protein, the partial peptide or its salt is useful as a reagent for the screening for candidate medical compounds. Excerpt(s): The present invention relates to a novel fas ligand-like protein having an apotosis-inducing activity, etc. and a DNA coding for the protein. A multicellular organism maintains its homeostasis ingeniously by controlling the proliferation and death of its cells. In the course of ontogenesis, many cells are eliminated through apotosis, and even in a mature organism the cells constituting its tissues maintain their functional integrity balancing proliferation against death. Cell death in this context is generally termed "programmed cell death", which is known to occur through the process of apotosis which is morphologically distinguished from that of necrosis, the

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accidental cell death caused by physical and chemical factors. Apoptotic cell death is characterized by blebbing of the cell membrane, chromatin condensation and DNA fragmentation, with the affected cells being eventually removed by phagocytic cells such as macrophages for reutilization (International Review of Cytology, 68, 251-306, 1980). Many physiological and pathological events related to apotosis have been identified until now and many attempts made to diagnose, prevent, or treat various diseases through induction or inhibition of the process of apotosis (Science, 267, 1456-1462, 1995). Apotosis is one of the vital phenomena which are attracting more than usual attention in the pharmaceutical industries. Web site: http://www.delphion.com/details?pn=US06590090__ ·

Fgl-2 knockout mice Inventor(s): Fung; Laisum (Toronto, CA), Marsden; Philip (Toronto, CA), Levy; Gary (Thornhill, CA) Assignee(s): Trillium Therapeutics Inc. (Toronto, CA) Patent Number: 6,642,433 Date filed: October 13, 2000 Abstract: A knockout mouse in which the Fgl-2 gene has been suppressed is described. The mouse is useful in studying the role of Fgl-2 in normal and disease states including viral hepatitis, allograph rejection, fetal loss, inflammatory bowel disease, lupus glomerulonephritis; acute respiratory disease syndrome, Whipple's disease, cancer and for developing therapies to treat these diseases. Excerpt(s): The present invention relates to mammals and cell lines in which the expression of the Fgl-2 gene has been suppressed. The invention also includes constructs that are useful in preparing the mammals and cell lines. Fulminant viral hepatitis is characterized by the rapid appearance of jaundice, coagulopathy and encephalopathy and reflects severe hepatocellular dysfunction and necrosis. Thrombosis is a common feature of fulminant hepatitis and may occur in viral infections complicated by disseminated intravascular coagulation. Monocytes/macrophages respond to infection with hepatitis viruses by generating procoagulant activity (PCA) and also produce monokines such as TNF and IL-2, which in turn can induce other cells like endothelial cells to produce PCA. Activation of the coagulation pathways is an important part of immune and inflammatory reactions and accounts for the fibrin deposition in these reactions. Furthermore, the inventors have shown that the elaboration of PCA by monocytes/macrophages parallels the susceptibility to fulminant hepatitis caused by murine hepatitis virus strain 3 (MHV-3). As described in applicant's co-pending application Ser. No. 09/442,143, which is incorporated herein by reference in its entirety, the applicant's identified the MHV-3 induced procoagulant as a direct prothrombinase Fgl-2 and the mouse and human sequences have been sequenced. Clinical conditions other than hepatitis in which Fgl-2 is implicated include allograft rejection, fetal loss, inflammatory bowel disease lupus glomerulonephritis, acute respiratory disease syndrome, Whipple's disease, and cancer. In view of the role of Fgl-2 in various diseases it is useful to prepare an Fgl-2 knockout model in order to further elucidate its function in these diseases and importantly to develop therapies to treat the diseases. Web site: http://www.delphion.com/details?pn=US06642433__

Patents 357

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HBV core antigen particles with multiple immunogenic components attached via peptide ligands Inventor(s): Murray; Kenneth (Edinburgh, GB) Assignee(s): Biogen, Inc. (Cambridge, MA) Patent Number: 6,627,202 Date filed: June 4, 2001 Abstract: This invention relates to hepatitis B virus ("HBV") core antigen particles that are characterized by multiple immunogen specificities. More particularly, the invention relates to HBV cote antigen particles comprising immunogens, epitopes, or other related structures, crosslinked thereto by ligands which are HBV capsid-binding peptides that selectively bind to HBV core protein. Such particles may be used as delivery systems for a diverse range of immunogenic epitopes, including the HBV capsid-binding peptides, which advantageously also inhibit and interfere with HBV viral assembly by blocking the interaction between HBV core protein and HBV surface proteins. Mixtures of different immunogens and/or capsid-binding peptide ligands may be crosslinked to the same HBV core particle. Such resulting multicomponent or multivalent HBV core particles may be advantageously used in therapeutic and prophylactic vaccines and compositions, as well as in diagnostic compositions and methods using them. Excerpt(s): This invention relates to hepatitis B virus ("HBV") core antigen particles that are characterized by multiple immunogen specificities. More particularly, the invention relates to HBV core antigen particles comprising immunogens, epitopes, or other related structures, crosslinked thereto by ligands which are HBV capsid-binding peptides that selectively bind to HBV core protein. Such particles may be used as delivery systems for a diverse range of immunogenic epitopes, including the HBV capsid-binding peptides, which advantageously also inhibit and interfere with HBV viral assembly by blocking the interaction between HBV core protein and HBV surface proteins. Mixtures of different immunogens, HBV capsid-binding peptide ligands, or both, may be crosslinked to the same HBV core particle. Such resulting multicomponent or multivalent HBV core particles may be advantageously used in therapeutic and prophylactic vaccines and compositions, as well as in diagnostic compositions and methods using them. The front-line of clinical immunotherapeutic regimens includes patient immunizations against infectious pathogens and other health-threatening agents. Despite the plethora of immunization agents, inoculations may afford, at best, partial immunity, requiring frequent re-immunizations. Such is the case for various conventional monovalent or polyvalent vaccines. And even among such vaccines, the number of single agent inoculants capable of eliciting immunity against a variety of immunogens is limited. Furthermore, antigenic variation among pathogens may limit the efficacy of conventional vaccines. Due to such obstacles, efforts have focused on methodologies for enhancing the immune system response to given immunogens. To that end, immunogenic conjugates have been produced by linking immunogens to hepatitis B virus ("HBV") core particles (also referred to as nucleocapsids or nucleocapsid shells), in efforts to enhance the immunogenicity of the linked immunogen, through the operation of T cell dependent and T cell independent determinants of HBV core antigen. See, for example, U.S. Pat. No. 4,818,527 and R. Ulrich et al., "Core Particles of Hepatitis B Virus as Carrier for Foreign Epitopes", Adv. Virus. Res., 50, pp. 141-82 (1998). Enhanced immunogenicity of epitopes of interest has also been approached via hybrid viral particle-forming proteins, comprising at least a portion of a naturally occurring viral particle forming protein, for example HBV surface antigen, and one or more epitopic sites of interest. See U.S. Pat No. 5,965,140. As evident

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from such efforts, proteins of HBV have been used as platforms for presenting immunogens of interest to the immune system. Web site: http://www.delphion.com/details?pn=US06627202__ ·

HCV-derived RNA polymerase gene Inventor(s): Kohara; Michinori (Chiba, JP), Toyoda; Tetsuya (1339-4, Tsubukuhonmachi, Kurume-shi, Fukuoka 830-0047, JP), Tsuchiya; Masayuki (Shizuoka, JP), Kohara; Kyoko (Chiba, JP), Higashi; Kazuhiro (Hyogo, JP) Assignee(s): Toyoda; Tetsuya (Fukuoka, JP), International Reagents Corporation (Hyogo, JP), Chugai Seiyaku Kabushiki Kaisha (Tokyo, JP) Patent Number: 6,639,053 Date filed: December 21, 2001 Abstract: The present invention provides a gene encoding an RNA polymerase which plays an important role in the reproduction of hepatitis C virus, and a method of screening using this gene or this RNA polymerase protein, thereby allowing easy performance of screening for substances which inhibit the RNA polymerase playing an important role in HCV reproduction. Excerpt(s): This application is a 371 of PCT/JP99/03381, filed Jun. 24, 1999. The present invention relates to an RNA polymerase gene derived from hepatitis C virus (referred to as "HCV" herein), a method of screening using this gene or this RNA polymerase protein, and a substance able to be isolated by this screening method. Generally known viral hepatitis includes hepatitis A which is mainly orally transmitted, and hepatitis B transmitted by means of the blood. Moreover, apart from these hepatitis, there is hepatitis called non-A, non-B hepatitis which is transmitted by means of blood transfusion. Since most of these infected with non-A, non-B hepatitis become chronic, and the incidence of development into cirrhosis and hepatoma is high, this is one disease for which the establishment of a certain means of treatment is urgently sought. Web site: http://www.delphion.com/details?pn=US06639053__

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Hepatitis B surface antigen vaccine Inventor(s): Thoma; Hans A. (Munchen, DE) Assignee(s): Medeva Holdings B.V. (Amsterdam, NL) Patent Number: 6,589,530 Date filed: June 7, 1995 Abstract: HBV surface antigen particles, prepared by recombinant DNA technology are described, said particles being composed of epitopes from the group of surface peptides and/or core peptide of non-A, non-B hepatitis virus, hepatitis A virus, or hepatitis virus B. Respective particles are especially characterized by a composition of different epitopes selected from pre-S and S peptides. There are also described DNA-sequences, plasmids, and cell lines coding for respective HBV surface antigen particles as well as a new vaccine containing the same. Excerpt(s): The invention relates to Hepatitis B surface antigen ("HBs antigen" or "HBsAG") particles which are composed of polypeptides prepared by recombinant DNA

Patents 359

processes, DNA sequences coding for these polypeptides and cell lines for the expression of the same. The present invention relates especially to new particles having increased immunogenicity. Advances in vaccine production techniques have made it possible to synthesize polypeptides corresponding to the HBs antigen in bacteria, yeast and mammalian cells. Transcription of eukaryotic genes in bacteria and yeast, however, adversely affects the efficaciousness of these polypeptides as antigens due to several drawbacks concerning the glycosilation and secretion of the polypeptides and composition of the particle formed therefrom. For example, in the case of the Hepatitis B virus, the polypeptide antigens produced in vivo are heavily glycosilated (Gerlich, 1984: J. Virol.: 52 (2), 396). In prokaryotes, glycosilation is not an essential process so that polypeptides produced by genetically engineered bacteria are either not glycosilated or are incompletely glycosilated. In either case, polypeptides corresponding to HBsAg, when expressed in bacteria, do not raise antibodies which will see HBsAg sufficiently well for an effective vaccine. Although yeast as a eukaryotic host is capable of more complete glycosilation, polypeptides corresponding to HbsAg expressed in yeast share the same deficiency as in the case of bacterial expression. (Murray et al., 1979: Nature, 282, 575; Valenzuela et al., 1982: Nature, 298, 347; Miyariohara et al., 1983: PNAS, 80, 1). Web site: http://www.delphion.com/details?pn=US06589530__ ·

Hepatitis B virus binding proteins and uses thereof Inventor(s): Shaul; Yosef (Sede-Gat, IL), Zemel; Romi (Tel Aviv, IL) Assignee(s): Yeda Research and Development Co., Ltd. (Rehovot, IL) Patent Number: 6,589,534 Date filed: September 30, 1999 Abstract: An isolated nucleic acid, a recombinant protein encoded thereby and uses thereof. The isolated nucleic acid including (a) a polynucleotide at least 60% identical to SEQ ID NOs:1, 3, 5 or portions thereof as determined using the Bestfit procedure of the DNA sequence analysis software package developed by the Genetic Computer Group (GCG) at the university of Wisconsin (gap creation penalty--50, gap extension penalty-3); (b) a polynucleotide encoding a polypeptide being at least 60 homologous with SEQ ID NOs:2, 4, 6 or portions thereof as determined using the Bestfit procedure of the DNA sequence analysis software package developed by the Genetic Computer Group (GCG) at the university of Wisconsin (gap creation penalty--50, gap extension penalty--3); or (c) a polynucleotide hybridizable with SEQ ID NOs:1, 3, 5 or portions thereof at 68.degree. C. in 6.times.SSC, 1% SDS, 5.times.Denharts, 10% dextran sulfate, 100.mu.g/ml salmon sperm DNA, and.sup.32 p labeled probe and wash at 68.degree. C. with 3.times.SSC and 0.1% SDS. Excerpt(s): The present invention relates to a group of genes, and the proteins encoded thereby, which are capable of interfering with Hepatitis B virus (HBV) infection and to methods for identifying, purifying, isolating and characterizing related genes and gene products. The present invention further relates to isolation of soluble forms of the cellular receptor(s) for HBV on hepatocytes from bodily fluids, including, but act limited to, urine, and to purification of these soluble form binding proteins by means including, but not limited to, affinity columns. The present invention further relates to the use of these genes and their translation products to establish experimental models for HBV infection, whether in cell culture or in animals. The present invention further relates to the use of these genes and their translation products for therapeutic purposes. The present invention further relates to the use of these genes and their translation products

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to screen for additional binding protein interactions. The present invention further relates to the use of these genes and their translation products to prepare specific detectors of these proteins, including, but not limited to, antibodies, phage-display libraries, specific PCR primers, lectin, DNA probes, RNA probes, and non-antibody proteins for diagnostic and therapeutic purposes. Hepatitis B virus (HBV) is an enveloped RNA virus that infects human liver and replicates via reverse-transcription of the pregenomic RNA Infected patients develop acute hepatitis, which is often selflimiting, but may develop into chronic hepatitis with high risk of liver cirrhosis and primary liver carcinoma in roughly 10% of all cases. The World Health Organization estimates that there will be 400 million carriers Worldwide in year 2000. Effective vaccines exist, but anti viral drugs with good and long term efficacy are not available. Little is known about how HBV infects liver cells and the HBV cellular receptor(s) remain unknown. Many proteins have been identified which bind to the viral envelope associated proteins, HBsAg, or related proteins, but none are considered genuine HBV receptors (reviewed in De et al., 1991 and in references cited therein). Some of these binding proteins are found in serum and some in hepatocytes. None of these molecules have been convincingly tied to infectivity, disqualifying them as genuine HBV receptors. These molecules are of three types, S binding proteins, preS2 binding proteins, and preS1 binding proteins. A brief summary of the characteristics of the three groups is provided herein. The S binding proteins: HBsAg containing only the S protein binds to a 34-kDa liver protein, which is identified as the phospholipid-binding protein endonexin II (also known as annexin V). Endonexin II has calcium channel activity and it thought to be located primarily, but not exclusively, intracellularly. The biological significance of this remains unclear, as the observed interaction may simply reflect the known ability of endonexin 11 to bind phospholipids, which are abundant in HBsAg lipoprotein. It was subsequently demonstrated that delipidated HBsAg had a drastically diminished capacity to bind endonexin II, leading to speculation that it might play a role in a postbinding membrane fusion event. Web site: http://www.delphion.com/details?pn=US06589534__ ·

Hepatitis C assay utilizing recombinant antigens Inventor(s): Lesniewski; Richard R. (8706 110th Ave., Kenosha, WI 53142), Dailey; Stephen H. (472 Tyler Ct., Vernon Hills, IL 60061), Casey; James M. (4110 Bayside Ct., #2C, Zion, IL 60099), Desai; Suresh M. (1408 Amy La., Libertyville, IL 60048), Devare; Sushil G. (2492 Farnsworth La., Northbrook, IL 60062), Gutierrez; Robin A. (34859 N. Hunt Club Rd., Gumee, IL 60031), Rupprecht; Kevin R. (720 Durham La., Grayslake, IL 60030), Stewart; James L. (4422 Sheffield Ct., Gumee, IL 60031), Dawson; George J. (914 S. Dymond Rd., Libertyville, IL 60048) Assignee(s): none reported Patent Number: 6,593,083 Date filed: October 17, 2000 Abstract: Unique recombinant antigens representing distinct antigenic regions of the Hepatitis C Virus (HCV) genome which can be used as reagents for the detection of antibodies and antigen in body fluids from individuals exposed to HCV. The present invention also provides an assay for detecting the presence of an antibody to an HCV antigen in a sample by contacting the sample with the recombinant antigens. Preferred assay formats include a screening assay, a confirmatory assay, a competition or neutralization assay and an immunodot assay.

Patents 361

Excerpt(s): This invention relates generally to an assay for identifying the presence in a sample of an antibody which is immunologically reactive with a hepatitis C virus antigen and specifically to an assay for detecting a complex of an antibody and recombinant antigens representing distinct regions of the HCV genome. Recombinant antigens derived from the molecular cloning and expression in a heterologous expression system of the synthetic DNA sequences representing distinct antigenic regions of the HCV genome can be used as reagents for the detection of antibodies and antigen in body fluids from individuals exposed to hepatitis C virus (HCV). Acute viral hepatitis is clinically diagnosed by a well-defined set of patient symptoms, including jaundice, hepatic tenderness, and an increase in the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase. Additional serologic immunoassays are generally performed to diagnose the specific type of viral causative agent Historically, patients presenting clinical hepatitis symptoms and not otherwise infected by hepatitis A, hepatitis B, Epstein-Barr or cytomegalovirus were clinically diagnosed as having non-A non-B hepatitis (NANBH) by default. The disease may result in chronic liver damage. Each of the well-known, immunologically characterized hepatitis-inducing viruses, hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis D virus (HDV) belongs to a separate family of viruses and has a distinctive viral organization, protein structure, and mode of replication. Web site: http://www.delphion.com/details?pn=US06593083__ ·

Hepatitis C virus culture system Inventor(s): Bartenschlager; Ralf (Nachdem Alten Schloss 22, D-55239 Gau-Odernheim, DE) Assignee(s): none reported Patent Number: 6,630,343 Date filed: March 31, 2000 Abstract: The hepatitis C virus (HCV) cell culture system according to the invention consists of human hepatoma cells, which are transfected with a HCV-RNA construct, that comprises the HCV specific RNA segments 5'to NTR, NS3, NS4A, NS4B, NS5A, NS5B, and 3'to NTR as well as a minimum of one marker gene for selection (selection gene). Excerpt(s): The invention relates to a hepatitis C virus (HCV) cell culture system, which comprises mainly eukaryotic cells containing transfected HCV specific genetic material, which means they are transfected with HCV specific genetic material. The hepatitis C virus (HCV) is one of the main causes worldwide of chronic and sporadic liver diseases. The history of most HCV infections does not involve any obvious clinical signs, but 8090% of the infected people become chronic carriers of the virus and 50% of these chronic carriers of the virus develop chronic hepatitis with different degrees of severity. Approx. 20% of the chronically infected develop a cirrhosis of the liver over 10 to 20 years, based on what a primary hepatocellular carcinoma can develop. Nowadays chronic hepatitis C is the main indication for liver transplantation. One currently available therapy involves high-dose administration of Interferon alpha or a combination of Interferon alpha and the purine nucleoside analogue Ribavirin. However, only approx. 60% of all treated persons respond to this therapy and with these, a new viraemia occurs in more than half of all cases after the discontinuation of the treatment. Due to the high prevalence, especially in industrialized countries, the serious effects of chronic infections and the lack of effective therapy, the development of a HCV specific chemotherapy is an

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important goal of pharmaceutical research and development. Such a goal, however, has been hampered by the lack of a suitable cell culture system, which enables the study of virus replication and pathogenesis in eukaryotic cells. Web site: http://www.delphion.com/details?pn=US06630343__ ·

Hepatitis vaccines containing 3-0-deacylated monophoshoryl lipid A Inventor(s): Hauser; Pierre (Chaumont-Gistoux, BE), Thiriart; Clothilde (Brussels, BE), Voet; Pierre (Izel, BE), Garcon-Johnson; Nathalie Marie-Josephe Claude (Wavre, BE) Assignee(s): SmithKline Beecham Biologicals (s.a.) (Rixensart, BE) Patent Number: 6,620,414 Date filed: August 21, 2001 Abstract: A vaccine formulation for the treatment or prophylaxis of hepatitis, especially hepatitis B, infections is provided comprising the hepatitis antigen and a suitable carrier such as alum in combination with 3-O-deacylated monophosphoryl lipid A. Combination vaccines including the vaccine formulation are also described. Excerpt(s): The present invention relates to novel vaccine formulations, methods for preparing them and to their use in therapy. In particular the present invention relates to novel formulations for treating Hepatitis infections and to combination vaccine formulations including a Hepatitis vaccine component. Viral hepatitis, caused by the A, B, C, D, and E hepatitis viruses, is a very common viral illness. Via the B and C viruses, in particular, it is also responsible for many cases of liver cancer. Thus the development of effective vaccines is critical and, despite notable successes, is still an on-going task. A review on modern hepatitis vaccines, including a number of key references, may be found in the Lancet, May 12th 1990 at page 1142 ff (Prof A. L. W. F. Eddleston). See also `Viral Hepatitis and Liver Disease` (Vyas, B. N., Dienstag, J. L., and Hoofnagle, J. H., eds, Grune and Stratton, Inc. (1984) and `Viral Hepatitis and Liver Disease` (Proceedings of the 1990 International Symposium, eds F. B. Hollinger, S. M. Lemon and H. Margolis, published by Williams and Wilkins). As used herein the expression `hepatitis antigen` is used to refer to any antigenic material derived from a hepatitis virus which may be used to induce immunity to the virus in humans. The hepatitis antigen may be, for example, a polypeptide obtained by recombinant DNA techniques or an attenuated strain of hepatitis virus which has optionally been inactivated by known methods. The invention extends to all hepatitis antigens, whether A, B, C, D, or E, examples of which are discussed below. Web site: http://www.delphion.com/details?pn=US06620414__

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Immunodominant human T-cell epitopes of hepatitis C virus Inventor(s): Leroux-Roels; Geert (Ghent, BE), Maertens; Geert (Bruges, BE), Deleys; Robert (Grimbergen, BE) Assignee(s): Innogenetics N.V. (Ghent, BE) Patent Number: 6,613,333 Date filed: November 19, 1997 Abstract: The present invention relates to a polypeptide of about 8 to about 100 amino acids comprising or consisting of at least 8 contiguous amino acids selected from the

Patents 363

core, and/or the NS3 regions of the HCV polyprotein, with said contiguous amino acids containing a T-cell stimulating epitope. Excerpt(s): The present invention describes immunodominant hepatitis C virus T cell epitopes useful in hepatitis C prophylactic and therapeutic vaccines, derived from the HCV core, E1, E2 ,and NS3 proteins. The present invention relates to the production of novel synthetic immunogens related to the hepatitis C virus core, E1, E2 and NS3 regions and to the use thereof in the production of vaccines, therapeutic agents and the like. More specifically, the present invention relates to polypeptide compositions containing HCV core, E1, E2 and NS3 T cell determinants. In the few years since its discovery, Hepatitis C virus (HCV) has been shown to be a major cause of acute and chronic liver disease. HCV is a single-stranded RNA virus with a genome of approximately 9400 nucleotides that consists of a 5' untranslated region (5'UR) of 341 nucleotides which precedes a single large open reading frame encoding a precursor polyprotein of about 3010 amino acids (Kato et al., 1990). The genetic organization of the viral genome is related to that of flavi- and pestiviruses, with the putative structural proteins located en the N-terminal region and a variety of non structural proteins located at the C-terminal end of the polyprotein. The structural proteins are the core protein (C, amino acids 1-191) followed by the putative envelope proteins E1 (amino acids 192-383) and E2/NS1 (amino acids 384-746). The terms E2 and NS1 are often used interchangeably. Another form of E2 is composed of amino acids 384 to 809 and a third form is associated with NS2. The non structural proteins are NS2, NS3, NS4 and NS5, of which at least NS4 and NS5 have been shown to be further processed into NS4A, NS4B, NS5A, and NS5B. Web site: http://www.delphion.com/details?pn=US06613333__ ·

In vitro activity assay for human hepatitis B virus (HBV) DNA polymerase, and its use for screening for inhibitors of HBV DNA polymerase Inventor(s): Oon; Chong Jin (Singapore, SG), Leong; Ai Lin (Singapore, SG), Lim; Gek Keow (Singapore, SG), Chen; Wei Ning (Singapore, SG) Assignee(s): Government of the Republic of Singapore (Singapore, SG) Patent Number: 6,593,082 Date filed: June 18, 2001 Abstract: The present invention provides an in vitro activity assay for human hepatitis B virus (HBV) DNA polymerase, which comprises using, as the 5' oligonucleotide in PCR amplification of HBV DNA polymerase from a sample, an oligonucleotide into which has been incorporated the SP6 viral polymerase promoter, directly transcribing and translating the PCR products in the presence of a radio-labelled agent and measuring the priming of the HBV DNA polymerase. The present invention also provides the use of such an assay to assay activity of various serum samples, to screen for inhibitors of the HBV DNA polymerase and to test and/or screen potential anti-HBV drugs for their ability to inhibit DNA priming activity of human HBV DNA polymerase. Excerpt(s): Polymerases are enzymes of fundamental importance to living organisms. They are responsible for the synthesis of nucleic acids and their transformation into other nucleic acids necessary for the synthesis of proteins. Polymerases are, therefore, found in all types of cells including the causative DNA virus for hepatitis B virus (HBV). Although such active vaccination programme has resulted in a decrease of HBV infection in the population, an increasing number of mutations located within the `a`

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epitope have been emerging. These vaccine-induced HBV mutants are of concern, as they are capable of escaping the currently available immuno-based diagnostic system and able to replicate independently. The fact that mutations on the `a` epitope of HBsAg give rise to amino acid substitutions in the overlapping HBV DNA polymerase, particularly by their location within the reverse transcriptase domain, may imply that these vaccine-induced mutants have altered reverse transcriptase activity, a key factor for the viral replication. Web site: http://www.delphion.com/details?pn=US06593082__ ·

Inhibitors of serine proteases, particularly hepatitis C virus NS3 protease Inventor(s): Harbeson; Scott L. (Cambridge, MA), Deininger; David D. (Arlington, MA), Tung; Roger D (Beverly, MA), Murcko; Mark A. (Holliston, MA), Bhisetti; Govinda R. (Lexington, MA), Farmer; Luc J. (Foxborough, MA) Assignee(s): Vertex Pharmaceuticals Incorporated (Cambridge, MA) Patent Number: 6,617,309 Date filed: June 6, 2001 Abstract: The present invention relates to compounds, methods and pharmaceutical compositions for inhibiting proteases, particularly serine proteases, and more particularly HCV NS3 proteases. The compounds, and the compositions and methods that utilize them, can be used, either alone or in combination to inhibit viruses, particularly HCV virus. Excerpt(s): The present invention relates to a novel class of compounds that are useful as protease inhibitors, particularly as serine protease inhibitors, and more particularly as hepatitis C NS3 protease inhibitors. As such, they act by interfering with the life cycle of the hepatitis C virus and are also useful as antiviral agents. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting HCV NS3 protease activity and consequently, may be advantageously used as therapeutic agents against the hepatitis C virus and other viruses that are dependent upon a serine protease for proliferation. This invention also relates to methods for inhibiting the activity of proteases, including hepatitis C virus NS3 protease and other serine proteases, using the compounds of this invention and related compounds. Infection by hepatitis C virus ("HCV") is a compelling human medical problem. HCV is recognized as the causative agent for most cases of non-A, non-B hepatitis, with an estimated human seroprevalence of 1% globally [Purcell, R. H., "Hepatitis C virus: Historical perspective and current concepts" FEMS Microbiology Reviews 14, pp. 181192 (1994); Van der Poel, C. L., "Hepatitis C Virus. Epidemiology, Transmission and Prevention in Hepatitis C Virus. Current Studies in Hematology and Blood Transfusion, H. W. Reesink, Ed., (Basel: Karger), pp. 137-163 (1994)]. Four million individuals may be infected in the United States alone [Alter, M. J. and Mast, E. E., "The Epidemiology of Viral Hepatitis in the United States, Gastroenterol. Clin. North Am. 23, pp. 437-455 (1994)]. Web site: http://www.delphion.com/details?pn=US06617309__

Patents 365

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Low dose entecavir formulation and use Inventor(s): Harianawala; Abizer (North Brunswick, NJ), Sprockel; Omar L. (Bridgewater, NJ), Colonno; Richard J. (Farmington, CT), Desai; Divyakant (West Windsor, NJ), Fakes; Michael G. (Belle Mead, NJ) Assignee(s): Bristol-Myers Squibb Co. (Princeton, NJ) Patent Number: 6,627,224 Date filed: February 23, 2001 Abstract: Compositions containing a low dose of entecavir are administered on a daily basis to treat hepatitis B virus infection and/or co-infections. Formulations for the oral administration of a low dose of entecavir are provided. Other pharmaceutically active substances can be included in the entecavir composition or can be separately administered for the treatment of hepatitis B virus infection or for the treatment of coinfected patients. Excerpt(s): is an antiviral agent currently undergoing clinical evaluation for the treatment of hepatitis B virus infection. Entecavir and its use in treating hepatitis B are disclosed by Zahler et al. in U.S. Pat. No. 5,206,244. This patent discloses that an effective antiviral dose for oral or parenteral administration will likely be in the range of about 1.0 to 50 mg/kg of body weight and that the desired dose may be administered several times daily at appropriate intervals. Improved methods for the synthesis of entecavir are disclosed by Bisacchi et al. in WO 98/09964. Web site: http://www.delphion.com/details?pn=US06627224__

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Method and apparatus for water purification Inventor(s): Beckius; Robert (Richland, WA), Powell; Mike (Kennewick, WA), Merrill; Ezra (Albuquerque, NM), Call; Charles J. (Pasco, WA), Shekarriz; Alireza (Columbia, MD), Hong; Seung-Ho (Richland, WA) Assignee(s): MesoSystems Technology, Inc. (Kennewick, WA) Patent Number: 6,623,603 Date filed: October 19, 1999 Abstract: A method and apparatus for purifying water by using thermal and/or thermocatalytic processes. The method and apparatus are particularly useful for processing impure water to remove and/or deactivate toxic inorganic, organic, and/or biological species such as Sarin, mustard gas, phosgene, cyanogen chloride, anthrax, E. coli, Giardia cysts, salmonella, hepatitis, and Norwalk viruses. In the thermal process, contaminated water is heated (preferably superheated) forming steam, whereby a majority of inorganic and biological species are removed or deactivated from the water. The steam is then condensed, forming liquid purified water. In the thermocatalytic process, the steam is brought into contact with a hydrolysis catalyst, preferably in the form of a coated surface or replaceable catalyst element. The hydrolysis catalyst, which may be a metal oxide, thermocatalytically deactivates at least 90% of the organic or biological species in the water, converting them to less toxic organic species or nonviable biological species. Various embodiments of the apparatus are provided, including portable configurations. Each of the embodiments include at least one boiler, at least one condenser, and a water reservoir arranged in heat exchange relationship so as to improve an overall operating efficiency of the apparatus. The apparatus is heated using

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a portable stove or other heat source, and a counterflow heat exchanger preheats water that is to be vaporized and cools the purified liquid water formed in a condenser. Excerpt(s): The present invention generally concerns water purification, and more specifically, the purification of water containing toxic species, using thermal and thermocatalytic processes and apparatus. It is often necessary to purify water by removing inorganic, organic, and biological species from the water before it can be used or consumed. Methods for removing particulate and chemical species from water are well known, and include distillation, reverse osmosis, freezing, ionization, photocatalytic treatment, and carbon filtration. Examples of such methods are disclosed in U.S. Pat. Nos. 5,007,994; 5,227,053; 5,133,858; and 4,717,476. In addition, there are many well-known methods for destroying bacteria in water, including boiling, using submicron filtration, and disinfectant processes using chlorine, bromine, iodine, or other strong oxidizers. Treatment with heat or disinfectants may also be used sterilize water containing harmful viral agents. In many instances, it is desired to have access to a portable means for purifying water. For example, it is often impractical for campers, hikers, mountain climbers, and others who are outdoors for extended period of time, to rely on treated water that they would be required to carry throughout an outing extending over several days. In these instances, it will be preferable to rely on local water sources, such as streams or lakes, which typically contain various particulate and mineral contaminants, including dirt, salt, algae, etc., and also may contain bacterial or viral contaminants. Although the methods and devices discussed above might be used to purify water flowing in a stream or lake water, some of the methods are unsuitable for portable use, because, e.g., they require heavy or bulky equipment, or substantial mechanical or electrical power. In view of the problem, several portable water purification devices have been developed, including those disclosed in U.S. Pat. Nos. 5, 273,649; 5,268,093; 5,244,579; and 3,635,799. Web site: http://www.delphion.com/details?pn=US06623603__ ·

Method for measurement of hepatitis C virus Inventor(s): Ohue; Chiharu (Wako, JP), Iida; Kumiko (Wako, JP), Yagi; Shintaro (Wako, JP), Aoyagi; Katsumi (Wako, JP) Assignee(s): Advanced Life Science Institute, Inc. (Saitama, JP) Patent Number: 6,623,921 Date filed: April 26, 2002 Abstract: A method for measurement of the hepatitis C virus (HCV) characterized by measuring HCV core antigen and HCV core antibody by their binding with probes in the presence of an anionic surfactant or a non-ionic surfactant, or both. Excerpt(s): The present invention relates to a method for detection of the hepatitis C virus (HCV), and more specifically it relates to a method for measurement of HCV core antigen or for simultaneous measurement of HCV core antigen and HCV core antibodies. The method is particularly effective for screening of multiple blood samples and the like. Hepatitis caused by infection with HCV (hepatitis C virus) becomes chronic with high incidence, and as the infection period is prolonged it often progresses to liver cirrhosis and hepatocellular carcinoma. However, since infection with HCV occurs mainly through blood and blood-derived components, it is possible to identify and eliminate the source of infection to block the infection route. Current methods of identifying infection sources are primarily methods of detecting antibodies against HCV

Patents 367

polypeptides, but methods are being sought that can identify infection sources with greater accuracy. Such methods are being sought because of the existence of a period of time known as the "window period" after HCV infection during which the antigen is present but antibodies are not yet produced. Antibody testing cannot determined whether serum taken during this period is infected or not. Therefore, there is a risk of secondary infection by the blood derived components, such as blood donation, blood components, factors from blood, contaminated specimens in the window period, because blood donor is screened by the antibody test that can not exclude such specimens. For this reason it has been necessary to detect HCV itself, that is, HCV particles, instead of antibodies against HCV polypeptides to reduce the risk. Web site: http://www.delphion.com/details?pn=US06623921__ ·

Methods and compositions to investigate infection by hepatitis B virus and agents to prevent and treat the infection Inventor(s): Isom; Harriet C. (Hershey, PA), Delaney, IV; William E. (San Bruno, CA) Assignee(s): The Penn State Research Foundation (University Park, PA) Patent Number: 6,610,471 Date filed: September 5, 2000 Abstract: Methods and compositions that use the hepatitis B virus genome, and fragments or extensions, in a baculovirus vector, to develop anti-HBV agents and to drive high-level expression of a desired gene in a cell of hepatic origin. Excerpt(s): Supported in part by research grants from the National Institutes of Health (CA73045 and CA23931). Methods and compositions are presented that use the hepatitis B virus genome, and fragments or extensions thereof, in a baculovirus vector, to develop anti-HBV agents. Hepatitis B virus (HBV) is a small, double-stranded DNA virus and is the prototype of the hepadnavirus family. HBV is a human pathogen capable of causing both acute and chronic hepatitis. The World Health Organization currently estimates that 350 million people are chronically infected with HBV. Persistent HBV infection is also associated with an increased risk of cirrhosis and hepatocellular carcinoma. Web site: http://www.delphion.com/details?pn=US06610471__

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Methods of treating hepatitis delta virus infection with.beta.-L-2'-deoxy-nucleosides Inventor(s): Bryant; Martin L. (Carlisle, MA), Sommadossi; Jean-Pierre (Birmingham, AL) Assignee(s): Idenix Pharmaceuticals Inc. (Cambridge, MA) Patent Number: 6,596,700 Date filed: May 29, 2001 Abstract: A method and composition for treating a host infected with hepatitis D comprising administering an effective hepatitis D treatment amount of a described 2'deoxy-.beta.-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof. Excerpt(s): This invention is in the area of methods and compositions for the treatment of a host infected with hepatitis delta virus (also referred to as "HDV") that includes

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administering an effective amount of a defined.beta.-L-2'-deoxy-nucleoside or a pharmaceutically acceptable salt or prodrug thereof. Type D hepatitis, the most severe form of viral hepatitis, is caused by infection with hepatitis D (delta) virus (HDV), a subviral satellite of hepatitis B virus (HBV) (Smedile, A. et al. Prog Liver Dis 1994, 12, 15775). Compared with other agents of viral hepatitis, acute HDV infection is more often associated with fulminant hepatitis, a rapidly progressive, often fatal form of the disease in which massive amounts of the liver are destroyed. Chronic type D hepatitis is typically characterized by necroinflammatory lesions, similar to chronic HBV infection, but is more severe, and frequently progresses rapidly to cirrhosis and liver failure, accounting for the disproportionate association of chronic HDV infection with terminal liver disease (Smedile, A. et al. Prog Liver Dis 1994, 12, 157-75; Rizzetto, M. et al. Ann Intern Med 1983, 98, 437-41). Although HDV infection affects fewer individuals than HBV alone, the resulting acute or chronic liver failure is a common indication for liver transplantation in Europe as well as North America (Smedile, A. and Rizzetto, M. Int J Clin Lab Res 1992, 22, 211-215; Wright, T. L. and Pereira, B. Liver Transplant Surgery 1995, 1, 30-42). Chronic disease affects 15 million persons worldwide, about 70,000 of whom are in the U.S. The Center for Disease Control estimates 1,000 deaths annually in the U.S. due to HDV infection (Alter, M. J. and Hadler, S. C. Prog Clin Biol Res 1993, 382, 243-50; Alter, M. J. and Mast, E. E. Gastroenterol Clin North Am 1994, 23, 437-55). There is currently no generally accepted effective therapy for type D hepatitis, and liver transplantation is the only option for the associated end-stage liver disease. Although interferon alpha has been moderately successful in treating some cases of type D hepatitis, the need for better treatment options is indicated by the very high doses required, variable responses, frequent relapse after cessation of treatment, and difficulties in drug administration (Thomas, H. C. et al. Prog Clin Biol Res 1987, 234, 27790; Hoofnagle, J. et al. Prog Clin Biol Res 1987, 234, 291-8; Rosina, F. et al. Prog Clin Biol Res 1987, 234, 299-303; Rosina, F. et al. Hepatology 1991, 13, 1052-6; Farci, P. et al. N Engl J Med 1994, 330, 88-94; Hadziyannis, S. J. J Hepatol 1991, 13(Suppl 1), S21-6; Di Marco, V. et al. J Viral Hegat 1996, 3, 123-8; Porres, J. C. et al. J Hepatol 1989, 9, 338-44). Web site: http://www.delphion.com/details?pn=US06596700__ ·

Non-A, non-B, non-C, non-D, non-E hepatitis reagents and methods for their use Inventor(s): Leary; Thomas P. (Kenosha, WI), Muerhoff; Anthony Scott (Kenosha, WI), Erker; James Carl (Hainesville, IL), Buijk; Sheri L. (Round Lake, IL), Desai; Suresh M. (Libertyville, IL), Dawson; George J. (Libertyville, IL), Schlauder; George G. (Skokie, IL), Simons; John N. (Grayslake, IL), Pilot-Matias; Tami J. (Green Oaks, IL), Mushahwar; Isa K. (Grayslake, IL) Assignee(s): Abbott Laboratories (Abbott Park, IL) Patent Number: 6,586,568 Date filed: June 6, 1995 Abstract: Hepatitis GB Virus (HGBV) nucleic acid and amino acid sequences useful for a variety of diagnostic and therapeutic applications, kits for using the HGBV nucleic acid or amino acid sequences, HGBV immunogenic particles, and antibodies which specifically bind to HGBV. Also provided are methods for producing antibodies, polyclonal or monoclonal, from the HGBV nucleic acid or amino acid sequences. Excerpt(s): This invention relates generally to a group of infectious viral agents causing hepatitis in man, and more particularly, relates to materials such as polynucleotides derived from this group of viruses, polypeptides encoded therein, antibodies which

Patents 369

specifically bind to these polypeptides, and diagnostics and vaccines that employ these materials. Hepatitis is one of the most important diseases transmitted from a donor to a recipient by transfusion of blood products, organ transplantation and hemodialysis; it also can be transmitted via ingestion of contaminated food stuffs and water, and by person to person contact. Viral hepatitis is known to include a group of viral agents with distinctive viral genes and modes of replication, causing hepatitis with differing degrees of severity of hepatic damage through different routes of transmission. In some cases, acute viral hepatitis is clinically diagnosed by well-defined patient symptoms including jaundice, hepatic tenderness and an elevated level of liver transaminases such as aspartate transaminase (AST), alanine transaminase (ALT) and isocitrate dehydrogenase (ISD). In other cases, acute viral hepatitis may be clinically inapparent. The viral agents of hepatitis include hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis delta virus (HDV), hepatitis E virus (HEV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Although specific serologic assays available by the late 1960's to screen blood donations for the presence of HBV surface antigen (HBsAg) were successful in reducing the incidence of post-transfusion hepatitis (PTH) in blood recipients, PTH continued to occur at a significant rate. H. J. Alter et al., Ann. Int. Med. 77:691-699 (1972); H. J. Alter et al., Lancet ii:838-841 (1975). Investigators began to search for a new agent, termed "non-A, non-B hepatitis" (NANBH), that caused viral hepatitis not associated with exposure to viruses previously known to cause hepatitis in man (HAV, HBV, CMV and EBV). See, for example, S. M. Feinstone et al., New Engl. J. Med. 292:767-770 (1975); Anonymous editorial, Lancet ii:64-65 (1975); F. B. Hollinger in B. N. Fields and D. M. Knipe et al., Virology, Raven Press, New York, pp. 2239-2273 (1990). Web site: http://www.delphion.com/details?pn=US06586568__ ·

Nuclear envelope protein recognized by atypical p-ANCA in patients with inflammatory bowel disease and autoimmune liver diseases Inventor(s): Worman; Howard J. (New York, NY), Terjung; Birgit (Swisttal, DE) Assignee(s): The Trustees of Columbia University in the City of New York (New York, NY) Patent Number: 6,627,458 Date filed: June 15, 2001 Abstract: The present invention is directed to the molecular characterization of the nuclear antigen recognized by atypical p-antineutrophil cytoplasmic antibodies (pANCA) in order to better diagnose patients with inflammatory bowel diseases such as ulcerative colitis (UC), and autoimmune liver diseases such as primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH). Molecular characterization of the target antigen comprises preparing cytoplasmic and nuclear extracts of human neutrophils, human HL-60 and murine 32D myeloid cells. Proteins should then be resolved by 1 and 2 dimensional gel electrophoresis and reactive proteins can then be detected by immunoblotting with sera from individuals, making certain to have both normal and disease controls. Atypical p-ANCA should then be affinity purified against the reactive protein and investigated for their immunofluorescence pattern using confocal microscopy. One could then detect the antigen that atypical p-ANCA can recognize and use that antigen to detect the prescence of atypical p-antineutrophil cytoplasmic antibodies so as to diagnose patients with inflammatory bowel diseases such as ulcerative colitis (UC), and autoimmune liver diseases such as sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH).

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Excerpt(s): Throughout this application, various publications are referenced by author and date. Full citations for these publications may be found listed alphabetically at the end of the specification immediately preceding the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein. Atypical "antineutrophil cytoplasmic antibodies" (ANCA) are present in patients with ulcerative colitis (UC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) ANCA represent a family of heterogenous autoantibodies directed against constituents of neutrophilic granulocytes. These autoantibodies have become valuable seromarkers for the diagnostic and therapeutic management of patients with systemic vasculitides such as Wegner granulomatosis and microscopic polyangiitis, in which they recognize well defined cytoplasmic antigens such as proteinase 3 and myeloperoxidase. Two well established ANCA staining patterns can be distinguished on ethanol-fixed neutrophils: a difuse cytoplasmic fluorescence pattern (c-ANCA) and a fine homogeneous labeling of the perinuclear cytoplasm (p-ANCA). Autoantibodies that are similar to p-ANCA in patients with systemic vasculitides are detected in individuals with chronic inflammatory bowel diseases (IBD) such as ulcerative colitis or autoimmune liver disorders such as primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH). Contrary to systemic vasculitides, the role of ANCA in these disorders is not clear. Various cytoplasmic proteins such as bactericidal/permeability increasing protein, catalase, cathepsin G, enolase, or lactoferrin have been proposed as putative target antigens of ANCA in these disorders, but reactivity to these proteins has only been detected in less than thirty five percent of cases. The predominant target antigen of ANCA in IBD and autoimmune liver disorders has not been identified. Since their target antigens are unknown, p-ANCA in patients with IBD or autoimmune liver disorders are generally referred to as atypical p-ANCA. Web site: http://www.delphion.com/details?pn=US06627458__ ·

Nucleotide vector composition containing such vector and vaccine for immunization against hepatitis Inventor(s): Whalen; Robert Gerald (Paris, FR), Michel; Marie-Louise (Paris, FR), Davis; Heather Lynn (Ottawa, CA) Assignee(s): Universite d'Ottawa (Ottawa, CA), Institut National de la Sant et de la Recherche Medical (Paris, FR), Institut Pasteur (Paris, FR) Patent Number: 6,635,624 Date filed: September 2, 1998 Abstract: The invention relates to methods of inducing an immunogenic response in a subject that include administering a nucleotide plasmid vector that includes a gene coding for a surface antigen protein derived from hepatitis B virus and a promoter for the expression of the gene. The invention also relates to vaccine compositions for protecting against hepatitis B virus. Excerpt(s): The present application relates to a vector for immunization against hepatitis. It is also related to a composition containing this vector. Immunization by injection of bare DNA into muscle tissues has been the object of several studies since the beginning of the 1990s. Web site: http://www.delphion.com/details?pn=US06635624__

Patents 371

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Oligonucleotide primers for efficient detection of hepatitis C virus (HCV) and methods of use thereof Inventor(s): Gorman; Kevin M. (Penfield, NY), Linnen; Jeffrey M. (San Diego, CA) Assignee(s): Ortho-Clinical Diagnostics, Inc. (Raritan, NJ) Patent Number: 6,638,714 Date filed: January 28, 2000 Abstract: Described herein are methods and kits for the detection of hepatitis C virus RNA is biological samples obtained from human subjects. The invention includes novel amplification primers and probes useful in the amplification of DNA derived from hepatitis C virus RNA, and kits and methods which incorporate the novel primers. Excerpt(s): The present invention pertains to improved methods for detecting nucleic acid sequences in biological samples, particularly sequences derived from infectious microorganisms. Hepatitis C Virus (HCV) is a parenterally transmitted virus responsible for the majority of cases of post-transfusion hepatitis and a substantial portion of sporadic (or community acquired) hepatitis cases worldwide. It is estimated that more than 1% of the world's population is infected with HCV. HCV infection is associated with acute hepatitis, chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Analysis of HCV coding sequences from around the world has revealed considerable sequence variation among individual viral isolates. Furthermore, analyses of HCV sequences from individual patients have shown that the virus circulates as so-called "quasi-species," which contain related but not identical sequences. The variation that exists among isolates and within individual patients is believed to be the result of the low fidelity of the virally-encoded RNA-dependent RNA polymerase. The degree of genetic variability of HCV has important implications for prevention, diagnosis, and control of infection. Web site: http://www.delphion.com/details?pn=US06638714__

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Oligonucleotides and methods for detecting hepatitis B viral nucleic acids Inventor(s): Hamdan; Hasnah (Riverside, CA), Pasupuleti; Vijaya (Irvine, CA), Lewinski; Michael (San Clemente, CA) Assignee(s): Quest Diagnostics Investments Incorporated (Wilmington, DE) Patent Number: 6,635,428 Date filed: December 4, 2001 Abstract: The present invention provides methods and compositions for determining the presence and/or amount of HBV nucleic acids in a test sample. In particular, substantially purified oligonucleotide primers and probes are described that can be used for qualitatively and quantitatively detecting HBV nucleic acid in a test sample by amplification methods. The present invention also provides primers and probes for generating and detecting control nucleic acid sequences that provide a convenient method for assessing internal quality control of the HBV assay. Excerpt(s): The present invention relates generally to compositions and methods for detecting hepatitis B viral nucleic acids in a test sample. The following discussion of the background of the invention is merely provided to aid the reader in understanding the invention and is not admitted to describe or constitute prior art to the present invention.

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One of the major causes of hepatitis are specific hepatitis viruses. There are at least six different viruses responsible for various types of hepatitis. Among them, hepatitis B virus (HBV) is the most thoroughly characterized and complex etiologic agent. The infective Dane particle consists of a viral core plus an outer surface coat. The core contains circular double-stranded DNA and DNA polymerase, and it replicated within the nuclei of infected hepatocytes. Surface coat is added in the cytoplasm and is produced in great excess; it can be detected in serum by immunologic means as hepatitis B surface antigen (HBsAg). Web site: http://www.delphion.com/details?pn=US06635428__ ·

Peptides for inducing cytotoxic T lymphocyte responses to hepatitus B virus Inventor(s): Ferrari; Carlo (Parma, IT), Chisari; Francis V. (Del Mar, CA), Penna; Amalia (Parma, IT), Missael; Gabriele (Parma, IT) Assignee(s): The Scripps Research Institute (La Jolla, CA) Patent Number: 6,607,727 Date filed: May 20, 1996 Abstract: Peptides are used to define epitopes that stimulate HLA-restricted cytotoxic T lymphocyte activity against hepatitis B virus antigens. The peptides are derived from regions of HBV polymerase, and are particularly useful in treating or preventing HBV infection, including methods for stimulating the immune response of chronically infected individuals to respond to HBV antigens. Excerpt(s): Cytotoxic T lymphocytes (CTLs) play an essential role in fighting cells infected with viruses, intracellular bacteria and parasites, and tumor cells. They do so by direct cytotoxicity and by providing specific and nonspecific help to other immunocytes such as macrophages, B cells, and other T cells. Infected cells or tumor cells process antigen through intracellular events involving proteases. The processed antigen is presented on the cellular surface in the form of peptides bound to HLA class I molecules to T cell receptors on CTLs. MHC class I molecules can also bind exogenous peptides and present them to CTLs without intracellular processing. At the present time it is difficult to accurately predict from the sequence of an antigenic protein how the protein will be processed and which peptide portions will bind HLA class I molecules and be presented to CTLs. Binding motifs have been predicted for some HLA class I molecules based on sequence analysis of peptides eluted from these molecules (Falk et al., Nature 351:290 (1991)). Further, of the peptides that are processed and do bind to HLA class I, which ones will contain CTL-recognizable epitopes is not yet predictable. Hepatitis B Virus ("HBV") is a non-lytic virus which has currently infected approximately 250 million people worldwide. HBV infection in adults typically leads to an acute disease in the majority of cases, and to a chronic disease state in a minority of patients. This ratio of acute to chronic is reversed when the infection occurs close to the time of birth. There is an increased incidence of hepatocellular carcinoma in chronic HBV infection. A small percentage of individuals who are infected with HBV in adulthood develop fulminant hepatitis associated with a strong immune response with high lethality. Web site: http://www.delphion.com/details?pn=US06607727__

Patents 373

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Pharmaceutical formulation useful for the treatment of hepatitis B, hepatitis C and other viral infections of the liver and a process for its preparation Inventor(s): Thyagarajan; Sadras Panchatcharam (Chennai, IN) Assignee(s): University of Madras (Chennai, IN) Patent Number: 6,589,570 Date filed: December 12, 2000 Abstract: The invention disclosed in this application relates to a pharmaceutical formulation prepared from the biotyped variety of the medicinal plant, Phyllanthus amarus which is useful for the treatment of Hepatitis B (both acute and chronic), Hepatitis C (both acute and chronic) and other related viral infections of the liver with antihepatotoxic and liver cell regenerating potentials and immunomodulating properties. The invention confirms, that when pars of the biotyped variety of the medicinal plant, Phyllanthus amarus are extraceted separately with a polar solvent alone, polar solvent and water in specific ratios and water alone and when such extracts are mixed together, the resultant formulation has all the essential antiviral and biological properties, while the individual polar or aqueous extracts alone does not possess one or more of these properties. The present invention also relates to a process for the preparation of the above said new pharmaceutical formulation with biological and chemical standardisation protocols. Excerpt(s): This invention relates to a pharmaceutical formulation useful for the treatment of Hepatitis B and Hepatitis C and other viral infections of liver. This invention particularly relates to a pharmaceutical formulation useful for the treatment of acute and chronic Hepatitis B & C virus infections prepared from the Indian biotyped medicinal plant, Phyllanthus amarus. This invention also relates to a process for the preparation of the pharmaceutical formulation useful for the treatment of acute and chronic Hepatitis B and Hepatitis C and other viral infections of the liver from the medicinal plant Phyllanthus amarus. It is needless to stress the need for a s drug that would keep the liver functioning at its optimum or the one that would be selectively active against the currently known etiological agents of acute and chronic viral diseases of the liver. This is important because the disease of the liver throw the entire human body out of gear. The exciting alphabet of viral Hepatitis includes a wide range of totally unrelated often highly unusual pathogenic human viruses like Hepatitis A virus (HAV), Hepatitis B virus (HSV), Hepatitis C virus (HCV), Hepatitis D virus (HDV), Hepatits E virus (HEV) etc. Of the viruses it has been clearly established that HBV, HCV and HDV are the ones that are associated with the development of chronic persistent/active hepatitis, cirrhosis of the liver and even hepatocellular carcinoma besides being associated with fulminant hepatitis and sub acute hepatic failure. The natural disease course in HBV is being summarized to understand the need for the effective management and treatment of Hepatitis B in a country. For normal adults with low viral production and an early immune response, the disease course is self limiting and usually asymptomatic (60-80% of all HBV infections). Individuals who replicate the virus in larger quantities, with a relatively late immune response have a self-limiting symptomatic acute hepatitis. Irrespective of whether initially symptomatic or asymptomatic, the infection becomes chronic in 5-10% of the individuals, 20-30% of them developing clinical sequelae such as chronic hepatitis, cirrhosis or hepatoma within years or decades. In neonates, however, the immune defence is still lacking (induction of tolerance), so that infected individuals do not develop acute hepatitis, but more of them become chronic camers (80-90%). Such carriers also progress frequently to chronic clinical sequelae faster. Between these two extremes are immunocompromised

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individuals, such as intravenous drug users, haemodialysis patients or transplant recipients, who are more likely to become chronic carriers than are healthy adults (1060%). (WHO Tech. Report Series 1987;754:18). Web site: http://www.delphion.com/details?pn=US06589570__ ·

Reporter gene system for use in cell-based assessment of inhibitors of the hepatitis C virus protease Inventor(s): Jackson; Roberta Lynn (San Diego, CA), Patick; Amy Karen (Escondido, CA), Potts; Karen Elizabeth (Solana Beach, CA) Assignee(s): Agouron Pharmaceuticals, Inc. (San Diego, CA) Patent Number: 6,599,738 Date filed: August 2, 2001 Abstract: A cell-based assay system in which the detection of the reporter gene activity, or secreted alkaline phosphatase (SEAP), is dependent upon the protease activity of the Hepatitis C virus NS3 gene product. This system can be used to assess the activity of candidate protease inhibitors in a mammalian cell-based assay system. The assay system is simpler than previously described assays due to the use of SEAP which allows the reporter gene activity to be quantified by measuring the amount of secreted gene product in the cell media by monitoring the conversion of luminescent or colorimetric alkaline phosphatase substrate. Excerpt(s): A cell-based assay system in which the detection of reporter gene activity (secreted alkaline phosphatase or SEAP) is dependent upon active Hepatitis C virus (HCV) NS3 protease. The assay system is useful in the in vitro screening, in a mammalian cell-based assay, of potential protease inhibiting molecules useful in the treatment of HCV. The advantages of using SEAP over more routinely used reporter genes such as beta-galactosidase or luciferase, is that a cell lysis step is not required since the SEAP protein is secreted out of the cell. The absence of a cell lysis step decreases intra- and inter-assay variability as well as makes the assay easier to perform then earlier assays. The NS2/3 is a metalloprotease and has been shown to mediate cleavage at the 2/3 junction site Grakoui, et al. (1993); Hijikata, M., et al., J. Virol. 67:4665-4675 1993. In contrast, the NS3 protease is required for multiple cleavages within the nonstructural segment of the polyprotein, specifically the 3/4A, 4A/4B, 4B/5A, and 5A/5B junction sites Bartenschlager et al. (1993); Eckart, M. R., et al., Biochem. Biophys. Res. Comm. 192:399-406 1993; Grakoui et al. (1993); Tomei et al. (1994). More recently, it is thought that the NS2/3 protease might actually be part of the HCV NS3 protease complex even though they have two functionally distinct activities. Although NS3 protease is presumed to be essential for HCV viability, definitive proof of its necessity has been hampered by the lack of an infectious molecular clone that can be used in cell-based experiments. However, recently two independent HCV infectious molecular clones have been developed and have been shown to replicate in chimpanzees. Kolykhalov, A. A., et al., Science 277:570-574 1997; Yanagi, M., et al., Proc. Natl. Acad. Sci. 94:8738-8743 1997. The requirement for NS3 in the HCV life cycle may be validated in these clones by using oligo nucleotide-mediated site directed mutagenesis to inactivate the NS3 catalytic serine residue and then determining whether infectious virus is produced in chimpanzees. Until these experiments are performed, the necessity of NS3 is inferred from cell-based experiments using the related yellow fever (YFV) and bovine viral diarrhea (BVDV) viruses. Mutagenesis of the YFV and BVDV NS3 protease homologs has shown that NS3 serine protease activity is essential for YFV

Patents 375

and BVDV replication. Chambers, T. J., et al., Proc. Natl. Acad. Sci. 87:8898-8902 1990; Xu, J., et al., J. Virol. 71:5312-5322 1997. In general, when investigators screen potential anti-viral compounds for inhibitory activity, it usually involves initial in vitro testing of putative enzyme inhibitors followed by testing the compounds on actual infected cell lines and animals. It is obvious that working with live virus in large scale screening activities can be inherently dangerous and problematic. While final testing of putative inhibitors in infected cells and animals is still necessary for preclinical drug development, for initial screening of candidate molecules, such work is cost-prohibitive and unnecessary. Furthermore, the inability to grow HCV in tissue culture in a reproducible quantitative manner prevents the evaluation of potential antiviral agents for HCV in a standard antiviral cytopathic effect assay. In response to this real need in the industry, development of non-infectious, cell-based, screening systems is essential. Web site: http://www.delphion.com/details?pn=US06599738__ ·

Sequences and methods for detection of hepatitis B virus Inventor(s): Nussbaumer; William A. (Timonium, MD), Berger; Dolores M. (Baltimore, MD), Fort; Thomas L. (Finksburg, MD), Hellyer; Tobin J. (Owings Mills, MD) Assignee(s): Becton, Dickinson and Company (Franklin Lakes, NJ) Patent Number: 6,583,279 Date filed: January 26, 2001 Abstract: Primers and probes derived from the HBV DNA polymerase gene which facilitate detection and/or quantification of all presently known genotypes of HBV. Disclosed sequences may be used in a variety of primer and probe constructs for detection of HBV nucleic acids. Excerpt(s): The present invention relates to materials and methods for detection of Hepatitis B viral nucleic acids, in particular to probes and primers for detection of Hepatitis B in hybridization and amplification assays. Hepatitis B virus (HBV) is a partially double-stranded DNA virus which uses a unique replication mechanism incorporating an intermediate reverse transcription step. It is a major causative agent of chronic hepatitis and has been implicated in liver cirrhosis and hepatocellular carcinoma. Accurate identification and quantitation of HBV DNA is important not only for detecting HBV infection but also for monitoring the efficacy of antiviral treatments. A simple assay for HBV DNA using branched-DNA (bDNA) probes has been used for quantitation but was found to be insufficiently sensitive to monitor serum virus levels in patients undergoing antiviral treatment. More recently, HBV DNA has been detected and quantitated in more sensitive PCR assays, using both the Amplicor.TM. HBV Monitor test and the TaqMan.TM. technology for real-time detection. The present invention provides probes and primers for detection of HBV nucleic acids which may provide a more rapid and sensitive means for detecting HBV than immunological and culture-based methods. Further the probes and primers of the invention may allow more reliable detection of naturally occurring variants of HBV, as they are based on an analysis of conserved regions of the HBV DNA polymerase gene. Web site: http://www.delphion.com/details?pn=US06583279__

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Synthesis, anti-human immunodeficiency virus, and anti-hepatitis B virus activities of 1,3-oxaselenolane nucleosides Inventor(s): Schinazi; Raymond F. (Decatur, GA), Chu; Chung K. (Athens, GA), Du; Jinfa (Irvine, CA) Assignee(s): The University of Georgia Research Foundation, Inc. (Athens, GA), Emory University (Atlanta, GA) Patent Number: 6,590,107 Date filed: March 5, 2001 Abstract: A method and composition for the treatment of HIV infection, HBV infection, or abnormal cellular proliferation in humans and other host animals is disclosed that includes the administration of an effective amount of a 1,3-oxaselenolane nucleoside or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier. Excerpt(s): This invention is in the area of synthetic nucleosides, and is specifically directed to 1,3-oxaselenolane nucleosides and their pharmaceutical uses, compositions, and method of preparation. In 1981, acquired immune deficiency syndrome (AIDS) was identified as a disease that severely compromises the human immune system, and that almost without exception led to death. In 1983, the etiological cause of AIDS was determined to be the human immunodeficiency virus (HIV). In 1985, it was reported that the synthetic nucleoside 3'-azido-3'-deoxythymidine (AZT) inhibits the replication of human immunodeficiency virus. Since then, a number of other synthetic nucleosides, including 2',3'-dideoxyinosine (DDI), 2',3'-dideoxycytidine (DDC), 2',3'-dideoxy-2',3'didehydrothymidine (D4T), and (1S,4R)-4-[2-amino-6-cyclopropyl-amino)-9H-purin-9yl]-2-cyclopentene-1-me thanol succinate ("159U89"), have been proven to be effective against HIV. In general, after cellular phosphorylation to the 5'-triphosphate by cellular kinases, these synthetic nucleosides are incorporated into a growing strand of viral DNA, causing chain termination due to the absence of the 3'-hydroxyl group. They can also or alternatively inhibit the viral enzyme reverse transcriptase or DNA polymerase. Web site: http://www.delphion.com/details?pn=US06590107__

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Synthetic antigens for the detection of antibodies to hepatitis C virus Inventor(s): Maertens; Geert (Brugge, BE), Van Heuverswijn; Hugo (Laarne, BE), Pollet; Dirk (Schilde, BE), Deleys; Robert J. (Three Bridges, NJ) Assignee(s): Innogenetics, N.V. (Ghent, BE) Patent Number: 6,576,417 Date filed: August 30, 2001 Abstract: Peptide sequences are provided which are capable of mimicking proteins encoded by HCV for use as reagents for screening of blood and blood products for prior exposure to HCV. The peptides are at least 5 amino acids long and can be used in various specific assays for the detection of antibodies to HCV, for the detection of HCV antigens, or as immunogens. Excerpt(s): The implementation of systematic testing for hepatitis B virus (HBV) has been instrumental in eliminating this virus from the blood supply. Nevertheless, a significant number of post-transfusion hepatitis (PTH) cases still occur. These cases are generally attributable to non-A, non-B hepatitis (NANBH) virus(es), the diagnosis of

Patents 377

which is usually made by exclusion of other viral markers. In order to detect potential carriers of HCV, it is necessary to have access to large amounts of viral proteins. In the case of HCV, there is currently no known method for culturing the virus, which precludes the use of virus-infected cultures as a source of viral antigens. The current first-generation antibody test makes use of a fusion protein containing a sequence of 363 amino acids encoded by the HCV genome. It was found that antibodies to this protein could be detected in 75 to 85% of chronic NANBH patients. In contrast, only approximately 15% of those patients who were in the acute phase of the disease, had antibodies which recognized this fusion protein (Kuo, G. et al. Science (1989) 244:362364). The absence of suitable confirmatory tests, however, makes it difficult to verify these statistics. The seeming similarity between the HCV genome and that of flaviviruses makes it possible to predict the location of epitopes which are likely to be of diagnostic value. An analysis of the HCV genome reveals the presence of a continuous long open reading frame. Viral RNA is presumably translated into a long polyprotein which is subsequently cleaved by cellular and/or viral proteases. By analogy with, for example, Dengue virus, the viral structural proteins are presumed to be derived from the amino-terminal third of the viral polyprotein. At the present time, the precise sites at which the polyprotein is cleaved can only be surmised. Nevertheless, the structural proteins are likely to contain epitopes which would be useful for diagnostic purposes, both for the detection of antibodies as well as for raising antibodies which could subsequently be used for the detection of viral antigens. Similarly, domains of nonstructural proteins are also expected to contain epitopes of diagnostic value, even though these proteins are not found as structural components of virus particles. 1: IX, 2: XVIII, 3: I, 4: III, 5: V, 6: IX+XVIII, 7: I+XVIII, 8: I+III+IX, 9: I+III+V+XVIII, 10: I+III+V+IX, 11: I+III+IX+XVIII, 12: I+III+V+IX+XVIII. Web site: http://www.delphion.com/details?pn=US06576417__ ·

Therapeutic nucleoside compound Inventor(s): Daluge; Susan Mary (Durham, NC) Assignee(s): SmithKline Beecham Corporation (Philadelphia, PA) Patent Number: 6,630,477 Date filed: October 12, 2001 Abstract: The present invention relates to (1R,4S)-4-(6-amino-9H-purin-9-yl)-2cyclopentene-1-methanol and its use in medical therapy for the treatment of hepatitis B infection. Excerpt(s): The present invention relates to (1R,4S)-4-(6-amino-9H-purin-9-yl)-2cyclopentene-1-methanol and its use in medical therapy. Hepatitis B virus (HBV) is a small DNA containing virus which infects humans. It is a member of the class of closely related viruses known as the hepadnaviruses, each member of which selectively infects either mammalian or avian hosts, such as the woodchuck and the duck. Recent insights into the mechanism of replication of the hepadnavirus genome indicate the importance of reverse transcription of an RNA intermediate, suggesting that the reverse transcriptase is a logical chemotherapeutic target. HBV is a viral pathogen of major worldwide importance. The virus is etiologically associated with primary hepatocellular carcinoma and is thought to cause 80% of the world's liver cancer. Clinical effects of infection with HBV range from headache, fever, malaise, nausea, vomiting, anorexia and abdominal pains. Replication of the virus is usually controlled by the immune response, with a course of recovery lasting weeks or months in humans, but infection may be

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more severe leading to persistent chronic liver disease outlined above. U.S. Pat. No. 4,916,224 discloses dideoxycarbocyclic nucleosides and their use in the treatment of HIV. Wang et al. (Bioorganic Et Medicinal Chemistry Letters 8, pp. 1585-1588, 1998) disclose the synthesis of L-carbocyclic 2',3'-didehydro-2',3'-dideoxyadensosine and its use in HIV infections. Web site: http://www.delphion.com/details?pn=US06630477__ ·

TNF-.alpha. production inhibitor comprising kavalactone as an active ingredient Inventor(s): Uchida; Masayuki (Odawara, JP), Yamada; Masashi (Tokyo, JP), Suma; Yukie (Tokyo, JP), Suzuki; Hiroto (Tokyo, JP), Murata; Natsuko (Odawara, JP), Okabe; Sachiko (Ageo, JP), Asakawa; Yoshinori (Tokushima, JP) Assignee(s): Meiji Dairies Corporation (Tokyo, JP) Patent Number: 6,608,105 Date filed: August 30, 2001 Abstract: The present invention provides a TNF-.alpha. production inhibitor containing a kavalactone as an active ingredient, which inhibitor has high safety, exerts an excellent effect of inhibiting TNF-.alpha. production, and is useful as a drug or an animal drug for preventing, ameliorating, or treating diseases such as cachexia attributed to cancer or infectious diseases, chronic rheumatoid arthritis, inflammatory diseases, osteoarthritis, systemic lupus erythematosus (SLE), rejection during bone marrow transplantation, multiple organ failure, AIDS, meningitis, hepatitis, and type-II diabetes. The present invention also provides a preventive, ameliorating, or therapeutic agent for diseases caused by abnormal production of TNF-.alpha., the agent containing a kavalactone as an active ingredient. Excerpt(s): The present invention relates to a TNF-.alpha. production inhibitor containing a kavalactone as an active ingredient, and to a preventive, ameliorating, or therapeutic agent for diseases caused by abnormal production of TNF-.alpha. Recent studies have shown that excessive production of TNF-.alpha. induces onset of a variety of diseases, including cachexia attributed to cancer or infectious diseases (Nature, 316: 552, 1985), septic shock (J. Immunol., 145: 4185, 1990; Science, 229: 869, 1985; Shock, 30: 1990), chronic rheumatoid arthritis (Ann. Rheum. Dis., 49: 665, 1990; Lancet, 344: 1105, 1994; Lancet, 344: 1125, 1994; British J. Rheum., 34: 334, 1995), inflammatory diseases such: as ulcerative colitis and Crohn disease (Arch. Dis. Child, 66: 561, 1991; Gastroenterology), osteoarthritis (Arthritis Rheum., 36: 819, 1993), Kawasaki's disease (Clin. Immunol. Immunopathol., 56: 29, 1990), multiple sclerosis (N. Engl. J. Med., 325(7): 467, 1991), Behchet's disease (J. Rheumatol., 17: 1107, 1990), systemic lupus erythematosus (SLE) (Arthritis Rheum., 32: 146, 1989), rejection during bone marrow transplantation (J. Exp. Med., 175: 405, 1992), multiple organ failure (Rinshoi, 17(20), 2006, 1991), malaria (Science, 237: 1210, 1987), AIDS (J. Acquir. Immune Defic. Syndr., 5: 1099, 1992), meningitis (Lancet, 1: 355,1987), hepatitis (Kozo Kanno, Kanzo, 33: 213, 1992), and type-II diabetes (Science, 259: 87, 1993). The aforementioned diseases caused by excessive production of TNF-.alpha. have hitherto been treated from a mere palliative approach by use of steroid agents, anti-inflammatory agents, antibiotics, etc., and drugs for fundamentally treating the diseases have not yet been developed. Web site: http://www.delphion.com/details?pn=US06608105__

Patents 379

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Treatment of chronic viral infections with M. vaccae Inventor(s): Stanford; Cynthia A. (Kent, GB), Rook; Graham A. W. (London, GB), Stanford; John L. (Kent, GB) Assignee(s): Stanford Rook Limited (London, GB) Patent Number: 6,596,282 Date filed: September 13, 2001 Abstract: The present invention provides the use of an M. vaccae preparation for the manufacture of a medicament for use in the treatment of a chronic viral infection, excluding an HIV infection. Chronic viral infections include HPV infection, such as HPV infection associated with cervical dysplasia, herpes virus infection, subacute sclerosing pan-encephalitis and hepatitis virus infection. Excerpt(s): The present invention relates to the use of M. vaccae in the treatment of viral infections, particularly chronic viral infections. British Specification No. 2156673 (International Patent Specification WO85/03639) describes immunotherapeutic agents comprising killed cells of M. vaccae. These agents are useful in the immunotherapy of mycobacterial disease, especially tuberculosis and leprosy. It is stated that use of this immunotherapeutic agent facilitates the removal of the persisting bacilli responsible for tuberculosis or leprosy which, as is well known, it is difficult to remove by chemotherapy alone. International Patent Specification PCT/GB85/00183 (WO85/05034) describes compositions for the alleviation of the symptoms of, and for the treatment or diagnosis of, arthritic disease which comprise as active ingredient the whole organism of M. vaccae. It is stated that the preparations of M. vaccae are useful for the treatment of various autoimmune diseases and especially arthritic conditions including rheumatoid arthritis, ankylosing spondylitis or Reiter's syndrome. Web site: http://www.delphion.com/details?pn=US06596282__

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Use of strains of parapoxvirus ovis against organ fibrosis Inventor(s): Siegling; Angela (Paris, FR), Theiss; Gudrun (Wuppertal, DE), HirthDietrich; Claudia (Wuppertal, DE), Knorr; Andreas (Erkrath, DE), Weber; Olaf (Woodbridge, CT), Schlapp; Tobias (Cologne, DE) Assignee(s): Bayer Aktiengesellschaft (Leverkusen, DE) Patent Number: 6,632,647 Date filed: July 11, 2001 Abstract: The present invention relates to the use, in humans, of inactivated parapoxviruses for the prophylaxis and treatment of diseases which are accompanied by an increased deposition of collagen, with it being possible for both internal organs, such as the liver, and the skin and its appended structures, to be affected. The invention relates, in particular, to liver fibrosis and/or liver cirrhosis consequent upon virus hepatitis, or to ethanol-induced liver diseases and to cystic fibrosis. Excerpt(s): The present invention relates to the use in humans of inactivated parapoxviruses in the prophylaxis and treatment of diseases which are accompanied by increased deposition of collagen, in connection with which both internal organs, such as liver, and the skin and its appended structures can be affected. The invention relates, in particular, to liver fibrosis and liver cirrhosis following viral hepatitis, or ethanolinduced liver diseases, and also cystic fibrosis. The present invention relates, in

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particular, to the use in humans of isolates of Parapoxvirus ovis, for example the strains D1701, orf-11, Greek orf strain 176, Greek orf strain 155, New Zealand (NZ) isolates, e.g. NZ2, NZ7 and NZ10, and also Baypamun.RTM., which is derived from D1701. In addition to the starting strains, the invention also relates to the descendants which are obtained by passaging and/or adaptation to particular cells, for example WI 38. In addition to the complete viruses, the invention also relates to parts or fragments of these viruses. Parts are to be understood as being genomic or subgenomic fragments which are expressed using suitable vectors, for example vaccinia, in suitable systems such as fibroblast cell cultures. Fragments are understood as being the fractions which are obtained by biochemical purification, such as chromatography, or the particles which are obtained after using physical methods, such as disruption by means of sonication. Web site: http://www.delphion.com/details?pn=US06632647__

Patent Applications on Hepatitis As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to hepatitis: ·

ANTIGENICALLY POLYPROTEIN

REACTIVE

REGIONS

OF

THE

HEPATITIS

A

VIRUS

Inventor(s): KHUDYAKOV, YURY E.; (DULUTH, GA), FIELDS, HOWARD A.; (MARIETTA, GA) Correspondence: NEEDLE & ROSENBERG P C; 127 PEACHTREE STREET N E; ATLANTA; GA; 30303-1811; US Patent Application Number: 20030187184 Date filed: November 23, 1998 Abstract: It is to be understood that the above description is intended to be illustrative and not restrictive. Many embodiments will be apparent to those of skill in the art upon reading the above description. The scope of the invention should, therefore, be determined not with reference to the above description, but should instead be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled. The disclosures of all articles and references, including patent applications and publications, are incorporated herein by reference for all purpose. Excerpt(s): Hepatitis A virus (HAV) is a morphologically, biochemically and immunologically distinct agent which produces infectious hepatitis A in humans after an incubation period of approximately 2 to 6 weeks. Hepatitis A is a liver disease which, although not commonly fatal, can induce long periods of debilitating illness. An estimated 1.4 million cases of hepatitis A are reported annually worldwide. The disease is commonly spread by direct contact with an infected individual or by HAVcontaminated drinking water and/or food. HAV has been characterized as a picornavirus belonging to the enterovirus group. Like other picornaviruses, HAV is 27 nm in diameter and contains a single-stranded, positive-strand infectious RNA genome 10

This has been a common practice outside the United States prior to December 2000.

Patents 381

coding for a single polyprotein which is subsequently processed into structural and nonstructural proteins. Four major capsid polypeptides have been described with molecular weights of 32,000 to 33,000 (VP1), 26,000 to 29,000 (VP2), 22,000 to 27,000 (VP3) and 10,000 to 14,000 (VP4). There appears to be only one serotype and significant antigenic variation has not been recognized among different HAV strains. HAV infection is typically diagnosed by the detection of IgM or IgG antibodies to the capsid proteins. Prior art, recombinant proteins or synthetic peptides have not successfully been used as alternate sources of antigen in an enzyme immunoassay (EIA) format for the detection of anti-HAV, a serum marker of infection, because of poor antigenic reactivity due to the strictly conformational nature of HAV antigenic epitopes. For more than 15 years, the only available source of immunoreactive proteins was from HAV grown in cell culture. In fact, inactivated cell culture derived HAV is used by all commercial companies who manufacture anti-HAV tests. Unfortunately, HAV is made in very small quantities in cell culture, has a limited animal host range, and is difficult to purify from infected cell cultures and animal tissues. In addition to the inconvenience and cost associated with the production, purification and standardization of cell culture derived HAV antigen, current commercially available assays are unable to discriminate between natural infections and vaccine induced immunity as emphasized in several publications (See, e.g., Jia, et al., J. Infect. Diseases 165:273-280 (1992); Robertson, et al., Vaccine 10(Supp. 1):106-109 (1992); and Robertson, et al., J. Med. Virol. 40:76-82 (1993)), because these tests utilize intact HAV and therefore will detect both kinds of immune responses. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

CD4+ T-lymphocyte-specific hepatitis C virus-epitopes Inventor(s): Gerlach, Jorn Tilman; (Muenchen, DE), Diepolder, Helmut; (Muenchen, DE) Correspondence: MORGAN, LEWIS & BOCKIUS LLP; 1701 MARKET STREET; PHILADELPHIA; PA; 19103-2921; US Patent Application Number: 20030186224 Date filed: March 26, 2003 Abstract: The invention relates to Hepatitis C virus epitopes which are specific in relation to CD4+ T lymphocytes, in addition to vaccinations which contain said epitopes. Excerpt(s): This application is a continuation of PCT/EP01/11263, filed Sep. 28, 2001 and EP00121138.2, filed Sep. 28, 2000, which is herein incorporated by reference in its entirety. The invention relates to Hepatitis C virus-epitopes, which are specific with respect to CD4.sup.+ T-lymphocytes, and to vaccines containing these epitopes. The Hepatitis C virus, termed HCV in the following, was identified in 1989 and is an RNA virus from the family of flaviviridae. It consists of one single strand of RNA of approx. 9400 nucleotides which code a precursor polyprotein of about 3000 amino acids in length. This polyprotein is translated in an open reading frame and split posttranslationally and proteolytically. The virus is highly variable and various virus isolates exist which are designated as genotypes and the geographical distribution of which varies largely. More than six genotypes throughout the world have now been differentiated. These genotypes are in turn subdivided into subtypes. The genetic variability is present inter-individually and intra-individually (within an infected individual). The intra-individual subtypes are the so-called HCV quasi-species which are related but different virus sequences occurring with imprecise replication.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Chimaeric hepadnavirus core antigen proteins Inventor(s): Brown, Alan Louis; (Beckenham, GB), Clarke, Berwyn Ewart; (Beckenham, GB), Rowlands, David John; (Beckenham, GB) Correspondence: NIXON & VANDERHYE P.C.; 8th Floor; 1100 North Glebe Road; Arlington; VA; 22201-4714; US Patent Application Number: 20030175296 Date filed: September 23, 2002 Abstract: Particles, useful as a delivery system for an epitope, are composed of a chimaeric hepadnavirus core antigen protein wherein a foreign amino acid sequence comprising an epitope is inserted in or replaces all or part of the sequence of amino acid residues from 68 to 90 in the case where the core antigen is hepatitis B core antigen or the corresponding amino acid sequence in the case of the core antigen of another hepadnavirus. Excerpt(s): This invention relates to the construction of chimaeric hepadnavirus core antigen proteins. Hepatitis B virus is a hepadnavirus virus with a partly double stranded genome of 3200 nucleotides. The viral DNA is surrounded by the viral coded core antigen (HBcAg) which is enclosed by the similarly coded surface antigen (Robinson, Ann. Rev. Microbiol. 31, 357-377, 1977). Removal of the surface antigen by mild detergent treatment leaves a core particle 27 nm in diameter composed of HBcAg and the viral DNA. HBcAg has been expressed in microbial cells as the native polypeptide and as a derivative fused to the terminal eight residues of betagalactosidase (see Murray et al, EMBO J. 3, 645-650, 1984 for refs). When synthesized in E. coli the core protein self assembles into 27 nm particles which can be visualized under the electron microscope (Cohen and Richmond, Nature, 296, 677-678, 1982) and which are immunogenic in laboratory animals (Stahl et al, Proc. Natl. Acad. Sci. USA 79, 16061610, 1982). The amino acid sequence of the core antigen shows a region towards the carboxy terminus which is homologous with that found in protamines (DNA binding proteins). By inference, it has been suggested that this part of the molecule interacts with DNA during assembly of core particles (Pasek et al, Nature, 282, 575-579, 1979). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Compositions and methods for treatment of hepatitis C virus-associated diseases Inventor(s): Kwoh, T. Jesse; (Carlsbad, CA), Anderson, Kevin P.; (Carlsbad, CA), Hanecak, Ronnie C.; (San Clemente, CA), Dorr, F. Andrew; (Solana Beach, CA), Nozaki, Chikateru; (Kumanoto, JP) Correspondence: LICATLA & TYRRELL P.C.; 66 E. MAIN STREET; MARLTON; NJ; 08053; US Patent Application Number: 20030171313 Date filed: May 11, 2001 Abstract: Antisense oligonucleotides are provided which are complementary to and hybridizable with at least a portion of HCV RNA and which are capable of inhibiting the function of the HCV RNA. These oligonucleotides can be administered to inhibit the

Patents 383

activity of Hepatitis C virus in vivo or in vitro. These compounds can be used either prophylactically or therapeutically to reduce the severity of diseases associated with Hepatitis C virus, and for diagnosis and detection of HCV and HCV-associated diseases. Methods of using these compounds are also disclosed. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 09/690,936 filed Oct. 18, 2000, which is a continuation of U.S. Ser. No. 08/988,321, filed Dec. 10, 1997, which is a continuation-in-part of U.S. Ser. No. 08/650,093, filed May 17, 1996, which is a continuation-in-part of U.S. Ser. No. 08/452,841, filed May 30, 1995, which in turn is a continuation-in-part of U.S. Ser. No. 08/397,220, filed Mar. 9, 1995, which is a continuation-in-part of U.S. Ser. No. 07/945,289, filed Sep. 10, 1992. This invention relates to the design and synthesis of antisense oligonucleotides which can be administered to inhibit the activity of Hepatitis C virus in vivo or in vitro and to prevent or treat Hepatitis C virus-associated disease. These compounds can be used either prophylactically or therapeutically to reduce the severity of diseases associated with Hepatitis C virus. These compounds can also be used for detection of Hepatitis C virus and diagnosis of Hepatitis C virus-associated diseases. Oligonucleotides which are specifically hybridizable with Hepatitis C virus RNA targets and are capable of inhibiting the function of these RNA targets are disclosed. Methods of using these compounds are also disclosed. The predominant form of hepatitis currently resulting from transfusions is not related to the previously characterized Hepatitis A virus or Hepatitis B virus and has, consequently, been referred to as Non-A, Non-B Hepatitis (NANBH). NANBH currently accounts for over 90% of cases of post-transfusion hepatitis. Estimates of the frequency of NANBH in transfusion recipients range from 5%-13% for those receiving volunteer blood, or 25-54% for those receiving blood from commercial sources. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Compositions of hepatitis C virus NS5B polymerase and methods for crystallizing same Inventor(s): Hong, Zhi; (Nanuet, NY), Weber, Patricia C.; (Yardley, PA), Mannarino, Anthony F.; (North Plainfield, NJ), Cable, Michael; (Freehold, NJ), Lesburg, Charles A.; (Weehawken, NJ) Correspondence: SCHERING-PLOUGH CORPORATION; PATENT DEPARTMENT (K6-1, 1990); 2000 GALLOPING HILL ROAD; KENILWORTH; NJ; 07033-0530; US Patent Application Number: 20030171874 Date filed: June 12, 2002 Abstract: The invention relates to the purification, crystallization of and structure of hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase. Also, crystallization conditions for NS5B are provided. Further, the atomic coordinates for the NS5B protein are disclosed. Examples of its use for the determination of the three-dimensional atomic structures of HCV NS5B or HCV NS5B in complex with substrates or substrate analogs or inhibitors are also provided. Excerpt(s): The present invention relates to compositions and crystals of a hepatitis C virus RNA dependent RNA polymerase called NS5B and to methods of producing such crystals. This invention relates to methods of using the structure coordinates of hepatitis C virus NS5B to solve the structure of homologous NS5B proteins or complexes containing the NS5B protein. Infection by hepatitis C virus (HCV) is a compelling

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human medical problem. HCV is recognized as the causative agent for most cases of non-A and non-B hepatitis, with an estimated human seroprevalence of 1% globally [Choo, et al., Science, 244:359-362 (1989); Kuo, et al., Science, 244:362-364 (1989); Purcell, FEMS Microbiology Reviews; 14:181-192 (1994); Van der Poel. Current Studies in Hematology and Blood Transfusion, H. W. Reesink, Ed., (Basel: Karger), pp. 137-163 (1994)]. Four million individuals may be infected in the United States alone [Alter, and Mast, Gastroenterol. Clin. North Am., 23:437-455 (1994)]. Upon first exposure to HCV, only about 20% of infected individuals develop acute hepatitis and appear to resolve the infection spontaneously. In the most instances (.about.80%), however, the virus establishes a chronic infection that persists for decades [Iwarson, FEMS Microbiology Reviews, 14: 201-204 (1994)]. This usually results in recurrent and progressively worsening liver inflammation, which often leads to more severe disease states such as cirrhosis and hepatocellular carcinoma [Kew, FEMS Microbiology Reviews, 14: 211-220 (1994); Saito, et al., Proc. Natl. Acad. Sci. USA 87: 6547-6549 (1990)]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Compounds, methods and compositions useful for the treatment of bovine viral diarrhea virus (BVDV) infection and hepatitis C virus (HCV) infection Inventor(s): Stephens, Chad E.; (Villa Roca, GA), Boykin, David; (Atlanta, GA), Wilson, W. David; (Atlanta, GA), Tidwell, Richard R.; (Pittsboro, NC), Kumar, Arvind; (Atlanta, GA), Brock, Kenny; (Auburn, AL), Dykstra, Christine C.; (Auburn, AL), Givens, Maurice Daniel; (Auburn, AL), Stringfellow, David A.; (Auburn, AL) Correspondence: JENKINS & WILSON, PA; 3100 TOWER BLVD; SUITE 1400; DURHAM; NC; 27707; US Patent Application Number: 20030199521 Date filed: January 11, 2002 Abstract: The present invention relates to novel compounds and methods that are useful in treating members of the Flaviviridae family of viruses. Compounds of the present invention will have a structure according to Formulas (I)-(VI) as recited throughout the application. Excerpt(s): The present application claims priority to U.S. Provisional Application No. 60/261,654, filed Jan. 13, 2001, the disclosure of which is incorporated herein by reference in its entirety. This invention relates to the treatment of bovine viral diarrhea virus (BVDV) and hepatitis C virus (HCV) infections. Bovine viral diarrhea virus (BVDV) is an enveloped, single-stranded, positive sense RNA virus in the genus Pestivirus and the family Flaviviridae. Based on the presence or absence of visible cytopathic effect when susceptible cell monolayers are infected, two pathogenic biotypes of BVDV, referred to as cytopathic and noncytopathic, have been identified. Perdrizet J A in: B. P. Smith (ed), Large Animal Internal Medicine, First Edition (Mosby Press, St Louis, 731-737 (1990)). A differentiation is also made between biotypes of BVDV (referred to as biotypes I and II) based on certain viral RNA sequences in the 5' untranslated region of the genome. Pellerin C, et al., Virology 203, 260-268 (1994); J. F. Ridpath et al., Virology 205, 66-74 (1994). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Convergent combinatory peptide libraries and their use for vaccination against hepatitis c virus Inventor(s): Gras-Masse, Helene; (Lille, FR), Bouzidl, Ahmil; (Lille, FR), Georges, Bertrand; (Lille, FR), Auriault, Claude; (Lille, FR) Correspondence: BIRCH STEWART KOLASCH & BIRCH; PO BOX 747; FALLS CHURCH; VA; 22040-0747; US Patent Application Number: 20030194747 Date filed: April 28, 2003 Abstract: The invention relates to the design and synthesis of immunogenic peptides corresponding to restricted regions of virus proteins involving a T cell immune response and to convergent combinatory peptide libraries derived from said regions.The invention applies, in particular, to the hepatitis C virus and to the production of corresponding vaccinal preparations. Excerpt(s): The invention relates to the design and synthesis of mixtures of immunogenic peptides corresponding to restricted regions of virus proteins and, in particular, of the hepatitis C virus (HCV) and their use to produce vaccinal preparations against said viruses. The hepatitis C virus was identified in 1989 (CHOO Q. L. et al., Science, 1989, 244, 359-361). It is the main causative agent of non-A, non-B chronic hepatitis parenterally transmitted. Infection by the HCV virus develops into a chronic pathology in 60 to 80 percent of the cases. Such infections are highly prevalent in the population at large, being in the order of 1 to 2 percent in the industrialized countries, particularly in Western Europe (ALTER H. J. et al., Blood, 1995, 85,1681-1695). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Enzymatic nucleic acid treatment of diseases or conditions related to hepatitis C virus infection Inventor(s): MacJack, Dennis; (Arvada, CO), Pavco, Pamela A.; (Lafayette, CO), McSwiggen, James; (Boulder, CO), Blatt, Lawrence; (Boulder, CO), Roberts, Elisabeth; (Federal Heights, CO) Correspondence: MCDONNELL BOEHNEN HULBERT & BERGHOFF; 300 SOUTH WACKER DRIVE; SUITE 3200; CHICAGO; IL; 60606; US Patent Application Number: 20030171311 Date filed: March 26, 2001 Abstract: The present invention relates to compounds, including enzymatic nucleic acid molecules, ribozymes, DNAzymes, nuclease activating compounds and chimeras such as 2',5'-adenylates, that modulate the expression and/or replication of hepatitis C virus (HCV). Excerpt(s): This patent application is a continuation-in-part of Blatt et al., U.S. Ser. No. (09/740,332), filed Dec. 18, 2000, which is a continuation-in-part of Blatt et al., U.S. Ser. No. (09/611,931), filed Jul. 7, 2000, which is a continuation-in-part of Blatt et al., Ser. No. 09/504,321, filed Feb. 15, 2000, which is a continuation-in-part of Blatt et al., U.S. Ser. No. 09/274,553, filed Mar. 23, 1999, which is a continuation-in-part of Blatt et al., U.S. Ser. No. 09/257,608, filed Feb. 24, 1999 (abandoned), which claims priority from Blatt et al., U.S. Ser. No. 60/100,842, filed Sep. 18, 1998, and McSwiggen et al., U.S. Ser. No. 60/083,217 filed Apr. 27, 1998, all of these earlier applications are entitled "ENZYMATIC

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NUCLEIC ACID TREATMENT OF DISEASES OR CONDITIONS RELATED TO HEPATITIS C VIRUS INFECTION". Each of these applications are hereby incorporated by reference herein in their entirety including the drawings. The Sequence Listing file named "MBHBOO-80sequenceListing.ST25" submitted on Compact Disc-Recordable (CD-R) medium ("010323.sub.--1557") in compliance with 37 C.F.R.sctn.1.52(e) is incorporated herein by reference. This invention relates to methods and reagents for the treatment of diseases or conditions relating to the hepatitis C virus infection. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Enzyme inhibitors Inventor(s): Neuner, Philippe Jean Sigfried; (Albano Laziale, IT), Summa, Vincenzo; (Velletri, IT) Correspondence: MERCK AND CO INC; P O BOX 2000; RAHWAY; NJ; 070650907 Patent Application Number: 20030207922 Date filed: September 10, 2002 Abstract: Diketoacids of Formula A are useful as inhibitors of viral polymerases. In particular hepatitis C virus RNA dependent RNA polymerase (HCV RdRp), hepatitis B virus polymerase (HBV pol) and reverse transcriptase of human immunodeficiency virus (HIV RT): 1The group R may be broadly chosen and is an organic moiety which contains 2 to 24 carbon atoms and includes an optionally cyclic or heterocyclic group in which the atom directly bonded to the adjacent carbonyl in the diketoacid is part of the ring structure. Excerpt(s): The present invention relates to compounds useful as enzyme inhibitors, in particular as inhibitors of enzymes involved in the transfer of phosphoryl groups and, especially as inhibitors of polymerases. The invention further relates to pharmaceutical compositions containing such compounds, and to their use in the treatment of viral infections. Polymerases are the enzymes which catalyse the formation of phosphodiester bonds in RNA and DNA. They play an essential role in viral replication and, therefore, are an important target in the fight against viral diseases such as human immunodeficiency virus (HIV), hepatitis, and poliomyelitis. U.S. Pat. No. 5,475,109 describes dioxobutanoic acids substituted with piperidine or similar N-substituted saturated cycloalkyls as inhibitors of the cap-dependent endonuclease of influenza virus. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Full-length GB virus C (hepatitis G virus) RNA transcripts are infectious in primary CD4 positive T cells and methods of treating HIV Inventor(s): Schmidt, Warren; (Oxford, IA), Stapleton, Jack; (Iowa City, IA), Wunschmann, Sabina; (Coralville, IA), Xiang, Jinhua; (Iowa City, IA) Correspondence: Gina N. Shishima; Fulbright & Jaworski L.L.P; Suite 2400; 600 Congress Avenue; Austin; TX; 78701; US Patent Application Number: 20030170870 Date filed: April 5, 2001

Patents 387

Abstract: GB virus C (GBV-C or hepatitis G virus) is a recently described flavivirus that frequently leads to chronic viremia in humans. Although associated with acute posttransfusion hepatitis, it is not clear if GBV-C is pathogenic for humans. A full-length cDNA was constructed from the plasma of a person with chronic GBV-C viremia. Peripheral blood mononuclear cells (PBMCs) transfected with full-length RNA transcripts from this GBV-C clone resulted in viral replication, demonstrating an isolated infectious GBV-C nucleic acid molecule. In addition to composition involving an isolated infectious GBV-C nucleic acid molecule, the present invention concerns methods of inhibiting and treating HIV infections. Excerpt(s): This application claims priority to U.S. provisional patent application Serial No. 60/253,390, filed Nov. 27, 2000, and U.S. provisional patent application Serial No. 60/195,597, filed on Apr. 6, 2000, which are herein incorporated by reference. The present invention relates generally to the fields of molecular biology and virology. More particularly, it concerns an infectious clone of GBV-C, which can be used in treatment of other related hepatitis viruses infections and HIV, as well as broader uses in therapeutic and preventative therapies. Hepatitis C virus (HCV) is responsible for causing hepatitis C, a disease that chronically affects approximately four million Americans, many of whom may develop liver disease. Hepatitis C annually accounts for as many as 1,000 liver transplants in the United States and between 8,000 and 10,000 deaths. There is no vaccine or preventative treatment against HCV infection and treatment regimens may cause unwanted side effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Glucamine salts for treating hepatitis virus infections Inventor(s): Bryant, Martin L.; (Carisle, MA), Partis, Richard A.; (Evanston, IL), Mueller, Richard A.; (Glencoe, IL) Correspondence: SENNIGER POWERS LEAVITT AND ROEDEL; ONE METROPOLITAN SQUARE; 16TH FLOOR; ST LOUIS; MO; 63102; US Patent Application Number: 20030195229 Date filed: December 17, 2002 Abstract: N-Substituted glucamine compounds of Formula I are effective in treatment of hepatitis infections, including hepatitis B and hepatitis C. In treating hepatitis infections, the compounds of Formula I may be used alone, or in combination with another antiviral agent selected from among nucleosides, nucleotides, immunomodulators, immunostimulants or various combinations of such other agents. Excerpt(s): The present invention relates to methods and compositions for treating hepatitis virus infections, especially hepatitis B virus infections, in mammals, especially humans. The methods comprise administering glucamine compounds in combination with nucleoside antiviral agents, nucleotide antiviral agents, mixtures thereof, or immunomodulating/-immunostimulating agents. Such combinations of anti-hepatitis viral agents show unexpected efficacy in inhibiting replication and secretion of hepatitis viruses in cells of mammals infected with these viruses. Over half the biologically important proteins are glycosylated and that glycosylation may vary with disease. Based upon this information, the use of drugs to control of glycosylation patterns, glycoforms, changes or rates of change will have a a biochemical effect and may provide a beneficial therapeutic result. Control of glycolipid and glycoprotein sugar patterns as well as their synthesis and degradation leads to basic physiological effects on mammals

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including humans, agricultural animals and pets. Possibly, this is through influences on, for example, N-linked glycans, O-linked glycans, glucosoaminoglycans, glycosphingolipids, glycophospholipids, lectins, immuneoglobulin molecules, antibodies, glycoproteins and their biochemical intermediates or conversion products. Modification of glycosalation site occupancy influences receptor and enzyme binding site specificity, selectivity, capacity, protein folding, enzyme activity, kinetics and energetics. Glycosidase and glycosyltransferase systems are two biochemical mechanisms that are suggested to affect such systems (Dwek, Raymond A., Glycobiology: Toward Understanding the Function of Sugars, Chemical Reviews, 96, 683-720(1996). Iminosugars are anti-viral drugs that can induce the inhibition of viral interactions with and within mammalian cells such as attachment to cells, penetration of cells, maturation within cells and release from cells. The mechanism involved may be glucosidase inhibition, glycosyl transferase inhibition or others as discussed above. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

HBV core antigen particles with multiple immunogenic components attached via peptide ligands Inventor(s): Murray, Kenneth; (Edinburgh, GB) Correspondence: FISH & NEAVE; 1251 AVENUE OF THE AMERICAS; 50TH FLOOR; NEW YORK; NY; 10020-1105; US Patent Application Number: 20030198649 Date filed: May 29, 2003 Abstract: This invention relates to hepatitis B virus ("HBV") core antigen particles that are characterized by multiple immunogen specificities. More particularly, the invention relates to HBV core antigen particles comprising immunogens, epitopes, or other related structures, crosslinked thereto by ligands which are HBV capsid-binding peptides that selectively bind to HBV core protein. Such particles may be used as delivery systems for a diverse range of immunogenic epitopes, including the HBV capsid-binding peptides, which advantageously also inhibit and interfere with HBV viral assembly by blocking the interaction between HBV core protein and HBV surface proteins. Mixtures of different immunogens and/or capsid-binding peptide ligands may be crosslinked to the same HBV core particle. Such resulting multicomponent or multivalent HBV core particles may be advantageously used in therapeutic and prophylactic vaccines and compositions, as well as in diagnostic compositions and methods using them. Excerpt(s): This invention relates to hepatitis B virus ("HBV") core antigen particles that are characterized by multiple immunogen specificities. More particularly, the invention relates to HBV core antigen particles comprising immunogens, epitopes, or other related structures, crosslinked thereto by ligands which are HBV capsid-binding peptides that selectively bind to HBV core protein. Such particles may be used as delivery systems for a diverse range of immunogenic epitopes, including the HBV capsid-binding peptides, which advantageously also inhibit and interfere with HBV viral assembly by blocking the interaction between HBV core protein and HBV surface proteins. Mixtures of different immunogens, HBV capsid-binding peptide ligands, or both, may be crosslinked to the same HBV core particle. Such resulting multicomponent or multivalent HBV core particles may be advantageously used in therapeutic and prophylactic vaccines and compositions, as well as in diagnostic compositions and methods using them. The front-line of clinical immunotherapeutic regimens includes patient immunizations against infectious pathogens and other health-threatening

Patents 389

agents. Despite the plethora of immunization agents, inoculations may afford, at best, partial immunity, requiring frequent re-immunizations. Such is the case for various conventional monovalent or polyvalent vaccines. And even among such vaccines, the number of single agent inoculants capable of eliciting immunity against a variety of immunogens is limited. Furthermore, antigenic variation among pathogens may limit the efficacy of conventional vaccines. Due to such obstacles, efforts have focused on methodologies for enhancing the immune system response to given immunogens. To that end, immunogenic conjugates have been produced by linking immunogens to hepatitis B virus ("HBV") core particles (also referred to as nucleocapsids or nucleocapsid shells), in efforts to enhance the immunogenicity of the linked immunogen, through the operation of T cell dependent and T cell independent determinants of HBV core antigen. See, for example, U.S. Pat. No. 4,818,527 and R. Ulrich et al., "Core Particles of Hepatitis B Virus as Carrier for Foreign Epitopes", Adv. Virus. Res., 50, pp. 141-82 (1998). Enhanced immunogenicity of epitopes of interest has also been approached via hybrid viral particle-forming proteins, comprising at least a portion of a naturally occurring viral particle forming protein, for example HBV surface antigen, and one or more epitopic sites of interest. See U.S. Pat. No. 5,965,140. As evident from such efforts, proteins of HBV have been used as platforms for presenting immunogens of interest to the immune system. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Hepatitis B virus binding proteins and uses thereof Inventor(s): Shaul, Yosef; (Mobile Post Sde Gat, IL), Zemel, Romi; (Tel Aviv, IL) Correspondence: G.E. EHRLICH (1995) LTD.; c/o ANTHONY CASTORINA; SUITE 207; 2001 JEFFERSON DAVIS HIGHWAY; ARLINGTON; VA; 22202; US Patent Application Number: 20030185857 Date filed: May 23, 2003 Abstract: An isolated nucleic acid, a recombinant protein encoded thereby and uses thereof. The isolated nucleic acid including (a) a polynucleotide at least 60% identical to SEQ ID NOs:1, 3, 5 or portions thereof as determined using the Bestfit procedure of the DNA sequence analysis software package developed by the Genetic Computer Group (GCG) at the university of Wisconsin (gap creation penalty--50, gap extension penalty-3); (b) a polynucleotide encoding a polypeptide being at least 60% homologous with SEQ ID NOs:2, 4, 6 or portions thereof as determined using the Bestfit procedure of the DNA sequence analysis software package developed by the Genetic Computer Group (GCG) at the university of Wisconsin (gap creation penalty--50, gap extension penalty-3); or (c) a polynucleotide hybridizable with SEQ ID NOs:1, 3, 5 or portions thereof at 68.degree. C. in 6.times.SSC, 1% SDS, 5.times. Denharts, 10% dextran sulfate, 100.mu.g/ml salmon sperm DNA, and.sup.32p labeled probe and wash at 68.degree. C. with 3.times.SSC and 0.1% SDS. Excerpt(s): This is a divisional of U.S. patent application Ser. No. 09/409,096, filed Sep. 30, 1999. The present invention relates to a group of genes, and the proteins encoded thereby, which are capable of interfering with Hepatitis B virus (HBV) infection and to methods for identifying, purifying, isolating and characterizing related genes and gene products. The present invention further relates to isolation of soluble forms of the cellular receptor(s) for HBV on hepatocytes from bodily fluids, including, but not limited to, urine, and to purification of these soluble form binding proteins by means including, but not limited to, affinity columns. The present invention further relates to

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the use of these genes and their translation products to establish experimental models for HBV infection, whether in cell culture or in animals. The present invention further relates to the use of these genes and their translation products for therapeutic purposes. The present invention further relates to the use of these genes and their translation products to screen for additional binding protein interactions. The present invention further relates to the use of these genes and their translation products to prepare specific detectors of these proteins, including, but not limited to, antibodies, phage-display libraries, specific PCR primers, lectins, DNA probes, RNA probes, and non-antibody proteins for diagnostic and therapeutic purposes. Hepatitis B virus (HBV) is an enveloped RNA virus that infects human liver and replicates via reverse-transcription of the pregenomic RNA. Infected patients develop acute hepatitis, which is often selflimiting, but may develop into chronic hepatitis with high risk of liver cirrhosis and primary liver carcinoma in roughly 10% of all cases. The World Health Organization estimates that there will be 400 million carriers Worldwide in year 2000. Effective vaccines exist, but anti viral drugs with good and long term efficacy are not available. Little is known about how HBV infects liver cells and the HBV cellular receptor(s) remain unknown. Many proteins have been identified which bind to the viral envelope associated proteins, HBsAg, or related proteins, but none are considered genuine HBV receptors (reviewed in De et al., 1997 and in references cited therein). Some of these binding proteins are found in serum and some in hepatocytes. None of these molecules have been convincingly tied to infectivity, disqualifying them as genuine HBV receptors. These molecules are of three types, S binding proteins, preS2 binding proteins, and preS1 binding proteins. A brief summary of the characteristics of the three groups is provided herein. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Hepatitis C inhibitor tri-peptides Inventor(s): Bailey, Murray D.; (Laval, CA), Llinas-Brunet, Montse; (Laval, CA), Ghiro, Elise; (Laval, CA) Correspondence: BOEHRINGER INGELHEIM CORPORATION; 900 RIDGEBURY RD; P O BOX 368; RIDGEFIELD; CT; 06877; US Patent Application Number: 20030191067 Date filed: December 17, 2002 Abstract: Compounds of formula (I): 1wherein R.sup.1 is hydroxyl or sulfonamide derivative; R.sup.2 is t-butyl or --CH.sub.2--C(CH.sub.3).sub.3 or --CH.sub.2cyclopentyl; R.sup.3 is t-butyl or cyclohexyl and R.sup.4 is cyclobutyl, cyclopentyl or cyclohexyl; or a pharmaceutically acceptable salt thereof, are described as useful as inhibitor of the HCV NS3 protease. Excerpt(s): The present invention relates to compounds, processes for their synthesis, compositions and methods for the treatment of hepatitis C virus (HCV) infection. In particular, the present invention provides novel peptide analogs, pharmaceutical compositions containing such analogs and methods for using these analogs in the treatment of HCV infection. Hepatitis C virus (HCV) is the major etiological agent of post-transfusion and community-acquired non-A non-B hepatitis worldwide. It is estimated that over 200 million people worldwide are infected by the virus. A high percentage of carriers become chronically infected and many progress to chronic liver disease, so-called chronic hepatitis C. This group is in turn at high risk for serious liver disease such as liver cirrhosis, hepatocellular carcinoma and terminal liver disease

Patents 391

leading to death. The mechanism by which HCV establishes viral persistence and causes a high rate of chronic liver disease has not been thoroughly elucidated. It is not known how HCV interacts with and evades the host immune system. In addition, the roles of cellular and humoral immune responses in protection against HCV infection and disease have yet to be established. Immunoglobulins have been reported for prophylaxis of transfusion-associated viral hepatitis, however, the Center for Disease Control does not presently recommend immunoglobulins treatment for this purpose. The lack of an effective protective immune response is hampering the development of a vaccine or adequate post-exposure prophylaxis measures, so in the near-term, hopes are firmly pinned on antiviral interventions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Hepatitis C virus codon optimized non-structural NS3/4A fusion gene Inventor(s): Sallberg, Matti; (Alvsjo, SE) Correspondence: KNOBBE MARTENS OLSON & BEAR LLP; 2040 MAIN STREET; FOURTEENTH FLOOR; IRVINE; CA; 92614; US Patent Application Number: 20030206919 Date filed: November 26, 2002 Abstract: Aspects of the present invention relate to the discovery of a novel hepatitis C virus (HCV) isolate. Embodiments include HCV peptides, nucleic acids encoding said HCV peptides, antibodies directed to said peptides, compositions containing said nucleic acids and peptides, as well as methods of making and using the aforementioned compositions including, but not limited to, diagnostics and medicaments for the treatment and prevention of HCV infection. Excerpt(s): This application is a continuation-in-part of and claims the benefit of priority to U.S. patent application Ser. No. 09/930591, filed Aug. 15, 2001, which claims the benefit of priority to U.S. patent application Ser. No. 09/705,547, filed Nov. 3, 2000, U.S. Provisional Patent Application No. 60/225,767, filed Aug. 17, 2000, and U.S. Provisional Patent Application No. 60/229,175, filed Aug. 29, 2000. All of the aforementioned applications are hereby expressly incorporated by reference in their entireties. Aspects of the present invention relate to the discovery of a novel hepatitis C virus (HCV) isolate. Embodiments include HCV peptides, nucleic acids encoding said HCV peptides, antibodies directed to said peptides, compositions containing said nucleic acids and peptides, as well as methods of making and using the aforementioned compositions including, but not limited to, diagnostics and medicaments for the treatment and prevention of HCV infection. Viruses are intracellular parasites that require the biochemical machinery of a host cell for replication and propagation. All virus particles contain some genetic information that encodes viral structural proteins and enzymes. The genetic material may be DNA or RNA, in double- or single stranded form. (Virology, Fields ed., third edition, Lippencott-Raven publishers, pp 72-83 (1996)). The viral nucleic acid is surrounded by a coat of proteins called the capsid. (Id.) In some viruses the capsid is surrounded by an additional layer comprised of a lipid membrane, referred to as the envelope. (Id. at 83-95). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Hepatitis C virus NS5B truncated protein and methods thereof to identify antiviral compounds Inventor(s): DelVecchio, Alfred M.; (West Chester, PA) Correspondence: SMITHKLINE BEECHAM CORPORATION; Corporate Intellectual Property - UW2220; P.O. Box 1539; King of Prussia; PA; 19406-0939; US Patent Application Number: 20030190606 Date filed: January 13, 2003 Abstract: The invention provides HCV NS5B polypeptides and DNA (RNA) encoding HCV NS5B polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing HCV NS5B polypeptides to screen for antiviral compounds. Excerpt(s): This application claims benefit to the earlier provisional U.S. application, Serial No. 60/069,208, filed on Dec. 11, 1997, the contents of which are incorporated herein by reference in their entirety. This invention relates to newly identified polynucleotides and polypeptides, and their production and uses, as well as their variants, agonists and antagonists, and their uses. In particular, in these and in other regards, the invention relates to novel polynucleotides and polypeptides of viruses of the Flaviviridae family, particularly a novel truncate of the Hepatitis C Virus (HCV) NS5B protein, as well as other variants disclosed herein, all hereinafter referred to as "HCV NS5B". First identified by molecular cloning in 1989 (Choo, et al., Science 244: 359362 (1989)), hepatitis C virus (HCV) is now widely accepted as the most common causative agent of post-transfusion non A, non-B hepatitis (NANBH) (Kuo, et al., Science 244:362-364 (1989)). Infection with HCV is a major cause of human liver disease throughout the world with seroprevalence in the general population ranging from 0.3 to 2.2% (van der Poel, et al., HEPATITIS C VIRUS; Amsterdam: Karger; pp. 137-163 (1994)) to as high as.about.10-20% in Egypt (Hibbs, et al., J. Infect. Dis. 168: 789-790 (1993)). Although the virus is most commonly transmitted via blood, the mode of transmission remains unknown for a large portion of infected individuals (Alter, M. J., Infect. Agents Dis. 2: 155-166 (1993)). Over 50% of infections by HCV progress to acute hepatitis associated with viremia and generally elevated serum alanine aminotranferase (ALT) levels (Alter, H. J., CURRENT PROSPECTIVES IN HEPATOLOGY; New York:Plenum; pp. 83-97 (1989)). Over half of the acute cases progress to a chronic infection with roughly 20% developing cirrhosis (Alter, H. J., supra). Chronic infection by HCV has also been linked epidemiologically to the development of hepatocellular carcinoma (HCC), especially in cirrhotic patients (Blum, et al., Hepatology 19: 251-258 (1994)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Hepatitis virus sentinel virus I (SVI) Inventor(s): Lin, Yu-Huei; (Sunnyvale, CA), Liu, Jen-Kuei; (Palo Alto, CA), Chen, Benjamin P.; (Fremont, CA), Bohenzky, Roy A.; (Mountain View, CA) Correspondence: Roche Diagnostics Corporation; 9115 Hague Road, Bldg. D; Indianapolis; IN; 46250-0457; US Patent Application Number: 20030198947 Date filed: June 3, 2003

Patents 393

Abstract: The invention relates to a new group of viruses, designated SVI. Isolated SVI viruses, polynucleotides and proteins from SVI viruses, and antibodies which bind SVI virus and SVI viral proteins are provided. The polynucleotides, proteins, and antibodies of the invention may be used to detect SVI virus or infection by SVI virus in a susceptible individual. Additionally, polynucleotides of the invention may be inserted into recombinant expression vectors recombinant production of viral proteins. Excerpt(s): The invention relates generally to the area of hepatitis viruses, and more particularly to a new group of hepatitis viruses, and methods and compositions for their detection and treatment. Strictly defined, the term "hepatitis" refers to an inflammation of the liver. A variety of different chemical, viral, and biological agents will induce hepatitis. However, the term hepatitis more commonly refers to an inflammation of the liver caused by a viral infection, particularly a hepatotrophic viral infection. Viral hepatitis can be divided into two gross categories: acute and chronic. Acute viral hepatitis is characterized by jaundice, malaise, nausea, and elevated blood liver enzymes. Although most cases of viral hepatitis resolve spontaneously, a portion of acute hepatitis victims (generally less than about 10%) develop fulminant necrotizing hepatitis, a disorder with very high morbidity and mortality. Interestingly, many cases of acute hepatitis are so mild as to pass unnoticed or be dismissed as "flu." Chronic hepatitis gives rise to a much more significant public health problem, and is the most common reason for liver transplant in the United States. Chronic hepatitis is characterized by exacerbations or "flare ups" with symptoms resembling acute hepatitis, as well as portal hypertension and cirrhosis (scarring of the liver) which leads to liver failure. Because acute hepatitis infections can go unnoticed, many chronic hepatitis patients are not diagnosed until their disease is quite advanced, limiting options for treatment. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Hepatitis-C virus testing Inventor(s): Simmonds, Peter; (Edinburgh, GB), Chan, Shui-Wan; (Cambridge, GB), Yap, Peng Lee; (Edinburgh, GB) Correspondence: ALSTON & BIRD LLP; BANK OF AMERICA PLAZA; 101 SOUTH TRYON STREET, SUITE 4000; CHARLOTTE; NC; 28280-4000; US Patent Application Number: 20030198946 Date filed: March 25, 2003 Abstract: New styles of hepatitis C virus (HCV), referred to as HCV-3 and HCV-4, have been identified and sequenced. Antigenic regions of HCV-2, HCV-3 and HCV-4 polypeptides have been identified. Immunoassays for HCV and antibodies thereto are described, which allow more complete screening of blood samples for HCV, and allow HCV genotyping. Excerpt(s): This application is a continuation of U.S. application Ser. No. 09/039,130, filed Mar. 13, 1998, which is a divisional of U.S. application Ser. No. 08/244,116, filed Jul. 15, 1994, now U.S. Pat. No. 5,763,159; the contents of which are herein incorporated by reference in their entirety. The present invention relates to the discovery of new types of hepatitis C virus, that we have termed type 3 (HCV-3) and type 4 (HCV-4). In particular, it relates to the etiologic agent of hepatitis C virus type 3 and 4, and to polynucleotides and immunoreactive polypeptides which are useful in immunoassays for the detection of HCV-3 and HCV-4 in biological samples; and also to the use of

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antigenic HCV-3 and HCV-4 specific polypeptides in vaccines. Acute viral hepatitis is a disease which may result in chronic liver damage. It is clinically diagnosed by a welldefined set of patient symptoms, including jaundice, hepatic tenderness, and an increase in the serum levels of alanine aminotransferase and aspartate aminotransferase. Serologic immunoassays are generally performed to diagnose the specific type of viral causative agent. Historically, patients presenting with symptoms of hepatitis and not otherwise infected by hepatitis A, hepatitis B, Epstein-Barr or cytomegalovirus were clinically diagnosed as having non-A, non-B hepatitis (NANBH) by default. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Human cellular protein gastrointestinal glutathione peroxidase as target for medical intervention against hepatitis C virus infections Inventor(s): Herget, Thomas; (Planegg, DE), Cotten, Matthew; (Munchen, DE), Obert, Sabine; (Munchen, DE) Correspondence: Leon R. Yankwich; Yankwich & Associates; 201 Broadway; Cambridge; MA; 02129; US Patent Application Number: 20030180719 Date filed: January 14, 2003 Abstract: The present invention relates to the human cellular protein glutathione peroxidase-gastrointestinal as a target for medical intervention against Hepatitis C virus (HCV) infections. Furthermore, the present invention relates to a method for the detection of compounds useful for prophylaxis and/or treatment of Hepatitis C virus infections and a method for detecting Hepatitis C virus infections in an individual or in cells. Also compositions, compounds, nucleic acid molecules (such as aptamers), monoor polyclonal antibodies are disclosed which are effective for the treatment of HCV infections, and methods for prophylaxis and/or treatment of Hepatitis C virus infections or for the regulation of Hepatitis C virus production are disclosed. Excerpt(s): The present application is a continuation-in-part of copending international application PCT/EP02/04167, filed Apr. 15, 2002, which claims priority to U.S. provisional application 60/283,345, filed Apr. 13, 2001. The present application also claims priority to German application DE 102 55 861.2 filed Nov. 29, 2002 and to U.S. provisional application No. 60/xxx,xxx filed Dec. 3, 2002. The present invention relates to the human cellular protein glutathione peroxidase-gastrointestinal (or gastrointestinal glutathione peroxidase, abbreviated GI-GPx) as a potential target for medical intervention against Hepatitis C virus (HCV) infections. Furthermore, the present invention relates to a method for the detection of compounds useful for prophylaxis and/or treatment of Hepatitis C virus infections and a method for detecting Hepatitis C virus infections in an individual or in cells. Also mono- or polyclonal antibodies are disclosed that are effective for the treatment of HCV infections together with methods for treating Hepatitis C virus infections or for the regulation of Hepatitis C virus production wherein genes or said antibodies may be used. The present invention also relates to chemical compounds and substances which are effective against Hepatitis C virus (HCV) infections. In particular, compositions comprising said compounds and/or substances, use of the compounds and/or substances for the preparation of compositions useful for the prophylaxis and/or treatment of HCV infections, as well as methods for preventing and/or treating HCV infections. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 395

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Immunogenic HBc chimer particles stabilized with an N-terminal cysteine Inventor(s): Birkett, Ashley J.; (Escondido, CA) Correspondence: WELSH & KATZ, LTD; 120 S RIVERSIDE PLAZA; 22ND FLOOR; CHICAGO; IL; 60606; US Patent Application Number: 20030185858 Date filed: February 21, 2002 Abstract: A chimeric, carboxy-terminal truncated hepatitis B virus nucleocapsid protein (HBc) is disclosed that is engineered for both enhanced stability of self-assembled particles and the display of an immunogenic epitope. The immunogenic epitope is peptide-bonded to one or more of the N-terminus, in the immunogenic loop or at the Cterminus of HBc, whereas the enhanced stability of self-assembled particles is obtained by the presence of at least one heterologous cysteine residue near the aminio-terminus of the chimer molecule. Methods of making and using the chimers are also disclosed. Excerpt(s): This a continuation-in-part of application Ser. No. 09/930,915, filed Aug. 15, 2001, whose disclosures are incorporated herein by reference. The present invention relates to the intersection of the fields of immunology and protein engineering, and particularly to a chimeric hepatitis B virus (HBV) nucleocapsid protein that is engineered for both enhanced stability of self-assembled particles via an N-terminal cysteine residue and the display of an immunogenic epitope. The family hepadnaviridae are enveloped DNA-containing animal viruses that can cause hepatitis B in humans (HBV). The hepadnavirus family includes hepatitis B viruses of other mammals, e.g., woodchuck (WHV), and ground squirrel (GSHV), and avian viruses found in ducks (DHV) and herons (HeHV). Hepatitis B virus (HBV) used herein refers to a member of the family hepadnaviridae that infects mammals, as compared to a virus that infects an avian host, unless the discussion refers to a specific example of a non-mammalian virus. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Immunomodulator Inventor(s): Hamuro, Junji; (Kawasaki-shi, JP), Murata, Yukie; (Kawasaki-shi, JP) Correspondence: OBLON, SPIVAK, MCCLELLAND, MAIER & NEUSTADT, P.C.; 1940 DUKE STREET; ALEXANDRIA; VA; 22314; US Patent Application Number: 20030203006 Date filed: April 3, 2003 Abstract: An immunomodulator is provided which is capable of oral intake for improvement, treatment and prevention of human immunological diseases and which is used to treat, improve and prevent human immunological diseases, especially, autoimmune diseases and allergic diseases such as hepatic cirrhosis, hepatitis, diabetes, inflammatory bowel diseases, chronic rheumatoid arthritis, asthma and cutaneous atopy, allergic diseases and cancers by a new method that can control the redox state of macrophages or monocytes, and can be incorporated into a drug, a food, a nutrient, and an infusion. The contents of oxidative glutathione and reductive glutathione in macrophages are monitored, and the ratio of oxidative glutathione and reductive glutathione is examined, whereby macrophages are classified into oxidative macrophages and reductive macrophages having different functions. The degree of progression of various autoimmune diseases is analyzed from this standpoint. On the

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basis of the results, an immunomodulator capable of oral intake which contains a substance having an activity of changing a content of reductive glutathione in macrophages to solve the above-mentioned problem and which is intended to treat, improve and prevent human immune diseases is provided. Excerpt(s): The present invention relates to a novel immunomodulator. More specifically, the present invention relates to an immunomodulator capable of oral intake which has a novel suppressive function of macrophages (hereinafter sometimes abbreviated as "M.PHI.") or monocytes. The immunomodulator may be used for treatment, improvement and prevention of human autoimmune diseases such as hepatic cirrhosis, hepatitis, diabetes, inflammatory bowel diseases, chronic rheumatoid arthritis, asthma and cutaneous atopy, allergic diseases and cancers. The present invention also relates to a drug, a food, a nutrient and an infusion containing the immunomodulator. As used herein, the term "immune system" refers to one's bodily system for defending itself from exogenous infection by virus, bacteria or the like, or from invasion the body with transformed cells (tumor cells and the like) formed by transformation of autologous cells. However, the immune system occasionally behaves abnormally, i.e., it functions excessively and acts to reject autologous components. On the other hand, the immune system sometimes functions deficiently, resulting in an immunocompromised state. Diseases revealing these abnormal responses are generally called immunological diseases. Examples thereof include diverse diseases, such as, for example, acute or chronic inflammatory diseases such as atopic cutaneous inflammatory diseases, pollinosis, asthma and sarcoidosis; autoimmune diseases such as allergic diseases, chronic rheumatoid arthritis, diabetes, SLE and chronic fatigue syndrome; hepatitis, hepatic cirrhosis, inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease; and cancer cachexia. These immunological diseases originate from complex pathological causes. Systemic immunodeficiency and functional deficiency originate from pathological inflammation accompanied by cell proliferation, differentiation or cell necrosis through local production of cytokines or inflammatory mediators. As cells that participate in immunity, T lymphocytes and B lymphocytes are well known, exhibiting a wide variety of functions as cells playing roles in cellular immunity and humoral immunity respectively. Meanwhile, macrophages and monocytes are cells that intimately participate in both cellular immunity and humoral immunity, and they intimately participate in rejection of non-self foreign bodies, for example, immunological diseases such as allergy and rheumatism, cancers and bacterial infection. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

In vitro system for replication of RNA-dependent RNA polymerase (RDRP) viruses Inventor(s): King, Robert W.; (West Chester, PA), Pasquinelli, Claudio; (Media, PA), Jeffries, Matthew W.; (Indianapolis, IN) Correspondence: STEPHEN B. DAVIS; BRISTOL-MYERS SQUIBB COMPANY; PATENT DEPARTMENT; P O BOX 4000; PRINCETON; NJ; 08543-4000; US Patent Application Number: 20030175683 Date filed: January 31, 2002 Abstract: An in vitro method to conduct genomic replication of the viral genomes of viruses that utilize RNA-dependent RNA polymerase for replication (RDRP viruses), such as HCV. The method employs a construct comprising the 3' and 5' untranslated regions (UTRs) of the viral genome which are operably linked on the 5' and 3' ends of a

Patents 397

reporter sequence, in antisense orientation, such that when viral replication is occurring within the cell which produces RDRP, the reporter protein will be made. The method of the invention provides an efficient means for measuring genomic replication in RDRP viruses, and also for the rapid screening of compounds for their ability to inhibit genomic replication of RDRP viruses, including the Hepatitis C virus (HCV). Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/265,437, filed Jan. 31, 2001, the contents of which are herein incorporated by reference in their entirety. This invention is directed toward the pharmaceutical and molecular biology arts, more particularly this invention is an in vitro system for the replication of the viral genomes of viruses that depend upon the enzyme RNAdependent RNA polymerase (RDRP) for replication. The method of the invention provides an efficient means for measuring genomic replication in RDRP viruses, and also for the rapid screening of compounds for their ability to inhibit genomic replication of RDRP viruses, including the Hepatitis C virus (HCV). It is known that viral genomes can be made of DNA or RNA and can be double-stranded or single-stranded. Typically, viral genomes encode viral coat proteins that serve to package the genome after replication, and also nonstructural proteins that facilitate enzymatic replication of the viral genome in conjunction with cellular enzymes. In the case of some viruses having a single-stranded RNA genome, one of the nonstructural proteins encoded by the viral genome is RNA-dependent RNA polymerase (RDRP), which is needed by the virus to replicate its genomic sequence. The viral enzyme RNA-dependent RNA polymerase is also called RNA replicase. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Inhibitors of hepatitis C virus protease Inventor(s): Joyce, Michael; (Edmonton, CA), Hindsgaul, Ole; (Edmonton, CA), Williams, Mark; (Edmonton, CA), Tyrrell, D. Lorne; (Edmonton, CA) Correspondence: BOZICEVIC, FIELD & FRANCIS LLP; 200 MIDDLEFIELD RD; SUITE 200; MENLO PARK; CA; 94025; US Patent Application Number: 20030176689 Date filed: December 13, 2002 Abstract: The present invention features HCV protease inhibitors, which act by affecting the activity of the HCV protease NS3, or by preventing its activation by NS4A. The invention also features methods of use of the inhibitors of the invention in the treatment of HCV infection in a subject. Excerpt(s): This application claims priority benefit to U.S. provisional application serial No. 60/340,574, filed Dec. 14, 2001, which application is incorporated herein by reference in its entirety. The invention generally relates to Hepatitis C virus (HCV) protease inhibitors, and their use in treatment of HCV infection. Hepatitis C Virus (HCV) is a global health problem with estimates of more than 1% of the world's population currently infected with the virus (Alter Hepatology 1997; 26:635-655). One of the truly outstanding characteristics of HCV is its ability to establish chronic infections in 65-80% of infected patients (Alter et al. NEJM 1999:340:556-562). Chronic infection with HCV can lead to serious sequellae including chronic active hepatitis, cirrhosis and hepatocellular carcinoma--usually manifest 10, 20 and 25 years respectively after the initial infection (Alter et al. NEJM 1992; 222:1899-1902; Iwarson et al. Clin. Infect. Dis. 1995; 20:1361-1370). End stage liver disease from HCV has become the leading

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indication for liver transplantation in North America. It has been suggested that there will be a 2-3 fold increase in liver transplantation in 10 years as a result of cirrhosis from hepatitis C. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Inhibitors of hepatitis C virus RNA-dependent RNA polymerase, and compositions and treatments using the same Inventor(s): Goble, Michael Paul; (San Diego, CA), Borchardt, Allen J.; (San Diego, CA) Correspondence: AGOURON PHARMACEUTICALS, INC.; 10350 NORTH TORREY PINES ROAD; LA JOLLA; CA; 92037; US Patent Application Number: 20030195239 Date filed: March 31, 2003 Abstract: Compounds of formula I are hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) inhibitors, and are useful in therapeutic and prophylactic treatment of persons infected with hepatitis C virus. 1 Excerpt(s): This application claims the benefit of U.S. Provisional Application Ser. No. 60/369,381, filed Apr. 1, 2002. The invention relates to agents that inhibit hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp). The invention also relates to the use of such compounds in pharmaceutical compositions and therapeutic treatments useful for inhibition of HCV replication. Hepatitis C virus (HCV) is a member of the hepacivirus genus in the family Flaviviridae. It is the major causative agent of non-A, non-B viral hepatitis and is the major cause of transfusion-associated hepatitis and accounts for a significant proportion of hepatitis cases worldwide. Although acute HCV infection is often asymptomatic, nearly 80% of cases resolve to chronic hepatitis. The persistent property of the HCV infection has been explained by its ability to escape from the host immune surveillance through hypermutability of the exposed regions in the envelope protein E2 (Weiner et al., Virology 180:842-848 (1991); Weiner et al. Proc. Natl. Acad. Sci. USA 89:3468-3472 (1992). About 60% of patients develop liver disease with various clinical outcomes ranging from an asymptomatic carrier state to chronic active hepatitis and liver cirrhosis (occurring in about 20% of patients), which is strongly associated with the development of hepatocellular carcinoma (occurring in about 1-5% of patients) (for reviews, see Cuthbert, Clin. Microbiol. Rev. 7:505-532 (1994); World Health Organization, Lancet 351:1415 (1998). The World Health Organization estimates that 170 million people are chronically infected with HCV, with an estimate of 4 million of these living in the United States. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Liver transmembrane protein gene Inventor(s): Jay, Gilbert; (North Bethesda, MD), Shu, Youmin; (Potomac, MD) Correspondence: ORIGENE TECHNOLOGIES, INCORPORATED; 6 TAFT COURT; SUITE 100; ROCKVILLE; MD; 20850; US Patent Application Number: 20030170639 Date filed: March 11, 2002

Patents 399

Abstract: The present invention relates to all facets of novel polynucleotides, the polypeptides they encode, antibodies and specific binding partners thereto, and their applications to research, diagnosis, drug discovery, therapy, clinical medicine, forensic science and medicine, etc. The polynucleotides are expressed in liver and are therefore useful in variety of ways, including, but not limited to, as molecular markers, as drug targets, and for detecting, diagnosing, staging, monitoring, prognosticating, preventing or treating, determining predisposition to, etc., diseases and conditions, such as hepatitis and carcinoma, especially relating to liver. Excerpt(s): SEQ ID NOS 1 and 2 show the nucleotide and amino acid sequences of human LAT-1. The present invention relates to all facets of LAT-1, polypeptides encoded by it, antibodies and specific binding partners thereto, and their applications to research, diagnosis, drug discovery, therapy, clinical medicine, forensic science and medicine, etc. The polynucleotides and polypeptides are useful in variety of ways, including, but not limited to, as molecular markers, as drug targets, and for detecting, diagnosing, staging, monitoring, prognosticating, preventing or treating, determining predisposition to, etc., diseases and conditions, such as hepatitis, cirrhosis, and carcinoma, especially relating to liver. The identification of specific genes, and groups of genes, expressed in pathways physiologically relevant to liver permits the definition of functional and disease pathways, and the delineation of targets in these pathways which are useful in diagnostic, therapeutic, and clinical applications. The present invention also relates to methods of using the polynucleotides and related products (proteins, antibodies, etc.) in business and computer-related methods, e.g., advertising, displaying, offering, selling, etc., such products for sale, commercial use, licensing, etc. The liver is the largest and most metabolically complex organ in the body. Its functions include, e.g., storage of iron, production of bile to facilitate digestion, detoxifications of various exogenous chemicals, including alcohol and many drugs, energy stockpiling (carbohydrates and fat), production of clotting factors, and manufacture of blood. There are a number of diseases which affect the liver, including, Alagille syndrome, alcoholic liver disease, alpha-1-antitrypsin deficiency, autoimmune hepatitis, Budd-Chiari syndrome, biliary atresia, Byler disease, liver cancer, Caroli disease, cirrhosis, CriglerNajjar syndrome, Dubin-Johnson syndrome, fatty liver, galactosemia, Gilbert syndrome, glycogen storage disease, hemangioma, hemochromatosis, hepatitis A-G, porphyria cutanea tarda, primary biliary cirrhosis, protoporphyria, erythrohepatic, Rotor syndrome, sclerosing cholangitis, and Wilson disease. Liver disease is of grave concern around the world. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Method for treating diabetic ulcers Inventor(s): Brem, Harold; (New York, NY) Correspondence: PATREA L. PABST; HOLLAND & KNIGHT LLP; SUITE 2000, ONE ATLANTIC CENTER; 1201 WEST PEACHTREE STREET, N.E.; ATLANTA; GA; 303093400; US Patent Application Number: 20030180259 Date filed: March 12, 2003 Abstract: A method and means have been developed to deliver a therapeutic dose or dosages of the angiogenic molecule, Vascular Endothelial Growth Factor (VEGF) that results in a statically significant decrease in the time to achieve 100% wound closure and accelerates the rate of healing in experimental diabetic ulcers. Toxicity is evaluated by

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measuring any local inflammatory response at the wound site, the systemic absorption of VEGF, and the effect on distant organs that may be particularly susceptible to VEGF therapy (e.g., retinopathy and hepatitis) The angiogenic response is quantified by measuring the change in collagen deposition, epithelialization, and the closure rates of diabetic ulcers after therapeutic dosing with ADV-VEGF. Sustained administration of VEGF stimulates and accelerates the healing process as evidenced by a reduced time to complete healing (defined by 100% epithelialization and no drainage) in experimental diabetic ulcers, with minimal to no toxicity. Important features of the method and reagents for use therein are that the VEGF is released into the ulcer in a sufficient quantity over a period of time for at least two to six weeks, or to closure of the wound. Excerpt(s): This application claims priority to U.S. Ser. No. 60/363,584 filed Mar. 12, 2002. The present invention is a method of tissue engineering, and specifically relates to administration of angiogenic factors directly to diabetic wound ulcers, in an effective amount for a sustained period of time effective to promote closure. Among the 16 million diabetic patients (diagnosed and undiagnosed) in the United States, an estimated 1200 amputations are performed each week (Pecoraro, et al., Diabetes Care. 1990; 13:213-521); 84% of which are preceded by a foot ulcer. Limb amputation in diabetics is associated with an increased risk for further amputation, with a five-year mortality rate of 39 to 68% (Reiber et al. Diabetes in America. Washington, D.C.; U.S. Government Printing Office, 1995:409-428). The direct costs of a lower extremity amputation range from $20,000 to $60,000. When failed vascular reconstruction, rehabilitation, and lost productivity within society are considered, these costs greatly exceed financial analysis. The grave consequences, pain, and suffering endured by patients with diabetic foot ulcers mandate determination of the best combination of therapies to prevent progression and, consequent occurrence of these complications. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Monoclonal antibodies to the human ldl receptor, their production and use Inventor(s): Dreano, Michel; (Collonges-sous-Saleve, FR), Yonah, Nachum; (Gedera, IL), Smolarsky, Moshe; (Rehovot, IL), Antonetti, Francesco; (Roma, IT), Belzer, Ilana; (Rishon Le Zion, IL), Suissa, Dany; (Rehovot, IL) Correspondence: BROWDY AND NEIMARK, P.L.L.C.; 624 NINTH STREET, NW; SUITE 300; WASHINGTON; DC; 20001-5303; US Patent Application Number: 20030186343 Date filed: January 15, 2003 Abstract: There are provided monoclonal antibodies to the LDL receptor which are useful for the identification and purification of LDL and in treatment of e.g. hepatitis C infection. Excerpt(s): The present invention relates to monoclonal antibodies which specifically recognise the human receptor for low-density lipoproteins (LDLR). These antibodies are useful e.g. for the identification and purification of human soluble LDLR (hsLDLR) in production processes as well as in the identification and treatment of diseases such as, hepatitis C infection (HCV). Cholesterol, a component of all eukaryotic plasma membranes, is essential for the growth and viability of cells in higher organisms. However, high serum levels of cholesterol cause disease and death by contributing to the formation of atherosclerotic plaques in arteries throughout the body. The major site of cholesterol synthesis in mammals is the liver. Appreciable amounts of cholesterol are

Patents 401

also formed by the intestine. The rate of cholesterol formation by these organs is highly responsive to the amount of cholesterol absorbed from dietary sources. Cells outside of the liver and intestine acquire cholesterol from the plasma rather than by synthesising it de novo. Cholesterol and other lipids are transported in body fluids by lipoproteins, which are classified according to increasing density. A lipoprotein is a particle consisting of a core of hydrophobic lipids surrounded by a shell of polar lipids and apoproteins. These lipoproteins have two roles: they solubilize highly hydrophobic lipids and they contain signals that regulate the movement of particular lipids in and out of specific target cells and tissues. Cholesterol is transported in body fluids by lowdensity lipoproteins (LDL) which binds to a specific receptor on the plasma membrane of non hepatic cells. The receptor-LDL complex is then internalised into the cells by a transport mechanism known as receptor mediated endocytosis (Goldstein et al. 1979). The low density lipoprotein (LDL) receptor is the prototype of a family of structurally related cell surface receptors that mediate endocytosis of multiple ligands in mammalian cells. The LDL receptor consists of 822 amino acid residues and exhibits a molecular weight of 164000. It is composed of several domains some of which share sequence homology with other proteins. Its NH.sub.2-terminal ligand-binding domain consists of 292 residues, arranged in 7 cysteine-rich imperfect repeats. Each repeat contains six cysteine residues which are disulphide bonded in the pattern one to three, two to five, and four to six. (Bieri et al. 1995). This domain is followed by four additional domains: the first consists of 400 amino acid residues and is homologous to the EGF receptor, the second consists of 58 amino acid residues rich in O-linked sugars, the third is a single trans-membrane domain of 22 amino acid residues and the fourth is a cytoplasmic domain of 50 amino acid residues (Sudhofet al. 1985), (Brown et al. 1986). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Multivalent vaccine composition Inventor(s): Boutriau, Dominique; (Rixensart, BE), Lemoine, Dominique; (Rixensart, BE), Desmons, Pierre Michel; (Rixensart, BE), Poolman, Jan; (Rixensart, BE), Capiau, Carine; (Rixensart, BE) Correspondence: SMITHKLINE BEECHAM CORPORATION; CORPORATE INTELLECTUAL PROPERTY-US, UW2220; P. O. BOX 1539; KING OF PRUSSIA; PA; 19406-0939; US Patent Application Number: 20030180316 Date filed: March 26, 2003 Abstract: A multi-valent vaccine composition is described comprising a conjugate of the capsular polysaccharide of H. influenzae b not adsorbed onto an aluminium adjuvant salt, and two or more further bacterial polysaccharides. A multi-valent vaccine composition is also described comprising a whole-cell pertussis component, tetanus toxoid, diphtheria toxoid, Hepatitis B surface antigen, a conjugate of the capsular polysaccharide of H. influenzae b, and a conjugate of a capsular polysaccharide of N. meningitidis type A or C (or both). Furthermore, a multi-valent vaccine composition is described comprising a whole-cell pertussis component, tetanus toxoid, diphtheria toxoid, and a low dose of a conjugate of the capsular polysaccharide of H. influenzae b. Excerpt(s): The present invention relates to new combination vaccine formulations. Combination vaccines (which provide protection against multiple pathogens) are very desirable in order to minimise the number of immunisations required to confer protection against multiple pathogens, to lower administration costs, and to increase

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acceptance and coverage rates. The well-documented phenomenon of antigenic competition (or interference) complicates the development of multi-component vaccines. Antigenic interference refers to the observation that administering multiple antigens often results in a diminished response to certain antigens relative to the immune response observed when such antigens are administered individually. Combination vaccines are known which can prevent Bordetella pertussis, Clostridium tetani, Corynebacterium diphtheriae, and optionally Hepatitis B virus and/or Haemophilus influenzae type b (see, for instance, WO 93/24148 and WO 97/00697). The present invention concerns the manufacture of the most ambitious multi-valent vaccines to date, the administration of which can prevent or treat infection by Bordetella pertussis, Clostridium tetani, Corynebacterium diphtheriae, Hepatitis B virus, Haemophilus influenzae and N. meningitidis, and preferably also Hepatitis A virus and/or Polio virus, wherein the components of the vaccine do not significantly interfere with the immunological performance of any one component of the vaccine. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Muscle-strengthening drugs and anti-inflammatory drugs Inventor(s): Daicho, Takao; (Shida-gun, JP), Ochiai, Akio; (Shimizu-shi, JP), Okada, Kenkichi; (Shinagawa-ku, JP), Nukaya, Haruo; (Shimizu-shi, JP), Kosuge, Masaki; (Shizuoka-shi, JP), Miura, Oto; (Musashino-shi, JP), Tsuji, Kuniro; (Shizuoka-shi, JP) Correspondence: OLIFF & BERRIDGE, PLC; P.O. BOX 19928; ALEXANDRIA; VA; 22320; US Patent Application Number: 20030203057 Date filed: December 12, 2002 Abstract: An object of the present invention is to provide a pharmaceutical agent or composition useful as a muscle-strengthening drug, an anti-inflammatory drug, an antiasthmatic, an antidiarrheal, an antidepressant, or a drug for the treatment of secondary diseases following cerebral infarction, motor paralysis, diminution of vision, hepatitis, inflammatory intestinal syndrome, functional enteropathy, functional cardiopathy, functional hepatopathy, functional nephropathy, dementia, climacteric symptoms, senile dementia and/or Alzheimer disease, and a dermatological agent or composition suitable for skin applications, which can treat or prevent muscle weakening and inflammation, in particular arthritis, by its muscle-strengthening and/or antiinflammatory actions, said agent or composition comprising isoflavone and/or isoflavone glycoside in combination with a pungent substance, a bitter substance or a sour substance, and cholic acid, and/or scymnol and/or a scymnol ester. The present invention relates to an agent or composition usuful as a muscle-strengthening drug, an anti-inflammatory drug, an antiasthmatic, an antidiarrheal, an antidepressant, or a drug for the treatment of secondary diseases following cerebral infarction, motor paralysis, diminution of vision, hepatitis, inflammatory intestinal syndrome, functional enteropathy, functional cardiopathy, functional hepatopathy, functional nephropathy, dementia, climacteric symptoms, senile dementia and/or Alzheimer disease, and/or an agent or composition to be applied to the skin, said agent or composition comprising isoflavone and/or isoflavone glycoside in combination with a pungent substance, a bitter substance or a sour substance, and cholic acid, and/or scymnol and/or a scymnol ester. Excerpt(s): The present invention relates to a novel agent or composition for use as a muscle-strengthening drug, an anti-inflammatory drug, an antiasthmatic, an

Patents 403

antidiarrheal, an antidepressant, or a drug for the treatment of secondary diseases following cerebral infarction (human stroke sequelae, secondary stroke damages or sequelae of brain infarction), motor paralysis, diminution of vision, hepatitis, inflammatory intestinal syndrome, functional enteropathy, functional cardiopathy, functional hepatopathy, functional nephropathy, dementia, climacteric symptoms, senile dementia and/or Alzheimer disease, and to an agent or composition to be applied to the skin. Serotonin and noradrenaline referred to as brain hormones control satisfaction of the will, and in turn, spiritual satisfaction. In response to satisfaction of the will, voluntary muscles are activated by adrenaline, an adrenal medullary hormone, secreted from adrenal medulla and chromaffin cells on nerve muscles. Serotonin, noradrenaline and adrenaline are also referred to as biogenic monoamines, and are oxidatively decomposed by an enzyme called monoamine oxidase within as long as 3 hours or reabsorbed into nerve tissues and so forth, resulting in the extinction of most effects of secreted monoamines. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

N4-acylcytosine-1,3- dioxolane nucleosides for treatment of viral infections Inventor(s): Watanabe, Kyoichi A.; (Stone Mountain, GA), Shi, Junxing; (Duluth, GA), Otto, Michael J.; (Lilburn, GA) Correspondence: KING & SPALDING; 191 PEACHTREE STREET, N.E.; ATLANTA; GA; 30303-1763; US Patent Application Number: 20030176319 Date filed: December 16, 2002 Abstract: The present invention is directed to a compound, method and composition of treating or preventing viral infections, in particular, human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections, in human patients or other animal hosts, comprising the administration of N.sup.4-acylcytosine-1,3-dioxolane and pharmaceutically acceptable salts, prodrugs, and other derivatives thereof. Excerpt(s): The present application claims priority to U.S. Ser. No. 60/341,555 filed on Dec. 14, 2001. The present invention is directed to compounds, methods and compositions for the treatment or prevention of viral infections using nucleoside analogues. More specifically, the invention describes N.sup.4-acyl-substituted cytosine nucleoside analogues, pharmaceutically acceptable salts, prodrugs, or other derivatives thereof, and the use thereof in the treatment of a viral infection, and in particular a human immunodeficiency virus (HIV) or hepatitis B virus (HBV) infection. In 1981, acquired immune deficiency syndrome (AIDS) was identified as a disease that severely compromises the human immune system, and that without exception leads to death. In 1983, the etiological cause of AIDS was determined to be what is now known as human immunodeficiency virus (HIV). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Novel 3-substituted urea derivatives and medicinal use thereof Inventor(s): Ishibuchi, Seigo; (Chuo-ku, Tokyo, JP), Sumichika, Hiroshi; (Chuo-ku, Tokyo, JP), Itoh, Katsuhiko; (Saitama-shi, Saitama, JP), Naka, Yoichi; (Nakatsu-shi, Ooita, JP) Correspondence: WENDEROTH, LIND & PONACK, L.L.P.; 2033 K STREET N. W.; SUITE 800; WASHINGTON; DC; 20006-1021; US Patent Application Number: 20030207939 Date filed: February 5, 2003 Abstract: The present invention relates to a urea derivative of the formula (1) 1wherein each symbol is as described in the specification, a pharmaceutically acceptable salt thereof and pharmaceutical use thereof. The compound of the present invention has a C5a receptor antagonistic action and is useful as an agent for the prophylaxis or treatment of diseases or syndromes due to inflammation caused by C5a [e.g., autoimmune diseases such as rheumatism, systemic lupus erythematosus and the like, sepsis, adult respiratory distress syndrome, chronic obstructive pulmonary disease, allergic diseases such as asthma and the like, atherosclerosis, cardiac infarction, brain infarction, psoriasis, Alzheimer's disease and serious organ injury (e.g., pneumonia, nephritis, hepatitis, pancreatitis and the like) due to activation of leukocytes caused by ischemia, trauma, burn, surgical invasion and the like]. In addition, it is useful as an agent for the prophylaxis or treatment of infectious diseases caused by bacteria or virus that invades via a C5a receptor. Excerpt(s): The present invention relates to a urea derivative showing a C5a receptor antagonistic action and useful for the prophylaxis or treatment of autoimmune diseases such as rheumatism and systemic lupus erythematosus and the like, sepsis, adult respiratory distress syndrome, chronic obstructive pulmonary disease, allergic diseases such as asthma and the like, atherosclerosis, cardiac infarction, brain infarction, psoriasis, Alzheimer's disease or serious organ injuries (e.g., pneumonia, nephritis, hepatitis and pancreatitis and the like) due to activation of leukocytes caused by ischemia, trauma, burn, surgical invasion and the like, a pharmaceutically acceptable salt thereof and pharmaceutical use thereof. When the complement system is activated, the protein of the complement system is enzymolysed and fragments having various physiological activities are produced. One of the fragments, complement component C5a, is a glycoprotein having a molecular weight of about 11,000, consists of 74 amino acids and has a strong inflammation inducing action. C5a has a broad range of actions such as smooth muscle contraction, promotion of blood vessel permeability, migration of leukocyte, degranulation of leukocyte, production of reactive oxygen species, reinforcement of antibody production, induction of production of cytokine, TNF (tumor necrosis factor), leukotriene and the like, and the like, and is said to be a causative substance of diseases such as autoimmune diseases (e.g., rheumatism and systemic lupus erythematosus and the like), sepsis, adult respiratory distress syndrome, chronic obstructive pulmonary disease, allergic diseases (e.g., asthma and the like), atherosclerosis, cardiac infarction, brain infarction, psoriasis, Alzheimer's disease, serious organ injuries (e.g., pneumonia, nephritis, hepatitis, pancreatitis and the like) due to activation of leukocytes caused by ischemia, trauma, burn, surgical invasion and the like, and the like [Annu. Rev. Immunol., vol. 12, pp. 775-808 (1994), Immunopharmacology, vol. 38, pp. 3-15 (1997), Curr. Pharm. Des., vol. 5, pp. 737-755 (1999) and IDrugs, vol. 2, pp. 686-693 (1999)]. Accordingly, a non-peptide small molecular compound having a C5a receptor antagonistic action is expected as a novel non-steroid type antiinflammatory drug. In addition, it can be expected as a

Patents 405

prophylactic or therapeutic drug of infectious diseases caused by bacteria or virus that invades via a C5a receptor. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Novel compounds as NS3-serine protease inhibitors of hepatitis C virus Inventor(s): Arasappan, Ashok; (Bridgewater, NJ), Bogen, Stephane L.; (Somerset, NJ), Jao, Edwin; (Warren, NJ), Njoroge, F. George; (Warren, NJ), Liu, Yi-Tsung; (Morris Township, NJ), Girijavallabhan, Viyyoor M.; (Parsippany, NJ), Madison, Vincent S.; (Mountain Lakes, NJ), Bennett, Frank; (Cranford, NJ), Saksena, Anil K.; (Upper Montclair, NJ), Venkatraman, Srikanth; (Woodbridge, NJ), Lovey, Raymond G.; (West Caldwell, NJ), Sannigrahi, Mousumi; (Summit, NJ), Chen, Kevin X.; (Edison, NJ), Nair, Latha G.; (Edison, NJ) Correspondence: SCHERING-PLOUGH CORPORATION; PATENT DEPARTMENT (K6-1, 1990); 2000 GALLOPING HILL ROAD; KENILWORTH; NJ; 07033-0530; US Patent Application Number: 20030207861 Date filed: January 21, 2003 Abstract: The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease. Excerpt(s): This patent application claims priority from U.S. provisional patent application Serial No. 60/350,931, filed Jan. 23, 2002. The present invention relates to novel hepatitis C virus ("HCV") protease inhibitors, pharmaceutical compositions containing one or more such inhibitors, methods of preparing such inhibitors and methods of using such inhibitors to treat hepatitis C and related disorders. This invention specifically discloses novel peptide compounds as inhibitors of the HCV NS3/NS4a serine protease. The invention disclosed in this application is related to that in patent application Ser. No. 10/052,386, filed Jan. 18, 2002. Hepatitis C virus (HCV) is a (+)-sense single-stranded RNA virus that has been implicated as the major causative agent in non-A, non-B hepatitis (NANBH), particularly in blood-associated NANBH (BB-NANBH)(see, International Patent Application Publication No. WO 89/04669 and European Patent Application Publication No. EP 381 216). NANBH is to be distinguished from other types of viral-induced liver disease, such as hepatitis A virus (HAV), hepatitis B virus (HBV), delta hepatitis virus (HDV), cytomegalovirus (CMV) and Epstein-Barr virus (EBV), as well as from other forms of liver disease such as alcoholism and primary biliar cirrhosis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Peptides for inducing cytotoxic T lymphocyte responses to hepatitis B virus Inventor(s): Chisari, Francis V.; (Del Mar, CA) Correspondence: TOWNSEND AND TOWNSEND AND CREW, LLP; TWO EMBARCADERO CENTER; EIGHTH FLOOR; SAN FRANCISCO; CA; 94111-3834; US Patent Application Number: 20030171538 Date filed: February 5, 2003 Abstract: Peptides are used to define epitopes that stimulate HLA-restricted cytotoxic T lymphocyte activity against hepatitis B virus antigens. The peptides are derived from regions of HBV polymerase, and are particularly useful in treating or preventing HBV infection, including methods for stimulating the immune response of chronically infected individuals to respond to HBV antigens. Excerpt(s): The present application is a continuation-in-part application of U.S. Ser. No. 08/100,870, filed Aug. 2, 1993, which is a continuation-in-part of U.S. Ser. No. 07/935,898, which is a continuation-in-part of U.S. Ser. No. 07/749,540, the disclosures of which are incorporated herein by reference. Cytotoxic T lymphocytes (CTLs) play an essential role in fighting cells infected with viruses, intracellular bacteria and parasites, and tumor cells. They do so by direct cytotoxicity and by providing specific and nonspecific help to other immunocytes such as macrophages, B cells, and other T cells. Infected cells or tumor cells process antigen through intracellular events involving proteases. The processed antigen is presented on the cellular surface in the form of peptides bound to HLA class I molecules to T cell receptors on CTLs. MHC class I molecules can also bind exogenous peptides and present them to CTLs without intracellular processing. At the present time it is difficult to accurately predict from the sequence of an antigenic protein how the protein will be processed and which peptide portions will bind HLA class I molecules and be presented to CTLs. Binding motifs have been predicted for some HLA class I molecules based on sequence analysis of peptides eluted from these molecules (Falk et al., Nature 351:290 (1991)). Further, of the peptides that are processed and do bind to HLA class I, which ones will contain CTLrecognizable epitopes is not yet predictable. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Pharmaceutical compositions for hepatitis C viral protease inhibitors Inventor(s): Chen, Shirlynn; (Somers, NY), Mei, Xiaohui; (Highland Mills, NY) Correspondence: BOEHRINGER INGELHEIM CORPORATION; 900 RIDGEBURY ROAD; P O BOX 368; RIDGEFIELD; CT; 06877; US Patent Application Number: 20030195228 Date filed: February 4, 2003 Abstract: Disclosed are pharmaceutical compositions of hepatitis C viral protease inhibitors having improved bioavailability, and methods of using these compositions for inhibiting the replication of the hepatitis C virus (HCV) and for the treatment of an HCV infection. These compositions include co-solvent systems, lipid based systems, solid dispersions and granulations, and all comprise the hepatitis C viral protease inhibitor, at least one pharmaceutically acceptable amine and optionally one or more additional ingredients.

Patents 407

Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/355,694, filed Feb. 7, 2002, which is herein incorporated by reference in its entirety. The present invention relates in general to pharmaceutical compositions of hepatitis C viral protease inhibitors having improved bioavailability, and methods of using these compositions for inhibiting the replication of the hepatitis C virus (HCV) and for the treatment of an HCV infection. See Tsantrizos et al., U.S. Application Ser. No. 09/760,946, filed on Jan. 16, 2001, (Boehringer Ingelheim (Canada), Ltd.), which application is herein incorporated by reference in its entirety and is hereinafter referred to as "Tsantrizos et al". See also the corresponding WO 00/59929 (Boehringer Ingelheim (Canada) Ltd.). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Pharmaceutically active pyrrolidine derivatives as bax inhibitors Inventor(s): Baxter, Anthony; (Abington, Oxon, GB), Bombrun, Agnes; (MonnetierMornex, FR), Schwarz, Mattias; (Thonex, CH), Halazy, Serge; (Vetraz-Monthoux, FR), Quattropani, Anna; (Carouge, CH), Thomas, Russel; (Boars Hill, Oxford, GB) Correspondence: BROWDY AND NEIMARK, P.L.L.C.; 624 NINTH STREET, NW; SUITE 300; WASHINGTON; DC; 20001-5303; US Patent Application Number: 20030171309 Date filed: April 28, 2003 Abstract: The present invention is related to new substituted pyrrolidine derivatives of formula (I). Said compounds are preferably for use as pharmaceutically active compounds. Specifically, pyrrolidine derivatives of formula (I) are useful in the treatment and/or prevention of neurodegenerative disorders, diseases associated with polygultamine tracts, epilepsy, ischemia, infertility, cardiovascular disorders renal hypoxia, hepatitis and AIDS. Said pyrrolidine derivatives display a modulatory and most notably a down-regulating-up to an inhibitory-activity with respect to the cellular death agonist Bax and/or the activation pathways leading to Bax and allows therefore to block the release of cytochrome (c). The present invention is furthermore related to novel pharmaceutically activity substituted pyrrolidine derivatives as well as to methods of their preparation, wherein X is selected from the group consisting of O, S, CR<6>R<7>, NOR<6>, NNR<6>R<7> A is selected from the group consisting of --(C.dbd.O)--, --(C.dbd.O)--O--, --C(.dbd.NH)--, --(C.dbd.O)--NH--, -(C.dbd.S)--NH, --SO2-, --SO2NH--; --CH2-; B is either a group --(C.dbd.O)-NR<8>R<9> or represents a heterocyclic residue having the formula (II) wherein Q is NR<10>, O or S; n is an integer selected of 0, 1 or 2; Y, Z and E form together with the 2 carbons to which they are attached a 5-6 membered aryl or heteroaryl ring. Excerpt(s): The present invention is related to new substituted pyrrolidine derivatives of formula I. Said compounds are preferably for use as pharmaceutically active compounds. Specifically, pyrrolidine derivatives of formula I are useful in the treatment and/or prevention of neurodegenerative disorders, diseases associated with polyglutamine tracts, epilepsy, ischemia, infertility, cardiovascular disorders, renal hypoxia, hepatitis and AIDS. Said pyrrolidine derivatives display a modulatory and most notably a down-regulating--up to an inhibitory--activity with respect to the cellular death agonist Bax and/or the activation pathways leading to Bax and allows therefore to block the release of cytochrome c. The present invention is furthermore related to novel pharmaceutically active substituted pyrrolidine derivatives as well as to

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methods of their preparation. The cell surface begins to bleb and expresses prophagocytic signals. The whole apoptotic cell then fragments into membrane-bound vesicles that are rapidly and neatly disposed of by phagocytosis, so that there is minimal damage to the surrounding tissue. The cell then separates from its neighbors. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Polypeptides, use thereof and process for producing the same Inventor(s): Takahara, Yoshiyuki; (Kanagawa, JP), Okutsu, Tomohisa; (Kanagawa, JP), Fukuda, Hisao; (Kanagawa, JP), Maekawa, Takami; (Kanagawa, JP), Yokoya, Fumihiko; (Kanagawa, JP) Correspondence: OBLON, SPIVAK, MCCLELLAND, MAIER & NEUSTADT, P.C.; 1940 DUKE STREET; ALEXANDRIA; VA; 22314; US Patent Application Number: 20030187185 Date filed: December 26, 2002 Abstract: A polypeptide having a production level specifically lowered in human diseased human livers. This polypeptide provides a novel diagnostic means for hepatitis by determining the production level of the polypeptide or an mRNA encoding the polypeptide in the liver. Excerpt(s): This application is a Continuation of International Application No. PCT/JP01/05415, hereby incorporated by reference as if fully set forth herein. The present invention relates to polypeptides having a production level specifically lowered in human livers having inflammation ("diseased livers") as well as their preparation methods and uses, i.e., methods for diagnosing hepatitis by determining the production level of the polypeptides in the liver and diagnostic kits for diagnosing hepatitis by determining the production level of the polypeptides in the liver. Hepatitis shows significantly varying clinical pictures or histopathological features depending on the cause, severity and stage. Thus, diagnosis/treatment of hepatitis requires a comprehensive judgment based on clinical pictures, histopathological observation and hepatic function tests, etc. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Prevention and treatment of HCV infection employing antibodies directed against conformational and linear epitopes Inventor(s): Foung, Steven K. H.; (Stanford, CA), Keck, Zhen-Yong; (Redwood City, CA) Correspondence: Choate, Hall & Stewart; Exchange Place; 53 State Street; Boston; MA; 02109; US Patent Application Number: 20030180284 Date filed: July 2, 2002 Abstract: Conformational epitopes of the envelope proteins E1 and E2 of the Hepatitis C virus (HCV) have been identified and characterized using a panel of monoclonal antibodies derived from patients infected with HCV. These conserved conformational and linear epitopes of the HCV protein E1 or E2 have been determined to be important in the immune response of humans to HCV and may be particularly important in neutralizing the virus. Based on the identification of these conformational epitopes,

Patents 409

vaccines containing peptides and mimotopes with these conformational epitopes intact may be prepared and administered to patients to prevent and/or treat HCV infection. The identification of four distinct groups of monoclonal antibodies with each directed to a particular epitope of E1 or E2 may be used to stratify patients based on their response to HCV and may be used to determine a proper treatment regimen. Excerpt(s): This application is a continuation-in-part of co-pending patent application U.S. Ser. No. 09/728,720, filed Dec. 1, 2000, which is a continuation-in-part of U.S. Ser. No. 09/430,489, filed Oct. 29, 1999, which is a continuation-in-part of patent application U.S. Ser. No. 09/187,057, filed Nov. 5, 1998. Each of these applications is incorporated herein by reference. The field of this invention is related to the preparation of human monoclonal antibodies (HMAb) to structurally conserved epitopes of HCV. Such antibodies can be found in a high proportion of patients and are useful, for example, in the diagnosis and therapy of HCV infection, including being useful in the identification of patients expected to benefit from certain therapeutic strategies. Hepatitis C virus (HCV) is an enveloped virus the genetic information for which is encoded in a 9.5 kb positive strand RNA genome. A highly conserved noncoding region of 341 bp is localized at the 5'-end of this viral genome, which is followed by a long open-reading frame coding for a polyprotein of approximately 3,010 amino acids. Two putative envelope glycoproteins E1 (gp35) and E2 (gp72) have been identified with 5 or 6 and 11 N-linked glycosylation sites, respectively. A high level of genetic variability is associated with the envelope genes. This variability is highly accentuated at the 5'-end of the E2 gene, where two hypervariable regions termed HVR1 and HVR2, have been described. Antibodies to HVR1 appear to mediate virus neutralization in cell culture and chimpanzee protection studies (Farci et al., 1996 Proc. Natl. Acad. Sci. USA 93:1539415399; Shimizu et al., 1994 J. Virol. 68:1494-1500; each of which is incorporated herein by reference). Unfortunately, antibodies to HVR1 tend to be isolate specific and over time drive the replication of new viral variants that the existing immune response does not recognize (Farci et al., 1994 Proc. Natl. Acad. Sci. USA 91:7792-7796; Weiner et al, 1992 Proc. Natl. Acad. Sci. USA 89:3468-3472; Kato et al., 1993 J. Virol. 67:3923-3930; each of which is incorporated herein by reference), although progress has been made at inducing a broader immune response to HVR1 related sequences (Puntoriero et al., 1998 EMBO Journal 17:3521-3533; incorporated herein by reference). HCV envelope antigens appear to be highly immunogenic when expressed in glycosylated forms (da Silva Cardoso et al., 1997 Ann. Hematol. 74:135-7; incorporated herein by reference). Preliminary data suggest the existence of conserved epitopes within the E2 protein (Lesniewski et al., 1995 J. Med. Virol. 45:415-22; incorporated herein by reference). The existence of neutralizing antibodies in serum from infected patients has been proposed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Preventives and remedies for chronic hepatitis Inventor(s): Tohdoh, Naoki; (Hyogo, JP), Enjoji, Takashi; (Osaka, JP), Murata, Masashi; (Osaka, JP) Correspondence: OBLON, SPIVAK, MCCLELLAND, MAIER & NEUSTADT, P.C.; 1940 DUKE STREET; ALEXANDRIA; VA; 22314; US Patent Application Number: 20030171276 Date filed: October 31, 2002 Abstract: To provide a prophylactic or therapeutic agent for chronic hepatitis, capable of inhibiting the binding of hepatitis virus and a target cell, thereby preventing or treating

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chronic hepatitis; and a fusion interferon capable of still more improving a viral clearance ratio at the termination of interferon administration. A prophylactic or therapeutic agent for chronic hepatitis, comprising an oligopeptide having the following characteristics: (A) having a binding affinity to a viral antigen protein; (B) inhibiting binding of virus to a receptor protein on a target cell for said virus; and (C) having homologies with said receptor protein at the amino acid sequence level; a fusion interferon containing an amino acid sequence of the above-mentioned oligopeptide; and method for treating chronic hepatitis in combination with the use of interferon, characterized by using the oligopeptide or a part thereof in combination with interferon. Excerpt(s): The present invention relates to a therapeutic agent for chronic hepatitis, comprising an oligonucleotide having an amino acid sequence or a part thereof, wherein the amino acid sequence is important for infection of hepatitis virus into a target cell. Concretely, the present invention relates to a therapeutic agent for chronic hepatitis, comprising an oligopeptide or a part thereof, the oligopeptide being capable of binding to an antigenic protein for hepatitis virus and having an action of inhibiting binding of virus to a receptor protein, or a compound prepared on the basis of its sequence. Also, the present invention relates to a fusion interferon comprising the oligopeptide and its partial amino acid sequence. Further, the present invention relates to a method for treating chronic hepatitis in combination with the use of interferon. Chronic type-B hepatitis and type-C hepatitis developed by infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) are grave viral diseases which are transformed into cirrhosis or hepatocellular carcinoma at a high ratio. In Japan, the number of hepatitis B virus carriers is said to be about one million, and that of hepatic C virus carriers is said to be about 1.3 millions. The carriers have been spread world-widely. HCV, which is a singlestranded RNA virus belonging to Flaviviridae, has been considered to transform to chronicity by factors for the virus side such as avoidance from the immune mechanism by gene mutation and factors from the host side such as decrease in the immunocompetence and the viral clearance ability. On the other hand, since HBV belonging to Hepadonaviridae is a double-stranded DNA virus, a mutation in a virus genome does not take place as much as it does in HCV; however, it transforms to chronicity by incorporation into chromosome DNA. Also in HBV, there is found fulmination caused by avoidance from the immune mechanism caused by mutation of a virus gene. Presently, the only one treatment method for eliminating the virus is an interferon treatment method. However, a ratio at which the virus is finally eliminated is 40% or so in HCV and 20% or so in HBV. In particular, in an interferon treatment method for the HCV, there is caused a difference in its therapeutic effect depending upon the status of the patient, such as serotype of HCV, virus amount and histological progression degree. In particular, in the case of genotype II and hyperviremia, it has been known that its amelioration effect is low and a virus clearance ratio is also low. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 411

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Reporter gene system for use in cell-based assessment of inhibitors of the hepatitis C virus protease Inventor(s): Potts, Karen Elizabeth; (Solana Beach, CA), Jackson, Roberta Lynn; (San Diego, CA), Patick, Amy Karen; (Escondido, CA) Correspondence: SHANKS & HERBERT; 1033 N. FAIRFAX STREET; SUITE 306; ALEXANDRIA; VA; 22314; US Patent Application Number: 20030175692 Date filed: July 10, 2002 Abstract: A cell-based assay system in which the detection of the reporter gene activity, or secreted alkaline phosphatase (SEAP), is dependent upon the protease activity of the Hepatitis C virus NS3 gene product. This system can be used to assess the activity of candidate protease inhibitors in a mammalian cell-based assay system. The assay system is simpler than previously described assays due to the use of SEAP which allows the reporter gene activity to be quantified by measuring the amount of secreted gene product in the cell media by monitoring the conversion of luminescent or calorimetric alkaline phosphatase substrate. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/129,611, filed Aug. 5, 1999. A cell-based assay system in which the detection of reporter gene activity (secreted alkaline phosphatase or SEAP) is dependent upon active Hepatitis C virus (HCV) NS3 protease. The assay system is useful in the in vitro screening, in a mammalian cell-based assay, of potential protease inhibiting molecules useful in the treatment of HCV. The advantages of using SEAP over more routinely used reporter genes such as beta-galactosidase or luciferase, is that a cell lysis step is not required since the SEAP protein is secreted out of the cell. The absence of a cell lysis step decreases intra- and inter-assay variability as well as makes the assay easier to perform then earlier assays. HCV is one of the major causes of parenterally transmitted non-A, non-B hepatitis worldwide. HCV is now known as the etiologic agent for Non-A Non-B hepatitis throughout the world. Mishiro et al., U.S. Pat. No. 5,077,193; Mishiro et al., U.S. Pat. No. 5,176,994; Takahashi et al, U.S. Pat. No. 5,032,511; Houghton et al., U.S. Pat. Nos. 5,714,596 and 5,712,088; as well as (M. Houghton, Hepatitis C Viruses, p.1035-1058 in B. N. Fields et al.(eds.), Field's Virology (3d. ed. 1996). HCV infection is characterized by the high rate (>70%) with which acute infection progresses to chronic infection (Alter, M. J. 1995. Epidemiology of hepatitis C in the west. Sem. Liver Dis. 15:5-14.). Chronic HCV infection may lead to progressive liver injury, cirrhosis, and in some cases, hepatocellular carcinoma. Currently, there are no specific antiviral agents available for the treatment of HCV infection. Although alpha interferon therapy is often used in the treatment of HCV-induced moderate or severe liver disease, only a minority of patients exhibit a sustained response Saracco, G. et al., J. Gastroenterol. Hepatol. 10:668-673 1995. Additionally, a vaccine to prevent HCV infection is not yet available and it remains uncertain whether vaccine development will be complicated by the existence of multiple HCV genotypes as well as viral variation within infected individuals Martell, M. et al., J. Virol. 66:3225-3229 1992; Weiner, et al., Proc. Natl. Acad. Sci. 89:3468-3472 1992. The presence of viral heterogeneity may increase the likelihood that drug resistant virus will emerge in infected individuals unless antiviral therapy effectively suppresses virus replication. Most recently, several of the HCV encoded enzymes, specifically the NS3 protease and NS5B RNA polymerase, have been the focus of intensive research, in vitro screening, and/or rational drug design efforts. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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RNA interference mediated inhibition of hepatitis B virus (HBV) using short interfering nucleic acid (siNA) Inventor(s): Morrissey, David; (Boulder, CO), McSwiggen, James A.; (Boulder, CO), Beigelman, Leonid; (Longmont, CO) Correspondence: MCDONNELL BOEHNEN HULBERT & BERGHOFF; 300 SOUTH WACKER DRIVE; SUITE 3200; CHICAGO; IL; 60606; US Patent Application Number: 20030206887 Date filed: September 16, 2002 Abstract: The present invention concerns methods and reagents useful in modulating hepatitis B virus (HBV) gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to short interfering nucleic acid (siNA) or short interfering RNA (siRNA) molecules capable of mediating RNA interference (RNAi) against against hepatitis B virus (HBV). Excerpt(s): This application claims the benefit of U.S. application Ser. Nos. 60/358,580, filed Feb. 20, 2002, and 60/393,924, filed Jul. 3, 2002. This application also claims priority to PCT US02/09187, filed Mar. 26, 2002, which claims the benefit of U.S. application Ser. No. 60/296,876, filed Jun. 8, 2001. The present invention concerns methods and reagents useful in modulating hepatitis B virus (HBV) gene expression and activity in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to short interfering nucleic acid (siNA) molecules capable of mediating RNA interference (RNAi) against HBV expression. The following is a discussion of relevant art pertaining to RNAi. The discussion is provided only for understanding of the invention that follows. The summary is not an admission that any of the work described below is prior art to the claimed invention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Stabilized HBc chimer particles as therapeutic vaccine for chronic hepatitis Inventor(s): Friede, Martin; (Cardiff, CA), Page, Mark; (Allestree, GB) Correspondence: WELSH & KATZ, LTD; 120 S RIVERSIDE PLAZA; 22ND FLOOR; CHICAGO; IL; 60606; US Patent Application Number: 20030198645 Date filed: February 21, 2003 Abstract: A method of treating chronic hepatitis B is disclosed that comprises administering a T cell-stimulating amount of a vaccine to a patient. The vaccine comprises an immunogenic amount of chimeric, carboxy-terminal truncated hepatitis B virus nucleocapsid (core) protein (HBc) that is engineered for both enhanced stability of self-assembled particles and the substantial absence of nucleic acid binding by those particles. The chimeric protein molecule can include one or more immunogenic epitopes peptide-bonded to one or more of the N-terminus, the immunogenic loop or the Cterminus of HBc. The enhanced stability of self-assembled particles is obtained by the presence of at least one heterologous cysteine residue near one or both of the aminoterminus and carboxy-terminus of the chimer molecule.

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Excerpt(s): This a continuation-in-part of application Ser. No. 10/080,299, filed Feb. 21, 2002 and Ser. No. 10/082,014 filed Feb. 22, 2002, whose disclosures are incorporated herein by reference. The present invention relates to the intersection of the fields of immunology and protein engineering, and particularly to a chimeric hepatitis B virus (HBV) nucleocapsid protein that is useful as the immunogen in a vaccine for treating patients with chronic hepatitis by enhancing the immune response towards the hepatitis B virus and is engineered for enhanced stability of self-assembled particles via one or both of a C-terminal and an N-terminal cysteine residue. Over 350 million people worldwide are chronically infected carriers of hepatitis B (HBV). HBV is a virus that infects the liver and causes an increased risk of chronic hepatitis, cirrhosis of the liver, and hepatocellular carcinoma (cancer of the liver). Hepatitis B is the cause of over 80 percent of hepatocellular carcinomas, and claims the lives of 1-2 million people worldwide every year, representing an important public health challenge and a growing market for new therapeutics. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Structure-based hepatitis c virus drug design Inventor(s): Bolognesi, Martino; (Siena, IT), Grandi, Guido; (Siena, IT) Correspondence: Chiron Corporation; 4560 Horton Street; Emeryville; CA; 94608; US Patent Application Number: 20030176662 Date filed: April 22, 2003 Abstract: The extracellular loop of CD81 is a cellular receptor for the E2 protein of hepatitis C virus. A CD81 crystal structure has been elucidated and is provided for use in the structure-based design of compounds which bind to CD81 and thus block the binding of HCV. Methods such as docking and de novodrug design can be used. Excerpt(s): All documents cited herein are incorporated by reference in their entirety. This invention is in the field of the use of structure-based drug design methods to identify compounds that bind to CD81, which is a cell-surface receptor for hepatitis C virus (HCV). Chronic HCV infection occurs in about 3% of the world's population. It is a major cause of liver disease, but effective anti-HCV drugs are not yet available. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Treating hepatitis C viral infections with thiosemicarbazone compounds Inventor(s): Altamura, Sergio; (Rome, IT), Koch, Uwe; (Albano Laziale, IT) Correspondence: MERCK AND CO INC; P O BOX 2000; RAHWAY; NJ; 070650907 Patent Application Number: 20030176503 Date filed: April 19, 2002 Abstract: Thiosemicarbazone compounds of formula: 1and pharmaceutically acceptable salts thereof are useful for treating infection by the hepatitis C virus, treating hepatitis C or a related condition, delaying the onset of hepatitis C or a related condition, preventing hepatitis C or a related condition, and inhibiting replication of the hepatitis C virus. In the formula Q is aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, or substituted cycloalkenyl; L is absent, -alkyl-, -alkenyl-, or -alkylS(O).sub.m-alkyl- -, wherein m is an integer from zero to 2; and R.sup.1 is --H or alkyl.

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Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/285,195 filed Apr. 20, 2001, the disclosure of which is hereby incorporated by reference in its entirety. The present invention is directed to the use of thiosemicarbazone compounds to treat infection by the hepatitis C virus, treat or delay the onset of hepatitis C, and inhibit replication of the hepatitis C virus. The hepatitis C virus (HCV) is the major causative agent of parenterally-transmitted and sporadic nonA, non-B hepatitis. It is believed that about 3 percent of the world's population and 2 percent of the U.S. population have been infected with this agent at some time. Exposure to HCV can result in an overt acute disease, but in most cases the virus establishes a chronic infection that causes liver inflammation and slowly progresses into liver failure and cirrhosis, as described for example in Iwarson, FEMS Microbiol. Rev. 1994, 14: 201204. Epidemiological surveys have also indicated an important role of HCV in the pathogenesis of hepatocellular carcinoma, as described for example in Kew, FEMS Microbiol. Rev. 1994, 14: 211-220. No vaccine or established therapy currently exists, although partial success has been achieved in a minority of cases by treatment with recombinant interferon-alpha, either alone or in combination with ribavirin. There is accordingly a need for the development of alternative anti-HCV therapies. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·

Treatment of hepatitis C with thymosin and peptide combination therapy Inventor(s): Rudolph, Alfred R.; (Los Altos Hills, CA) Correspondence: ROTHWELL, FIGG, ERNST & MANBECK, P.C.; 1425 K STREET, N.W.; SUITE 800; WASHINGTON; DC; 20005; US Patent Application Number: 20030185799 Date filed: February 7, 2003 Abstract: A method and pharmaceutical combination for treating hepatitis C by administering to a hepatitis C patient an effective amount of at least one alpha thymosin peptide, in combination with administration to the hepatitis C patient of an effective amount of at least one interferon, and optionally in combination with administration of at least one antiviral agent such as ribavirin. Excerpt(s): This application is a continuation-in-part of PCT/US01/41549, filed Aug. 6, 2001, which claims benefit from U.S. Provisional Application Serial No. 60/223,312, filed Aug. 7, 2000. This application also is a continuation-in-part of PCT/US01/41550, filed Aug. 6, 2001, which claims benefit from U.S. Provisional Application Serial No. 60/223,317, filed Aug. 7, 2000. This invention relates generally to the pharmacological treatment of hepatitis C virus infection in patients. Hepatitis C virus (HCV) is the putative agent in the majority of cases of post-transfusion acquired hepatitis. Despite improvement in the quality of the blood-donor pool and the implementation of testing of donated blood, the incidence of acute infection among persons receiving transfusions is still significant. Chronic hepatitis develops in at least half the patients with acute HCV infection (representing about 90% of patients with non-A, non-B hepatitis (NANB)), and cirrhosis develops in at least 20% of this group. A variety of drugs have been evaluated with the aim of halting or slowing the progression of HCV-related diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of recombinant hepatitis B core particles to develop vaccines against infectious pathogens and malignancies Inventor(s): Zavala, Fidel; (New York, NY), Birkett, Ashley J.; (Escondido, CA) Correspondence: DARBY & DARBY P.C.; P. O. BOX 5257; NEW YORK; NY; 10150-5257; US Patent Application Number: 20030185854 Date filed: February 7, 2003 Abstract: The present invention relates to methods and compositions for augmenting CD8+ T cell responses to an antigen in a mammal, comprising the use of recombinant hepatitis B core particles (rHEP) to present said antigen. The invention further relates to a method of boosting the rHEP particle-induced CD8+ T cell responses using secondary immunization with a recombinant vaccinia virus expressing the same antigen (rVAC). The methods and compositions of the present invention can be useful for prophylaxis and treatment of various infectious and neoplastic diseases. Excerpt(s): The successful elimination of pathogens, neoplastic cells, or self-reactive immune mechanisms following prophylactic or therapeutic immunization depends to a large extent on the ability of the host's immune system to become activated in response to the immunization and mount an effective response, preferably with minimal injury to healthy tissue. The rational design of vaccines initially involves identification of immunological correlates of protection--the immune effector mechanism(s) responsible for protection against disease--and the subsequent selection of an antigen that is able to elicit the desired adaptive response. Once this appropriate antigen has been identified, it is essential to deliver it effectively to the host's immune system. New vaccines are presently under development and in testing for the control of various infectious and neoplastic diseases. In contrast to older vaccines which were typically based on liveattenuated or non-replicating inactivated pathogens, modern vaccines are composed of synthetic, recombinant, or highly purified subunit antigens (e.g., recombinant or synthetic polypeptides, nucleic acids, or recombinant bacterial or viral vectors capable of inducing antibodies as well as T cell responses [see, e.g., Liljeqvist and Sthal, J. Biotech, 73:1-33, 1999]). Subunit vaccines are designed to include only the antigens required for protective immunization and are believed to be safer than whole-inactivated or liveattenuated vaccines. However, the purity of the subunit antigens and the absence of the self-adjuvanting immunomodulatory components associated with attenuated or killed vaccines often result in weaker immunogenicity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with hepatitis, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “hepatitis” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on hepatitis.

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You can also use this procedure to view pending patent applications concerning hepatitis. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. BOOKS ON HEPATITIS Overview This chapter provides bibliographic book references relating to hepatitis. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on hepatitis include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “hepatitis” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on hepatitis: ·

Hepatitis C Handbook Source: Berkeley, CA: North Atlantic Books and Frog, Ltd. 1999. 473 p. Contact: Available from North Atlantic Books and Frog, Ltd. P.O. Box 12327, Berkeley, CA 94712. (800) 337-2665 or (510) 559-8277. Fax (510) 559-8279. E-mail: [email protected]. Website: www.northatlanticbooks.com. PRICE: $25.00 plus shipping and handling. ISBN: 1556433131. Summary: Hepatitis C is a common, recently discovered viral infection usually contracted from the use of intravenous drugs, often decades previously, or less commonly by blood or blood products prior to the introduction of blood screening protocols. This handbook offers an overview of hepatitis C virus (HCV) and focuses on the significance of the diagnosis and on lifestyle changes that may prove helpful. The author guides the patient to an informed and balanced choice between the currently available range of treatment options, including interferon and other antiviral agents as

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well as Chinese herbal remedies. The author hopes to empower readers and so provides detailed medical information about symptoms, lifestyle changes, real life experiences with the disease, and treatment strategies. The first chapter offers facts and figures about the virus and its prevalence; transmission, epidemiology, and the origins of the virus are discussed in Chapter 2, along with professional briefings regarding the prevention of the further proliferation of HCV. Information regarding the various tests that patients are likely to encounter are covered in Chapter 3, together with a discussion of the implications of a diagnosis and whether or not to get tested. Other chapters in the first section cover special situations, including coinfection with other types of hepatitis, children, hemophilia, and Cooley's anemia. The second section offers three chapters that concentrate on the response to having HCV. This section is designed to enable the reader to go through the process of coming to terms with their condition, to better participate as a member of their own health care team, and to deal with members of the medical profession. The third section summarizes the main treatment options open to HCV patients. Chapters cover conventional treatments, traditional Chinese medicine, Western herbal medicine (including medicinal mushrooms), Ayurvedic medicine, vitamins and minerals (and amino acids), homeopathy, miscellaneous treatments, and naturopathy (the 'no treatment' option). The fourth section covers lifestyle options, including diet, alcohol, drugs, exercise, yoga, Qu Gong, and stress management. The final section offers a wealth of resources for readers, including additional technical information, a glossary, a list of resources, and a subject index. Each chapter also includes references. ·

Transfusion and Viral Infections: Prevention of Transfusion - Transmitted AIDS and Hepatitis Source: Management of Blood Transfusion Services. Contact: World Health Organization, Health Laboratory Technology and Blood Safety Unit, 20 Avenue Appia, 1211 Geneva 27. Summary: This book chapter discusses efforts to reduce the risk of transfusion transmitted Acquired immunodeficiency syndrome (AIDS) and hepatitis. Topics covered include prevention of post-transfusion viral hepatitis B; non-A and non-B hepatitis; donor selection and screening; screening methods; and efforts to produce more and safer plasma derivatives.

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Viral Hepatitis: Biological and Clinical Features, Specific Diagnosis, and Prophylaxis. 2nd ed Source: New York, NY. Raven Press, Ltd. 1991. 203 p. Contact: Available from Raven Press. 1185 Avenue of the Americas, Dept. 5B, New York, NY 10036. (800) 777-2836 or (212) 930-9500. Fax (212) 869-3495. PRICE: $91.50 plus shipping (as of 1995). ISBN: 0881677272. Summary: This book examines fundamental aspects of the hepatitis viruses, A, B, C, D, and E, and the variety of host responses to infection. The authors also discuss practical aspects for the clinician, the epidemiologist, and the laboratory investigator. Topics include risk factors, diseases, modes of transmission, the serologic profiles that should be obtained to yield a correct diagnosis, and methods for the prevention of viral hepatitis by passive and active immunization. In addition, instructions are given for the proper screening of donors to diminish or almost to eliminate the risk of posttransfusion hepatitis. Following exposure to blood, stepwise procedures are listed for the physician to follow: when to request serological tests; when to give normal immune globulin or

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hepatitis B immune globulin; and when to vaccinate. Extensive references are included with each chapter, and a subject index concludes the volume. ·

Viral Hepatitis: Practical Evaluation and Treatment Source: Kirkland, WA: Hogrefe and Huber Publishers. 1995. 248 p. Contact: Available from Hogrefe and Huber Publishers. Seattle Main Office, P.O. Box 2487, Kirkland, WA 98083-2487. (800) 228-3749 or (206) 820-1500. Fax (206) 823-8324. PRICE: $49 plus shipping (as of 1995). ISBN: 0889371334. Summary: This book provides up to date practical information on the diagnosis, treatment, and prevention of the viral hepatitis. Designed for a broad based audience of primary care providers, the book includes 15 chapters on the following topics: an overview of viral hepatitis; hepatitis A; hepatitis A vaccine; acute hepatitis B; chronic hepatitis B; special circumstances with HBV; prevention of hepatitis B; treatment of hepatitis B; diagnosis and transmission of hepatitis C; clinical features of hepatitis C; special topics in hepatitis C; treatment of hepatitis C; delta hepatitis; hepatitis E; and fulminant hepatic failure. The book explains diagnosis, clinical features, epidemiology and transmission, natural history, prevention, and treatment for each form of hepatitis. Each chapter includes an outline and summary of approach. A subject index concludes the volume. (AA-M).

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Management of Hepatitis C: NIH Consensus Development Conference Program and Abstracts Source: Bethesda, MD: National Institutes of Health. 1997. 139 p. Contact: Available from NIH Consensus Program Information Center. P.O. Box 2577, Kensington, MD 20891. (888) 644-2667. Fax (301) 816-2494. PRICE: Single copy free. Summary: This document presents abstracts of the NIH Consensus Development Conference on the Management of Hepatitis C, held in March 1997 in Bethesda, Maryland. It notes the conference's agenda, panel, speakers, and planning committee members. The document was designed for the use of panelists and participants in the conference and as a pertinent reference document for anyone interested in the conference deliberations. The abstracts are presented in four sections: the natural history of hepatitis C, diagnostic considerations, the epidemiology and spread of hepatitis C, and therapeutic issues. Specific topics covered include the clinical spectrum of disease, blood donors with hepatitis C, hepatitis C and hepatocellular carcinoma (liver cancer), hepatitis C and alcohol, diagnostic tests for hepatitis C, the role of liver biopsy, the epidemiology of hepatitis C, the sexual and perinatal spread of hepatitis C virus infection, the use of interferon alfa-2b, ribavirin treatment, drug side effects, predictive factors for a beneficial response to drug therapy in hepatitis C, the treatment of patients with liver cirrhosis, retreatment with interferon, and cost effectiveness considerations. Each abstract includes brief references.

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Hepatitis C: From Pathogenesis to Prognosis Source: Thousand Oaks, CA: Amgen, Inc. 1997. 32 p. Contact: Available from Amgen Professional Services. 1840 DeHavilland Drive, Thousand Oaks, CA 91320-1789. (800) 77-AMGEN. PRICE: Single copy free to health professionals.

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Summary: This document summarizes the current understanding of hepatitis C virus (HCV), from its pathogenesis to present research on treatment and cure options. HCV infection results in a chronic disease state in 50 to 70 percent of cases and is now the most common cause of chronic liver disease in the United States. It is highly infectious; known routes of transmission include blood and blood products, injection drug use, and sexual contacts. The virus has been cloned and is now well characterized with respect to both structural and nonstructural proteins. Molecular cloning technology has resulted in the development of specific and sensitive screening, diagnostic, and monitoring assays for HCV. In addition, tests to determine the quantity of viral RNA in blood and to define areas of the viral genome have been developed. Both viral load and genome have been suggested to be predictive of patient response to therapy. Other factors associated with response to treatment include age, presence of iron overload, duration of infection, mode of transmission, and the level of serum bile salts. The development of effective vaccines against hepatitis C is difficult, in part because of the quasispecies nature of HCV. The authors conclude that increased knowledge of the epidemiology and natural history of hepatitis C, coupled with greater understanding of how these diagnostic assays can guide the use of available and future therapies, is crucial in combatting this disease. 8 figures. 4 tables. 53 references. (AA-M). ·

Hepatitis C: Diagnostic Techniques and Monitoring Strategies Source: Thousand Oaks, CA: Amgen, Inc. 1997. 32 p. Contact: Available from Amgen Professional Services. 1840 DeHavilland Drive, Thousand Oaks, CA 91320-1789. (800) 77-AMGEN. PRICE: Single copy free to health professionals. Summary: This document summarizes the present diagnostic techniques and monitoring strategies used as part of the management of hepatitis C virus (HCV). HCV infection results in a chronic disease state in 50 to 70 percent of cases and is now the most common cause of chronic liver disease in the United States. It is highly infectious; known routes of transmission include blood and blood products, injection drug use, and sexual contacts. The virus has been cloned and is now well characterized with respect to both structural and nonstructural proteins. Molecular cloning technology has resulted in the development of specific and sensitive screening, diagnostic, and monitoring assays for HCV. In addition, tests to determine the quantity of viral RNA in blood and to define areas of the viral genome have been developed. Both viral load and genome have been suggested to be predictive of patient response to therapy. The authors review HCV diagnostic and monitoring tests, including liver enzymes, serological assays, virological assays, genotyping and serotyping, and liver biopsy. The discovery of antibodies to HCV or elevated ALT in a patient with or without symptoms of liver disease frequently culminates in the diagnosis of hepatitis C. The sequence of tests used to confirm the diagnosis may depend on the patient's known risk factors and the type of test (ALT, anti-HCV, or both) that initially established the likelihood of infection. The authors conclude that once the diagnosis of HCV infection is confirmed, determination of the presence or absence of cirrhosis, HCV RNA concentration, and genotype or serotype are important predictive factors in determining which patients are most likely to respond to therapy. 8 figures. 8 tables. 66 references. (AA-M).

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Be in Charge: A Guide to Living with Chronic Hepatitis B and C Source: Kenilworth, NJ: Schering Corporation. 1998. 100 p.

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Contact: Available from Scherling Corporation. 2000 Galloping Hill Road Kenilworth, NJ 07033. (800) 446-8766 or (908) 298-4000. Fax (908) 298-4490. PRICE: Single copy free for patients; available to health professionals through local sales representatives. Summary: This handbook offers an upbeat, colorful approach to the information that patients need in order to live a long and health life while coping with chronic hepatitis (liver infection) B and C. Twelve chapters include an overview of hepatitis, how the liver functions, viruses and viral infections, stopping the spread of the virus (transmission), diagnosis, treatment options for chronic hepatitis B or C, taking care of symptoms, the role of proper nutrition and diet therapy, coping with the emotions of living with hepatitis, gaining support from family and friends, managing work and finances, and research and prevention strategies currently under investigation. Throughout the handbook there are tools, such as quizzes, to keep readers sharp on the facts being provided, and places for jotting down thoughts or questions for the physician. Each chapter also lists action steps that can be a starting point for taking control of one's own life and fighting the virus. The Resource List at the end of the handbook includes information about important resources, including groups that may be able to help readers continue learning about the disease and how to combat it. The handbook is illustrated with extensive line drawings, brightly colored graphics, and checklists of steps to undertake. ·

My Mom Has Hepatitis C Contact: Hatherleigh Press, 5-22 46 Ave Ste 200, Long Island City, NY, 11101, (800) 3672550, http://www.hatherleigh.com. Summary: This monograph educates preschool and elementary school children about hepatitis C. The story concerns two children who learn to deal with their mother's infection with hepatitis C as the family experiences the first year of diagnosis, treatment, and change. It discusses transmission; prevention; and emotional issues for children such as worry about who will take care of them, anger at changes in their lives, sadness, grieving, and guilt that they may have caused the illness.

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Living With Hepatitis C: Everything You Need to Know Contact: Firefly Books Incorporated, 4 Daybreak Ln, Westport, CT, 06880-2157, http://www.fireflybooks.com. Summary: This monograph explains the disease hepatitis C, its transmission, symptoms, prevention, and treatment. The monograph explains the different types of hepatitis, the function of the liver, the effect of hepatitis on the liver and on the health of the patient with hepatitis C, how hepatitis is diagnosed, drugs used for treatment, and their side effects. The monograph also discusses liver transplantation in the event of liver failure; the things a patient can do to promote good health, such as a healthy diet and avoiding smoking and alcohol; complementary therapies that are being tried and some that should be avoided; antiviral therapies and vaccines being researched; and how others can help the patient live with hepatitis C.

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Management of Chronic Viral Hepatitis Source: New York, NY: Marcel Dekker, Inc. 2002. 380 p. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. Website: www.dekker.com. PRICE: $150.00 plus shipping and handling.

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Summary: This monograph offers 13 chapters on the management of chronic viral hepatitis (liver inflammation), bringing the advances of clinical and basic research into the doctor's office. Thus, each chapter begins with a brief clinical case presentation that illustrates a practical and challenging viral hepatitis dilemma. The case study format of the chapters addresses the real life intricacies of managing patients who present with viral hepatitis, and explains how current antiviral research may benefit each patient. The authors, recognized authorities in viral hepatitis, report the latest advances in diagnostic and therapeutic modalities, and discuss how these scientific breakthroughs may benefit patients. Specific topics include hepatitis B virology of acute and chronic infection, including HBV variants; antigen, antibody, and molecular testing for hepatitis C virology; current treatment of chronic hepatitis B; future approaches to the treatment of chronic hepatitis B; the treatment of chronic hepatitis B in transplant recipients; alternative therapies for chronic hepatitis C; current treatment options for hepatitis C; persistently normal alanine aminotransferase levels in individuals with hepatitis C; retreatment of hepatitis C in patients who do not respond to interferon treatment; treatment of chronic hepatitis C in transplant recipients; treatment of chronic hepatitis B and C in patients coinfected with HIV; treatment of hepatitis D; and future options in therapy for hepatitis C, including protease and Helicase inhibitors. The text concludes with a subject index. ·

Viral Hepatitis and HIV/AIDS Integration : A Resource Guide for HIV/AIDS Programs Summary: This monograph provides guidelines for the inclusion of hepatitis prevention and treatment into human immunodeficiency syndrome (HIV)/acquired immunodeficiency syndrome (AIDS)/sexually transmitted disease (STD) programs. The monograph outlines a hepatitis prevention/treatment integration plan that identifies stakeholders, conducts a needs assessment, establishes a strategic plan, develops public health policies, and secures legislation and/or funding for such a program.

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Living With Hepatitis B: A Survivor's Guide Contact: Hatherleigh Press, 5-22 46 Ave Ste 200, Long Island City, NY, 11101, (800) 3672550, http://www.hatherleigh.com. Summary: This monograph provides medical, emotional, financial, and nutritional information to help anyone diagnosed with chronic hepatitis B to understand and cope with the disease. It explains the disease hepatitis B, its diagnosis, tests and biopsies, transmission, prevention, and its effect on the liver. The monograph also discusses healthy nutrition for an individual with hepatitis B, emotional effects of the disease, and financial concerns due to disability and the cost of lifelong medical care. Other topics covered include types of treatment; when a liver transplant becomes necessary; liver cancer; coinfection with HIV/AIDS, hepatitis C, and hepatitis D; hepatitis B in children; and research trends.

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A Patient-Expert Walks You Through Everything You Need to Learn and Do: The First Year: Hepatitis B: An Essential Guide for the Newly Diagnosed Contact: Publishers Group West Incorporated, 1700 4th St, Berkeley, CA, 94710-1711, (510) 528-1444, http://www.pgw.com. Summary: This monograph provides people who have hepatitis B virus (HBV) infection with up-to-date information on HBV so that they can take an active role in their treatment. The monograph takes the reader step-by-step through everything they need

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to do and learn each day of their first week after a diagnosis of HBV, each subsequent week of the first month, and the following 11 months of the first year. Each day, week, or month is divided into living and learning sections. The living section focuses on the problem of living with a chronic disease, and the learning section presents facts about the topic being discussed. The monograph begins with advice on coming to terms with the diagnosis. Subsequent chapters deal with discussing one's conditon with family, friends, and coworkers; selecting a medical team; managing fatigue and stress; making modifications to one's diet and in one's physical activity level; handling sexual and social relationships; becoming an HBV activist; having, raising, or adopting childen; and coping with depression. In addition, the monograph considers issues related to work and disability, alternative therapies, addictions, and complications. Throughout the monograph, sections focus on the emotional issues surrounding HBV and offer suggestions and personal advice from others who have HBV. ·

Hepatitis C: A Personal Guide to Good Health Contact: Publishers Group West Incorporated, 1700 4th St, Berkeley, CA, 94710-1711, (510) 528-1444, http://www.pgw.com. Summary: This monograph summarizes and updates existing knowledge about hepatitis C virus (HCV) infection. Part one provides information on the discovery of HCV, the features of HCV and other types of hepatitis, the effect of HCV on the liver, modes of transmission, and symptoms. Part two describes the ways HCV is diagnosed, confirmed, and monitored, focusing on blood tests, genotype testing, liver function tests, imaging studies, and liver biopsies. Other topics include the medical and surgical therapies available to treat HCV, including interferon/ribavirin therapy and liver transplantation; alternative and complementary therapies used to treat HCV such as herbs, massage, acupuncture, and other stress-reduction techniques; and the role of diet and exercise in HCV treatment. Part three describes steps individuals can take to assume responsibility for their health. Topics include reaching out for support from physicians, family and friends, coworkers, support groups, professional counselors, and substance abuse specialists as well as stopping the spread of HCV by protecting oneself and others from HCV, supporting efforts to educate others about the dangers of HCV, and advocating for more research.

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Living With Hepatitis C: A Survivor's Guide Contact: Hatherleigh Press, 5-22 46 Ave Ste 200, Long Island City, NY, 11101, (800) 3672550, http://www.hatherleigh.com. Summary: This monograph, for individuals with hepatitis C, offers guidance and answers for individuals infected with hepatitis C. It provides guidance and answers to individuals infected with hepatitis C, their friends and family. It discusses the nature of the disease and how it affects the body; how to understand blood tests and biopsies; how to avoid infecting others; healthy nutrition; what to expect if a liver transplant is needed; how to deal with emotions and grief; children with Hepatitis C; how an individual can protect him/herself from enormous medical costs; and what to expect in the future regarding new research and new drugs.

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A Curriculum Guide for Public - Safety and Emergency - Response Workers: Prevention of Transmission of Human Immunodeficiency Virus and Hepatitis B Virus Contact: US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Information Resources Branch, 4676 Columbia Pky C13, Cincinnati, OH, 45226, (800) 356-4674, http://www.cdc.gov/niosh/homepage.html. Summary: This teaching guide provides a model curriculum for training public safety and Emergency medical services (EMS) personnel in prevention practices specific to occupational exposure to Human immunodeficiency virus (HIV) and HepatitisB virus. Each is defined, and a glossary of related terms and descriptive case studies included. The curriculum builds on guidelines developed by the National Institute for Occupational Safety and Health in collaboration with the Centers for Disease Control (CDC). Topics addressed include what responses are appropriate in given instances for fire service, law enforcement, correctional facility, paramedic, and emergency medical technician personnel; the use of protective equipment; universal precautions; specific workplace prevention measures; decontamination procedures; and the management of exposures. A lecture outline with accompanying tips for trainers, overheads, and a comprehensive listing of information sources for each worker group concludes the guide.

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Viral Hepatitis: Diagnosis, Treatment, Prevention Source: New York, NY: Marcel Dekker, Inc. 1997. 532 p. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. PRICE: $175.00. ISBN: 0824794168. Summary: This text familiarizes readers with current methods of diagnosis, treatment, and prevention of human viral hepatitis. Sixteen chapters cover: methods and applications of molecular diagnostic testing for viral hepatitis; the hepatitis A virus; the molecular biology and immunopathology of the hepatitis B virus; the prevention and therapy of clinical disease arising from the hepatitis B virus; the hepatitis C virus; the hepatitis D virus; the epidemiology and biology of the hepatitis E virus; other hepatitis viruses including the hepatitis G virus; the role of hepatitis viruses in acute liver failure; hepatocellular carcinoma and viral hepatitis; extrahepatic manifestations of chronic viral hepatitis; the overlap of chronic viral hepatitis and autoimmune hepatitis; liver transplantation and viral hepatitis B, D, and C; viral hepatitis in marrow and stem-cell transplant patients; viral hepatitis in the immunocompromised host; and the role of iron in chronic viral hepatitis. The authors evaluate diagnostic serological techniques such as ELISAs and PCRs; highlight nonhuman primate and transgenically created animal models used in disease transmission studies, virus isolation, and serological assays and vaccine development; review the management of fulminant hepatic failure and hepatitis in the immunocompromised patient; discuss how diagnosis may be complicated by predominant extrahepatic manifestations; assess various vaccines recent licensing and future prospects; and appraise the cost effectiveness of medical treatments with antiviral agents, the role of liver transplantation, and preventive measures. Each chapter includes extensive references, and a subject index concludes the volume.

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First Year Hepatitis B: An Essential Guide for the Newly Diagnosed Source: New York, NY: Marlowe and Company. 2002. 264 p.

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Contact: Available from Marlowe and Company. 161 William Street, 16th Floor, New York, NY 10038. PRICE: $15.95 plus shipping and handling. ISBN: 1569245339. Summary: Viral hepatitis B (liver infection) is one of the most preventable medical conditions due to the availability of a hepatitis B vaccine, yet an estimated 100,000 people in the United States are infected each year, and 6,000 die from complications. When the author of this book was diagnosed in 1993, he decided to be proactive in his quest to understand and manage his illness. In this book, the author walks readers stepby-step through everything they need to do and learn each day of their first week after diagnosis, each subsequent week of the first month, and the following eleven months of the first year. In nontechnical language, the author covers a wide range of practical, medical, and lifestyle issues, beginning with coming to terms with the diagnosis and then continuing with strategies for accomplishing necessary lifestyle changes; guidelines and tips for diet modification; how to discuss the condition with family, friends, and coworkers; how to choose a medical team; stress management and exercise; current medical research and medications; how to handle sexual and social relationships; effective alternative therapies; and support group resources. The book concludes with a glossary of terms, a list of resources, and a subject index. ·

Viral Hepatitis: An Epidemic in the Making? New Approaches to the Prevention, Diagnosis, and Treatment of Viral Hepatitis Source: Bethesda, MD: American Gastroenterological Association. 200x. 36 p. Contact: Available from American Gastroenterological Association. 7910 Woodmont Avenue, Seventh Floor, Bethesda, MD 20814. (301) 654-2055. Fax (301) 652-3890. E-mail: [email protected]. PRICE: Single copy free. Also available at http://www.gastro.org/phys-sci/viral-hep.html. Summary: Viral hepatitis is a major public health concern and the most common cause of chronic liver disease, cirrhosis (scarring), and hepatocellular carcinoma (liver cancer). This monograph explores current strategies used to prevent, diagnose, and manage the major forms of viral hepatitis seen in the United States. All cases of hepatitis A and hepatitis B infection are potentially preventable, and new therapies have proven to be beneficial for many patients with hepatitis C; however, research for a vaccine to prevent hepatitis C is still underway. The costs associated with viral hepatitis are significant, particularly for hepatitis B and C. When quality of life is factored into the equation, the costs are even greater. However, there has been significant progress in recent years in the understanding of the diagnosis, epidemiology, natural history, prevention, and treatment of viral hepatitis. The monograph enables readers to identify the critical elements of screening, prevention, and treatment protocols for hepatitis A, E, B, and C; to recognize the signs and symptoms of the several forms of viral hepatitis; to explain to patients the importance of preventing viral hepatitis; and to improve quality of care and the clinical outcomes of patients with viral hepatitis. Tables and figures illustrate the monograph. 14 figures. 4 tables. 79 references.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in PrintÒ). IMPORTANT

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NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “hepatitis” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “hepatitis” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “hepatitis” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): ·

"Live" Discussion on New Classification of Chronic Hepatitis by Masao Omata (Editor); ISBN: 4893701258; http://www.amazon.com/exec/obidos/ASIN/4893701258/icongroupinterna

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A Code of Practice for Implementation of the UK Hepatitis B Immunisation: Guidelines for the Protection of Patients and Staff; ISBN: 0727909231; http://www.amazon.com/exec/obidos/ASIN/0727909231/icongroupinterna

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A decade of viral hepatitis : abstracts, 1969-1979 by Arie Jeremy Zuckerman; ISBN: 0444801901; http://www.amazon.com/exec/obidos/ASIN/0444801901/icongroupinterna

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A Guide to Hepatitis C (1996); ISBN: 0727910973; http://www.amazon.com/exec/obidos/ASIN/0727910973/icongroupinterna

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A Seroepidemiological survey of hepatitis B amongst Fiji health care workers; ISBN: 9822030177; http://www.amazon.com/exec/obidos/ASIN/9822030177/icongroupinterna

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Advances in Hepatitis Research by Francis V. Chisari (Editor); ISBN: 089352218X; http://www.amazon.com/exec/obidos/ASIN/089352218X/icongroupinterna

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All You Wanted to Know About Hepatitis by Savitri Ramaiah (Editor); ISBN: 8120722256; http://www.amazon.com/exec/obidos/ASIN/8120722256/icongroupinterna

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Assessment and Management of Risks Associated With Hepatitis B: Effectiveness of Intervention (Medac, 90) by Maurice R. Hilleman, R. Gordon Douglas (Editor); ISBN: 1560530235; http://www.amazon.com/exec/obidos/ASIN/1560530235/icongroupinterna

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Assessment and Management of Risks Associated With Hyperlipidemia, Osteoporosis, and Hepatitis B: Effectiveness of Intervention (Medical Advisory Co) by R. Gordon Douglas (Editor) (1991); ISBN: 1560530227; http://www.amazon.com/exec/obidos/ASIN/1560530227/icongroupinterna

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Atlas of Infectious Diseases: Intraabdominal Infections, Hepatitis, and Gastroenteritis (Atlas of Infectious Diseases) by B. Lorber (Editor); ISBN: 1878132474; http://www.amazon.com/exec/obidos/ASIN/1878132474/icongroupinterna

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Australia Antigen and Viral Hepatitis by International Symposium on Basic Progres, et al (1973); ISBN: 3805516118; http://www.amazon.com/exec/obidos/ASIN/3805516118/icongroupinterna

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Autoimmune Hepatitis by Mikio Nishioka (1994); ISBN: 0444881964; http://www.amazon.com/exec/obidos/ASIN/0444881964/icongroupinterna

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B3 LEAFLET (50)HEPATITIS B CAMPAIGN by DS; ISBN: 1903346541; http://www.amazon.com/exec/obidos/ASIN/1903346541/icongroupinterna

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Blood Sweat and Tears: The Hepatitis C Scandal by Glenys Spray (1998); ISBN: 0863276474; http://www.amazon.com/exec/obidos/ASIN/0863276474/icongroupinterna

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427

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Blood Transfusion Id Card and Book: For Safer Blood at the Time of Aids, Hepatitis, Vds, Etc by Antun Murkovic (1989); ISBN: 0929602005; http://www.amazon.com/exec/obidos/ASIN/0929602005/icongroupinterna

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Care of the Maternity Patient With Hepatitis B Infection: Clinical Features and PeriNatal Inplications by Martin (1993); ISBN: 0683172204; http://www.amazon.com/exec/obidos/ASIN/0683172204/icongroupinterna

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Chronic Active Hepatitis: The Mayo Clinic Experience (Gastroenterology Series, Vol 2) by Albert J. Czaja, et al; ISBN: 0824776151; http://www.amazon.com/exec/obidos/ASIN/0824776151/icongroupinterna

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Chronic Hepatitis: New Concepts of Pathogenesis, Diagnosis and Treatment (Falk Workshop) by H. P. Dienes (Editor), et al; ISBN: 0792387635; http://www.amazon.com/exec/obidos/ASIN/0792387635/icongroupinterna

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Chronic Hepatitis: Proceedings of the International Symposium on Chronic Hepatitis, Taipei, 28-29 November 1985 (International Congress Series, No 70 by Yun-Fan Liaw (Editor); ISBN: 0444808221; http://www.amazon.com/exec/obidos/ASIN/0444808221/icongroupinterna

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Chronic Hepatitis: Proceedings of the International Symposium on Problems of Chronic Hepatitis, Montecatini by International Symposium on Problems of Chronic Hepatitis Montecatini T, et al (1976); ISBN: 3805523211; http://www.amazon.com/exec/obidos/ASIN/3805523211/icongroupinterna

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Chronic Viral Hepatitis: Diagnosis and Therapeutics by Raymond S., Md. Koff (Editor), George Y., Md, Phd Wu (Editor); ISBN: 0896038807; http://www.amazon.com/exec/obidos/ASIN/0896038807/icongroupinterna

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Chronically evolving viral hepatitis; ISBN: 3211823506; http://www.amazon.com/exec/obidos/ASIN/3211823506/icongroupinterna

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Chronically Evolving Viral Hepatitis (Archives of Virology Supplementum, No 4) by C. De Bac, et al; ISBN: 0387823506; http://www.amazon.com/exec/obidos/ASIN/0387823506/icongroupinterna

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Classic Papers in Viral Hepatitis (Classic Papers Series) by Christine A. Lee (Editor), et al (1988); ISBN: 1870026101; http://www.amazon.com/exec/obidos/ASIN/1870026101/icongroupinterna

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Clinical Practice Guidelines for Viral Hepatitis by Austin; ISBN: 0899707548; http://www.amazon.com/exec/obidos/ASIN/0899707548/icongroupinterna

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Clinicians' Guide to Viral Hepatitis by Christopher J. Tibbs, Heather M. Smith; ISBN: 0340763043; http://www.amazon.com/exec/obidos/ASIN/0340763043/icongroupinterna

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Conquering Hepatitis C by Willis C., MD Maddrey; ISBN: 1896998062; http://www.amazon.com/exec/obidos/ASIN/1896998062/icongroupinterna

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Contagious and Non-Contagious Infectious Diseases Sourcebook: Basic Information About Contagious Diseases Like Measles, Polio, Hepatitis B, and Infectious Mononucleosis, and Non-Contagious Infectious Diseases lik (Health Reference Series, Vol 8) by Karen Bellenir (Editor), Peter D. Dresser (Editor) (1995); ISBN: 0780800753; http://www.amazon.com/exec/obidos/ASIN/0780800753/icongroupinterna

428 Hepatitis

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Contemporary Diagnosis and Management of Hepatitis C by Zobair M. Younossi, et al; ISBN: 1884065848; http://www.amazon.com/exec/obidos/ASIN/1884065848/icongroupinterna

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Coping Successfully with Hepatitis C (Self-help) by Richard English, Graham Foster; ISBN: 1841190705; http://www.amazon.com/exec/obidos/ASIN/1841190705/icongroupinterna

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Current Hepatitis C Infection by McHutchinson, et al (2002); ISBN: 1858739543; http://www.amazon.com/exec/obidos/ASIN/1858739543/icongroupinterna

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Detection of Hepatitis C Virus-Core & Envelope (E2) Proteins in the Liver: A Tool to Study Patients With Non-A to E Hepatitis (Acta Biomedica Lovansiensa, 261) by Chris Verslype (2002); ISBN: 9058672298; http://www.amazon.com/exec/obidos/ASIN/9058672298/icongroupinterna

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Diagnostic Methods in Viral Hepatitis : proceedings of a symposium held in London, January 7, 1978; ISBN: 0845116517; http://www.amazon.com/exec/obidos/ASIN/0845116517/icongroupinterna

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Dr. Melissa Palmer's Guide to Hepatitis & Liver Disease: What You Need to Know by Melissa Palmer; ISBN: 0895299224; http://www.amazon.com/exec/obidos/ASIN/0895299224/icongroupinterna

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Etiological Role of Hepatitis C Virus in Lymphomagenesis by Gasztonyi Beata, et al (2003); ISBN: 9630579529; http://www.amazon.com/exec/obidos/ASIN/9630579529/icongroupinterna

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Everything You Need to Know About Hepatitis (Need to Know Library) by Virginia Aronson; ISBN: 0823931005; http://www.amazon.com/exec/obidos/ASIN/0823931005/icongroupinterna

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Everything You Need to Know About Hepatitis C (Need to Know Library) by Chris Hayhurst; ISBN: 0823936139; http://www.amazon.com/exec/obidos/ASIN/0823936139/icongroupinterna

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GARDNER DIAGNOSTIC METHODS IN VIRAL HEPATITIS by PS GARDNER; ISBN: 047156401X; http://www.amazon.com/exec/obidos/ASIN/047156401X/icongroupinterna

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Guidance for Clinical Health Care Workers: Protection Against HIV and Hepatitis by Northern Ireland (1990); ISBN: 0113212496; http://www.amazon.com/exec/obidos/ASIN/0113212496/icongroupinterna

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Guide to Hepatitis Liver Disease ('Gan bing quan shu', in traditional Chinese, NOT in English) by Dr. Palmer (Author); ISBN: 9574695131; http://www.amazon.com/exec/obidos/ASIN/9574695131/icongroupinterna

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Guidelines for Prevention of Transmission Human Immunodeficiency Virus and Hepatitis B; ISBN: 0016002539; http://www.amazon.com/exec/obidos/ASIN/0016002539/icongroupinterna

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Guidelines for Prevention of Transmission of Human Immunodeficiency Virus & Hepatitis Virus to Health-Care & Public-Safety Workers (1989); ISBN: 0788136224; http://www.amazon.com/exec/obidos/ASIN/0788136224/icongroupinterna

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Guidelines for Prevention of Transmission of Human Immunodeficiency Virus and Hepatitis B Virus to Health-Care and Public Safety Workers Response to p (1989); ISBN: 9990470073; http://www.amazon.com/exec/obidos/ASIN/9990470073/icongroupinterna

Books

429

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Healing Hepatitis C with Modern Chinese Medicine by Qingcai Zhang; ISBN: 0967721369; http://www.amazon.com/exec/obidos/ASIN/0967721369/icongroupinterna

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Healing Hepatitis Naturally by Doctors' Prescription for Healthy Living, Naomi Judd (Introduction); ISBN: 1893910156; http://www.amazon.com/exec/obidos/ASIN/1893910156/icongroupinterna

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Hepatitis by John Strang, Michael Farrell (1991); ISBN: 0948830956; http://www.amazon.com/exec/obidos/ASIN/0948830956/icongroupinterna

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Hepatitis (Diseases and Disorders) by Barbara Sheen, Lucent Books (2002); ISBN: 1590180410; http://www.amazon.com/exec/obidos/ASIN/1590180410/icongroupinterna

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Hepatitis (Diseases and People) by Alvin Silverstein, et al (1994); ISBN: 0894904671; http://www.amazon.com/exec/obidos/ASIN/0894904671/icongroupinterna

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Hepatitis A by Robert J. Gerety (Editor); ISBN: 0122806700; http://www.amazon.com/exec/obidos/ASIN/0122806700/icongroupinterna

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Hepatitis A by Ian D. Gust, Stephen M. Feinstone (1988); ISBN: 0849357675; http://www.amazon.com/exec/obidos/ASIN/0849357675/icongroupinterna

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Hepatitis A to G [DOWNLOAD: ADOBE READER] by Alan M.D. Berkman, Nicholas Bakalar (2001); ISBN: B00005KH6V; http://www.amazon.com/exec/obidos/ASIN/B00005KH6V/icongroupinterna

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Hepatitis and blood transfusion; proceedings; ISBN: 0808907794; http://www.amazon.com/exec/obidos/ASIN/0808907794/icongroupinterna

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Hepatitis B by Robert Gerety (Editor); ISBN: 0122806727; http://www.amazon.com/exec/obidos/ASIN/0122806727/icongroupinterna

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Hepatitis B and C Carrier to Cancer by Sarin, Okuda; ISBN: 8178670151; http://www.amazon.com/exec/obidos/ASIN/8178670151/icongroupinterna

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Hepatitis B and C: Management and Treatment by Theirry Poynard (2003); ISBN: 1841843695; http://www.amazon.com/exec/obidos/ASIN/1841843695/icongroupinterna

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Hepatitis B and d Protocols by Robert Kiyoshi Hamatake (Editor), Johnson Y. N. Lau (Editor) (2004); ISBN: 1588291081; http://www.amazon.com/exec/obidos/ASIN/1588291081/icongroupinterna

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Hepatitis B and the Prevention of Cancer of the Liver: Selected Publications of Baruch S. Blumberg (World Scientific Series in 20th Century Biology , Vol 5) by Baruch S. Blumberg (Editor), Barach S. Blumberg (Editor); ISBN: 9810232179; http://www.amazon.com/exec/obidos/ASIN/9810232179/icongroupinterna

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Hepatitis B in the Asian- V1 by Zuckerman; ISBN: 1860160638; http://www.amazon.com/exec/obidos/ASIN/1860160638/icongroupinterna

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Hepatitis B Protocols (Methods in Molecular Medicine) by Johnson Y. N. Lau (Editor), Robert Hamatake (Editor) (2004); ISBN: 1588291057; http://www.amazon.com/exec/obidos/ASIN/1588291057/icongroupinterna

·

Hepatitis B Vaccine: Proceedings of the International Symposium on Hepatitis B Vaccine Held in Paris (France), 8-9 December, 1980 (Inserm Science Series; No 18) by France)/ Maupas, P. International Symposium on Hepatitis B Vaccine 1980 Paris

430 Hepatitis

(Editor); ISBN: 0444803254; http://www.amazon.com/exec/obidos/ASIN/0444803254/icongroupinterna ·

Hepatitis B Vaccines in Clinical Practice by Ronald W. Ellis (Editor); ISBN: 0824787803; http://www.amazon.com/exec/obidos/ASIN/0824787803/icongroupinterna

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Hepatitis B Virus and Primary Liver Cancer by P. Maupas (Editor), Joseph L. Melnick (Editor) (1981); ISBN: 380551784X; http://www.amazon.com/exec/obidos/ASIN/380551784X/icongroupinterna

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Hepatitis B virus antigens in tissues by M. B. Ray; ISBN: 0839114257; http://www.amazon.com/exec/obidos/ASIN/0839114257/icongroupinterna

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Hepatitis B Virus: Molecular Mechanisms in Disease and Novel Strategies for Therapy by Rajen Koshy (Editor), et al (1998); ISBN: 1860940072; http://www.amazon.com/exec/obidos/ASIN/1860940072/icongroupinterna

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Hepatitis B Virus: Selected Topics (Journal - Intervirology , Vol 38, No 1-2) by W.H. Gerlich (Editor) (1995); ISBN: 3805562527; http://www.amazon.com/exec/obidos/ASIN/3805562527/icongroupinterna

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Hepatitis B: A Sexually Transmitted Disease in Heterosexuals: Proceedings of a Symposium Held in Barcelona, 6-7 May, 1990 (International Congress S) by P. Piot, F.E. Andre (Editor); ISBN: 044481356X; http://www.amazon.com/exec/obidos/ASIN/044481356X/icongroupinterna

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Hepatitis B: The Hunt for a Killer Virus by Baruch S. Blumberg; ISBN: 069100692X; http://www.amazon.com/exec/obidos/ASIN/069100692X/icongroupinterna

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Hepatitis B: The Virus, the Disease and the Vaccine by Irving Millman (Editor), et al (1984); ISBN: 0306417235; http://www.amazon.com/exec/obidos/ASIN/0306417235/icongroupinterna

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Hepatitis C by G. Csmos, et al; ISBN: 0387548238; http://www.amazon.com/exec/obidos/ASIN/0387548238/icongroupinterna

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Hepatitis C; ISBN: 3540548238; http://www.amazon.com/exec/obidos/ASIN/3540548238/icongroupinterna

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Hepatitis C (A Volume in the Biomedical Research Reports) by T. Jake Liang (Editor), et al (2000); ISBN: 0124478700; http://www.amazon.com/exec/obidos/ASIN/0124478700/icongroupinterna

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Hepatitis C Directory of New Medical and S by Science Life Consu (Author); ISBN: 0788316214; http://www.amazon.com/exec/obidos/ASIN/0788316214/icongroupinterna

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Hepatitis C Free: Alternative Medicine VS, The Drug Industry, The People Speak by Lloyd Wright; ISBN: 0967640431; http://www.amazon.com/exec/obidos/ASIN/0967640431/icongroupinterna

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Hepatitis C Infection: Management and Treatment by Serge Gauthier (Editor), Thierry Poynard; ISBN: 1853179094; http://www.amazon.com/exec/obidos/ASIN/1853179094/icongroupinterna

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Hepatitis C information : a guidebook for people with the disease and health professionals; ISBN: 0730959570; http://www.amazon.com/exec/obidos/ASIN/0730959570/icongroupinterna

Books

431

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Hepatitis C Protocols (Methods in Molecular Medicine, No 19) by Johnson Y. N. Lau (Editor) (1998); ISBN: 0896035212; http://www.amazon.com/exec/obidos/ASIN/0896035212/icongroupinterna

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Hepatitis C Virus (Current Studies in Hematology and Blood Transfusion, No 61) by H.W. Reesink (Editor) (1994); ISBN: 380555866X; http://www.amazon.com/exec/obidos/ASIN/380555866X/icongroupinterna

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Hepatitis C Virus : From Laboratory to Clinic by Mark A. Feitelson (Author) (2002); ISBN: 0521799597; http://www.amazon.com/exec/obidos/ASIN/0521799597/icongroupinterna

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Hepatitis C, Other Liver Disorders and Liver Health: A Practical Guide by Geoffrey C. Farrell (2002); ISBN: 0864331576; http://www.amazon.com/exec/obidos/ASIN/0864331576/icongroupinterna

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Hepatitis C. Leben mit dem neuen Virus. by Regina Naumann (Author); ISBN: 343104025X; http://www.amazon.com/exec/obidos/ASIN/343104025X/icongroupinterna

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Hepatitis C: A Personal Guide to Good Health by Beth Ann Petro Roybal, Emmet B. Keeffe (Introduction); ISBN: 1569751838; http://www.amazon.com/exec/obidos/ASIN/1569751838/icongroupinterna

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Hepatitis C: Directory of New Medical & Scientific Reviews With Subject Index by Science, Life Consults (1995); ISBN: 0788305700; http://www.amazon.com/exec/obidos/ASIN/0788305700/icongroupinterna

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Hepatitis C: Other Liver Disorders and Liver Health by Geoffrey C. Farrell (2002); ISBN: 0803610629; http://www.amazon.com/exec/obidos/ASIN/0803610629/icongroupinterna

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Hepatitis C: Practical, Medical, and Spiritual Guidelines for Daily Living with HCV by Mark Jenkins, Robert E., Md. Larsen; ISBN: 1568383681; http://www.amazon.com/exec/obidos/ASIN/1568383681/icongroupinterna

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Hepatitis C: State of the Art at the Millennium by A. Branch; ISBN: 3131272511; http://www.amazon.com/exec/obidos/ASIN/3131272511/icongroupinterna

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Hepatitis C: State of the Art at the Millennium: A Bound Compilation of Issues 1 and 2 of Seminars in Liver Disease (2000 by C. L., Jr Branch, L. B. Seeff (2000); ISBN: 0865779988; http://www.amazon.com/exec/obidos/ASIN/0865779988/icongroupinterna

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Hepatitis C: The Silent Epidemic by Carol Turkington; ISBN: 0809229579; http://www.amazon.com/exec/obidos/ASIN/0809229579/icongroupinterna

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Hepatitis C: The Silent Epidemic (Authoritative Guide) by Fred K. Md Askari, et al; ISBN: 0738204382; http://www.amazon.com/exec/obidos/ASIN/0738204382/icongroupinterna

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Hepatitis C: The Silent Killer by Carol Turkington, et al; ISBN: 0809229587; http://www.amazon.com/exec/obidos/ASIN/0809229587/icongroupinterna

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Hepatitis Delta Virus and Its Infection (Progress in Clinical and Biological Research Series, Vol 234) by Mario Rizzetto (Editor), et al; ISBN: 0471635537; http://www.amazon.com/exec/obidos/ASIN/0471635537/icongroupinterna

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Hepatitis Delta Virus: Molecular Biology, Pathogenesis, and Clinical Aspects: Proceedings of the Fourth International Symposium on Hepatitis Delta V (Progress in

432 Hepatitis

Clinical and Biological Research, V. 382) by Greece) / Taylor, John M./ Bonino, Ferruccio International Symposium on Hepatitis Delta Virus 1992 Rhodes (Editor), et al; ISBN: 0471588334; http://www.amazon.com/exec/obidos/ASIN/0471588334/icongroupinterna ·

Hepatitis E: Index of New Information and Guide-Book for Consumers, Reference and Research by Marcus Stevenson (2003); ISBN: 0788328948; http://www.amazon.com/exec/obidos/ASIN/0788328948/icongroupinterna

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Hepatitis Market by Biotechnology News Staff (1990); ISBN: 0962339121; http://www.amazon.com/exec/obidos/ASIN/0962339121/icongroupinterna

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Hepatitis Viruses by J.-H. James Ou (Editor); ISBN: 0792375734; http://www.amazon.com/exec/obidos/ASIN/0792375734/icongroupinterna

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Hepatitis Viruses by David E. Bernstein (Editor), et al; ISBN: 1879772116; http://www.amazon.com/exec/obidos/ASIN/1879772116/icongroupinterna

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Hepatitis Viruses (Iarc Monographs on the Evaluation of Carcinogenic Risks to Humans , Vol 59) (1994); ISBN: 9283212592; http://www.amazon.com/exec/obidos/ASIN/9283212592/icongroupinterna

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Hepatitis Viruses and Hepatocellular Carcinoma: Approaches Through Molecular Biology and Ecology by Kusuya Nishioka, et al; ISBN: 0125199309; http://www.amazon.com/exec/obidos/ASIN/0125199309/icongroupinterna

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Hepatitis Viruses of Man by Arie Jeremy Zuckerman; ISBN: 0127821503; http://www.amazon.com/exec/obidos/ASIN/0127821503/icongroupinterna

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Hepatitis, Hepatitisfolgen. by Klaus-Peter Maier (Author); ISBN: 3135851052; http://www.amazon.com/exec/obidos/ASIN/3135851052/icongroupinterna

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Hepatitis: A Virus Transmission by Blood Products ((Journal: Vox Sanguinis Ser.; Vol. 67, Supplement1, 1994)) by C Prowse (Editor), et al (1994); ISBN: 3805560060; http://www.amazon.com/exec/obidos/ASIN/3805560060/icongroupinterna

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Hepatitis-associated antigen and viruses by Arie Jeremy Zuckerman; ISBN: 0444103961; http://www.amazon.com/exec/obidos/ASIN/0444103961/icongroupinterna

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Herbs for Hepatitis C and the Liver (Medicinal Herb Guide.) by Stephen Harrod Buhner; ISBN: 1580172555; http://www.amazon.com/exec/obidos/ASIN/1580172555/icongroupinterna

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HIV, hepatitis and injection drug use in British Columbia : pay now or pay later? by John S. Millar; ISBN: 0772636125; http://www.amazon.com/exec/obidos/ASIN/0772636125/icongroupinterna

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HIV/AIDS and Hepatitis: Everything You Need to Know to Protect Yourself and Others by Douglas D. Schoon (1994); ISBN: 1562531751; http://www.amazon.com/exec/obidos/ASIN/1562531751/icongroupinterna

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Hope for Hepatitis C by Dr. Michael Wald; ISBN: 0967159709; http://www.amazon.com/exec/obidos/ASIN/0967159709/icongroupinterna

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Human viral hepatitis : hepatitis-associated antigen and viruses by Arie Jeremy Zuckerman; ISBN: 0444108491; http://www.amazon.com/exec/obidos/ASIN/0444108491/icongroupinterna

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Immunisation Against Hepatitis B; ISBN: 0727901990; http://www.amazon.com/exec/obidos/ASIN/0727901990/icongroupinterna

Books

433

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Immunization Safety Review: Hepatitis B and Demyelinating Neurological Diseases by Kathleen Stratton, et al (2002); ISBN: 0309084695; http://www.amazon.com/exec/obidos/ASIN/0309084695/icongroupinterna

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Intra-Abdominal Infections, Hepatitis, and Gastroenteritis (WINDOWS/MACINTOSH CD-ROM) by Mandell, Bennett Lorber; ISBN: 0443078769; http://www.amazon.com/exec/obidos/ASIN/0443078769/icongroupinterna

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Investigation of an epidemic of hepatitis a in Palau, January-June 1985 : report; ISBN: 9822030215; http://www.amazon.com/exec/obidos/ASIN/9822030215/icongroupinterna

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Laboratory Diagnosis of Hepatitis Viruses: 18A (Cumitech Ser.) by Max A. Chernesky, et al (1984); ISBN: 9990058156; http://www.amazon.com/exec/obidos/ASIN/9990058156/icongroupinterna

·

Liver Disorders Sourcebook: Basic Consumer Health Information About the Liver, and How It Works; Liver Diseases, Including Cancer, Cirrhosis, Hepatitis and Toxic and Drug Relate (Health Reference Series) by Joyce Brennfleck Shannon (Editor) (2000); ISBN: 0780803833; http://www.amazon.com/exec/obidos/ASIN/0780803833/icongroupinterna

·

Living Healthy With Hepatitis C: Natural and Conventional Approaches to Recover Your Quality of Life by Harriet A. Washington; ISBN: 0440236088; http://www.amazon.com/exec/obidos/ASIN/0440236088/icongroupinterna

·

Living with Hepatitis B: A Survivor's Guide by Gregory T. Everson, et al (2002); ISBN: 1578260841; http://www.amazon.com/exec/obidos/ASIN/1578260841/icongroupinterna

·

Living with Hepatitis C by Richard English, Graham Foster; ISBN: 1854879138; http://www.amazon.com/exec/obidos/ASIN/1854879138/icongroupinterna

·

Living with Hepatitis C: A Survivor's Guide, Third Revised Edition by Gregory T. Everson, Hedy Weinberg (2002); ISBN: 1578261082; http://www.amazon.com/exec/obidos/ASIN/1578261082/icongroupinterna

·

Living With Hepatitis C: Everything You Need to Know (Your Personal Health) by Jenny Heathcote, et al (2003); ISBN: 1552977390; http://www.amazon.com/exec/obidos/ASIN/1552977390/icongroupinterna

·

Loving Joe Gallucci: Love and Life with Hepatitis C by Kate Genovese, Melissa Palmer; ISBN: 1891929895; http://www.amazon.com/exec/obidos/ASIN/1891929895/icongroupinterna

·

Management for Chronic Hepatitis C by Shaun A. McCarthy (2002); ISBN: 1587631180; http://www.amazon.com/exec/obidos/ASIN/1587631180/icongroupinterna

·

Management of Chronic Viral Hepatitis by Stuart C. Gordon (Editor); ISBN: 0824705823; http://www.amazon.com/exec/obidos/ASIN/0824705823/icongroupinterna

·

Management of Chronic Viral Hepatitis by Robert D. Goldin, Graham R. Foster (2003); ISBN: 1841840882; http://www.amazon.com/exec/obidos/ASIN/1841840882/icongroupinterna

·

Management of Hepatitis C, January 1989 Through January 1997 by Ronald L. Gordner (1998); ISBN: 0160615836; http://www.amazon.com/exec/obidos/ASIN/0160615836/icongroupinterna

434 Hepatitis

·

Manual for hepatitis B antigen testing by Mary Ashcavai; ISBN: 0721614272; http://www.amazon.com/exec/obidos/ASIN/0721614272/icongroupinterna

·

Modern Concepts of Acute and Chronic Hepatitis by Gary Gitnick (Editor) (1989); ISBN: 0306428954; http://www.amazon.com/exec/obidos/ASIN/0306428954/icongroupinterna

·

Molecular Basis of Autoimmune Hepatitis by Ian G. McFarlane (1996); ISBN: 1570593396; http://www.amazon.com/exec/obidos/ASIN/1570593396/icongroupinterna

·

Molecular Biology of Human Hepatitis Viruses by J. Monjardino (1998); ISBN: 186094048X; http://www.amazon.com/exec/obidos/ASIN/186094048X/icongroupinterna

·

Molecular Biology of the Hepatitis B Virus by Alan McLachlan (Editor); ISBN: 0849355168; http://www.amazon.com/exec/obidos/ASIN/0849355168/icongroupinterna

·

Molecular Components of Hepatitis B Virus (Developments in Molecular Virology; 6) by Mark Feitelson (1985); ISBN: 0898386969; http://www.amazon.com/exec/obidos/ASIN/0898386969/icongroupinterna

·

My Mom Has Hepatitis C by Hedy Weinberg, et al (2000); ISBN: 1578260752; http://www.amazon.com/exec/obidos/ASIN/1578260752/icongroupinterna

·

New Trends in Hepatology: The Proceedings of the Annual Meeting of the Italian National Programme on Liver Cirrhosis and Viral Hepatitis, San Miniato (Pisa), Italy, 7-9 january by Paolo Gentilini (Editor), M.U. Dianzani (Editor) (1996); ISBN: 0792387031; http://www.amazon.com/exec/obidos/ASIN/0792387031/icongroupinterna

·

Non-A, Non-B Hepatitis by R. Gerety; ISBN: 0122806808; http://www.amazon.com/exec/obidos/ASIN/0122806808/icongroupinterna

·

OSHA Bloodborne Pathogens Manual and CD, Introductory But Comprehensive OSHA (Occupational Safety and Health) Training for the Managers and Employees in a Worker Safety Program, For All Industries But Especially for Infection Control and Infectious Disease Training in Healthcare Settings, Hospitals, Health Systems, Doctors, Nurses, Dentists, EMS, and Allied Health Personnel, Including Detailed Introductions to AIDS, HIV, Hepatitis B, and Hepatitis C by Daniel Farb, Bruce Gordon (2003); ISBN: 1932634940; http://www.amazon.com/exec/obidos/ASIN/1932634940/icongroupinterna

·

Pathology of Viral Hepatitis by R. D. Goldin (Editor), et al; ISBN: 0340596643; http://www.amazon.com/exec/obidos/ASIN/0340596643/icongroupinterna

·

Pipeline Perspectives: Hepatitis B & C - Antivirals Challenge the Interferons? [DOWNLOAD: PDF] by Datamonitor (Author); ISBN: B0000AUH6H; http://www.amazon.com/exec/obidos/ASIN/B0000AUH6H/icongroupinterna

·

Pocket Reference to Hepatitis C Infection by Rosenberg, Khakoo (2002); ISBN: 1858739578; http://www.amazon.com/exec/obidos/ASIN/1858739578/icongroupinterna

·

Preventing Hepatitis by Richard E Sampliner; ISBN: 0875272290; http://www.amazon.com/exec/obidos/ASIN/0875272290/icongroupinterna

·

Proceedings of an International Symposium on Anti-Viral Agents in Chronic Hepatitis B Virus Infection by R. Williams (Editor), et al; ISBN: 0444809015; http://www.amazon.com/exec/obidos/ASIN/0444809015/icongroupinterna

Books

435

·

Proceedings of the European Symposium on Hepatitis B by Saul Krugman, Sheila Sherlock (1981); ISBN: 0865550085; http://www.amazon.com/exec/obidos/ASIN/0865550085/icongroupinterna

·

Progress in Hepatitis B Immunization by P. Coursaget, M.J. Tong; ISBN: 0861962494; http://www.amazon.com/exec/obidos/ASIN/0861962494/icongroupinterna

·

Progress in Hepatology 2 - Interferon Therapy on Chronic Hepatitis C by K. Okabe, et al; ISBN: 0444823794; http://www.amazon.com/exec/obidos/ASIN/0444823794/icongroupinterna

·

Protection Against Blood-Borne Infections in the Workplace: HIV and Hepatitis by Great Britain (1995); ISBN: 0113219539; http://www.amazon.com/exec/obidos/ASIN/0113219539/icongroupinterna

·

Public health 2000 : hepatitis C--the silent epidemic : hearing before the Subcommittee on Human Resources of the Committee on Government Reform and Oversight, House of Representatives, One Hundred Fifth Congress, second session, March 5, 1998; ISBN: 0160572347; http://www.amazon.com/exec/obidos/ASIN/0160572347/icongroupinterna

·

PULSE Plus: Hepatitis C Video by Primedia; ISBN: 1401892795; http://www.amazon.com/exec/obidos/ASIN/1401892795/icongroupinterna

·

Recent Advances in the Study of Hepatitis C Virus (Intervirology, Vol 37, No 2) by O. Hino (Editor) (1994); ISBN: 3805560591; http://www.amazon.com/exec/obidos/ASIN/3805560591/icongroupinterna

·

Research in Chronic Viral Hepatitis (Archives of Virology. Supplementum 8) by W. H. Gerlich (Editor); ISBN: 0387824979; http://www.amazon.com/exec/obidos/ASIN/0387824979/icongroupinterna

·

Roferon-A in Chronic Viral Hepatitis: Treatment, Clinical Outcomes, CostEffectiveness (Gesundheit Und Okonomie; Bd. 6) by David Schwicker, Kurt Banz (1994); ISBN: 3906752666; http://www.amazon.com/exec/obidos/ASIN/3906752666/icongroupinterna

·

Safety in Health Service Laboratories: Hepatitis B; ISBN: 0118837818; http://www.amazon.com/exec/obidos/ASIN/0118837818/icongroupinterna

·

Sexually Transmitted Diseases Sourcebook: Basic Information About Herpes, Chlamydia, Gonorrhea, Hepatitis, Nongonoccocal Urethritis, Pelvic Inflammatory Disease, Syphilis, AIDS, and More (Health Reference Series, Vol 26) by Linda M. Ross (Editor), Peter Dresser (Editor) (1997); ISBN: 0780802179; http://www.amazon.com/exec/obidos/ASIN/0780802179/icongroupinterna

·

Standards for adjudicating claims presented by veterans suffering from hepatitis C, cerebral malaria, and Persian Gulf illnesses : hearing before the Subcommittee on Benefits of the Committee on Veterans' Affairs, House of Representatives, One Hundred Fifth Congress, second session, July 16, 1998; ISBN: 0160581737; http://www.amazon.com/exec/obidos/ASIN/0160581737/icongroupinterna

·

Strategic Perspectives: Hepatitis B and C - Strategic Developments in an Immature Market [DOWNLOAD: PDF] by Datamonitor (Author); ISBN: B00008R3YW; http://www.amazon.com/exec/obidos/ASIN/B00008R3YW/icongroupinterna

·

Study Guide for Viral Hepatitis - Practical Evaluation and Treatment: A Training System for Nurses by Carole A. Mutzebaugh; ISBN: 0889371849; http://www.amazon.com/exec/obidos/ASIN/0889371849/icongroupinterna

436 Hepatitis

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Sygeplejepersonales lµnderygbesvµr : med afsnit om hepatitis og andre helbredsforhold by Henrik Vinterberg; ISBN: 8773591033; http://www.amazon.com/exec/obidos/ASIN/8773591033/icongroupinterna

·

The 2002 Official Patient's Sourcebook on Hepatitis C: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN: 0597832412; http://www.amazon.com/exec/obidos/ASIN/0597832412/icongroupinterna

·

The Bible Cure for Hepatitis and Hepatitis C (Bible Cure Series) by Don, M.D. Colbert (2002); ISBN: 0884198294; http://www.amazon.com/exec/obidos/ASIN/0884198294/icongroupinterna

·

The Blood Conspiracy: How to Avoid Getting AIDS and Hepatitis in a Transfusion by Joleen Swain Ottosen, Marilyn Ross (Editor) (1993); ISBN: 0963296337; http://www.amazon.com/exec/obidos/ASIN/0963296337/icongroupinterna

·

The Cure of Chronic Hepatitis B: One Man's Cure One Family's Experience by Kunmi Oluleye, et al (1997); ISBN: 0965480194; http://www.amazon.com/exec/obidos/ASIN/0965480194/icongroupinterna

·

The First Year---Hepatitis B: An Essential Guide for the Newly Diagnosed by William Finley Green, Hari Conjeevaram; ISBN: 1569245339; http://www.amazon.com/exec/obidos/ASIN/1569245339/icongroupinterna

·

The First Year--Hepatitis C: An Essential Guide for the Newly Diagnosed by Cara Bruce, Lisa Montanarelli; ISBN: 156924541X; http://www.amazon.com/exec/obidos/ASIN/156924541X/icongroupinterna

·

The Hepatitis C Handbook by Matthew Dolan, et al (1999); ISBN: 1556433131; http://www.amazon.com/exec/obidos/ASIN/1556433131/icongroupinterna

·

The Hepatitis C Help Book: A Groundbreaking Treatment Program Combining Western and Eastern Medicine for Maximum Wellness and Healing by Misha Ruth Cohen, et al (2001); ISBN: 0312263368; http://www.amazon.com/exec/obidos/ASIN/0312263368/icongroupinterna

·

The Hepatitis C Sourcebook by Howard J. Worman; ISBN: 0737305967; http://www.amazon.com/exec/obidos/ASIN/0737305967/icongroupinterna

·

The Hepatitis C Viruses by C. H. Hagedorn (Editor), C. M. Rice (Editor); ISBN: 3540653589; http://www.amazon.com/exec/obidos/ASIN/3540653589/icongroupinterna

·

The Hepatitis delta virus and its infection : proceedings of an International Symposium on Hepatitis Delta Virus, held in Saint Vincent, Italy, June 19 to 20, 1986; ISBN: 0845150847; http://www.amazon.com/exec/obidos/ASIN/0845150847/icongroupinterna

·

The Hepatitis Delta Virus: Proceedings of the Third International Symposium on Hepatitis Dela Virus, Held in Washington, D.C., October 26-28, 1989 (Progress in Clinical and Biological Research, V. 364) by D.C International Symposium on Hepatitis Delta Virus 1989 Washington, et al; ISBN: 0471560731; http://www.amazon.com/exec/obidos/ASIN/0471560731/icongroupinterna

·

The Lec Rat: A New Model for Hepatitis and Liver Cancer by M. Mori, et al; ISBN: 038770079X; http://www.amazon.com/exec/obidos/ASIN/038770079X/icongroupinterna

Books

437

·

The Molecular Medicine of Viral Hepatitis by Tim J. Harrison (Editor), Arie J. Zuckerman (Editor); ISBN: 0471969966; http://www.amazon.com/exec/obidos/ASIN/0471969966/icongroupinterna

·

The Non-responding Hepatitis C Patient: Options and Variables (Round Table Series (RTS)) by Bruce R. Bacon (Editor); ISBN: 1853154377; http://www.amazon.com/exec/obidos/ASIN/1853154377/icongroupinterna

·

The Official Patient's Sourcebook on Autoimmune Hepatitis: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN: 0597834180; http://www.amazon.com/exec/obidos/ASIN/0597834180/icongroupinterna

·

The Official Patient's Sourcebook on Hepatitis A: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN: 0597833907; http://www.amazon.com/exec/obidos/ASIN/0597833907/icongroupinterna

·

The Official Patient's Sourcebook on Hepatitis B: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN: 0597833915; http://www.amazon.com/exec/obidos/ASIN/0597833915/icongroupinterna

·

The Unique Hepatitis Delta Virus (Medical Intelligence Unit) by Gail Dinter-Gottlieb (Editor) (1995); ISBN: 157059144X; http://www.amazon.com/exec/obidos/ASIN/157059144X/icongroupinterna

·

The War Against Hepatitis B: A History of the International Task Force on Hepatitis B Immunization by William A. Muraskin; ISBN: 0812232674; http://www.amazon.com/exec/obidos/ASIN/0812232674/icongroupinterna

·

Therapies for Viral Hepatitis by Raymond F. Schinazi, et al; ISBN: 1901769011; http://www.amazon.com/exec/obidos/ASIN/1901769011/icongroupinterna

·

Treatment Algorithm 2002: Hepatitis B and C [DOWNLOAD: PDF] by Datamonitor (Author); ISBN: B00008R3Q1; http://www.amazon.com/exec/obidos/ASIN/B00008R3Q1/icongroupinterna

·

Triumph Over Hepatitis C by Lloyd Wright; ISBN: 096764044X; http://www.amazon.com/exec/obidos/ASIN/096764044X/icongroupinterna

·

Triumph Over Hepatitis C : An Alternative Medicine Solution Revised Edition by Lloyd Wright, Aunika Stratton (Editor); ISBN: 0967640415; http://www.amazon.com/exec/obidos/ASIN/0967640415/icongroupinterna

·

Understanding Hepatitis by James L., M.D. Achord; ISBN: 1578064368; http://www.amazon.com/exec/obidos/ASIN/1578064368/icongroupinterna

·

Understanding Hepatitis Chart by Anatomical Chart (2003); ISBN: 1587794187; http://www.amazon.com/exec/obidos/ASIN/1587794187/icongroupinterna

·

Viral and Autoimmune Hepatitis: Morphologic and Pathogenetic Aspects of Cell Damage in Hepatitis With Potential Chronicity (Progress in Pathology) by Hans Peter, Dr. Dienes (1989); ISBN: 0895742802; http://www.amazon.com/exec/obidos/ASIN/0895742802/icongroupinterna

·

Viral Hepatitis by Arie J. Zuckerman (Editor), et al; ISBN: 0443057974; http://www.amazon.com/exec/obidos/ASIN/0443057974/icongroupinterna

·

Viral hepatitis by Raymond S. Koff; ISBN: 0471036951; http://www.amazon.com/exec/obidos/ASIN/0471036951/icongroupinterna

·

Viral Hepatitis by Saul. Krugman; ISBN: 0721655386; http://www.amazon.com/exec/obidos/ASIN/0721655386/icongroupinterna

438 Hepatitis

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Viral Hepatitis by F. Blaine Hollinger (Editor), et al; ISBN: 078174055X; http://www.amazon.com/exec/obidos/ASIN/078174055X/icongroupinterna

·

Viral Hepatitis (1978); ISBN: 0891680136; http://www.amazon.com/exec/obidos/ASIN/0891680136/icongroupinterna

·

Viral Hepatitis by T. J. Harrison, E. A. Fagan; ISBN: 1859960251; http://www.amazon.com/exec/obidos/ASIN/1859960251/icongroupinterna

·

Viral Hepatitis (Proceedings in Life Sciences) by F. Callea, et al (1986); ISBN: 0387167307; http://www.amazon.com/exec/obidos/ASIN/0387167307/icongroupinterna

·

Viral hepatitis : 1981 international symposium; ISBN: 0891680403; http://www.amazon.com/exec/obidos/ASIN/0891680403/icongroupinterna

·

Viral hepatitis : laboratory and clinical science; ISBN: 0824718011; http://www.amazon.com/exec/obidos/ASIN/0824718011/icongroupinterna

·

Viral hepatitis and acquired immunodeficiency syndrome; ISBN: 997754011X; http://www.amazon.com/exec/obidos/ASIN/997754011X/icongroupinterna

·

Viral hepatitis and delta infection : proceedings of an International Symposium on Viral Hepatitis, June 10-11, 1983, Torino, Italy; ISBN: 0845101439; http://www.amazon.com/exec/obidos/ASIN/0845101439/icongroupinterna

·

Viral Hepatitis and Delta Infection: Proceedings of an International Symposium on Viral Hepatitis, June 10-11, 1983, Turin, Italy by International Symposium on Viral Hepatitis, et al; ISBN: 0471834351; http://www.amazon.com/exec/obidos/ASIN/0471834351/icongroupinterna

·

Viral Hepatitis and Hepatocellular Carcinoma by C. Ding-Shinn, S. Juei-Low; ISBN: 9021917807; http://www.amazon.com/exec/obidos/ASIN/9021917807/icongroupinterna

·

Viral Hepatitis and Liver Disease by Girish Vyas, et al; ISBN: 0808916785; http://www.amazon.com/exec/obidos/ASIN/0808916785/icongroupinterna

·

Viral Hepatitis and Liver Disease; ISBN: 084514247X; http://www.amazon.com/exec/obidos/ASIN/084514247X/icongroupinterna

·

Viral hepatitis and liver disease : proceedings of the International Symposium on Viral Hepatitis and Liver Disease : molecules today, more cures tomorrow : Tokyo, May 10-14, 1993, (1993 ISVHLD); ISBN: 443170132X; http://www.amazon.com/exec/obidos/ASIN/443170132X/icongroupinterna

·

Viral Hepatitis and Liver Disease: Proceedings by A.J. Zuckerman (Editor); ISBN: 0471612707; http://www.amazon.com/exec/obidos/ASIN/0471612707/icongroupinterna

·

Viral Hepatitis and Liver Disease: Proceedings of the 1990 International Symposium on Viral Hepatitis and Liver Disease: Contemporary Issues and Fu by International Symposium on Viral Hepatitis and Liver Disease, et al; ISBN: 0683041207; http://www.amazon.com/exec/obidos/ASIN/0683041207/icongroupinterna

·

Viral Hepatitis and Liver Disease: Proceedings of the International Symposium on Viral Hepatitis and Liver Disease: Molecules Today, More Cures by Kusuya Nishioka; ISBN: 038770132X; http://www.amazon.com/exec/obidos/ASIN/038770132X/icongroupinterna

Books

439

·

Viral Hepatitis B Infection in the Western Pacific Region: Vaccine and Control by S.K. Lam, et al (1984); ISBN: 9971950804; http://www.amazon.com/exec/obidos/ASIN/9971950804/icongroupinterna

·

Viral Hepatitis C, d and E: Proceedings of the International Meeting on Non-A, NonB Hepatitis, Tokyo, 27-30 September, 1989 (International Congress) by Toshio Shikata, et al; ISBN: 0444811176; http://www.amazon.com/exec/obidos/ASIN/0444811176/icongroupinterna

·

Viral Hepatitis in China: Problems and Control Strategies (Monographs in Virology, Vol. 19) by Yu-Mei Wen, et al (1992); ISBN: 3805553641; http://www.amazon.com/exec/obidos/ASIN/3805553641/icongroupinterna

·

Viral Hepatitis Report (Technical Report No 512) by Who; ISBN: 9241205121; http://www.amazon.com/exec/obidos/ASIN/9241205121/icongroupinterna

·

Viral Hepatitis Update (Intervirology) by S. Iino (Editor), O. Hino (Editor) (1999); ISBN: 3805569629; http://www.amazon.com/exec/obidos/ASIN/3805569629/icongroupinterna

·

Viral Hepatitis: 1981 International Symposium by Wolf Szmuness, et al; ISBN: 0898597374; http://www.amazon.com/exec/obidos/ASIN/0898597374/icongroupinterna

·

Viral Hepatitis: A Contemporary Assessment of Etiology, Epidemiostributors to the Book Trade, Doubleday, by 2D, University of California San Francis Symposium on Viral Hepatitis (1978); ISBN: 0898597382; http://www.amazon.com/exec/obidos/ASIN/0898597382/icongroupinterna

·

Viral Hepatitis: A Handbook for Clinicians and Scientists by Elizabeth Ann Fagan, Tim J. Harrison (2000); ISBN: 0387916202; http://www.amazon.com/exec/obidos/ASIN/0387916202/icongroupinterna

·

Viral Hepatitis: Biological and Clinical Features, Specific Diagnosis and Prophylaxis by F. Blaine Hollinger, et al; ISBN: 0881677272; http://www.amazon.com/exec/obidos/ASIN/0881677272/icongroupinterna

·

Viral Hepatitis: Current Status and Issues by Edouard Kurstak, et al (1993); ISBN: 0387823875; http://www.amazon.com/exec/obidos/ASIN/0387823875/icongroupinterna

·

Viral Hepatitis: Diagnosis, Therapy, and Prevention by Steven Specter (Editor) (1999); ISBN: 0896034240; http://www.amazon.com/exec/obidos/ASIN/0896034240/icongroupinterna

·

Viral Hepatitis: Diagnosis, Treatment, Prevention by Richard A. Willson (Editor); ISBN: 0824794168; http://www.amazon.com/exec/obidos/ASIN/0824794168/icongroupinterna

·

Viral Hepatitis: From a to E by Richard Westlund (Editor) (1994); ISBN: 1879772019; http://www.amazon.com/exec/obidos/ASIN/1879772019/icongroupinterna

·

Viral Hepatitis: Parenteral Hepatitis (B, C and D) (Soviet Medical Reviews Series, Section E) by A. Bluger, G. Borisova; ISBN: 3718653567; http://www.amazon.com/exec/obidos/ASIN/3718653567/icongroupinterna

·

Viral Hepatitis: Practical Evaluation and Treatment by Teddy F. Bader, Ted Bader; ISBN: 0889371334; http://www.amazon.com/exec/obidos/ASIN/0889371334/icongroupinterna

440 Hepatitis

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Viral Hepatitis: Scientific Basis and Clinical Management by Arie J. Zuckerman (Editor), Howard C. Thomas (Editor) (1997); ISBN: 0443047081; http://www.amazon.com/exec/obidos/ASIN/0443047081/icongroupinterna

·

Viral Hepatitis: Second International Max V. Pettenkofer Symposium (Infectious Diseases and Antimicrobial Agents, 4) by Germany)/ Overby, Lacy R.; Deinhardt, Friedrich and Deinhardt, Jean International Max Von Pettenkofer Symposium 1982 Munich (Editor) (1983); ISBN: 0824770463; http://www.amazon.com/exec/obidos/ASIN/0824770463/icongroupinterna

·

Viral Hepatitis: Standardization in Immuniprophylaxis of Infections by Hepatitis Viruses by G. Papavangelou, W. Hennessen; ISBN: 380553826X; http://www.amazon.com/exec/obidos/ASIN/380553826X/icongroupinterna

·

Viral Hepatitis-A Contemporary Assessment of Etiology, Epidemiology, Pathogenesis and Prevention by G. N. Vyas; ISBN: 0856261823; http://www.amazon.com/exec/obidos/ASIN/0856261823/icongroupinterna

·

Viren. Die heimlichen Herrscher. Wie Grippe, Aids und Hepatitis unsere Welt bedrohen. by Ernst-Ludwig Winnacker (Author); ISBN: 3821815981; http://www.amazon.com/exec/obidos/ASIN/3821815981/icongroupinterna

·

Virus Hepatitis (Clinifcs in Gastroenterology) by Sherlock.; ISBN: 0721682367; http://www.amazon.com/exec/obidos/ASIN/0721682367/icongroupinterna

·

Virus hepatitis A sampai E di Indonesia by H. Ali Sulaiman; ISBN: 9798129733; http://www.amazon.com/exec/obidos/ASIN/9798129733/icongroupinterna

·

Virus Hepatitis and Its Control by Yvonne Cossart (1982); ISBN: 0721607144; http://www.amazon.com/exec/obidos/ASIN/0721607144/icongroupinterna

·

Virus Hepatitis and Kidney (Nephron, Vol 61, No 3, 1992) by V.A. Mioli (Editor) (1992); ISBN: 3805556217; http://www.amazon.com/exec/obidos/ASIN/3805556217/icongroupinterna

·

Vivir con Hepatitis by Gregpru T., Dr. Everson, et al; ISBN: 8488066724; http://www.amazon.com/exec/obidos/ASIN/8488066724/icongroupinterna

·

When Your Doctor is Wrong, Hepatitis B Vaccine and Autism by Judy Converse (2002); ISBN: 1401029736; http://www.amazon.com/exec/obidos/ASIN/1401029736/icongroupinterna

·

Winning the Hepatitis C Battle: Understanding the Disease and How to Treat It Successfully by Shekhar, MD Challa (2003); ISBN: 0974388300; http://www.amazon.com/exec/obidos/ASIN/0974388300/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “hepatitis” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 11

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed

Books

441

·

A résumé of current information on infectious hepatitis; with a selected annotated list of references, by T. C. Lonie. Author: South Pacific Commission.; Year: 1966; Noumea, New Caledonia, 1959

·

Australia antigen and hepatitis. Authors: Baruch S. Blumberg [et al.]. Author: Blumberg, Baruch S.,; Year: 1965; Cleveland, CRC Press [c1972]

·

Carriers of hepatitis B antigen and transfusion hepatitis in Finland. Author: Helske, Timo.; Year: 1966; Copenhagen, Munksgaard, 1974

·

Experimental viral hepatitis. Author: Piazza, Marcello.; Year: 1961; Springfield, Ill., Thomas [c1969]

·

Final report on an attempt to establish a laboratory test object for the growth and detection of the hepatitis virus, April 1, 1959, to January 31, 1960 [by] Gerald A. LoGrippo, principal investigator [et al.]. Author: Henry Ford Hospital.; Year: 1966; Detroit?] 1960

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Hepatitis frontiers. Editors: Frank W. Hartman [et al. Author: Hartman, Frank W. (Frank Wilbur),; Year: 2002; Boston, Little, Brown [c1957]

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Hepatitis-associated antigen and viruses. Author: Zuckerman, Arie J.; Year: 1965; Amsterdam, North-Holland Pub. Co., 1972; ISBN: 0720073004

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Infectious hepatitis in Europe and the Mediterranean basin during World War I and II. Author: Bachmann, L.; Year: 1965; [Washington? 194-?]

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Infectious hepatitis, 1961. Author: Canada. Dominion Bureau of Statistics.; Year: 1966; Ottawa, Dominion Bureau of Statistics, Health and Welfare Division, Public Health Section, 1962

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Infective hepatitis; studies in East Anglia during the period 1943-47, by F. O. MacCallum [and others]. Author: MacCallum, F. O.; Year: 1963; London, H. M. Stationery Off., 1951

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Researches on the etiological agent of viral hepatitis and of the changes in the fine structure of the hepatic cells which take place during infection [by] B. Babudieri [et al.] with the technical assistance of F. Tangucci. Author: Babudieri, B. (Brenno); Year: 2001; Roma, 1965

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Serum hepatitis in Swedish track-finders. Author: Ringertz, Olof.; Year: 1962; Stockholm, Dept. of Epidemiology, National Bacteriological Laboratory, 1971

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Studies on viral hepatitis and hepatitis B (Australia) antigen. Author: Iwarson, Sten.; Year: 1964; Göteborg, 1973

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The Australia antigen hepatitis associated antigen (HAA) and corresponding antibodies. Editor, J. P. Soulier. Author: Soulier, J. P. (Jean Pierre); Year: 1963; Basel, Karger, 1970

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The epidemiology of posttransfusion hepatitis; basic blood and plasma tabulations. Author: Allen, J. Garrott (Joseph Garrott),; Year: 1961; Stanford, Calif., 1972

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Therapy for viral hepatitis and prevention of hepatocellular carcinoma Author: Omata, Masao.; Year: 1961; Tokyo; New York: Springer, c2004; ISBN: 4431402802 http://www.amazon.com/exec/obidos/ASIN/4431402802/icongroupinterna

in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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VA health care: improvements needed in Hepatitis C disease management practices: report to the Chairman, Subcommittee on National Security, Veterans' Affairs and International relations, Committee on Government Reform, House of Representatives. Author: United States. General Accounting Office.; Year: 1964; Washington, D.C.: United States General Accounting Office, [2003]

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Viral hepatitis (review) by P. N. Wahi and V. K. Srivastava. Author: Wahi, P. N.; Year: 2001; New Delhi, Indian Council of Medical Research, 1966

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Viral hepatitis. Niels Tygstrup, guest editor. Author: Tygstrup, Niels.; Year: 1964; London, Philadelphia, Saunders [c1974]

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Viral hepatitis; report on a European symposium convened by the World Health Organization, Prague, 29 September-3 October 1964. Author: World Health Organization. Regional Office for Europe.; Year: 2002; Copenhagen, 1965

Chapters on Hepatitis In order to find chapters that specifically relate to hepatitis, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and hepatitis using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “hepatitis” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on hepatitis: ·

Hepatitis B. [Adults and Older Adults: Immunization and Prophylaxis] Source: in Office of Disease Prevention and Health Promotion, U.S. Public Health Service. Put Prevention Into Practice: Clinician's Handbook of Preventive Services. 2nd ed. Germantown, MD: International Medical Publishing, Inc. 1998. p. 337-344. Contact: Available from International Medical Publishing, Inc. Reiter's Scientific and Professional Books, 2021 K Street, NW, Washington, DC 20006. (800) 591-2713 or (202) 223-3327. Fax (202) 296-9103. PRICE: $20.00 plus shipping and handling. ISBN: 1883205328. Also available from the U.S. Government Printing Office. Superintendent of Documents, P.O. Box 371954, Pittsburgh, PA 15250-7954. (202) 512-1800. Fax (202) 5122250. Summary: At least 200,000 new cases of hepatitis B virus (HBV) infection occur each year in the United States. Most of them occur in young adults, primarily as a result of blood or sexual contact. HBV infection causes significant morbidity and mortality, and up to 10 percent of adults with acute infection become chronically infected. The risk of liver cirrhosis, failure, and cancer is significantly increased in people with chronic HBV infection. This chapter on hepatitis immunization and prophylaxis in adults is from a handbook on preventive services published by the U.S. Government. Hepatitis B vaccine is 95 percent effective in preventing infection. For persons experiencing percutaneous or sexual contact with HBV, administration of hepatitis B immune globulin is approximately 75 percent effective in preventing infection. This chapter summarizes the recommendations of major authorities, including the Advisory Committee on Immunization Practices, the American Academy of Family Physicians, the American College of Obstetricians and Gynecologists, the American College of Physicians, and the U.S. Preventive Services Task Force, for immunization and prophylaxis against HBV in

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adults. The basics of hepatitis B immunization are discussed: vaccine types, schedule, immunity, dose and administration, contraindications and precautions, adverse reactions, patient education, and vaccine storage and handling. The basics of hepatitis B postexposure prophylaxis are also noted: indications, schedule, dose and administration, contraindications and precautions, and adverse reactions. The chapter concludes with a brief list of patient and provider resources. 2 tables. 8 references. ·

Autoimmune Hepatitis: Diagnosis and Treatment Source: in McDonald, J.W.D.; Burroughs, A.K.; Feagan, B.G., eds. Evidence Based Gastroenterology and Hepatology. London, UK: BMJ Publishing Group. 1999. p. 360371. Contact: Available from BMJ Publishing Group. BMA Books, BMA House, Tavistock Square, London WCIH 9JR. Fax 44 (0)20 7383 6402. E-mail: [email protected]. Website: www.bmjbooks.com. PRICE: Contact publisher for price. Summary: Autoimmune hepatitis (AIH) is a self perpetuating, necroinflammatory disease of unknown etiology, which is characterized by a loss of tolerance towards the patient's own liver tissue. The disease may lead to liver cirrhosis (scarring) and liver failure. This chapter on the diagnosis and treatment of autoimmune hepatitis is from a book that emphasizes the approaches of evidence based medicine in gastroenterology (the study of the gastrointestinal tract and gastrointestinal diseases) and hepatology (the study of the liver and liver diseases). The authors note that AIH is a syndrome characterized by a set of epidemiological, laboratory, and clinical features: female predominance (female to male ratio is 4 to 1), overrepresentation of the HLA alleles DR3 and DR4, hypergammaglobulinemia, circulating autoantibodies, response to immunosuppressive therapy, and coexistence of extrahepatic (outside the liver) autoimmune diseases. In the majority of patients, the disease progresses without major symptoms, and the diagnosis is not made until symptoms of severe liver disease are present. Jaundice is present in a large proportion of patients at diagnosis. Patients' complaints include fatigue, anorexia, abdominal pain (10 to 20 percent of patients), and fever (20 percent of patients). Diagnosis requires the assessment of typical clinical and laboratory features; histology confirms disease activity and stage but by itself is not sufficient for diagnosis. Corticosteroids should be administered until remission, incomplete response, treatment failure, or unacceptable adverse effects occur. Remission is defined by the absence of symptoms, resolution of liver inflammation by liver histology, and a normalization of liver enzymes with the exception of AST, which may remain up to twice normal levels. Patients who fail to enter remission after 4 years of conventional treatment are regarded as potential candidates for liver transplantation. Liver transplantation has resulted in excellent long term survival rates that exceed 90 percent after 5 years. 3 figures. 4 tables. 46 references.

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What is Hepatitis B?: An Introduction Source: in Everson, G.T.; Weinberg, H. Living with Hepatitis B: A Survivor's Guide. Long Island, NY: Hatherleigh Press. 2002. p.1-17. Contact: Available from Hatherleigh Press. 5-22 46th Avenue Suite 200, Long Island City, NY 11101. (800) 528-2550. E-mail: [email protected]. Website: http://store.yahoo.com/hatherleighpress/index.html. PRICE: $15.95 plus shipping and handling. ISBN: 1578260841. Summary: Chronic hepatitis B can lead to cirrhosis (liver scarring), liver cancer, and the need for liver transplantation. This introductory chapter is from a book that helps

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readers diagnosed with hepatitis B virus (HBV) infection educate themselves about the disease and its treatment. The authors discuss some basic facts and statistics about hepatitis B, the history and discovery of the hepatitis B virus and vaccines, and information about viruses in general and other forms of viral hepatitis. Throughout the chapter the authors include quotes from real people who are living with hepatitis. 1 figure. 1 reference. ·

Hepatitis B: Prognosis and Treatment Source: in McDonald, J.W.D.; Burroughs, A.K.; Feagan, B.G., eds. Evidence Based Gastroenterology and Hepatology. London, UK: BMJ Publishing Group. 1999. p. 305321. Contact: Available from BMJ Publishing Group. BMA Books, BMA House, Tavistock Square, London WCIH 9JR. Fax 44 (0)20 7383 6402. E-mail: [email protected]. Website: www.bmjbooks.com. PRICE: Contact publisher for price. Summary: Hepatitis B virus (HBV) infection, together with hepatitis C and alcohol abuse, is among the leading causes of cirrhosis and hepatocellular carcinoma (HCC) worldwide. This chapter on the diagnosis and treatment of hepatitis B is from a book that emphasizes the approaches of evidence based medicine in gastroenterology (the study of the gastrointestinal tract and gastrointestinal diseases) and hepatology (the study of the liver and liver diseases). The natural history of chronic hepatitis is variable according to phenotypic and ethnic background, and is also influenced by viral coinfections and toxic cofactors. At least 20 percent of patients develop clinically significant liver disease in the long term. Presence of markers of HBV replication and of continuing liver necroinflammation predict an adverse outcome. Interferon therapy results in stable clearance of HBeAg in 25 percent of all patients chronically infected by type HBV, but only rarely results in HBsAg clearance. Interferon therapy results in stable clearance of HBV DNA in 25 percent of all patients chronically infected by HBe minus HBV. Lamivudine is effective in clearing HBV DNA and normalizing ALT during therapy in 65 percent of patients, but its long term effectiveness is unknown. The authors conclude that there is no acceptable evidence for a protective effect of interferon therapy against the development of hepatocellular carcinoma (HCC) in HBV related cirrhosis. 4 figures. 2 tables. 150 references.

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What Is Hepatitis C?: An Introduction Source: in Everson, G.T. and Weinberg, H. Living with Hepatitis C: A Survivor's Guide. New York, NY: Hatherleigh Press. 1999. p. 1-14. Contact: Available from Hatherleigh Company, Ltd. 1114 First Avenue, Suite 500, New York, NY 10021. (800) 367-2550 or (212) 832-1039. Website: hatherleigh.com. PRICE: $14.95 plus shipping and handling. ISBN: 1578260345. Summary: Hepatitis C is a viral infection that causes inflammation, injury, and ultimately scarring of the liver (cirrhosis). This chapter introducing hepatitis C is from a book that offers information and guidance for people living with hepatitis C. The authors explain in nontechnical language some basic facts and statistics about hepatitis C, its history and discovery, and information about viruses and other forms of viral hepatitis. Hepatitis C is primarily a blood to blood virus, so loved ones cannot easily be infected by the patient with hepatitis C. However, hepatitis C can put a heavy strain on relationships. The authors portray the hepatitis C virus as a slow moving time bomb that can lurk in the liver for decades, silently injuring the liver and setting the stage for complications. The earlier the diagnosis, the better the choices that are available for long

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term care and supportive measures such as good nutrition. The chapter concludes with information about research into a potential cure for hepatitis C. The chapter includes lengthy quotes from patients with hepatitis, which offer the patients' perspectives, insights, and experiences to the reader. 1 figure. 1 reference. ·

Hepatitis C: Diagnosis and Treatment Source: in McDonald, J.W.D.; Burroughs, A.K.; Feagan, B.G., eds. Evidence Based Gastroenterology and Hepatology. London, UK: BMJ Publishing Group. 1999. p. 294304. Contact: Available from BMJ Publishing Group. BMA Books, BMA House, Tavistock Square, London WCIH 9JR. Fax 44 (0)20 7383 6402. E-mail: [email protected]. Website: www.bmjbooks.com. PRICE: Contact publisher for price. Summary: Hepatitis C is often characterized by a progression to chronic disease. This chapter on the diagnosis and treatment of hepatitis C is from a book that emphasizes the approaches of evidence based medicine in gastroenterology (the study of the gastrointestinal tract and gastrointestinal diseases) and hepatology (the study of the liver and liver diseases). The author of this chapter notes that since chronic hepatitis C is generally silent, its diagnosis often happens in conjunction with investigation for another disease. Systematic screening should be recommended in subjects who have a history of blood transfusion or intravenous drug addiction. The ELISA is the appropriate test for screening. In ELISA positive subjects, the presence of chronic infection is established by the detection of serum HCV RNA by polymerase chain reaction (PCR). A liver biopsy is recommended in patients who are HCV RNA positive with increased ALT levels in order to assess the severity of the liver disease and determine whether there is an indication for therapy. Combination therapy with interferon and ribavirin is now standard therapy, and results in a sustained response in approximately 40 percent of patients. Genotyping of the virus and the measure of baseline viral load are useful to assess the probability of sustained response and to determine the appropriate duration of combination therapy. 5 tables. 66 references.

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Hepatitis E: An Overview Source: in Coggins, C.H., Hancock, E.W., and Levitt, L.J., eds. Annual Review of Medicine: Selected Topics in the Clinical Sciences. Palo Alto, CA: Annual Reviews Inc. 1996. Volume 47: 257-266. Contact: Available from Annual Reviews Inc. 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303-0139. (800) 523-8635. Fax (415) 424-0910. PRICE: $52.00. ISBN: 0824305477. ISSN: 00664219. Individual article reprints available from Annual Reviews Preprints and Reprints. (800) 347-8007 or (415) 259-5017. Base price $13.50 per article. Summary: Hepatitis E virus (HEV) has recently been cloned and sequenced and new diagnostic tests have been developed. These tests have been used to begin to characterize the natural history and epidemiologic features of HEV infection. In this entry from the Annual Review of Medicine, the authors provide an overview of hepatitis E. Topics include virology, the clinical features of hepatitis E, diagnostic tests used to confirm the disease, pathogenesis and immunity considerations, epidemiology, and prevention. The authors call for additional research on disease transmission, the reservoir of the virus, and the natural history of protective immunity. 1 figure. 3 tables. 55 references. (AA-M).

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Hepatitis Infections Source: in Frigoletto, F.D.; Little, G.A., eds. Guidelines for Perinatal Care. 3rd ed. Elk Grove Village, IL: American Academy of Pediatrics. 1992. Contact: Available from American Academy of Pediatrics. 141 Northwest Point Road, P.O. Box 927, Elk Grove Village, IL 60204. (800) 433-9016 or (708) 228-5005. PRICE: $34.95 (member), $39.95 (nonmember). Summary: In a pregnant woman, hepatitis B virus infection may result in severe disease for the mother and chronic infection for the newborn, including chronic hepatitis, cirrhosis, and primary hepatocellular carcinoma. Transmission from mother to neonate apparently occurs most often during delivery. Neonates born to mothers who have HBV during the last trimester of pregnancy or during the postpartum period are at high risk of acquiring infection. Women in the U.S. of Asian, Pacific Island, Haitian, sub-Saharan Africa, or Alaskan Eskimo descent are at highest risk, along with prostitutes and users of illicit injectable drugs. Neonates born to mothers who are HBsAg-positive should be bathed carefully as soon as possible to remove the maternal blood and secretions. The importance of proper hygiene, especially handwashing, should be emphasized to the mother.

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Treatment of Chronic Hepatitis B and C: HIV-Coinfected Patients Source: in Gordon, S.C. Management of Chronic Viral Hepatitis. New York, NY: Marcel Dekker Inc. 2002. p. 295-318. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. Website: www.dekker.com. PRICE: $150.00 plus shipping and handling. ISBN: 0824705823. Summary: Liver enzyme abnormalities are very common in patients infected with the human immunodeficiency virus (HIV). Chronic viral hepatitis B and C are among the leading etiological factors associated with hepatocellular (liver) injury. Improved treatments for HIV utilizing highly active antiretroviral therapy (HAART) with multidrug regimens has resulted in increased life expectancy. This change has affect the course and natural history of hepatitis B and C and increased the importance of liver disease in HIV infected patients. This chapter on HIV patients coinfected with hepatitis B and C is from a monograph on the management of chronic viral hepatitis (liver inflammation), bringing the advances of clinical and basic research into the doctor's office. This chapter uses a brief clinical case presentation in order to address the real life intricacies of managing patients who present with viral hepatitis. The case patient is a 40 year old white man with HIV and hepatitis B virus (HBV); his hepatitis B flared in the setting of immune reconstitution. Adding or substituting lamivudine 100 milligrams per day back into the regimen was effective in suppressing HBV replication, and the patient showed dramatic clinical improvement over the next 8 weeks, returning to baseline liver function. The authors note that before HAART, early HIV associated mortality and significant immunosuppression were associated with minimal to mild consequences of hepatitis viral infections in these patients. Immune reconstitution of HIV infected patients with HAART has changed the course of disease outcomes. There is now a critical need to understand the natural history and the value of treatment intervention for hepatitis viruses. 1 figure. 2 tables. 51 references.

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Hepatitis and Dialysis Source: in Lameire, N. and Mehta, R.L., eds. Complications of Dialysis. New York, NY: Marcel Dekker, Inc. 2000. p. 673-696. Contact: Available from Marcel Dekker, Inc. Cimarron Road, P.O. Box 5005, Monticello, NY 12701. (800) 228-1160 or (845) 796-1919. Fax (845) 796-1772. E-mail: [email protected]. International E-mail: [email protected]. Website: www.dekker.com. PRICE: $250.00 plus shipping and handling. ISBN: 0824788710. Summary: Patients on maintenance hemodialysis are at increased risk for parenterally transmitted hepatitis viruses. This chapter on hepatitis and dialysis is from a book that offers a comprehensive, multidisciplinary resource for the nephrologist and caregiver providing dialysis, covering all aspects of dialysis therapies and their complications. The authors of this chapter focus mainly on hepatitis B virus (HBV) and hepatitis C (HCV), which remain the most problematic viral hepatic (liver) infections in hemodialysis patients; hepatitis G virus (HGV) is discussed briefly in the final section of the chapter. For each of these types, the authors consider pathogenesis, transmission and preventive measures, epidemiology (prevalence and incidence), vaccination, and implications for kidney transplantation. Besides the known parenterally transmitted hepatitis viruses, other yet undefined but potentially dangerous viruses may exist. Every nephrologist (kidney specialist) faces some dialysis patients who have inexplicable liver disease in which no responsible virus has been identified. The authors stress that it is therefore advisable to consider all patients as potentially infectious, especially since the level of transaminase is not always a reliable marker for the detection of liver damage in the dialysis population. Isolation procedures are warranted not only for viral infection but also for bacterial infection such as certain drug resistant strains. 2 figures. 4 tables. 243 references.

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Hepatitis and Renal Disease Source: in Nissenson, A.R., Fine, R.N., and Gentile, D.E., eds. Clinical Dialysis. 3rd ed. Norwalk, CT: Appleton and Lange. 1995. p. 574-606. Contact: Available from Appleton and Lange. 25 Van Zant Street, P.O. Box 5630, Norwalk, CT 06856. (800) 423-1359 or (203) 838-4400. PRICE: $175.00. ISBN: 0838513794. Summary: This chapter from a textbook of clinical dialysis covers hepatitis and renal disease. The author first provides an overview of hepatitis, including related definitions, terms, and concepts; the serology and epidemiology; the clinical course; and prophylaxis and treatment methods. The author then addresses the renal implications of hepatitis, including nephrologic complications, the influence of hepatitis on renal disorders, hepatitis in dialysis units, diagnostic considerations, and the prevention of hepatitis transmission in dialysis settings. One section also discusses the risk factors to health care workers of hepatitis B exposure. 12 tables. 577 references.

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Acute Hepatitis and Acute Hepatic Failure Source: in Okuda, K., ed.,et al. Hepatobiliary Diseases: Pathophysiology and Imaging. Malden, MA: Blackwell Science, Inc. 2001. p. 79-102. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail: [email protected]. Website: www.blackwell-science.com. PRICE: $275.00. ISBN: 086542649X.

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Summary: This chapter on acute hepatitis (liver inflammation) and acute hepatic (liver) failure is from a textbook that familiarizes the reader with various imaging modalities, the information they provide, and the merits of each, in order to facilitate the combined use of different imaging techniques in the diagnosis and management of hepatobiliary (liver and bile tract) diseases. The authors note that most cases of acute hepatitis represent hepatitis virus infection, while a small percentage involve drug-induced hepatitis. The disease is clinically characterized by loss of appetite, lassitude (fatigue), colored urine, jaundice (yellowing of the skin and eyes), and sometimes flu-like symptoms with fever. The authors discuss the pathophysiology of acute hepatitis, hepatitis A infection, hepatitis B infection, hepatitis C infection, hepatitis D infection, hepatitis E infection, acute hepatitis caused by other (non A-E) viruses, and imaging features in acute hepatitis. The second section of the chapter discusses acute and subacute hepatic failure, a syndrome in which severely impaired liver function develops acutely in a person without previous liver disease and that includes the development of encephalopathy (involvement of the brain tissues). In this section, the authors cover etiology, pathophysiology, clinical features, imaging features, and treatments. 20 figures. 1 table. 66 references. ·

Acute Hepatitis Source: in Beckingham, I.J., ed. ABC of Liver, Pancreas and Gallbladder. London, UK: BMJ Publishing Group. 2001. p.9-11. Contact: Available from BMJ Publishing Group. BMA Books, BMA House, Tavistock Square, London WCIH 9JR. Fax 44 (0)20 7383 6402. E-mail: [email protected]. Website: www.bmjbooks.com. PRICE: Contact publisher for price. ISBN: 0727915312. Summary: This chapter on acute hepatitis is from an atlas of the liver, pancreas and gallbladder. Topics covered include the types of acute hepatitis, the physical signs in viral hepatitis, acute liver failure (fulminant hepatitis), diagnostic strategies, and the management of acute viral hepatitis. Both the diagnostic approach and the management techniques are dependent on the type of hepatitis present. The author cautions that symptoms of hepatitis are non-specific and often occur without the development of jaundice. Serum alanine transaminase is the most useful screening test for hepatitis in general practice. The chapter concludes with summary points of the concepts discussed. 4 figures. 5 tables.

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Alternative Therapies for Chronic Hepatitis C Source: in Gordon, S.C. Management of Chronic Viral Hepatitis. New York, NY: Marcel Dekker Inc. 2002. p. 159-186. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. Website: www.dekker.com. PRICE: $150.00 plus shipping and handling. ISBN: 0824705823. Summary: This chapter on alternative therapies for chronic hepatitis C is from a monograph on the management of chronic viral hepatitis (liver inflammation), bringing the advances of clinical and basic research into the doctor's office. This chapter uses a brief clinical case presentation in order to address the real life intricacies of managing patients who present with viral hepatitis. The case patient is a 45 year old man with chronic hepatitis C and hyperlipidemia (excessive amounts of lipids in the blood) who was referred for antiviral treatment. Because of the patient's coronary artery disease, a decision was made to avoid ribavirin. In light of the low response rate to interferon monotherapy, adjunctive therapies were discussed, including the use of thymic

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peptides, aspirin like drugs, amantadine, and botanicals. The risks and benefits of iron reduction therapy were also discussed. After reviewing the alternatives, the patient opted to avoid all treatment until the availability of better antiviral options. The authors note that the need for alternative therapies for the treatment of hepatitis C is based on the realization that, despite major advanced in antiviral therapy, many patients fail to respond to the best agents currently available. Efficacy may be limited in some patients due to dose limiting toxicities, such as depression or anemia, or the presence of relative contraindications to therapy (cardiac disease, renal failure) that preclude the use of these agents. The role of aspirin like compounds seems to be limited to easing the side effects of interferon. 1 figure. 1 table. 67 references. ·

Chronic Hepatitis: General Features, Autoimmune Chronic Disease Source: in Sherlock, S.; Dooley, J. Diseases of the Liver and Biliary System. Malden, MA: Blackwell Science, Inc. 2002. p.321-333. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail: [email protected]. Website: www.blackwell-science.com. PRICE: $178.95. ISBN: 0632055820. Summary: This chapter on chronic hepatitis, defined as a chronic inflammatory reaction in the liver, is from a textbook that presents a comprehensive and up-to-date account of diseases of the liver and biliary system. The chapter covers clinical presentation (symptoms), hepatic (liver) histology, the role of liver biopsy, and classification, then describes three types of autoimmune chronic hepatitis: Type 1 (formerly called lupoid), Type 2, and primary biliary cirrhosis and immune cholangitis. The chapter then focuses on chronic autoimmune hepatitis (type 1), discussing etiology, hepatic pathology, clinical features, differential diagnosis, treatment, course and prognosis, and syncytial giant-cell hepatitis. 16 figures. 13 tables. 40 references.

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Chronic Viral Hepatitis Source: in Beckingham, I.J., ed. ABC of Liver, Pancreas and Gallbladder. London, UK: BMJ Publishing Group. 2001. p.12-14. Contact: Available from BMJ Publishing Group. BMA Books, BMA House, Tavistock Square, London WCIH 9JR. Fax 44 (0)20 7383 6402. E-mail: [email protected]. Website: www.bmjbooks.com. PRICE: Contact publisher for price. ISBN: 0727915312. Summary: This chapter on chronic viral hepatitis is from an atlas of the liver, pancreas and gallbladder. After a brief section on transmission, the authors discuss presentation of chronic viral liver disease, hepatitis B and its treatment, and hepatitis C and its treatment. Viral hepatitis is relatively common in the United Kingdom and consists primarily of hepatitis C. The disease usually presents with abnormal alanine transaminase activity (a measure of liver function). Disease progression in hepatitis C is usually slow (the median time to development of cirrhosis, or liver scarring, is approximately 30 years). Liver biopsy is essential in managing chronic viral hepatitis The authors note that new treatments for hepatitis C (interferon and ribavirin) and hepatitis B (lamivudine) have improved the chances of eliminating these pathogens from chronically infected patients. The chapter concludes with summary points of the concepts discussed. 7 figures. 3 tables.

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Future Hepatitis C Virus Therapy: Protease and Helicase Inhibitors and Beyond Source: in Gordon, S.C. Management of Chronic Viral Hepatitis. New York, NY: Marcel Dekker Inc. 2002. p. 347-373. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. Website: www.dekker.com. PRICE: $150.00 plus shipping and handling. ISBN: 0824705823. Summary: This chapter on future developments in the treatment of hepatitis C patients is from a monograph on the management of chronic viral hepatitis (liver inflammation), bringing the advances of clinical and basic research into the doctor's office. This chapter uses a brief clinical case presentation in order to address the real life intricacies of managing patients who present with viral hepatitis. The case patient is a 29 year old man with chronic hepatitis C apparently acquired from a blood transfusion after a bicycle accident as a child. While the patient had no clinical symptoms referable to the liver disease, he was concerned about the long term effect of the HCV infection and was eager to undergo treatment. He undertook a 48 week protocol treatment with interferon and ribavirin, tolerated the regimen well, but had no significant virological response. The author considers the next treatment options for this patient. Currently, therapies for chronic HDV infection are directed at enhancing the host's immune defenses against viral infection. The author focuses on the prospects for the development of new HCV antiviral agents based on more detailed understanding of the mechanisms of HCV viral replication. The effectiveness of most antiviral agents depends on their ability to block one or more steps in the viral life cycle without significantly affecting host cell physiology. Inhibiting the function of viral proteins and virus specific alterations in cellular proteins are potential strategies for blocking viral replication and increasing the likelihood of virus eradication. 6 figures. 1 table. 60 references.

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Treatment of Chronic Hepatitis B: Future Approaches Source: in Gordon, S.C. Management of Chronic Viral Hepatitis. New York, NY: Marcel Dekker Inc. 2002. p. 91-118. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. Website: www.dekker.com. PRICE: $150.00 plus shipping and handling. ISBN: 0824705823. Summary: This chapter on future treatment options for hepatitis B is from a monograph on the management of chronic viral hepatitis (liver inflammation), bringing the advances of clinical and basic research into the doctor's office. This chapter uses a brief clinical case presentation in order to address the real life intricacies of managing patients who present with viral hepatitis. The case patient is a 39 year old white man who was referred in consultation seeking a second opinion regarding his well known history (10 years) of chronic hepatitis B. The authors use this case to consider the role of long term therapeutic agents, the indications for lamivudine therapy, new antivirals that may be in the research stages, and strategies to improve the host immune response and thus obtain an immunological clearance of the hepatitis B virus (HBV). The authors conclude that although significant advances have been made in the treatment of chronic hepatitis B, there is still a high proportion of these patients in whom a sustained eradication of the viral infection cannot be achieved with either interferons or lamivudine monotherapy. However, combination therapy has been shown to improve the success rate in chronic hepatitis C and HIV; the authors speculate that it may also be helpful in the treatment of chronic hepatitis B patients. The preliminary experience with combination therapy of interferons and lamivudine has been frustrating. A wide range of novel antiviral

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approaches such as cytokine therapy, vaccine adjuvant, DNA vaccines, antisense therapy, and other forms of gene therapy are currently under investigation. 3 figures. 1 table. 72 references. ·

Hepatitis B Virology: Acute and Chronic Infection: Wild-Type HBV and HBV Variants Source: in Gordon, S.C. Management of Chronic Viral Hepatitis. New York, NY: Marcel Dekker Inc. 2002. p. 1-32. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. Website: www.dekker.com. PRICE: $150.00 plus shipping and handling. ISBN: 0824705823. Summary: This chapter on hepatitis B virology is from a monograph on the management of chronic viral hepatitis (liver inflammation), bringing the advances of clinical and basic research into the doctor's office. Three brief clinical case presentations address the real life intricacies of managing patients who present with viral hepatitis. The authors focus on wild type hepatitis B viruses (HBV) and HBV variants. Case 1 presented with acute hepatitis, as evidenced by the presence of HBsAg and IgM antiHBc. The authors comment on the need for prophylaxis for this patient's wife. Case 2 had perinatally (during birth) acquired HBV infection with exacerbation of chronic hepatitis B. This patient may benefit from antiviral therapy if the exacerbation does not result in sustained HBeAg seroconversion. Because of his family history of hepatocellular carcinoma (HCC, liver cancer), surveillance for HCC is recommended. Case 3 most likely was infected with a precore variant, as evidenced by the detection of HBV DNA despite the presence of anti HBe. 6 figures. 1 table. 85 references.

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Hepatitis B Virus and Hepatitis Delta Virus Source: in Sherlock, S.; Dooley, J. Diseases of the Liver and Biliary System. Malden, MA: Blackwell Science, Inc. 2002. p.285-303. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail: [email protected]. Website: www.blackwell-science.com. PRICE: $178.95. ISBN: 0632055820. Summary: This chapter on hepatitis B virus (HBV) and hepatitis Delta virus (HDV) is from a textbook that presents a comprehensive and up-to-date account of diseases of the liver and biliary system. The chapter includes three sections: acute HBV, chronic HBV, and HDV. Specific topics include epidemiology, the clinical course and features of each disease, prevention strategies for acute HBV, clinical relapse and reactivation of the hepatitis B virus, laboratory tests to monitor chronic HBV, needle liver biopsy, course and prognosis, treatment strategies, and screening for hepatocellular carcinoma (liver cancer). Each section offers a list of references for additional reading. 20 figures. 11 tables. 103 references.

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Hepatitis C Virus Source: in Sherlock, S.; Dooley, J. Diseases of the Liver and Biliary System. Malden, MA: Blackwell Science, Inc. 2002. p.305-319. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail:

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[email protected]. Website: www.blackwell-science.com. PRICE: $178.95. ISBN: 0632055820. Summary: This chapter on hepatitis C virus (HCV) is from a textbook that presents a comprehensive and up-to-date account of diseases of the liver and biliary system. The chapter covers molecular virology of this disease, serological (blood) tests, immune response, epidemiology, natural history, clinical course, hepatic histology, hepatitis C and serum autoantibodies, associated diseases, diagnosis, prognosis, prevention (including vaccines), treatment strategies, and hepatic (liver) transplantation. Combination therapy with interferon alpha and ribavirin is the current standard of care for chronic hepatitis C. This offers a 30 to 65 percent change of sustained virological response, depending on various factors in particular the HCV genotype. However, the cost and availability makes all the present treatments out of reach of millions of people with HCV worldwide. 9 figures. 7 tables. 129 references. ·

Persistently Normal Alanine Aminotransferase Levels in Individuals with Hepatitis C Source: in Gordon, S.C. Management of Chronic Viral Hepatitis. New York, NY: Marcel Dekker Inc. 2002. p. 217-232. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. Website: www.dekker.com. PRICE: $150.00 plus shipping and handling. ISBN: 0824705823. Summary: This chapter on persistently normal alanine aminotransferase (ALT) levels in individuals with hepatitis C is from a monograph on the management of chronic viral hepatitis (liver inflammation), bringing the advances of clinical and basic research into the doctor's office. Initial treatment protocols for hepatitis C virus (HCV) used criteria for study enrollment based on recommendations for hepatitis B; that is, patients with elevated ALT levels. In addition, many patients with normal ALT were initially not even suspected to be infected with HCV. The authors note that the concept of the 'healthy carrier' of HCV should be dispelled. Still in question is why some patients have ALT which remains persistently normal. Although advances have been made in understanding this cohort, questions remain regarding histology, natural history, viral levels, and genotypes as well as response to therapy in patients with persistently normal ALT. To date, there is no compelling evidence that patients with persistently normal ALT are significantly different from patients with abnormal ALT. Nevertheless, the treatment of individuals with hepatitis C viremia and normal ALT has not been formally recommended. Longer treatment trials with larger numbers of patients using combination therapy and newer antivirals are necessary before definitive recommendations regarding the proper therapy of this unique cohort of hepatitis C infected patients can be made. 1 table. 29 references.

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Screening for Hepatitis B Virus Infection Source: in U.S. Preventive Services Task Force (USPSTF). Guide to Clinical Preventive Services. 2nd ed. Germantown, MD: International Medical Publishing, Inc. 1996. p. 269276. Contact: Available from International Medical Publishing, Inc. Reiter's Scientific and Professional Books, 2021 K Street, NW, Washington, DC 20006. (800) 591-2713 or (202) 223-3327. Fax (202) 296-9103. PRICE: $24.00 plus shipping and handling. ISBN: 1883205131. Also available from the U.S. Government Printing Office. Superintendent of

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Documents, P.O. Box 371954, Pittsburgh, PA 15250-7954. (202) 512-1800. Fax (202) 5122250. Summary: This chapter on screening for hepatitis B virus (HBV) infection is from a guide to clinical preventive services published by the U.S. Preventive Services Task Force. Screening with hepatitis B surface antigen (HBsAg) to detect active (acute or chronic) HBV infection is recommended for all pregnant women at their first prenatal visit. The test may be repeated in the third trimester in women who are initially HBsAg negative but are at increased risk of HBV infection during pregnancy. Routine screening of the general population is not recommended. Certain persons at high risk may be screened to assess eligibility for vaccination. The chapter discusses the accuracy of screening tests, the effectiveness of early detection, and the recommendations of other groups. The chapter concludes with a summary of recommended clinical interventions. 56 references. (AA-M). ·

Current Treatment of Chronic Hepatitis B Source: in Gordon, S.C. Management of Chronic Viral Hepatitis. New York, NY: Marcel Dekker Inc. 2002. p. 65-89. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. Website: www.dekker.com. PRICE: $150.00 plus shipping and handling. ISBN: 0824705823. Summary: This chapter on the current treatment of hepatitis B is from a monograph on the management of chronic viral hepatitis (liver inflammation), bringing the advances of clinical and basic research into the doctor's office. This chapter uses a brief clinical case presentation in order to address the real life intricacies of managing patients who present with viral hepatitis. The case patient is a 25 year old Asian American man who presented for evaluation of recently discovered hepatitis B surface antigenemia. The patient has a significant family history of liver disease with his father having had a diagnosis of hepatocellular carcinoma (liver cancer) and chronic hepatitis B. Because the patient had persistent replication with HBeAg and HBV DNA present at follow up 3 months later, treatment was advised. The role of interferon and lamivudine were discussed and he elected to receive therapy with lamivudine. The patient had rapid normalization of liver chemistries with clearance of serum HBV DNA within 12 weeks of start of the therapy. The authors note that the treatment options for chronic HBV have broadened considerably with the advent of lamivudine, the first of undoubtedly many newer agents for therapy. There is still, however, an important role for interferon therapy in well selected patients, particularly as its successful use clearly leads to loss of HBsAg. Factors to weigh in choosing an initial agent include the patient's likely tolerance of interferon side effects and predictors of successful response, notably low pretherapy HBV DNA and elevated ALT levels. The absence of severe side effects with lamivudine makes compliance easy, although by not using interferon therapy, the patient may at least theoretically be deprived of a chance of subsequent HBsAg clearance. 2 figures. 2 tables. 72 references.

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Management of the Medically Compromised Patient: Hematology, Oncology, Hepatitis, and AIDS Source: in McDonald, R.E. and Avery, D.A., eds. Dentistry for the Child and Adolescent. 7th ed. St. Louis, MO: Mosby, Inc. 2000. p. 600-625.

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Contact: Available from Harcourt Health Sciences. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 325-4177. Fax (800) 874-6418. Website: www.harcourthealth.com. PRICE: $72.00 plus shipping and handling. ISBN: 0815190174. Summary: This chapter on the management of the medically compromised patient is from a textbook on dentistry for the child and adolescent that is designed to help undergraduate dental students and postdoctoral pediatric dentistry students provide comprehensive oral health care for infants, children, teenagers, and individuals with various disabilities. The authors of this chapter focus on patients dealing with disorders of blood disease, cancer, hepatitis, and AIDS. The authors stress that in order to achieve optimal oral health for these medically compromised patients, the dentist and physician must establish a close working relationship. To minimize the risk of possible complications that may affect their general physical health, these patients need an aggressive prevention oriented program. The authors discuss hemophilia, viral hepatitis, AIDS (including the oral manifestations of HIV infection), leukemia, bone marrow or stem cell transplantation, and solid tumors. For each condition, the authors cover symptoms, etiology, treatment options, complications, risks to the dental staff, and dental treatment planning, including pain control. 4 figures. 6 tables. 40 references. ·

Retreatment of Hepatitis C: Interferon Nonresponders Source: in Gordon, S.C. Management of Chronic Viral Hepatitis. New York, NY: Marcel Dekker Inc. 2002. p. 233-261. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. Website: www.dekker.com. PRICE: $150.00 plus shipping and handling. ISBN: 0824705823. Summary: This chapter on the retreatment of hepatitis C patients who have not responded to interferon (IFN) therapy is from a monograph on the management of chronic viral hepatitis (liver inflammation), bringing the advances of clinical and basic research into the doctor's office. This chapter uses a brief clinical case presentation in order to address the real life intricacies of managing patients who present with viral hepatitis. The case patient is a 49 year old man who was diagnosed with subclinical chronic hepatitis C virus (HCV) infection. The patient received interferon therapy and tolerated it well, with minimal adverse effects. However, viral titer, after 3 months on interferon monotherapy, showed persistence of the HCV. He was considered a nonresponder and interferon therapy was discontinued. Additional treatments, including a longer course of interferons and a course of combination therapy with interferon and ribavirin, were undertaken. There was no substantial change in viral titer, although slight improvement in aminotransferase (ALT) levels was seen. The author discusses retreatment with alternative forms of interferon, and using adjunctive therapy, including iron reduction therapy, amantadine and rimantadine, ursodeoxychlic acid (UDCA), and nonsteroidal antiinflammatory drugs (NSAIDs). 4 tables. 92 references.

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Treatment of Chronic Hepatitis C: Transplant Recipients Source: in Gordon, S.C. Management of Chronic Viral Hepatitis. New York, NY: Marcel Dekker Inc. 2002. p. 263-293. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. Website: www.dekker.com. PRICE: $150.00 plus shipping and handling. ISBN: 0824705823.

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Summary: This chapter on the treatment of chronic hepatitis C in transplant recipients is from a monograph on the management of chronic viral hepatitis (liver inflammation), bringing the advances of clinical and basic research into the doctor's office. This chapter uses a clinical case presentation in order to address the real life intricacies of managing patients who present with viral hepatitis. The case patient was a 45 year old female who presented with chronic hepatitis C with cirrhosis (liver scarring). She was referred for liver transplantation 1 year after diagnosis, due to deterioration of her condition. Although her hepatitis recurred after transplant and contributed to three serious episodes of rejection, the patient is now clinically stable. Recurrent hepatitis occurs in 40 to 80 percent of patients; it is usually found during the first year posttransplant. Recurrence of HCV infection leads to cirrhosis in 10 percent of patients 5 years after transplant. The clinical presentation of HCV recurrence and acute graft infection after transplantation varies from asymptomatic or minimal liver damage to an influenza like syndrome with or without jaundice. Risk factors involved in a more severe recurrence are still being studied. Immunosuppressive medications result in increased viral proliferation and a worse outcome of hepatitis C recurrence. Histological features are important, but can be confusing in differentiating HCV recurrence from other post transplantation complications such as acute rejection. Combination therapy with inferon and ribavirin may lead to an improved liver histology in patients with severe recurrence, but few patients have a sustained viral response and further advances in the management of this group of patients are required. 1 figure. 4 tables. 107 references. ·

Treatment of Chronic Hepatitis B in Transplant Recipients Source: in Gordon, S.C. Management of Chronic Viral Hepatitis. New York, NY: Marcel Dekker Inc. 2002. p. 119-157. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. Website: www.dekker.com. PRICE: $150.00 plus shipping and handling. ISBN: 0824705823. Summary: This chapter on the treatment of hepatitis B in transplant recipients is from a monograph on the management of chronic viral hepatitis (liver inflammation), bringing the advances of clinical and basic research into the doctor's office. Three clinical case presentations address the real life intricacies of managing patients who present with viral hepatitis. Originally, a high rate of graft infection and early graft failure, as well as frequent patient death, led to skepticism about the use of orthotopic liver transplantation (OLT) for chronic HBV infection. Marked improvements in long term survival have resulted from the use of low dose immunosuppressive therapy and administration of indefinite hepatitis B immune globulin. The goals of treatment of HBV infection include decreasing viral load, lessening infectivity, decreasing the level of hepatic inflammation, preventing or slowing the development of cirrhosis (liver scarring) and liver failure, delaying time to liver transplantation, and prevention of liver cancer. Lamivudine alone or in combination with hepatitis B immune globulin (HBIG) has been shown to be effective in the long term management of recipients of liver transplants. The combination of lamivudine and HBIG is probably the best current therapy, since lamivudine monotherapy, especially in the setting of immunosuppression, has a very high mutation rate leading to resistance and active viral replication in more than 40 percent of patients after 2 years of therapy posttransplantation. Patients with severe recurrent HBV infection, including fibrosing cholestatic hepatitis (FCH), can undergo liver retransplantation but costs are extremely high and long term survival is inferior to that of patients undergoing a first liver transplantation. 2 figures. 3 tables. 165 references.

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Viral Hepatitis: General Features, Hepatitis A, Hepatitis E and Other Viruses Source: in Sherlock, S.; Dooley, J. Diseases of the Liver and Biliary System. Malden, MA: Blackwell Science, Inc. 2002. p.267-283. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail: [email protected]. Website: www.blackwell-science.com. PRICE: $178.95. ISBN: 0632055820. Summary: This chapter on viral hepatitis (liver inflammation) is from a textbook that presents a comprehensive and up-to-date account of diseases of the liver and biliary system. The chapter covers general features of viral hepatitis and then focuses on hepatitis A and hepatitis E (other variants are covered in later chapters) and other viruses that have an impact on the liver. Topics include pathology, clinical types, investigations, differential diagnosis, prognosis, treatment, and follow-up; and specific viruses, including hepatitis A virus, hepatitis E virus, hepatitis G virus, hepatitis TT virus, yellow fever, infectious mononucleosis (Epstein-Barr virus), other viruses (cytomegalovirus, herpes simplex) and hepatitis due to exotic viruses. For each type of virus, the authors review epidemiology, clinical features, diagnostic tests, prevention, and treatment. Each section offers a list of references for additional reading. 15 figures. 4 tables. 89 references.

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Hepatitis Infection Source: in Sweet, R.L. and Gibbs, R.S. Infectious Diseases of the Female Genital Tract. Baltimore, MD: Williams and Wilkins. 1990. p. 158-169. Contact: Available from Williams and Wilkins. Book Order Department, 428 East Preston Street, Baltimore, MD 21202. (800) 638-0672. PRICE: $68 (shipping $6.90). ISBN: 0683080393. Summary: This chapter, from a book about infectious diseases of the female genital tract, focuses on the epidemiology, mode of transmission, and clinical aspects of hepatitis B, because of the major impact of hepatitis on the fetus and neonates. Maternal infection during pregnancy with the hepatitis B virus is increasingly recognized as a threat to the fetus and neonate. The authors also note that clinically apparent icteric hepatitis is only part of the disease spectrum; silent infections (carrier state) may result in chronic and progressive disease in the mother and her offspring. Tables summarize the nomenclature of hepatitis antigens and antibodies; the clinical and epidemiologic features of acute viral hepatitis; and a practical laboratory guide for the differential diagnosis of viral hepatitis. 3 figures. 3 tables. 57 references.

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Hepatitis B Virus Source: in Hollinger, F.B., et al. Viral Hepatitis: Biological and Clinical Features, Specific Diagnosis, and Prophylaxis. 2nd ed. New York, NY: Raven Press, Ltd. 1991. p. 73-138. Contact: Available from Raven Press. 1185 Avenue of the Americas, Dept. 5B, New York, NY 10036. (800) 777-2836 or (212) 930-9500. Fax (212) 869-3495. PRICE: $91.50 plus shipping (as of 1995). ISBN: 0881677272. Summary: This chapter, from a book that examines the fundamental aspects of viral hepatitis, discusses the hepatitis B virus (HBV). Topics covered include the history of this disease; the infectious agent itself; its clinical features, including incubation period, the clinical signs and symptoms of acute viral hepatitis, laboratory evaluation,

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pathogenesis and pathology of acute viral hepatitis, management issues, extrahepatic manifestations of viral hepatitis, chronic viral hepatitis, the management of chronic hepatitis, and the immunopathogenesis of viral hepatitis B; immunodiagnosis, including viral hepatitis serologic profiles; epidemiology, including modes of spread, factors influencing the development of persistent infection, and association of HBV with primary hepatocellular carcinoma; and prevention and control considerations, notably risk factors, routine practices, immune globulin immunoprophylaxis, established hepatitis B vaccines, factors influencing the immune response, alternative hepatitis B vaccines, and suggested guidelines for immunoprophylaxis. 21 figures. 16 tables. 715 references. ·

Gastrointestinal Disease and Hepatitis Source: in Andersen, R.D., et al. Infections in Children: A Sourcebook for Educators and Child Care Providers. Aspen Publishers, Inc. 1994. p. 137-146. Contact: Available from Aspen Publishers, Inc. 7201 McKinney Circle, Frederick, MD 21701. (800) 638-8437 or (301) 417-7500. PRICE: $36. ISBN: 0834203871. Summary: This chapter, from a handbook for educators and child care providers on infections in children, addresses gastrointestinal disease and hepatitis. The chapter covers vomiting; diarrhea; common causes of infectious diarrhea, including rotavirus, Escherichia coli, campylobacter species, salmonella, and shigella; hepatitis A; hepatitis B; and hepatitis C. In each section, the authors review the illness and its symptoms, consider etiology, review transmission and its prevention, and remind readers of the situations in which consultation of a health care provider is indicated. 3 references.

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Hepatitis Viruses Source: in Gonik, B., ed. Viral Diseases in Pregnancy. New York, NY: Springer-Verlag. 1994. p. 156-184. Contact: Available from Springer-Verlag New York, Inc. 175 Fifth Avenue, New York, NY 10010. (800) 777-4643. PRICE: $87.00 (as of 1996). ISBN: 0387942076 or 3540942076. Summary: This chapter, from a medical text on viral diseases in pregnancy, deals with hepatitis A, B, C, D, and E. For each strain of hepatitis, the author provides a description of the virus and then discusses epidemiology, pathogenesis, clinical manifestations, pregnancy effects and effects on the fetus and neonate, diagnosis, prevention, and treatment. The author notes that variations do exist in incubation periods, modes of transmission, fulminance, and effects during pregnancy. 6 figures. 2 tables. 268 references.

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Management of Chronic Active Hepatitis Source: in Danzi, J.T.; Scopelliti, J.A., eds. Office Management of Digestive Diseases. Malvern, PA: Lea and Febiger. 1992. p. 143-151. Contact: Available from Lea and Febiger. P.O. Box 1496, Baltimore, MD 21298-9724. (800) 638-0672. PRICE: $45. ISBN: 0812114361. Summary: This chapter, from a medical textbook about the office management of common gastrointestinal diseases, discusses the management of chronic active hepatitis. Topics include the clinical manifestations of the disease; the suggestive clinical profiles for chronic hepatitis B, hepatitis C, autoimmune chronic active hepatitis, drug-related chronic active hepatitis, and Wilson's disease; the use of liver biopsy to confirm a

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diagnosis; and the management of each of the types of chronic disease noted above. 4 figures. 1 table. 8 references. ·

Hepatitis C: An Overview Source: in Coggins, C.H., et al, eds. Annual Review of Medicine: Selected Topics in the Clinical Sciences. Palo Alto, CA: Annual Review, Inc. 1995. Volume 46: 309-317. Contact: Available from Annual Reviews, Inc. 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303. (800) 347-8007 or (415) 259-5017 for reprints of individual articles; (800) 523-8635 for subscriptions. E-mail [email protected]. PRICE: $47 including shipping and handling. ISBN: 0824305450. ISSN: 0066-4219. Summary: This entry from the Annual Review of Medicine provides readers with an overview of hepatitis C virus (HCV). Topics include structure and genotypes; diagnostic tests; epidemiology; HCV related hepatitis and cirrhosis; HCV associated hepatocellular carcinoma; treatment options, including the use of interferon and liver transplantation; and HCV vaccines. 1 figure. 41 references.

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Therapy of Acute and Chronic Viral Hepatitis Source: in Schrier, R.W., et al., eds. Advances in Internal Medicine. Vol 39. St. Louis, MO: Mosby-Year Book, Inc. 1994. p. 241-275. Contact: Available from Mosby Year-Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 426-4545. Fax (800) 535-9935. E-mail: [email protected]. PRICE: $72.95. ISBN: 0815183127. ISSN: 00652822. Summary: This entry, from a yearbook of advances in internal medicine, outlines the therapy of acute and chronic viral hepatitis. Viral hepatitis comprises at least five different diseases caused by five different viruses: hepatitis A, B, C, D or delta, and E. All five viruses can cause acute hepatitis; types B, C, and D can also cause persistent infection and chronic hepatitis. Acute viral hepatitis is probably the most common cause of jaundice and acute liver failure worldwide. Similarly, chronic viral hepatitis is probably the most common cause of cirrhosis and hepatocellular carcinoma. Therapy of acute and chronic viral hepatitis has recently been advanced by breakthroughs in the understanding of the hepatitis viruses and by development of several safe and potent antiviral substances. This review focuses largely on alpha interferon, with a few comments relating to other antiviral and immunomodulatory agents that have been found promising in early studies. Despite the benefits of alpha interferon therapy in many patients with chronic viral hepatitis, several shortcomings of this therapy are evident: less than 50 percent of patients respond, side effects can be problematic, and some patients are not appropriate for therapy. 5 figures. 4 tables. 151 references.

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Acute Viral Hepatitis Source: in Brandt, L., et al., eds. Clinical Practice of Gastroenterology. Volume Two. Philadelphia, PA: Current Medicine. 1999. p. 831-839. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. Website: www.wbsaunders.com. PRICE: $235.00 plus shipping and handling. ISBN: 0443065209 (two volume set); 0443065217 (volume 1); 0443065225 (volume 2). Summary: Viral infection is the most common cause of acute and chronic liver disease in the world. This chapter on acute viral hepatitis (liver infection) is from a lengthy

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textbook that brings practitioners up to date on the complexities of gastroenterology practice, focusing on the essentials of patient care. The author notes that the spectrum of clinical illness due to hepatitis infection is extraordinarily broad. In many patients, infection is asymptomatic and entirely subclinical; in others, acute, life threatening liver failure may occur. At present, there is no specific, effective treatment for acute viral hepatitis with the exception of liver transplant for patients with acute irreversible liver failure. Hepatitis viruses are classified into two distinct groups: the enterically transmitted (through the digestive tract), nonenveloped agents, including hepatitis A virus (HAV) and hepatitis E virus (HEV); and the bloodborne, enveloped agents, including hepatitis B virus (HBV), hepatitis D virus (HDV), and hepatitis C virus (HCV). A fourth bloodborne agent, the hepatitis G virus (HGV) appears unlikely to be a true hepatitis virus and is not covered in this chapter. The enterically transmitted hepatitis viruses survive exposure to bile, are shed in feces, and produce infections that are generally self limited although they may cause severe hepatitis and acute liver failure; chronic disease is not seen. In contrast, the bloodborne enveloped hepatitis viruses are disrupted by exposure to bile or detergents, are not shed in feces, and may be associated with prolonged viremia (presence of the virus in the blood), persistent infectivity, and progression to chronic liver disease. Effective and safe vaccines are available for immunoprophylaxis against HAV and HBV infections (the latter vaccine also prevents HDV infection). Immunoprophylaxis against infection with other hepatitis viruses is not currently available. 10 figures. 4 tables. 21 references.

Directories In addition to the references and resources discussed earlier in this chapter, a number of directories relating to hepatitis have been published that consolidate information across various sources. The Combined Health Information Database lists the following, which you may wish to consult in your local medical library:12 ·

Directory of Plain Language Health Information Source: Ottawa, Ontario: Canadian Public Health Association. 1999. 104 p. Contact: Available from Canadian Public Health Association. 400-1565 Carling Avenue, Ottawa, Ontario, K1Z 8R1. (613) 725-3769. Fax (613) 725-9826. E-mail: [email protected]. PRICE: $19.95 plus shipping and handling. Also available at www.pls.cpha.ca for free. ISBN: 189432403X. Summary: Patient education materials are often written at a level that is higher than the reading level of the people who need the materials. This directory lists 'plain language' patient education materials. An extensive introductory chapter in the directory describes how patient education materials are evaluated and offers specific information about the best strategies to create plain language materials. Each piece of health information in the directory is rated according to its design assessment, in order to help readers make informed decisions about choosing materials. Part I is a list of health subjects presented in alphabetical order, in the style of a typical index. The page number after a listing notes where to find that piece of health information in Part II. Part II is a list of

12

You will need to limit your search to “Directory” and “hepatitis” using the "Detailed Search" option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find directories, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Select your preferred language and the format option “Directory.” Type “hepatitis” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months.

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organizations and their contact information. Below the contact information is a list of the plain language health titles produced by the organization. Each title is grouped under a grade level heading, is numbered, and has a design rating. Part III is an alphabetical list of all the organizations in Part II. Materials related to digestive system diseases include allergies, constipation and soiling in children, cholesterol, hepatitis, constipation, diabetes and diet therapy, exercise for weight control, food choices, nutrition, heart health, immunization, low fat cooking, nausea, vomiting, diarrhea, smoking, and weight loss. Appendices to the directory include a guide to the S.M.O.G. readability formula, clear design tips, and plain language tips. The Directory is also available at www.pls.cpha.ca on the Internet. ·

Sources of Health Materials for African Americans, American Indian-Alaska Natives, Asians, Hispanics, Pacific Islanders Source: Washington, DC: Office of Minority Health Resource Center. October 1997. 56 p. Contact: Available from Office of Minority Health Resource Center. P.O. Box 37337, Washington, DC 20013-7337. (800) 444-6472. Website: www.omhrc.gov. PRICE: Single copy free. Summary: This bibliography lists sources of health materials that are written specifically for the needs of certain ethnic groups. This bibliography includes five sections: African Americans, American Indians (including Alaska Natives), Asians, Hispanics, and Pacific Islanders. The first section concentrates on health materials identified by the Office of Minority Health Resource Center (OMH-RC) as specifically targeting African Americans and includes resources on nutrition, exercise, and AIDS educational materials. This section also includes cancer, chemical dependency, diabetes, heart disease and stroke, infant mortality, and the associated risk factors. The second section lists culturally sensitive printed health materials identified for American Indians and includes sources of information for AIDS, cancer, child development, diabetes, high blood pressure, nutrition, and substance abuse. The third section includes culturally sensitive health materials identified in various Asian languages and lists resources on nutrition, exercise, and AIDS education. The fourth section covers health materials specifically targeting different Hispanic populations, noting that culturally sensitive and universally appropriate Spanish language materials for this diverse population are difficult to obtain and some do not take culture, linguistics and other factors that may influence health behaviors into consideration. The final section lists sources that produce or distribute health promotion materials for Pacific Islander populations. The listing includes sources of information for AIDS, diabetes, hepatitis, sexually transmitted diseases, and thalassemia, as well as other health areas. Each of the five sections offers a brief introduction, a listing of subject topics covered, and the organizations or publishers that serve as sources for the health materials. Representative publications (including audiovisual materials) are listed and briefly annotated under each organization.

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Complete Directory for People with Chronic Illness. 4rd ed Source: Lakeville, CT: Grey House Publishing, Inc. 2000. 1047 p. Contact: Available from Grey House Publishing, Inc. Pocket Knife Square, Lakeville, CT 06039. (860) 435-0868. Fax (860) 435-0867. PRICE: $165.00. ISBN: 0939300931. Summary: This directory provides a comprehensive overview of the support services and information resources available for people with any of 80 specific chronic illnesses. It presents information on various organizations, educational materials, publications, and databases. A chapter is devoted to each chronic illness and includes a brief

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description of it. The digestive diseases covered include celiac disease, Crohn's disease, gastrointestinal disorders, hepatitis, liver disease, substance abuse, and ulcerative colitis. The description of each disease is followed by subchapters that identify national and State associations and agencies, libraries, research centers, reference books, children's books, magazines, newsletters, pamphlets, videotapes and films, support groups and hotlines, and websites. In addition, the directory includes a chapter on death and bereavement, as well as a chapter on Wish Foundations for terminally and chronically ill children.

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CHAPTER 8. MULTIMEDIA ON HEPATITIS Overview In this chapter, we show you how to keep current on multimedia sources of information on hepatitis. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Video Recordings An excellent source of multimedia information on hepatitis is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “hepatitis” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “hepatitis” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on hepatitis: ·

Hepatitis C: A Viral Mystery Source: Boston, MA: Fanlight Productions. 2000. (videocassette). Contact: Available from Fanlight Productions. 4196 Washington Street, Boston, MA 02131. (800) 937-4113 or (617) 469-4999. Fax (617) 469-3379. E-mail: [email protected]. Website: www.fanlight.com. PRICE: $195.00 plus shipping and handling. Summary: Hepatitis C is a viral disease of the liver which affects nearly four million Americans. The virus is primarily spread through blood contamination. There is no vaccine and no definite cure for the infection. This documentary videotape profiles several individuals who are living with this serious, chronic illness. In addition to discussing the available medical treatments, the program explores alternative options for treatment, including dietary changes, herbal therapies, meditation, guided imagery, and Qi Gong. The program reviews the modes of transmission of hepatitis C virus (HCV), including through blood transfusions, IV drug use, unsafe sex practices or

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multiple sexual partners, and tattooing and body piercing. The program interviews Dr. Stephen Steady, a hepatologist (liver specialist) who reminds viewers that many people with HCV infections are asymptomatic, but complications can be rampant, affecting other organ systems and overall quality of life (primarily through fatigue). The program reviews the drug therapy options (interferon and ribavirin, predominantly), noting that these treatments are effective only in 40 percent of the patients with hepatitis C, yet they can cause many side effects of their own. The program concludes with a look at the need for liver transplantation for some patients with hepatitis C, the important role of hepatitis C education for prevention, and support groups for patients with the illness. ·

Hepatitis C: The Silent Scourge Source: Princeton, NJ: Films for the Humanities and Sciences. 1996. (videocassette). Contact: Available from Films for the Humanities and Sciences. P.O. Box 2053, Princeton, NJ 08543-2053. (800) 257-5126 or (609) 275-1400. Fax (609) 275-3767. E-mail: [email protected]. Website: www.films.com. PRICE: $99.00 plus shipping and handling. Order number CAF6419. Summary: Hepatitis C virus (HCV) is a disease that is transmitted primarily by contact with infected blood and that manifests few symptoms. As many as 3.5 million people in the United States are believed to carry the virus, and many are not even aware that they have been exposed; 10,000 die from it each year. This program, hosted by Drs. Miriam Alter and Harold Margolis of the Centers for Disease Control and Prevention (CDC), explains current knowledge about the newest strain of the hepatitis virus, and its causes, treatment, and prevention. The program is designed like a news report and begins with an overview of the role and functions of the liver. The program then reviews the various forms of the hepatitis virus, noting that all of them cause liver inflammation and cirrhosis and can lead to symptoms like the flu, dark urine, or jaundice (yellowing of the skin). The narrators review the ways each type is transmitted, the symptoms, the treatment and side effects, prognostic factors, the availability of immunization, and risk factors. The program goes into more depth on hepatitis C, interviewing patients and health care providers. A brief section describes the use of liver transplantation as the final option for end stage liver failure caused by hepatitis. Another section interviews Thelma King Theil, the chair of the Hepatitis Foundation International, who focuses on the activities of the organization, particularly those related to prevention.

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AIDS, Herpes, and Hepatitis: Prevention Measures for Infection Control Contact: VideoLink, Division of Media Productions, 1027 Quincy Ave, Scranton, PA, 18510, (800) 648-3858. Summary: In this videorecording, infection-control measures for the viruses which cause Acquired immunodeficiency syndrome (AIDS), herpes, and hepatitis are presented for an audience of health professionals. The symptoms of each virus, its means of transmission, and its incubation period are included. High-risk groups of potential carriers are listed. The need for constant vigilance in following infectioncontrol procedures because of the possibility of asymptomatic carriers is stressed. A variety of disinfection and sterilization procedures are shown. Procedures for pregnant employees and accidental exposures are also suggested.

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Hepatitis C: Diagnosis, Clinical Management, and Prevention Source: Cedar Grove, NJ: Hepatitis Foundation International. November 22, 1997. (videocassette, audiocassette, manual).

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Contact: Available from Hepatitis Foundation International. 30 Sunrise Terrace, Cedar Grove, NJ 07009. (800) 891-0707. PRICE: $15.00 each for videotape and reference text; $10.00 for audiocassette tape. Summary: These materials on hepatitis C are from a satellite video conference sponsored by the Hepatitis Foundation International and the Centers for Disease Control and Prevention. The packet includes a videotape of the conference itself, an audiotape of the discussions from the conference, and the accompanying reference manual. The program featured speakers on eight topics: burden and prevalence, risk factors and epidemiology, serology, chronic hepatitis C infection in children, followup laboratory tests and clinical evaluation, the natural history of hepatitis C virus infection, treatment, and counseling messages. One case study is also presented. The slides from the program are reproduced in the manual. The manual includes a section on risk assessment with examples of questions to identify patients at risk for HCV infection and to determine whether serologic testing may be indicated. Screening recommendations for HCV infection are provided in chart format. An additional section compiles some concerns expressed by patients diagnosed with hepatitis C. The manual concludes with a reprint of the 1997 National Institutes of Health Consensus Statement and an article on advising patients who seek alternative medical therapies such as chiropractic, acupuncture, homeopathy, and herbal remedies. Additional handouts to stimulate and support physician patient communication are provided, as well as a list of resources noting organizations that can provide patients with information on hepatitis. The manual is spiral bound. ·

Silent Stalker: A Video Promoting Prevention of Hepatitis and Substance Abuse Source: Cedar Grove, NJ: Hepatitis Foundation International. 2000. (videocassette). Contact: Available from Hepatitis Foundation International. 30 Sunrise Terrace, Cedar Grove, NJ 07009-1423. (800) 891-0707. E-mail: [email protected]. Website: www.hepfi.org. PRICE: $35.00 plus shipping and handling. Summary: This health promotion video describes hepatitis, a viral infection of the liver. The program begins in black and white, with spooky music, and introduces hepatitis as the Silent Stalker; various people are shown running in fear from a mysterious assailant. Then, young adult narrators stress that knowledge is power, which can be used to prevent hepatitis. The anatomy and physiology of the liver is briefly reviewed; the liver's roles as the body's chemical power plant, storage for energy supply, protein manufacturer (to build and repair muscles), and protector against germs, viruses, and poisons from alcohol and drugs. The program notes that the body usually offers pain to indicate damage or disease, however, the liver is an uncomplaining organ, so it can be under great stress or damage without symptoms. Hepatitis B and hepatitis C are reviewed, and viewers are encouraged to get the hepatitis B vaccine. The narrators then review the strategies to prevent hepatitis C, including avoiding shared injectable drug equipment (needles), making sure that body piercing or tattooing needles used are sterilized, and practicing safe sex by using a condom. The narrators stress that they are not judging peoples' activities, just providing information and encouraging viewers to make healthy decisions for themselves. The theme of 'you've got the power' (to prevent infection) is reiterated. The program concludes with the same people that were shown fleeing at the beginning; the ending is filmed in color, with upbeat music and smiling faces. Contact information for the Hepatitis Foundation International is also provided (www.hepfi.org; 800-891-0707).

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What You Really Need to Know About Hepatitis Source: [Toronto, Ontario, Canada]: Videos for Patients. 1995. (videocassette). Contact: Available from Medical Audio Visual Communications, Inc. Suite 240, 2315 Whirlpool Street, Niagara Falls, NY 14305. Or P.O. Box 84548, 2336 Bloor Street West, Toronto, Ontario M6S 1TO, Canada. (800) 757-4868 or (905) 602-1160. Fax (905) 602-8720. PRICE: $99.00 (Canadian); contact producer for current price in American dollars. Order Number VFP024. Summary: This patient education videotape provides information about hepatitis. The videotape begins with a brief sketch featuring comedian John Cleese and narrator Dr. Robert Buckman illustrating the difficulties sometimes experienced by patients during the traditional doctor's explanation. Topics include the main types of hepatitis (hepatitis A, B, and C), how hepatitis viruses are transmitted, symptoms, diagnostic considerations, what to do while an attack of hepatitis is happening, treatment options, how to reduce the risk of transmitting or contracting hepatitis, long-term liver damage caused by hepatitis, and immunization against hepatitis. Dr. Buckman presents the medical facts, using models, simple diagrams, and graphics to supplement his explanation, and avoiding medical jargon as much as possible.

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AIDS and Hepatitis-B Precautions Source: Tucson, AZ: Medfilms, Inc. Contact: Available from Medfilms, Inc. 6841 North Cassim Place, Tucson, AZ 85704. (602) 575-8900. PRICE: $190 (discounts for buying two or more). Summary: This program is intended to solve two infection control training problems: 1) employees with unreasonable fear of infection, and 2) employees who are aware of the danger of infection but who continue to take risks. It explains how AIDS and hepatitis B affect the body, how the viruses are transmitted, and the risk associated with needlestick. The program puts the risk of infection in perspective by emphasizing the safety of 'casual contact.' Four precautions for protection against infection are described. (AA-M).

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Hepatitis B: The Enemy Within Source: Princeton, NJ: Films for the Humanities and Sciences. 1996. (videocassette). Contact: Available from Films for the Humanities and Sciences. P.O. Box 2053, Princeton, NJ 08543-2053. (800) 257-5126 or (609) 275-1400. Fax (609) 275-3767. E-mail: [email protected]. Website: www.films.com. PRICE: $99.00 plus shipping and handling. Order number CAF6423. Summary: This program, featuring Dr. Harold Margolis and Dr. Frank Mahoney of the Centers for Disease Control and Prevention, explains current knowledge about hepatitis B, and its causes, treatment, and prevention. The program is designed like a news report and begins with an overview of the role and functions of the liver. The program then reviews the various forms of the hepatitis virus, noting that all forms cause liver inflammation and cirrhosis and can cause symptoms like the flu, dark urine, or jaundice (yellowing of the skin). The narrators then review how each type of hepatitis is transmitted, the symptoms, the treatment and side effects, prognostic factors, the availability of immunization, and risk factors for hepatitis A and C. The program then goes into more depth on hepatitis B, interviewing patients and health care providers. One young woman (age 26) who contracted hepatitis B at birth, describes her

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experiences with the disease and the psychosocial impact it has had on her life. The program discusses occupational risk factors, transmission, the geographic incidence and prevalence of hepatitis B, its typical course, and the problems associated with the development of chronic active hepatitis. A brief section describes the use of liver transplantation as the final option for end stage liver failure caused by hepatitis. The program then focuses on immunization programs, including those designed to vaccinate babies at birth, infants (during routine immunization), and adolescents. There is also some discussion about the difficulties of instituting successful vaccination programs for some high risk groups, including intravenous (IV) drug users and people with multiple sexual partners. ·

Hepatitis 101: Basic Tools for Teaching Liver Wellness and Hepatitis Prevention Source: Silver Spring, MD: Hepatitis Foundation International. 2002. (videorecording). Contact: Available from Hepatitis Foundation International. 504 Blick Drive, Silver Spring, MD 20904. (800) 891-0707. Fax: (301) 622-4702. E-mail: [email protected]. Website: www.hepfi.org. PRICE: $37.00; plus shipping and handling. Summary: This tutorial videotape was developed to help teachers, counselors, outreach workers, and health professionals offer effective and easy to communicate messages about liver wellness, and the prevention of viral hepatitis and substance abuse. Viral hepatitis is a disease caused by viruses that damage the liver. Serious cases can lead to life-threatening liver cirrhosis (or scarring), liver failure and eventually liver cancer. The most common forms of viral hepatitis include hepatitis A, hepatitis B and hepatitis C. This program focuses on hepatitis C and the risk factors that increase one's likelihood of contracting the disease, notably substance abuse. The program uses memorable analogies that everyone can relate to in their daily lives to motivate individuals to avoid liver damaging activities and to adopt healthier lifestyle behaviors.

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Double Jeopardy: Clinical Management of the HIV/Hepatitis C Co-Infected Patient Contact: University of Washington Center for Health Education and Research, Northwest AIDS Education and Training Center, 901 Boren Ave Ste 1100, Seattle, WA, 98104-3596, (206) 221-4964, http://depts.washington.edu/nwaetc/. Summary: This video examines the medical treatment options available to individuals with the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and hepatitis C coinfection. The video, through the experiences of a patient with both HIV and hepatitis C, outlines how HIV-positive persons are particularly susceptible to hepatitis C and explains the medical treatments available to HIV-positive individuals with hepatitis C.

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AIDS, Hepatitis and the Emergency Responder: Update Contact: Commonwealth Films, 223 Commonwealth Ave, Boston, MA, 02116, (617) 2625634. Summary: This video focuses on the risks of exposure to bloodborne pathogens, especially HIV and Hepatitis B, that emergency responders face. Starting with scenes of a city night and a drive-by shooting, the video urges the use of universal precautions and other measures to prevent the transmission of HIV and hepatitis for personnel involved in emergency situations. Following a discussion on HIV transmission and high-risk behaviors, the video discusses hepatitis, especially Hepatitis B. Modes of transmission are outlined, and OSHA standards, vaccination information, and universal

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precautions are explained. The video concludes with a short discussion on medical waste and the best ways to dispose of used sharps and needles. ·

Hepatitis: A Silent Killer Source: Cedar Grove, NJ: Hepatitis Foundation International. 1994. (videocassette). Contact: Available from Hepatitis Foundation International. 30 Sunrise Terrace, Cedar Grove, NJ 07009. (800) 891-0707 or (201) 239-1035. Fax (201) 857-5044. PRICE: $24.95 plus shipping and handling. Summary: This video presents a health update on viral hepatitis. After an introduction that reviews the anatomy and physiology of the liver, various health care providers describe how all types of hepatitis affect the liver. The program continues with a discussion of the 5 types of hepatitis (A, B, C, D, and E) and how each is transmitted and treated. The program covers incidence, epidemiology, details of transmission, symptoms, diagnosis, risk factors and behaviors, complications of hepatitis infection, treatment options (including liver transplantation), and vaccination. The program includes an interview with Thelma King Thiel, the founder and CEO of the Hepatitis Foundation International, as well as interviews with two young people who have chronic hepatitis infections.

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Management of the HIV/Hepatitis C Co-Infected Patient Contact: Albany Medical Center, Division of HIV Medicine, 66 Hackett Blvd, Albany, NY, 12209-1750, (518) 262-4439, http://www.amc.edu/Patient/HIV/hiv.htm. Summary: This video presents information about the medical treatment of hepatitis C in incarcerated individuals co-infected with the human immunodeficiency syndrome (HIV)/acquired immune deficiency syndrome (AIDS). The video covers the epidemiology of hepatitis C among HIV-positive incarcerated individuals and why this population is at risk for this opportunistic infection (OI). It also reviews the diagnosis and treatment of hepatitis C.

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AIDS and Hepatitis - B Precautions Contact: Medfilms, Incorporated, 6841 N Cassim Pl, Tucson, AZ, 85704, (520) 575-8900. Summary: This videorecording addresses two infection-control training problems: Professional employees who know better, but still take risks; and employees with an unreasonable fear of infection. The videorecording puts the risk of infection in perspective. It eliminates unreasonable fear and teaches the importance of proper precautions. From it, the viewer will learn: How Acquired immunodeficiency syndrome (AIDS) and Hepatitis B affect the body, how the viruses are transmitted, the risk associated with needle sticks, the absence of risk from casual contact, and the four protocols recommended by the Centers for Disease Control and Prevention (CDC) for protection against infection. (Producer's abstract).

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AIDS and Hepatitis B: What's Your Risk? Contact: Gulf Publishing Company, PO Box 2608, Houston, TX, 77252-2608, (713) 5294301. Summary: This videorecording discusses the guidelines necessary for all categories of health care workers to minimize their risk of exposure to Acquired immunodeficiency syndrome (AIDS) and Hepatitis B. The Human immunodeficiency virus (HIV) and the

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Hepatitis B virus are defined, and the routes of transmission discussed. The OSHAdefined risk categories based on level of contact to blood and body fluids are explained. The universal blood and body fluids guidelines are discussed. The importance of protective clothing and proper disposal, in relation to all employees in a health care setting, is emphasized. ·

Universal Precautions: AIDS and Hepatitis B Prevention for the Medical Office Contact: Medcom Incorporated, PO Box 6003, Cypress, CA, (800) 541-0253. Summary: This videorecording focuses on prevention of exposure to HIV and Hepatitis B virus (HBV). What HIV and HBV are, and how they can be transmitted in an occupational setting, are discussed. Symptoms are described. The videorecording discusses the Occupational Safety and Health (OSHA) regulations on infectious bloodborne diseases and the universal precautions that have been established for healthcare workers to prevent occupational exposure. Safe work practices are illustrated, including the use of barrier methods of protection, and needle and sharps disposal. Standard equipment care, disinfection techniques, and biohazard waste disposal are explained.

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From mother to child: A cycle of tragedy: A video and users guide for health care workers on hepatitis B virus infection designed for self-study or groups Source: Atlanta, GA: Centers for Disease Control and Prevention, U.S. Department of Health and Human Services. 1993. 52 pp., 1 videotape (23 minutes, VHS 1/2 inch). Contact: Available from Centers for Disease Control and Prevention, 1600 Clifton Road, N.E., Atlanta, GA 30333. Telephone: (404) 639-3535 / e- mail: [email protected] / Web site: http://www.cdc.gov. Summary: This videotape and users' guide were designed for a broad range of health care workers. The video discusses Hepatitis B virus (HBV) infection, includes recommendations on prenatal screening and immunizations for infants, and stresses the importance that the health care workers protect themselves by taking the HBV vaccine. The users' guide supports and reinforces the message of the videotape with additional information. The users' guide describes the learning objectives, provides instructions for trainers or individual users, provides descriptions of the disease, its epidemiology, prevention, clinical features, recommendations on perinatal screening and treatment, handouts, suggested questions for use in training sessions, test questions and answers, and a resource list.

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Hepatitis A, B, C, D and E Source: Atlanta, GA: Emory University School of Medicine. 1990. Contact: Available from Emory University School of Medicine. Lynne Wise, Department of Medical Education, 69 Butler Street, SE, Atlanta, GA 30303. (404) 616-3556. PRICE: $100 plus $5 shipping and handling. (RENTAL $45 for 2 weeks). Order Number 90-01. Summary: This videotape covers all of the known types of viral hepatitis, but concentrates on Hepatitis B. The tape opens with a discussion of the mechanisms of injury to the liver and continues with a detailed look at the prevalence of hepatitis B (200,000 cases per year in the U.S.) and the various known risk factors. Extensive coverage is given to the serologic findings in both acute and chronic disease. Finally, the author outlines the current treatment with interferon and the use of vaccines. (AA).

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Your baby: Protecting your baby against hepatitis B Source: Atlanta, GA: Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, U.S. Department of Health and Human Services. 1993. 1 videotape (19 minutes, VHS 1/2 inch). Contact: Available from Hepatitis Branch, National Center for Infectious Diseases, Division of Viral and Rickettsial Diseases, Atlanta, GA 30333. Telephone: (404) 332-4555 hepatitis hotline. Summary: This videotape for pregnant women discusses how people get hepatitis B, adult symptoms, carriers, the importance of testing mothers before birth so babies can get treatment at birth and early in life, and the importance of adults getting immunizations to prevent liver cancer. Different vignettes in the video show a baby dying, a young man getting liver cancer, a young woman getting hepatitis B from a sexual encounter, and parents making sure their infant gets all three shots for protection against hepatitis B.

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Hepatitis C: Unknown Epidemic Source: Princeton, NJ: Films for the Humanities and Sciences. 1998. (videocassette). Contact: Available from Films for the Humanities and Sciences. P.O. Box 2053, Princeton, NJ 08543-2053. (800) 257-5126 or (609) 275-1400. Fax (609) 275-3767. E-mail: [email protected]. Website: www.films.com. PRICE: $99.00 to purchase; $75.00 for rental; plus shipping and handling. Order number BVL9342. Summary: This videotape offers a segment of ABC's Nightline program that explores the epidemic of hepatitis C virus (HCV) infection in the United States. In this program, ABC News anchor Forrest Sawyer investigates the virus with Dr. Miriam Alter, epidemiologist at the Centers for Disease Control and Prevention; Dr. Jerome Groopman, professor at Harvard Medical School; and Andi Thomas, founder of the advocacy group Hep-C ALERT. Together they examine topics including risk factors associated with the disease, improvements in blood screening, the results of targeted looks back at past blood recipients, and the need for additional funding to increase research. Hepatitis C is characterized as a definite health epidemic: 15 percent of the people who get infected successfully fight it off; in 80 percent of those infected, the disease becomes chronic; and in 5 percent of those infected, HCV results in liver cirrhosis (scar tissue), which can then lead to cancer and death. It is virtually impossible to predict who will be in which category. The disease is spread predominantly through needle sharing, sexual contact, and blood transfusions occurring prior to the 1990's. The disease has been called the silent epidemic because it was only identified 10 years ago and the infection remains symptomless for decades. The three panelists interviewed share their information and differences of opinions on the wisdom of getting tested for HCV, the magnitude of the public health problem of the disease, the need for targeted look back for people who received blood transfusions, and the emotions of dealing with the disease.

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Hepatitis B: Patient information Source: Cedar Grove, NJ: American Liver Foundation. n.d. 1 videotape (10 minutes, 1/2 inch VHS). Contact: Available from American Liver Foundation, 2021 A Pontius Avenue, Los Angeles, CA 90025. Telephone: (310) 477-4615 / fax: (310) 478- 4685 / e-mail: [email protected] / Web site: www.liver411.com.

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Summary: This videotape portrays a physician talking with a young Asian woman about liver cancer and its primary cause, hepatitis B: how hepatitis B spread, symptoms and the usual course of liver cancer, the body's ability to fight hepatitis B, carriers, effectiveness and safety of vaccinations, and populations at higher risk of contracting hepatitis B. ·

Hepatitis B: A Family's Story. Our Family, Our Strength Source: St. Paul, MN: Hepatitis B Coalition. 1995. (videorecording). Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Fax (612) 647-9131. PRICE: $10.00. Summary: This videotape program educates viewers about hepatitis B and its potential impact. The first part of the program, presented in the Cambodian language, features a narrator who introduces Dr. Hie-Won Hann, a physician helping Asian families fighting hepatitis B. The program shows Dr. Hann interviewing a pregnant Cambodian woman; a second scenario features Dr. Hann and the woman's family, who have all come in to learn more about hepatitis B. Topics covered include the complications of hepatitis B (acute disease, liver cancer), chronic infection with hepatitis B, how to protect a baby from getting hepatitis B, testing family members, protecting uninfected family members, treating the chronic carrier, how the disease is transmitted (perinatal, sexual transmission, and close familial contact, i.e., sharing toothbrushes, razors, etc.), why the disease is common among Asian people, and the importance of achieving widespread vaccination. The videorecording comes with an English and a Cambodian copy of the script. The second part of the tape, presented in English, features Dr. Haing S. Ngor introducing the history of Indo-Chinese people in the U.S. and stressing the important place that family serves in these cultures. The remainder of the tape is the same as the Cambodian language part, but in English.

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Hidden Epidemic: Unraveling the Mysteries of Hepatitis C Source: Silver Spring, MD: Hepatitis Foundation International. 2002. (videorecording). Contact: Available from Hepatitis Foundation International. 504 Blick Drive, Silver Spring, MD 20904. (800) 891-0707. Fax: (301) 622-4702. E-mail: [email protected]. Website: www.hepfi.org. PRICE: $45.00; plus shipping and handling. Summary: This videotape program provides an overview of hepatitis A, hepatitis B, and hepatitis C, with an emphasis on the latter. The program includes interviews with liver specialists, hepatitis patients, and patient advocated. The program includes basic information on the physiology of the liver, cirrhosis (scarring of the liver), treatment options, transplantation, and coping skills (managing a chronic disease). The video is designed to education patients, family members, and the general public about viral hepatitis.

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Kev Koom Siab. [Immunization and Hepatitis B] Source: St. Paul, MN: Hepatitis B Coalition. 1992. (videorecording). Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Fax (612) 647-9131. PRICE: $10.00. Summary: This videotape program shows a television health care show on immunization, including that for hepatitis B. Presented in the Hmong language, with English subtitles, the program incorporates historical and present-day footage of

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Hmong people at work and at play, during war and during peacetime. The cultural values of the Hmong are introduced during this photo montage; these include not fighting or arguing, remaining united, and sharing knowledge. The show then runs a clip showing vaccination schedules and recommendations for infants and children, from birth through age 15 years. Vaccines for hepatitis B, DTP, Hib, MMR, and polio are discussed. Each disease is also briefly reviewed, including its symptoms and potential complications. After the clip, the narrator interviews two health care workers who elaborate on the information just provided. Topics include the importance of recordkeeping, how vaccination is different than medication prescribed to treat a present illness, the need for hepatitis B vaccination for older children and adults, the differences between hepatitis A and hepatitis B, perinatal transmission of hepatitis B, and the blood test used to diagnose hepatitis B. Other vaccines and illnesses are also discussed, including the side effects to expect from each vaccine. ·

Benh Viem Gan B va Gia Dinh Bac Tam. [Hepatitis B and Uncle Tam's Family] Source: St. Paul, MN: Hepatitis B Coalition. 1995. (videorecording). Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Fax (612) 647-9131. PRICE: $10.00. Summary: This videotape program, presented in Vietnamese, stresses to viewers the importance of vaccination against hepatitis B virus, which can cause chronic liver disease and liver cancer. The program features a young Vietnamese couple who have just learned that they are going to have a son, and that the pregnant woman is a hepatitis B carrier. The program features the cultural tradition of children as the future and emphasizes that all babies should be immunized against hepatitis B. Other topics covered include the protocol for immunization, the schedule for vaccination, preventing hepatitis B (the film depicts a brother and sister sharing a toothbrush, which is one method of virus transmission), young adults and hepatitis B, the use of condoms to prevent hepatitis B transmission, the recommended health monitoring for people who are hepatitis B carriers, the incidence of hepatitis B in the Vietnamese American population, diagnostic tests used to determine carrier status, immunizing older children, and the complications of hepatitis B infection. Various scenarios depict the family life and social settings of a typical Vietnamese American family. An English language transcript of the video is provided.

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Hepatitis B: The hidden danger Source: Philadelphia, PA: SmithKline Beecham Pharmaceuticals. 1993. 1 videotape (14 minutes, VHS). Contact: Available from SmithKline Beecham Pharmaceuticals, One Franklin Plaza, 200 North 16th Street, Philadelphia, PA 19101. Telephone: (215) 751-4000. Available at no charge. Summary: This videotape, intended for public safety workers, presents scenarios in which hepatitis B can be transmitted. These scenarios are followed by discussions with people who actually contracted the disease. Another version of the tape for health care workers is also available.

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Viral Hepatitis and Blood Borne Pathogens: The Invisible Threat Source: Silver Spring, MD: Hepatitis Foundation International. 2002. (videorecording).

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Contact: Available from Hepatitis Foundation International. 504 Blick Drive, Silver Spring, MD 20904. (800) 891-0707. Fax: (301) 622-4702. E-mail: [email protected]. Website: www.hepfi.org. PRICE: $45.00; plus shipping and handling. Summary: Viral hepatitis is a disease caused by viruses that damage the liver. Serious cases can lead to life-threatening liver cirrhosis (or scarring), liver failure and eventually liver cancer. The most common forms of viral hepatitis include hepatitis A, hepatitis B and hepatitis C. This program focuses on hepatitis B and C and the risk factors that increase one's likelihood of contracting the disease, notably substance abuse. The video is designed for an adult audience. Topics include prevention of hepatitis B and C, AIDS, substance abuse, cirrhosis, and transmission of hepatitis. ·

Update on Management of Hepatitis C Source: Kansas City, MO: American Academy of Family Physicians. 2000. (videocassette). Contact: Available from American Academy of Family Physicians. 8880 Ward Parkway, Kansas City, MO 64114-2797. (800) 274-2237. PRICE: $17.95 for members; $25.00 for nonmembers, plus shipping and handling. Summary: Viral hepatitis remains the most common cause of liver disease worldwide and infection with the hepatitis C virus (HCV) has become a serious health problem in the United States. This continuing education program assists family physicians in this new challenge of the identification and diagnosis of patients at greatest risk of HCV infection. While there is, as yet, no known cure for HCV, early medical intervention and lifestyle changes can significantly improve the prognosis. Infection with HCV can lead to chronic hepatitis, cirrhosis (liver scarring), and hepatocellular carcinoma (HCC, liver cancer). Unlike hepatitis A and B, there is no vaccination available to prevent hepatitis C, nor are there any preexposure or postexposure prophylaxis (prevention) options. This program reviews the epidemiology of HCV, identification of patients at risk, diagnosis, HCV related liver disease, and management approaches, including interferon monotherapy, combination therapy, side effects, contraindications, and ongoing medical monitoring. The program includes a video tape and a study guide; the latter includes references and a patient education handout, as well as a posttest with which viewers can qualify for continuing education credit. 6 figures. 13 tables. 31 references.

Audio Recordings The Combined Health Information Database contains abstracts on audio productions. To search CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find audio productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Sound Recordings.” Type “hepatitis” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on hepatitis: ·

Plenary Session: Vaccine Development and Testing: Global View - Hepatitis and AIDS Source: 3rd National Forum on AIDS and Hepatitis B. Washington, DC, November 2122, 1988.

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Contact: National Foundation for Infectious Diseases, 4733 Bethesda Ave Ste 750, Bethesda, MD, 20814-5228, (301) 656-0003, http://www.nfid.org. Sound Solution, PO Box 566074, Dallas, TX, 75356, (214) 258-6144. Summary: This sound recording contains proceedings of the 3rd National Forum on AIDS and Hepatitis B held in Washington, DC on November 21-22, 1988. It discusses the history of the Hepatitis B vaccine and relates it to the ongoing efforts to develop a vaccine for the Human immunodeficiency virus (HIV). What retroviruses are, how the antigenic response occurs, and how the Hepatitis B surface antigen was discovered are recounted. The difficulty surrounding effective vaccine development for Acquired immunodeficiency syndrome (AIDS)is emphasized. The cost-effectiveness of vaccines and their applications to improving the quality of human life are explored.

Bibliography: Multimedia on Hepatitis The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in hepatitis (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on hepatitis: ·

AIDS & hepatitis-B precautions [videorecording] Source: by Elizabeth A. Criss; produced by Medfilms Inc; Year: 1988; Format: Videorecording; Tucson, Ariz.: Medfilms, c1988

·

AIDS and hepatitis [sound recording]: the facts Source: by Susan Kellerhals; Year: 1987; Format: Sound recording; Broomfield, CO: Contemporary Learning, p1987

·

AIDS and hepatitis B precautions [videorecording] Source: by Elizabeth A. Criss; produced by Medfilms, Inc; Year: 1986; Format: Videorecording; Tucson, AZ: Medfilms, c1986

·

Alcoholic hepatitis [videorecording] Source: Dept. of Medicine, Emory University, School of Medicine; Year: 1978; Format: Videorecording; Atlanta: Georgia Regional Medical Television Network: [for loan or sale by A. W. Calhoun Medical Library], 1978

·

Aseptic procedures for dental treatment of hepatitis B patients [videorecording] Source: produced by the College of Allied Health Sciences, the Office of Educational Services and the Division of Continuing Education, Medical University of South Carolina; Year: 1985; Format: Videorecording; Carrboro, NC: Health Sciences Consortium, c1984, 1985

·

Current aspects of type B hepatitis [slide] Source: Laboratory Training and Consultation Division, Bureau of Laboratories, Center for Disease Control; Year: 1977; Format: Slide; [Atlanta]: The Center; [Buffalo, N.Y.: for sale by Communications in Learning, 1977]

·

Detection of hepatitis associated antigen [slide]: HAA (Australia antigen Source: Minneapolis War Memorial Blood Bank, inc.; [made by] Telstar Productions, inc; Year: 1972; Format: Slide; Minneapolis, Minn.: Minneapolis War Memorial Blood Bank; [St. Paul, Minn.: for sale by Telstar Productions] c1972

·

Developing an immunization program for hepatitis B virus [videorecording] Source: [presented by] the American Hospital Association; produced through the facilities of the

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Media Center; Year: 1982; Format: Videorecording; [Chicago, Ill.]: The Association, c1982 ·

Drug-induced hepatitis [videorecording] Source: Dept. of Medicine, Emory University, School of Medicine; Year: 1979; Format: Videorecording; Atlanta: Emory Medical Television Network: [for loan or sale by A. W. Calhoun Medical Library], 1979

·

Family fight [videorecording]: hepatitis Source: produced by Epidemiology and Audiovisual Services; Year: 1984; Format: Videorecording; Muncie, Ind.: Ball Memorial Hospital, c1984

·

Hepatitis: diagnosis and differentiation by liver biopsy [slide] Source: Don Paul Jones, John Belamaric; Year: 1976; Format: Slide; New York: Medcom, c1976

·

Hepatitis [videorecording] Source: Dept. of Medicine, Emory University, School of Medicine; Year: 1979; Format: Videorecording; Atlanta: Emory Medical Television Network: [for loan and sale by A. W. Calhoun Medical Library], 1979

·

Hepatitis A, B, & C [videorecording]: viruses and their detection Source: presented by Department of Medicine, Emory University, School of Medicine; Year: 1980; Format: Videorecording; Atlanta: Emory Medical Television Network, 1980

·

Hepatitis B & I.V. drug abuse [slide] Source: P.D. Welsby; Year: 1984; Format: Slide; Chelmsford, Essex, UK: Graves Medical Audiovisual Library, [1984]

·

Hepatitis B vaccine [videorecording] Source: presented by Department of Medicine, Emory University, School of Medicine; Year: 1982; Format: Videorecording; Atlanta, Ga.: Emory Medical Television Network, 1982

·

Hepatitis B vaccine [videorecording] Source: Marshfield Medical Foundation, in cooperation with Marshfield Clinic & St. Joseph's Hospital; Year: 1983; Format: Videorecording; Marshfield, WI: Marshfield Regional Video Network, 1983

·

Isolation cleaning for hepatitis and lice [slide] Source: Communications in Learning, inc; Year: 1978; Format: Slide; [Buffalo]: Communications in Learning, [1978]

·

Management of viral hepatitis [slide] Source: University of Michigan, Medical Center, Independent Study Unit, Department of Postgraduate Medicine and Health Professions Education; Year: 1974; Format: Slide; Ann Arbor: The University: [for loan or sale by its Medical Center Media Library], c1974

·

Morphology of acute viral hepatitis [videorecording] Source: American Society of Clinical Pathologists; Year: 1976; Format: Videorecording; Chicago: The Society, c1975

·

Mouse hepatitis virus [videorecording] Source: Learning Resources and Communications, Television Division, J. Hillis Miller Health Center, University of Florida; Year: 1983; Format: Videorecording; Gainesville, Fla.: The Division, [1983]

·

Viral hepatitis: epidemiology, prevention, control [videorecording] Source: Brooke Army Medical Center; Year: 1970; Format: Videorecording; Fort Sam Houston, Tex.: Academy of Health Sciences, 1970

·

Viral hepatitis [motion picture] Source: [presented by] the United States Army; Year: 1952; Format: Motion picture; United States: War Office, 1952

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Viral hepatitis [slide] Source: Inge Gurevich, Burke A. Cunha; Year: 1985; Format: Slide; Garden Grove, Calif.: Medcom, c1985

·

Viral hepatitis [videorecording]: etiology, diagnosis, treatment Source: Brooke Army Medical Center; Year: 1970; Format: Videorecording; Fort Sam Houston, Tex.: Academy of Health Sciences, 1970

·

Viral hepatitis [videorecording]: recent developments and prospects for prevention Source: Emory Univ. School of Medicine; Year: 1975; Format: Videorecording; Atlanta:

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Georgia Regional Medical Television Network: [for loan and sale by A. W. Calhoun Medical Library], 1975 ·

Viral hepatitis update [videorecording] Source: [presented by] Audio-Video Digest Foundation; a Shotwell Image Group Production; Year: 1983; Format: Videorecording; Glendale, Calif.: The Foundation, c1983

·

Viral hepatitis, differential diagnosis [videorecording] Source: produced by Paradox Films, Inc.; presented by Hepatitis Information Center, Abbott Laboratories, Diagnostics Division; Year: 1981; Format: Videorecording; North Chicago, IL: The Laboratories, c1981

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CHAPTER 9. PERIODICALS AND NEWS ON HEPATITIS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover hepatitis.

News Services and Press Releases One of the simplest ways of tracking press releases on hepatitis is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing.

PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “hepatitis” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance.

Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to hepatitis. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “hepatitis” (or synonyms). The following was recently listed in this archive for hepatitis: ·

Roche's Pegasys shown advantageous for treatment of hepatitis B Source: Reuters Medical News Date: October 28, 2003

·

Roche scores again with Pegasys data in hepatitis B Source: Reuters Industry Breifing Date: October 28, 2003

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·

Shorter interferon/ribavirin course effective for chronic hepatitis C types 2 and 3 Source: Reuters Industry Breifing Date: October 27, 2003

·

Roche's Pegasys helps untreated hepatitis C Source: Reuters Industry Breifing Date: October 27, 2003

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New drug hope for millions of hepatitis C victims Source: Reuters Health eLine Date: October 27, 2003

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Hepatitis C protease inhibitor reduces viral load Source: Reuters Medical News Date: October 27, 2003

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Acute hepatitis linked to nevirapine treatment of HIV Source: Reuters Medical News Date: October 22, 2003

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Pregnancy can be good for women with hepatitis C Source: Reuters Health eLine Date: October 16, 2003

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Hepatitis A may protect some against allergy Source: Reuters Health eLine Date: October 08, 2003

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Hepatitis A exposure plus receptor genotype may protect against atopy Source: Reuters Medical News Date: October 08, 2003

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Large, healthcare-related hepatitis outbreaks traced to unsafe injection practices Source: Reuters Medical News Date: September 25, 2003

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Schering-Plough to do head-to-head hepatitis test Source: Reuters Industry Breifing Date: September 23, 2003

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Hepatitis threatens to wipe out two Amazon tribes Source: Reuters Health eLine Date: September 23, 2003

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Hepatitis A hits jam band followers Source: Reuters Health eLine Date: September 04, 2003

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Assay detects hepatitis C antibody in oral fluids, dried blood spots Source: Reuters Medical News Date: September 01, 2003

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Britain says it will pay recipients of hepatitis C-contaminated blood Source: Reuters Medical News Date: August 29, 2003

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Britain says it will pay hepatitis C victims Source: Reuters Health eLine Date: August 29, 2003

Periodicals and News

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Wane of hepatitis C drugs wound Schering-Plough Source: Reuters Industry Breifing Date: August 25, 2003

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Vaccination and HIV antiretroviral therapy lower hepatitis B infection rates Source: Reuters Medical News Date: August 22, 2003

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Prenylation inhibitors impair hepatitis delta virus assembly Source: Reuters Industry Breifing Date: August 13, 2003

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Antiviral efficacy of adefovir dipivoxil similar regardless of hepatitis B genotype Source: Reuters Industry Breifing Date: August 08, 2003

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UK company seeks partner to market novel hepatitis C test in Europe Source: Reuters Industry Breifing Date: August 06, 2003

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Hepatitis B virus reactivation common during breast cancer chemotherapy Source: Reuters Medical News Date: August 04, 2003

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Japanese deer meat can transmit hepatitis E virus Source: Reuters Medical News Date: August 01, 2003

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Hepatitis C coinfection hampers benefits of HAART in HIV patients Source: Reuters Medical News Date: July 30, 2003

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Alcohol ups hepatitis C virus replication Source: Reuters Health eLine Date: July 22, 2003

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Alcohol enhances hepatitis C virus replicon expression Source: Reuters Medical News Date: July 22, 2003

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EU approves label change for Pegasys/Copegus used to treat hepatitis C Source: Reuters Medical News Date: July 18, 2003

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Ribapharm loses hepatitis C drug ruling, stock falls. Source: Reuters Industry Breifing Date: July 16, 2003

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Aromatic cations inhibit bovine virus, proxy for hepatitis C Source: Reuters Industry Breifing Date: July 10, 2003

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Report questions early treatment of hepatitis C Source: Reuters Health eLine Date: July 08, 2003

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Sniffing, snorting drugs may raise hepatitis C risk Source: Reuters Health eLine Date: July 04, 2003

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Innogenetics gets positive hepatitis trial results Source: Reuters Industry Breifing Date: July 03, 2003

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Hepatitis C infects about 500,000 people in Germany Source: Reuters Industry Breifing Date: June 25, 2003

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Gilead returns rights to hepatitis B drug Source: Reuters Industry Breifing Date: June 24, 2003

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Hepatitis A case evades U.S. investigators Source: Reuters Medical News Date: June 19, 2003

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Tattoos source of hepatitis without symptoms: study Source: Reuters Health eLine Date: June 02, 2003

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Hepatitis C acquired through tattooing often asymptomatic Source: Reuters Medical News Date: June 02, 2003

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Isis begins phase II trial of hepatitis C drug in combination with standard therapy Source: Reuters Industry Breifing Date: May 29, 2003

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Genetic variability of hepatitis C virus may influence treatment outcome Source: Reuters Medical News Date: May 26, 2003

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Roche inks $230 million hepatitis deal with Maxygen Source: Reuters Industry Breifing Date: May 22, 2003

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Combination regimen helps quell refractory hepatitis C Source: Reuters Medical News Date: May 14, 2003

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Enzon, NPS shares fall on sluggish hepatitis C drug sales Source: Reuters Industry Breifing Date: May 13, 2003

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Gene therapy may hold key to treating hepatitis B Source: Reuters Health eLine Date: May 12, 2003

The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine.

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Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name.

Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “hepatitis” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests.

Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “hepatitis” (or synonyms). If you know the name of a company that is relevant to hepatitis, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.

BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “hepatitis” (or synonyms).

Newsletters on Hepatitis Find newsletters on hepatitis using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go to the following hyperlink: http://chid.nih.gov/detail/detail.html. Limit your search to “Newsletter” and “hepatitis.” Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter.” Type “hepatitis” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: ·

Needle tips and Hepatitis B Coalition news Source: Saint Paul, MN: Hepatitis B Coalition, and Immunization Action Coalition. 1993. semiannual.

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Contact: Available from Immunization Action Coalition, 1573 Selby Avenue, Suite 234, Saint Paul, MN 55104. Telephone: (651) 647-9009 / fax: (651) 647-9131 / e-mail: [email protected], [email protected] / Web site: http://www.immunize.org. Summary: This newsletter is addressed to the health professional. It includes a variety of material about immunization against communicable diseases, with special emphasis on hepatitis B. The newsletter includes a catalog of publications, videos, and resources, many available in Spanish, Hmong, Cambodian, Laotian, Vietnamese, Tagalog, Russian, Chinese, or Korean, and designed for use with populations of foreign origin.

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “hepatitis” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on hepatitis: ·

Hepatitis B in Asia Source: Asian Pacific Gastroenterology News. Issue 4: 12-13. June 2000. Contact: Available from Blackwell Science Asia. 54 University Street, Carlton, Victoria 3053, Australia. 61 3 9347 0300. Fax 61 3 9347 5001. E-mail: [email protected]. Summary: Five to 20 percent of the population of Asia and Africa are chronically infected with hepatitis B virus (HBV). This article reviews the main issues related to hepatitis B in Asia, including the evaluation and treatment of infected but asymptomatic subjects, the so-called HBV carriers; the continued horizontal spread of HBV infection, emergence of HBV mutants, and implementation of vaccination programs. The author contends that the term 'carrier' should therefore be deleted from the terminology of hepatitis B and should be replaced by 'chronic hepatitis B virus infection.' Evaluation of a subject with chronic HBV infection should include a reliable ALT (repeated three times), an HbeAg test, and if needed, an HBV DNA ultrasound and liver biopsy. The prevalence of HBV and hepatitis C (HCV) in chronic liver disease has been reported to be approximately 15 percent in the Asian region. In several countries in Asia, vaccination against HBV has been successfully included in the EPI program. This has led to a substantial reduction in the chronic HBV infection in the pediatric population. 1 table. 6 references.

·

Here's the Score!: Hepatitis B Vaccine is Safe and Effective Source: Needle Tips and the Hepatitis B Coalition News. 9(1): 6. Spring-Summer 1999. Contact: Available from Immunization Action Coalition. Hepatitis B Coalition. 1573 Selby Avenue, Suite 234, St. Paul, MN 55104. (651-) 647-9009. Fax (651) 647-9131. Website: www.immunize.org. Summary: Hepatitis B vaccines provide protection against serious and life threatening liver diseases, including cancer of the liver. This article reviews the safety and efficacy of

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hepatitis B vaccine. The author notes that recent news items have questioned the safety of hepatitis B vaccines and suggested associations between the vaccine and multiple sclerosis (MS) and other autoimmune disorders. The author emphasizes that these news reports have not included the results of expert panels who have carefully reviewed the data and found no scientific evidence of a causal relationship between hepatitis B vaccine and MS and other disorders. The author describes this review process and refers readers to numerous vaccine safety resources (telephone numbers and websites). The author stresses that parents should not be misled by the occasional inflammatory reports in the press. Hepatitis B vaccines are very safe and effective and should continue to be given to all children as part of their routine vaccination schedule. ·

Be As Sure As You Can Be!: Give Babies Hepatitis B Vaccine at Birth Source: Needle Tips and the Hepatitis B Coalition News. 10(1): 3. Spring-Summer 2000. Contact: Available from Hepatitis B Coalition. Immunization Action Coalition, 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Fax (612) 647-9131. E-mail: [email protected]. Website: www.winternet.com. Summary: In the past year, the successful strategy of initiating hepatitis B immunization at birth has been interrupted by concerns regarding thimerosal, the commonly used vaccine preservative. This article briefly reviews the concerns with thimerosal, then notes that vaccine manufacturers now have sufficient supplies of preservative free hepatitis B vaccine to meet the vaccination needs of all children in the United States. Advisory groups have recommended that routine newborn vaccination policies be reintroduced in hospitals where they were discontinued. In addition, both advisory groups (the Centers for Disease Control and Prevention, or CDC, and the American Academy of Pediatrics, AAP) have emphasized that hepatitis B vaccination should not be delayed for infants born to HBsAg negative mothers as was recommended by the AAP in July 1999. The article lists and discusses five reasons that infant vaccine is critical: prevention of perinatal hepatitis B virus (HBV) infection; hepatitis B vaccination at birth provides a safety net; infants and children are exposed to HBV even though their mothers are HBsAg negative; infant immunization is part of the nation's strategy to eliminate HBV transmission; and the birth dose of hepatitis B vaccine increases completion of the three dose series and other childhood vaccines. 1 reference.

·

Research Agenda for Viral Hepatitis (editorial) Source: Liver Update. 9(2): 1-2. Fall 1995. Contact: Available from American Liver Foundation. 1425 Pompton Avenue, Cedar Grove, NJ 07009. (800) 233-0179 or (201) 857-2626 or (201) 256-2550. Summary: In this editorial, the authors call for an escalated research agenda for viral hepatitis. They stress that research efforts should be directed toward understanding the natural history of disease, defining the pathogenetic mechanisms of these viral infections, and developing effective preventive and therapeutic means to control the infections. They discuss the hepatitis B virus, the hepatitis C virus, other hepatotropic viruses, prevention with vaccination, and treatment options, including liver transplantation.

·

Labor and Delivery and Nursery Unit Guidelines to Prevent Hepatitis B Virus Transmission Source: Needle Tips and the Hepatitis B Coalition News. 12(1): 17. Summer 2002.

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Contact: Available from Hepatitis B Coalition. Immunization Action Coalition, 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Fax (612) 647-9131. E-mail: [email protected]. Website: www.winternet.com. Summary: These guidelines can be used to help a hospital establish standing orders for preventing perinatal hepatitis B virus (HBV) transmission in the labor and delivery and nursery units. The guidelines stress that procedures must already be in place to review the hepatitis B surface antigen (HBsAg) test results of all pregnant women at the time of hospital admission and to give immunoprophylaxis within 12 hours after birth to infants of HBsAg-positive mothers and infants of mothers who do not have documentation of HBsAg test results in their charts. Administration of hepatitis B (HepB) vaccine at birth to all infants is recommended by CDC's Advisory Committee on Immunization Practices, the American Academy of Pediatrics, the American Academy of Family Physicians, and the American College of Obstetricians and Gynecologists. ·

Assault on Your Liver: Inside the ABCs (and DEFGs) of Viral Hepatitis Source: Mayo Clinic Women's Healthsource. 3(7): 4, 5. July 1999. Contact: Available from Mayo Foundation for Medical Education and Research. 200 First Street SW, Rochester, MN 55905. Summary: This health newsletter article describes the different strains of viral hepatitis and their impact on the liver. The liver is a noncomplaining organ, which functions to filter out harmful chemicals, fight infection, and convert energy for the body's use. When hepatitis hits, however, illnesses can range from mild to potentially life threatening. The author describes how to tell the difference between each type of hepatitis, whether risk factors are present or not, and what happens after infection. Blood tests are used to diagnose hepatitis. Some tests detect specific antibodies the body produces in response to infection with a particular hepatitis virus; others measure how well the liver is functioning; others actually test for the virus itself. The author lists the epidemiology and incubation of each type (hepatitis A through E), then reminds readers of the transmission of each type. Treatment, vaccination options, risk factors, and preventive measures are then noted. Hepatitis A is spread through the fecal oral route (not washing hands properly after contact with infected feces), ingestion of contaminated food and water, or close personal contact with an infected person (anal or oral). Hepatitis B is transmitted through contact with body fluids containing HBV, sexual contact, or sharing contaminated needles. Hepatitis E is associated with contaminated water. Vaccinations are available for hepatitis A, B, and D (hepatitis B vaccine prevents hepatitis D infection); no vaccine is available for hepatitis C or E. One sidebar reviews strategies for optimum liver care, with or without the presence of hepatitis.

·

Viral Hepatitis: A Decade of Discovery and Progress in Prevention Source: Mayo Clinic Health Letter. 13(8): 4-5. August 1995. Contact: Available from Mayo Clinic Health Letter. Subscription Services, P.O. Box 53889, Boulder, CO 80322-3889. (800) 333-9037. Summary: This newsletter article familiarizes readers with recent advances in the prevention and treatment of viral hepatitis. Topics covered include the causes of hepatitis; the viruses that cause hepatitis; acute versus chronic hepatitis; treatment options, based on the severity of the hepatitis; prevention, notably minimizing lifestyle risk factors; and research avenues yet to be explored. One sidebar in the article lists the

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indications for the hepatitis A or B vaccine and one summarizes the five types of viral hepatitis (A, B, C, D, and E), transmission, and the severity of illness associated with each. ·

Hepatitis C: Shedding Light on the Shadow Epidemic Source: Harvard Health Letter. 24(9): 1-3. July 1999. Contact: Available from Harvard Medical School Health Publications Group. Harvard Health Letter, P.O. Box 420300, Palm Coast, FL 32142-0300. (800) 829-9045. E-mail: [email protected]. Summary: When people learn they have hepatitis C, their initial reaction is often disbelief and confusion. Many of those carrying this silent and sometimes deadly bloodborne virus feel perfectly healthy and learn of their infection only after donating blood or having routine blood tests. This newsletter article reports on a recent effort by the Centers for Disease Control and Prevention (CDC) to improve people's awareness by launching a hepatitis C public information campaign. People who are not now infected with HCV are not likely to get it unless they use IV drugs. Improved blood screening has made the risk of contracting HCV from a transfusion exceedingly low. However, most people who have HCV don't realize they're carrying the virus, which can lurk in the liver for decades before symptoms appear. It is important for people to know they have HCV so they can avoid alcohol (which accelerates liver damage), undergo frequent blood tests to monitor their liver function, and consider treatments with antiviral drugs that can reduce or eliminate the virus in some people. The majority of carriers remain fairly healthy, but at least 20 to 30 percent eventually develop cirrhosis (scarring of the liver caused by prolonged inflammation). Several blood tests can determine if a person has been infected with HCV. The author describes these tests and then briefly outlines the treatment options for HCV. One sidebar offers the contact information (telephone numbers and websites) for three resource organizations. 2 references.

Academic Periodicals covering Hepatitis Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to hepatitis. In addition to these sources, you can search for articles covering hepatitis that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for hepatitis. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DIÒ Advice for the PatientÒ can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with hepatitis. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to hepatitis: Alglucerase ·

Systemic - U.S. Brands: Ceredase http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202625.html

Alpha 1 -Proteinase Inhibitor, Human ·

Systemic - U.S. Brands: Prolastin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202022.html

Antihemophilic Factor ·

Systemic - U.S. Brands: Alphanate; Bioclate; Helixate; Humate-P; Hyate:C; Koate-HP; Kogenate; Monarc-M; Monoclate-P; Recombinate http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202671.html

Azathioprine ·

Systemic - U.S. Brands: Imuran http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202077.html

Factor Ix ·

Systemic - U.S. Brands: BeneFix; Mononine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202674.html

Hepatitis A Vaccine Inactivated ·

Systemic - U.S. Brands: Havrix; Vaqta http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202902.html

Hepatitis B Vaccine Recombinant ·

Systemic - U.S. Brands: Engerix-B http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202281.html

Interferon Alfacon-1 ·

Systemic - U.S. Brands: Infergen http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203504.html

Interferons, Alpha ·

Systemic - U.S. Brands: Alferon N; Intron A; Roferon-A http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202299.html

Lamivudine ·

Systemic - U.S. Brands: Epivir; Epivir-HBV http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202292.html

·

Systemic - U.S. Brands: Epivir; Epivir-HBV http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202791.html

·

Systemic - U.S. Brands: Epivir; Epivir-HBV http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203689.html

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Peginterferon Alfa-2B ·

Systemic - U.S. Brands: PEG-Intron http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500287.html

Ribavirin and Interferon Alfa-2B, Recombinant ·

Systemic - U.S. Brands: Rebetron http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500032.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug ConsultÔ Mosby’s Drug ConsultÔ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.

PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html.

Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to hepatitis by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “hepatitis” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact

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information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for hepatitis: ·

FIAU http://www.rarediseases.org/nord/search/nodd_full?code=491

·

Monoclonal antibody to hepatitis B virus (human) http://www.rarediseases.org/nord/search/nodd_full?code=151

·

Oxandrolone (trade name: Hepandrin) http://www.rarediseases.org/nord/search/nodd_full?code=328

·

Thymosin alpha-1 http://www.rarediseases.org/nord/search/nodd_full?code=40

·

CY-1899 http://www.rarediseases.org/nord/search/nodd_full?code=597

·

Hepatitis B immune globulin, intravenous (trade name: H-BIGIV) http://www.rarediseases.org/nord/search/nodd_full?code=735

·

Thymalfasin (trade name: Zadaxin) http://www.rarediseases.org/nord/search/nodd_full?code=902

·

Interferon beta (recombinant human) http://www.rarediseases.org/nord/search/nodd_full?code=96

If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute13: ·

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

·

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

·

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

·

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

·

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

·

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

·

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

13

These publications are typically written by one or more of the various NIH Institutes.

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·

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

·

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

·

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

·

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

·

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

·

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

·

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

·

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

·

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

·

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

·

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

·

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

·

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

·

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

·

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.14 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:15 ·

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

·

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

·

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

·

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

·

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

·

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

14

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 15 See http://www.nlm.nih.gov/databases/databases.html.

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·

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

·

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “hepatitis” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “hepatitis” (or synonyms) into the “For these words:” box. The following is a sample result: ·

Hepatitis C Update: Recommendations from the NIH and CDC Source: JAAPA. Journal of the American Academy of Physician Assistants. 11(12): 35-37. December 1998. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Fax (201) 573-4956. Summary: In March 1997, the National Institutes of Health (NIH) conducted a consensus development conference on the management of hepatitis C virus (HCV) infection. In July 1998, the Centers for Disease Control and Prevention (CDC) held a consultants meeting on HCV, from which it developed recommendations for the prevention and control of HCV infection and related chronic disease. This article reviews these two sets of recommendations, summarizing and comparing the guidelines in the areas of screening, counseling, monitoring, and treatment. The CDC recommends screening persons at low risk of HCV infection with the enzyme immunoassay (EIA) HCV antibody test, which has a sensitivity of greater than 97 percent. If indicated, the recombinant immunoblot assay is used as a confirmation test. The NIH, on the other hand, recommends measurement of HCV RNA with the polymerase chain reaction, if indicated, as a confirmatory test of a positive EIA. The CDC recommends that people who test positive for HCV should be counseled about being evaluated for their disease and possibly being treated. They should be instructed about reducing the risk of transmitting the virus to another person and refraining from donating blood or other body tissues. The CDC recommends vaccination against hepatitis A in a person who has chronic HCV infection; the NIH recommends vaccination against hepatitis A and B. Liver biopsy remains the gold standard for assessing disease activity, including progression to fibrosis and cirrhosis. Treatment is recommended when findings on liver biopsy include periportal or bridging fibrosis and a moderate degree of inflammation and necrosis. Patients who have had one or more episodes of decompensated cirrhosis (ascites, variceal bleedings, or encephalopathy) should be referred to a center that performs liver transplantation. 1 figure. 3 references.

·

Terminology of Chronic Hepatitis: International Working Party Report Source: American Journal of Gastroenterology. 90(2): 181-189. February 1995.

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Summary: In this article, the authors present the proceedings of two panels on chronic hepatitis of the World Congresses of Gastroenterology (WCPG) working party. The authors hope that the suggested terms, definitions, and codes can: be used by clinicians and laboratory physicians as they jointly care for patients; keep the language in hepatology contemporary; and help to create data that lend themselves to improved computerized coding and retrieval in the interest of patient service and research. After a discussion of background and objectives, the authors present definitions, synonyms, and clinical, laboratory, and histological findings for the following conditions: autoimmune hepatitis; chronic hepatitis B; chronic hepatitis D; chronic hepatitis C; chronic drug hepatitis; primary biliary cirrhosis; primary sclerosing cholangitis; Wilson's disease of the liver; and alpha-1-antitrypsin deficiency. One brief section discusses the grading and staging of chronic hepatitis. 2 tables. 28 references. ·

Guidelines for Prevention of Transmission of Human Immunodeficiency Virus and Hepatitis B Virus to Health - Care and Public - Safety Workers. A Response to P.L. 100 - 607, The Health Contact: US Government Printing Office, PO Box 371954, Pittsburgh, PA, 15250-7954, (202) 512-1800, http://www.access.gpo.gov. CDC National Prevention Information Network, PO Box 6003, Rockville, MD, 20849-6003, (800) 458-5231, http://cdcnpin.org. Summary: Intended for use by an audience that is technically informed on existing principles of infection control, this report provides an overview of HIV for health care and public safety workers. It also presents information concerning the protection of workers against acquisition of Hepatitis B virus, whose mode of transmission is similar to those of HIV. Developed by the National Institute of Occupational Safety and Health (NIOSH), it includes specific risk-control recommendations, as well as information on the medical management of persons who have sustained workplace exposure to either virus. Information is provided for fire fighters, emergency medical services (EMS) personnel, and law enforcement and correctional facility personnel. Because of the risks of exposure associated with parenteral (including open wound) and mucous membrane exposure to blood and other potentially infectious body fluids, observance of universal precautions is urged as a cornerstone of worker safety.

·

Hepatitis B Virus Infection Without Immunological Markers After Open-Heart Surgery Source: Lancet. 345(8946): 355-357. February 11, 1995. Summary: Posttransfusion hepatitis is still an important problem, despite the screening of blood donors for hepatitis B virus (HBV) and hepatitis C virus infections. This article reports on a study in which the researchers assessed whether HBV DNA might be detected by PCR in prospectively collected serum samples of patients with unexplained posttransfusion hepatitis but no immunological HBV markers. They found HBV DNA in 4 (20 percent) of 20 patients with unexplained posttransfusion hepatitis and in 5 patients with mildly increased aminotransferases. The clinical course of these HBV infections was usually mild and self-limiting. The researchers conclude that low-titre, immunologically negative HBV infections do exist and might represent a significant cause of post-transfusion hepatitis.

·

Health Care Workers and AIDS and Hepatitis B Contact: United Food and Commercial Workers International Union, 1775 "K" St NW, Washington, DC, 20006-1598.

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Summary: This brochure educates health care workers about their risk of exposure to the viruses that cause AIDS and Hepatitis B. The more readers understand about disease transmission factors, the better able they will be to prevent infection. The brochure defines AIDS and explains how people can and cannot become infected with the AIDS virus. The risk of AIDS to health care workers is put into perspective, and readers are cautioned to avoid blood or body fluid contact with patients. Hepatitis B virus (HBV) is defined, and its effects and transmission are explained. In many ways Hepatitis B poses a greater danger to health care workers than the AIDS virus. The use of the Hepatitis B vaccine is urged, and precautions for preventing the transmission of the HIV and HBV to patient/resident care workers, housekeeping workers, laundry workers, and kitchen/dietary workers are outlined. ·

National Hepatitis C Prevention Strategy Contact: CDC National Prevention Information Network, PO Box 6003, Rockville, MD, 20849-6003, (800) 458-5231, http://www.cdcnpin.org. Summary: This comprehensive plan for health care professionals and policy makers addresses the prevention and control of hepatitis C virus (HCV) infection and its consequences. This strategy strives to protect the public's health by outlining guidelines for prevention and control of HCV infection, providing credible information on hepatitis C to enhance healthy decisions and promoting healthy living through strong partnerships with national, state, and local organizations in both the public and private sectors. The principle components of the plan are: (1) education of health care and public health professionals to improve the identification of persons at risk for HCV infection and ensure appropriate counseling, diagnosis, medical management and treatment; (2) education of the public and persons at risk for infection about risk factors for HCV transmission, and the need for testing and medical evaluation; (3) clinical and public health activities to identify, counsel, and test persons at risk for HCV infection and medical evaluation or referral for those found to be infected; (4) outreach and community-based programs to prevent practices that put people at risk for HCV infection, and to identify persons who need to get tested; (5) surveillance to monitor acute and chronic disease trends and evaluate the effectiveness of prevention and medical care activities; and (6) research to better guide prevention efforts.

·

Recommendations for Preventing Transmission of Human Immunodeficiency Virus and Hepatitis B Virus to Patients During Exposure-Prone Invasive Procedures Source: MMWR. Morbidity and Mortality Weekly Report. 40(RR-8): 1-9. July 12, 1991. Contact: Available from National Prevention Information Network. P.O. Box 6003, Rockville, MD 20850. (800) 458-5231. PRICE: Single copy free. Summary: This document has been developed by the Centers for Disease Control (CDC) to update recommendations for prevention of transmission of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in the health-care setting. Current data suggest that the risk for such transmission from a health-care worker to a patient during an invasive procedure is small. This document contains recommendations to provide guidance for prevention of HIV and HBV transmission during those invasive procedures that are considered exposure-prone. A brief appendix provides a definition of invasive procedures. 44 references. (AA-M).

·

Hepatitis B Update. Revised ed Source: St. Paul, MN: Hepatitis B Coalition. 1996. 13 p.

Physician Resources 499

Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. PRICE: $5.00. Summary: This document, designed for use by health care professionals, discusses contemporary and prevention issues of hepatitis B. Focusing on the Asian-American population, the document provides an overview of hepatitis B, its incidence and prevalence; transmission of hepatitis B; risk factors; hepatitis B virus (HBV) structure and nomenclature; clinical presentation; laboratory testing and interpretation; treatment; natural history; correlation with primary hepatocellular carcinoma (PHC); use of the hepatitis B vaccine; administration and dosage of the vaccine; and post-exposure recommendations. One section presents an excerpt from the most recent recommendations of the Immunization Practices Advisory Committee (ACIP) regarding hepatitis B vaccination. 1 figure. 9 tables. 49 references. ·

1988 State EMS AIDS/Hepatitis B Legislation Survey Contact: Utah Department of Health, Bureau of Emergency Medical Services, PO Box 142004, Salt Lake City, UT, 84114-2852, (801) 538-6435, http://www.health.state.ut.us/ems. Summary: This fact sheet presents findings of a survey of State laws and legislation, both past and pending, specific to Acquired immunodeficiency syndrome (AIDS) and Hepatitis B virus. Provisions for emergency medical services (EMS) and prehospital care providers are noted and include a wide variety of items related to Human immunodeficiency virus (HIV).

·

Guidelines for Implementation of Hepatitis B and HIV School Employee Trainings Contact: Office of the Superintendent of Public Instruction, Old Capitol Bldg, Legion Way & Washington St, Olympia, WA, 98504, (360) 753-1142. Summary: This manual is designed to assist school districts, as employers, in meeting the following requirements: Washington Industrial Safety and Health Act (WISHA) Chapter 296-62-08001 and 08050 which outline the requirements and procedures for protection of workers with occupational exposure to bloodborne pathogens; and Chapter 392-198 WAC, which describes the mandatory and supplemental course content for training public school employees in the transmission, prevention, and treatment of the Human immunodeficiency virus (HIV) and Acquired immunodeficiency syndrome (AIDS). Section A provides guidelines for meeting legislation requirements. Section B gives recommended course content for school employee HIV/AIDS and Hepatitis B training.

·

Value of Knowledge of HIV/Hepatitis Infection to the Surgeon and Patient Contact: Johns Hopkins Hospital, Department of Medicine, Moore Clinic, 600 N Wolf St 3rd Carnegie, Baltimore, MD, 21287, (410) 955-6414, http://www.hopkinsmedicine.org/. Summary: This paper discusses issues related to Acquired immunodeficiency syndrome (AIDS) in relation to policies regarding knowledge of Human immunodeficiency virus (HIV) and hepatitis infection in a patient prior to surgery. It addresses two major complications: Changing conduct of the operation, and altering the type of operation performed. It also discusses reliability of the HIV-antibody test, policy exclusivity for HIV, and whether informed consent should be mandatory for HIV testing.

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·

Guidelines for Informing School Employees about Preventing the Spread of Infectious Diseases, Including Hepatitis B and AIDS/HIV Infections and Policies for Dealing With HIV - Infected Persons in Contact: California Department of Education, Office of Healthy Kids, Healthy California Unit, PO Box 944272, Sacramento, CA, 94244-2720, (916) 322-4018. Summary: This policy statement gives guidelines for schools and school districts regarding information to be given to school employees about universal precautions to prevent the spread of all infectious diseases. It includes specific suggestions about Acquired immunodeficiency syndrome (AIDS) and Hepatitis B. School districts are required by law to provide this information. The guidelines give an overview of infection control precautions and present the rationale for implementing these precautions. It looks at the risk of infection with Human immunodeficiency virus (HIV) and Hepatitis B, and explains the symptoms of both infections and methods by which the viruses are transmitted. Means of precaution are explained, and universal precautions listed. The need for school policies on infectious diseases is discussed.

·

Oregon Health Division's Guidelines for Schools With Children Who Have Hepatitis B Virus or Human Immunodeficiency Virus Infections Contact: Oregon Department of Human Services, Health Division, Center for Disease Prevention and Epidemiology, HIV/STD/TB Program, PO Box 14450, Portland, OR, 97214-0450, (503) 731-4029, http://www.ohd.hr.state.or.us/hiv/welcome.htm. Summary: This policy statement includes recommended guidelines for Oregon school administrators who are developing procedures on safely educating children with Hepatitis B or Acquired immunodeficiency syndrome (AIDS). It gives background information on the illnesses and studies legal and confidentiality issues. General recommendations cover education about the two viruses and use of infection-control procedures. The HIV-specific recommendations include one that says it is expected that HIV-infected school-age children will be able to attend school without restriction.

·

Hepatitis C : Diagnosis : Clinical Management : Prevention : A Live Satellite Videoconference Contact: US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Center for HIV STD and TB Prevention, 1600 Clifton Rd NE MS E06, Atlanta, GA, 30333, (404) 639-8063, http://www.cdc.gov/nchstp/od/nchstp.html. Summary: This program discusses issues related to the hepatitis C virus (HCV) addressed during a satellite videoconference on November 22, 1997. The program supplies the reader with summaries of presentations given at the conference that cover topics such as epidemiology, risk assessment, prevention, serology, chronic infection in children, diagnostic tests, screening, follow-up laboratory tests and clinical evaluation, the history of HCV, medical treatment, alternative therapies, and counseling. It provides the reader with a sample questionnaire that can be used to discern if a patient is at risk for HCV and the epidemiology of HCV in those persons with certain risk factors. The program describes the different types of diagnostic tests available for HCV, and explains how to counsel patients before and after testing. It supplies the reader with information resources about HCV, and the general statement of the National Institutes of Health (NIH) on the disease. The program describes how to counsel patients with HCV who are looking to undertake alternative medical therapies for their condition.

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·

Recommendations and Universal Precautions for the Prevention of the Transmission of HIV, Hepatitis B and Other Blood-Borne Pathogens in Healthcare Settings Source: Morbidity and Mortality Weekly Report Supplemental Jun 1 1988;36(SU-2):3-18. Morbidity and Mortality Weekly Report Recommendations and Reports Aug 21 1986;37(RR-24):377-388. Contact: CDC National Prevention Information Network, PO Box 6003, Rockville, MD, 20849-6003, (800) 458-5231, http://www.cdcnpin.org. Summary: This publication is a combination of two reports by the Centers for Disease Control and Prevention that cover precautions for the prevention of the transmission of HIV, hepatitis B, and other bloodborne pathogens in healthcare settings such as hospitals, clinics, laboratories, and other workplaces where the possibility exists of transmission through contact with contaminated blood and body fluids. Specific precautions covered include screening of patients, decontamination procedures, use of gloves and other protective barriers, waste management, and general management of exposures.

·

HIV, Hepatitis - B, Hepatitis - C: Blood - Borne Diseases; Nurses' Risks, Rights, and Reponsibilities Contact: American Nurses Association, 600 Maryland Ave SW Ste 100W, Washington, DC, 20024-2571, (202) 651-7000, http://www.nursingworld.org. Summary: This publication outlines the protective measures against workplace exposure to HIV, hepatitis-B (HBV), and hepatitis-C that should be provided by employers to nurses and other health care employees under the rules of the Occupational Safety and Health Administration (OSHA). It also lists the responsibilities of employees. Access to and use of protective equipment, patient rights, immunizations, reporting exposure and compliance with post-exposure follow-up, participation on safety committees, and peer support are covered.

·

Recommendations for Preventing Transmission of Human Immunodeficiency Virus and Hepatitis B Virus to Patients During Exposure - Prone Invasive Procedures Contact: CDC National Prevention Information Network, PO Box 6003, Rockville, MD, 20849-6003, (800) 458-5231, http://www.cdcnpin.org. Summary: This report contains recommendations from the Centers for Disease Control and Prevention (CDC) on preventing transmission of HIV and the Hepatitis B virus to patients during invasive procedures. It advises health care workers to follow universal precautions, which require that blood and body fluids of all patients be handled as if they contain bloodborne pathogens. For the protection of patients, equipment and devices that enter sterile areas of the body should be sterilized before being used on each patient; equipment and devices that touch intact mucous membrane should be sterilized when possible or undergo high-level disinfection; and equipment and devices that do not touch the patient or that touch only intact skin need cleaning with a detergent. The report looks into incidence of the transmission of Hepatitis B virus and HIV during invasive procedures. It concludes with recommendations, which say that all health care workers should adhere to universal precautions; currently available data provide no basis for recommendations to restrict the practice of health care workers infected with either virus who perform invasive procedures but not exposure-prone ones. The recommendations also say that exposure-prone procedures should be identified by medical, surgical, and dental organizations and institutions; heath care

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workers who perform such procedures should know their HIV-antibody status and their Hepatitis B status; and infected workers should not perform exposure-prone procedures unless they have been advised by an expert review panel on when they may continue to perform such procedures. Mandatory testing is not recommended, and health care workers whose practices are modified because of infection status should be provided other opportunities to continue with appropriate patient-care activities. Patients who have had exposure-prone procedures performed by infected workers should be notified on a case-by-case basis. ·

Hepatitis B: A Summary of the Occupational Health Concern Contact: Canadian Centre for Occupational Health and Safety, 250 Main St E, Hamilton, (905) 572-2981, http://www.ccohs.ca. Summary: This report describes Hepatitis B, a bloodborne disease that can be transmitted in ways similar to transmission of Human immunodeficiency virus (HIV), which causes Acquired immunodeficiency syndrome (AIDS). The report discusses Hepatitis B in the workplace, occupations with increased risk of exposure, tests and treatment programs for the disease, and preventive measures, including immunizations, and personal and workplace hygiene.

·

Protection Against Viral Hepatitis: Recommendations of the Immunization Practices Advisory Committee (ACIP) Contact: US Government Printing Office, PO Box 371954, Pittsburgh, PA, 15250-7954, (202) 512-1800, http://www.access.gpo.gov. Massachusetts Medical Society, Medical Publishing Group, CSPO Box 9121, Waltham, MA, 02254, (800) 843-6356. Summary: This report discusses hepatitis transmission and risk factors, many of which are the same as those for the Human immunodeficiency virus (HIV), the etiologic agent of Acquired immunodeficiency syndrome (AIDS). Infection control and vaccines are also discussed.

·

Recommendations for Prevention and Control of Hepatitis C Virus (HCV) Infection and HCV-Related Chronic Disease Contact: US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Center for Health Statistics, Office of the Morbidity and Mortality Weekly Report Series, 1600 Clifton Rd NE M/S C-08, Atlanta, GA, 30333, (404) 332-4555, http://www.cdc.gov. CDC National Prevention Information Network, PO Box 6003, Rockville, MD, 20849-6003, (800) 458-5231, http://www.cdcnpin.org. Summary: This report discusses the hepatitis C virus (HCV), how it is treated, and how it can be prevented. The report examines the epidemiology of HCV. It discusses the screening tests, history, general treatment, and postexposure prophylaxis for HCV. The report explains the ways that HCV can be transmitted from person to person and how the virus can be spread through bodily fluid. It identifies the most serious high risk behaviors such as injection drug use and certain sexual practices. The report cites the risks associated with health care work. It lists the persons who should be tested regularly for HCV and the procedures involved in the HCV testing process. The national surveillance for acute HCV, laboratory discoveries of anti-HCV positive tests, serological surveys, and surveillance of chronic liver disease are discussed. The report makes predictions and recommendations about the future of HCV.

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Health Emergency 2003: The Spread of Drug-Related AIDS and Hepatitis C Among African Americans and Latinos Contact: Harm Reduction Coalition, East Coast Office, 22 W 27th St 5th Fl, New York, NY, 10001, (212) 213-6376, http://www.harmreduction.org. Dogwood Center, PO Box 187, Princeton, NJ, 08542, (609) 924-4797. Summary: This report examines the spread of the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and hepatitis C virus (HCV) among African Americans and Latino injecting drug users (IDUs). The report discusses the epidemiology of HIV/AIDS among African-American and Latino IDUs, the need for culturally competent needle exchange programs, how these groups are disadvantaged in the American healthcare system, and how their needs should be addressed.

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Hepatitis Report: A Critical Review of the Research and Treatment of Hepatitis C Virus (HCV) and Hepatitis and HIV Coinfection Source: New York, NY: Treatment Action Group. 2000. 134 p. Contact: Treatment Action Group. 350 Seventh Avenue, Suite 1603, New York, NY 10036. (212) 972-9022. Fax (212) 971-9019. Website: www.treatmentactiongroup.org. PRICE: Single copy free. Summary: This report is designed to bring clinicians, allied health care workers, and patients up to date on hepatitis C virus (HCV), including epidemiology, natural history, diagnosis, pathogenesis, and treatment. After an analysis of peer reviewed articles, over 40 researchers, clinicians, primary care physicians, government health administrators, industry representatives, and patients with viral hepatitis were interviewed for this report. Eleven chapters cover epidemiology, modes of transmission, and risk factors; pathogenesis, viral dynamics, and immunologic response; natural history, clinical manifestations, and prognostic indicators of disease progression and survival of HCV infection; diagnostic considerations; the use of interferon to treat HCV infection; the mechanism of HCV resistance to interferon; experimental treatments and new areas of research; hepatitis and HIV coinfection; current opinions and controversies in HCV infection; research and policy recommendations; and clinician's response. The natural history chapter reminds readers that not all patients with HCV inexorably deteriorate to end stage liver disease, liver transplantation, or death. The diagnosis of HCV is often complex with multiple tests and the confusion of liver biopsy evaluation. The role of HCV in response to HIV therapy is largely unknown. Approximately only half of HCV patients respond to current therapies, but the report considers whether perhaps only half may actually need therapy in the long term. Unfortunately, clinicians cannot determine which patients will progress to fibrosis and end stage liver disease and so most patients are treated, especially if they have some scarring without cirrhosis. Interferon remains the mainstay of therapy, with pegylated IFNs providing new advances. Each chapter includes illustrations and a list of references.

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Review of Adolescent School-Based Hepatitis B Vaccination Projects Source: Atlanta, GA: Centers for Disease Control and Prevention, Hepatitis Branch. 1996. 115 p. Contact: Available from Information/Distribution, National Immunization Program. Mailstop E-34, CDC, 1600 Clifton Road NE, Atlanta, GA 30333. Fax (404) 639-8828. PRICE: Single copy free to health professionals.

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Summary: This report on adolescent school-based hepatitis B vaccination is part of a resource kit designed to be used in a hepatitis B prevention program. These materials were developed to help facilitate the implementation of 1995 recommendations of the Advisory Committee on Immunization Practices (ACIP) which emphasized the need for vaccination of all 11 to 12 year old children who have not previously received hepatitis B vaccine. Catchup vaccination of adolescents is a key element in the strategy to eliminate hepatitis B virus (HBV) in the United States and presents an opportunity to provide other preventive health services to this underserved population. The report summarizes the experience of 13 different school-based projects and contains information on issues such as obtaining consent, selecting appropriate grades to target, educating teachers and students, and obtaining support from school officials, health department staff, and primary care providers. In addition, the report describes a variety of approaches to mobilize resources for school programs. 1 figure. 26 tables. 3 references. (AA-M). ·

Comments on OSHA's Advance Notice of Proposed Rulemaking to Control Occupational Exposures to Hepatitis B and AIDS Contact: Service Employees International Union, Education and Support Fund, 1313 L St NW, Washington, DC, 20005, (202) 898-3443, http://www.seiu.org. Summary: This report presents comments from the Service Employees International Union (SEIU) regarding development of standards for infection-control procedures by the Occupational Safety and Health Act. It comments on issues not adequately covered in the Joint Advisory Notice, on the basis of a survey conducted by SEIU of infectioncontrol procedures in 100 departments of health and correctional facilities across the United States. It urges the agency to define scope of coverage on the basis of potential exposure to Human immunodeficiency virus (HIV) infection and Acquired immunodeficiency syndrome (AIDS) or other bloodborne diseases. Modes of transmission and protective equipment are discussed, as well as vaccination programs, training, and education.

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Fatal and Severe Hepatitis Associated with Rifampin and Pyrazinamide for the Treatment of Latent Tuberculosis Infection--New York and Georgia, 2000 Source: Morbidity and Mortality Weekly Report Weekly Apr 20 2001;50(15):289-291. Summary: This report presents two case reports to illustrate that the two-month regimen of rifampin (RIF) and pyrazinamide (PZA) for the treatment of latent tuberculosis infection (LBTI) can cause severe hepatitis in some people. The first case is that of a 53-year-old incarcerated man who was treated with 600 mg RIF and 1750 mg PZA daily while receiving treatment for hypertension. The patient died of liver necrosis and failure as a result of hepatitis following LTBI treatment. The second case is that of a 59-year-old woman who received 600 mg RIF and 2000 mg PZA for LTBI. She was also receiving treatment for nasal allergies and asthma and had a history of anaphylactic reactions to penicillin and an estrogen sulfates blend. On the 49th and last day of treatment this patient was admitted to a hospital because of jaundice and altered mental states. After treatment with 40 mg prednisone daily, the patient recovered. In these cases biochemical monitoring did not help avoid liver injury. The report advises that patients with LTBI and risk factors for active TB should be offered treatment and should receive instruction and reminders about the symptoms of hepatitis and of stopping medication if symptoms develop. Cases of severe hepatitis that develop in patients being treated for LTBI should be reported to the CDC.

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Prevention, Diagnosis, and Management of Viral Hepatitis: A Guide for Primary Care Physicians Source: Chicago, IL: American Medical Association. 1995. 21 p. Contact: Available from American Medical Association. Division of Health Science, 515 North State Street, Chicago, IL 60610. (312) 464-5563. Fax (613) 464-5842. PRICE: $1.50. Item Number AA36.94-802.225M.1/95. Summary: This report reflects the views of experts and the medical literature as of January 1995 on the prevention, diagnosis, and management of viral hepatitis. Topics include the viral characteristics and epidemiology of hepatitis A, B, C, D, and E; the clinical manifestations of acute and chronic hepatitis; diagnostic considerations; management issues for acute and chronic hepatitis; and prevention of hepatitis A, B, and C. The author stresses that, because patients with hepatitis may be asymptomatic, primary care physicians must be aware of the epidemiology and clinical manifestations of acute and chronic hepatitis. The report concludes with a list of abbreviations used and a list of selected readings. 4 figures. 10 tables. 28 references. (AA-M).

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Baseline Study of the Relationship Between Injecting Drug Use, HIV and Hepatitis C Among Male Injecting Drug Users in Lahore Contact: World Health Organization, Joint United Nations Programme on HIV/AIDS, 20 Avenue Appia, CH-1211 Geneva, http://www.unaids.org. Summary: This report reviews a study of injecting drug users (IDUs) in Lahore, Pakistan, that shows the correlation between injection drug use and the transmission of the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and hepatitis C. The report discusses the research methodology employed and identifies the demographic and socioeconomic characteristics of individuals studied. Study findings focus on individuals' drug use history and patterns, their knowledge of HIV/AIDS and hepatitis C, and their sexual practices and behaviors. The report makes recommendations to prevent HIV/AIDS and hepatitis C among injection drug users. The study findings will have implications for the formulation of strategies regarding drug abuse in Pakistan, and for the development of appropriate and effective plans for programs of HIV/AIDS awareness and prevention.

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Recommendations for Preventing Transmission of Human Immunodeficiency Virus and Hepatitis B Virus From Health Care Workers to Patients and From Patients to Health Care Workers Through Contact: Wisconsin Department of Health and Family Services, Division of Public Health, Bureau of Communicable Diseases, PO Box 2659, Madison, WI, 53701-2659, (608) 267-5287, http://www.dhfs.state.wi.us/aids-hiv/index.htm. Summary: This report summarizes the basis and implementation of recommendations for preventing transmission of HIV and hepatitis B virus (HBV) between health care workers (HCWs) and patients during medical/dental procedures. It discusses the relevant epidemiological features, transmission, and natural history of HIV and HBV; morbidity among HCWs; transmission of HIV/HBV to patients; and prevention of HIV/HBV transmission in health care settings. The report offers recommendations for infection control, testing, immunization, significant exposures, legally required reporting and retrospective patient notification, and dissemination of the recommendations.

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Prevention of Hepatitis A Through Active or Passive Immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP) Source: MMWR Morbidity and Mortality Weekly Report Recommendations and Reports 1999 (October 1);48(RR-12):1-37. Contact: US Government Printing Office, PO Box 371954, Pittsburgh, PA, 15250-7954, (202) 512-1800, http://www.access.gpo.gov. CDC National Prevention Information Network, PO Box 6003, Rockville, MD, 20849-6003, (800) 458-5231, http://www.cdcnpin.org. Summary: This report updates the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices' (ACIP) 1996 recommendations on the prevention of hepatitis A through immunization (MMWR 1996;45[RR-15].) and includes (1) new data about the epidemiology of hepatitis A; (2) recent findings about the effectiveness of community-based hepatitis A vaccination programs; and (3) recommendations for the routine vaccination of children in states, counties, and communities with rates that are twice the 1987-1997 national average or greater and consideration of routine vaccination of children in states, counties, and communities with rates exceeding the 1987-1997 national average. Unchanged in this report are previous recommendations regarding the vaccination of persons in groups at increased risk for hepatitis A (i.e., travelers, men who have sex with men, users of injecting and noninjecting drugs, persons who have clotting-factor disorders, persons working with nonhuman primates, and persons with chronic liver disease) or its adverse consequences and recommendations regarding the use of immune globulin for protection against hepatitis A.

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Hepatitis C & Incarcerated Populations : The Next Wave for Correctional Health Initiatives Contact: Association of State and Territorial Health Officials, 1275 K St NW Ste 800, Washington, DC, 20005-4006, (202) 371-9090, http://www.astho.org. Summary: This report, for health care professionals and correctional facility personnel, discusses the impact of the hepatitis C virus (HCV) on incarcerated populations. It identifies factors that prevent HCV-infected incarcerated individuals from seeking treatment such as: (1) the fear that health problems could prolong incarceration, (2) the possibility that available treatment for HCV may have worse side effects than the symptoms of the disease itself, and (3) factors that may preclude an HCV-infected patient from treatment eligibility or dissuade individuals from treatment. The report provides preventative strategies such as surveillance, counseling, education, and provision of discharge referrals. Samples of state's collaboration initiatives for addressing the issue of HCV in correctional facilities, conclusions, and recommendations are provided.

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Hepatitis C and Incarcerated Populations: The Next Wave for Correctional Health Initiatives Source: Washington, DC: Association of State and Territorial Health Officials. 2000. 28 p. Contact: Available from Association of State and Territorial Health Officials (ASTHO). 1275 K Street, NW, Suite 800, Washington, DC 20005-4006. (202) 371-9090. Fax (202) 3719797. PRICE: Single copy free. Also available for free in PDF format at www.astho.org/infectious/documents/hivaids/HepC-Incarcerated.pdf.

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Summary: This report, Hepatitis C and Incarcerated Populations, was prepared as part of the Association of State and Territorial Health Officials (ASTHO) Prison Project with support from the National Center for Infectious Diseases of the Centers for Disease Control and Prevention (CDC). The mission of the Prison Project is to help focus and stimulate disease prevention activities in correctional settings. An estimated 20 to 40 percent of inmates are infected with the hepatitis C virus (HCV). The rates are higher among injection drug users and inmates infected with HIV. This report discusses the realities of responding to HCV within the incarceration setting, reviews the challenges to intervention, and illustrates how a number of states are responding to this issue. The report makes eleven recommendations: the CDC should develop specific guidelines for the prevention and control of HCV in incarcerated populations; funding should be made available for community interventions to address HCV prevention, screening, diagnosis, and treatment of at risk populations prior to incarceration; states should consider integrating viral hepatitis into existing HIV and AIDS programs; public health officials should acknowledge corrections' role in community health; intervention strategies should involved collaboration between corrections and public health and other involved groups such as community-based organizations; states should be enlisted to help outline guidelines that address HCV infection among incarcerated patients; states should assume a high HCV infection rate among incarcerated patients; the Federal Government should lift the restriction on the use of federal funds for needle exchange services; states should explore the removal of legal barriers such as drug paraphernalia and prescription laws; injection drug users should be referred to the most appropriate source for counseling and treatment; and strategies that address HCV and incarcerated populations must recognize and address factors that can modify the approach to care (i.e., overcrowded, overstressed correctional health care systems, questionable quality of care, lack of continuity care, and comorbid conditions). 32 references. ·

Viral Hepatitis : An Epidemic in the Making? New Approaches to the Prevention, Diagnosis, and Treatment of Viral Hepatitis Contact: American Liver Foundation, 75 Maiden Ln Ste 603, New York, NY, 10038-4826, (973) 256-2550, http://www.liverfoundation.org. Summary: This report, written for the medical community, provides information on the hepatitis A virus (HAV), hepatitis E virus (HEV), hepatitis B virus (HBV), and the hepatitis C virus (HCV). The report examines the virology, diagnosis, history, risk factors, epidemiology, symptoms, diagnosis, treatment, and prevention of hepatitis. A list of references, a self-test to assess health professionals' knowledge of the material, and an evaluation of the report are provided.

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Guidelines for CMV, Hepatitis B and AIDS (Acquired Immune Deficiency Syndrome) Pupils in School Settings Contact: National Association of School Nurses, PO Box 1300, Scarborough, ME, 040701300, (207) 883-2117, http://www.nasn.org. Summary: This statement, which offers guidelines to follow regarding students with Cytomegalovirus, Hepatitis-B, and Acquired immunodeficiency syndrome (AIDS), is provided to Los Angeles, CA County schools. It emphasizes prevention, but specifies that children with these infections should not be excluded from schools. The guidelines focus on early and comprehensive notification to all staff persons who test positive for Human immunodeficiency virus (HIV) antibodies, reassignment of any pregnant women who may be in routine contact with them, and medical intervention if known exposure occurs. The guidelines place responsibility for keeping staff informed on the

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school nurse. They advise proper hygiene for all staff members who come into contact with infected persons, specify high-risk groups, and discuss the Hepatitis-B virus vaccine.

The NLM Gateway16 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.17 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “hepatitis” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 119541 1581 1025 2135 29 124311

HSTAT18 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.19 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.20 Simply search by “hepatitis” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

16

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

17

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 18 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 19 20

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists21 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.22 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.23 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: ·

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

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Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

The Genome Project and Hepatitis In the following section, we will discuss databases and references which relate to the Genome Project and hepatitis.

Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).24 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information.

21 Adapted from 22

http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 23 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 24 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “hepatitis” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for hepatitis: ·

Halothane hepatitis Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?234350

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Giant cell hepatitis, neonatal Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?231100

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Delta antigen-interacting protein a Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?605360

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Aryl hydrocarbon receptor-interacting protein; aip Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?605555

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Hepatitis B vaccine, response to Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?142395

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Hepatitis A virus cellular receptor 1; HAVCR1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?606518

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Retinoic acid receptor, beta; RARB Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?180220

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Hepatitis, neonatal cholestatic, due to deficiency of delta(4)-3-oxosteroid 5-betareductase Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?235555

Genes and Disease (NCBI - Map) The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: ·

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

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Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

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Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease,

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glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html ·

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

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Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

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Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

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Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html

Entrez Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: ·

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “hepatitis” (or synonyms) into the search box and click “Go.”

Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database25 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database26 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 26 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission. 25

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To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “hepatitis” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on hepatitis can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to hepatitis. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly.

The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below.

Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to hepatitis. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “hepatitis”:

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·

Guides on hepatitis Hepatitis http://www.nlm.nih.gov/medlineplus/hepatitis.html Hepatitis A http://www.nlm.nih.gov/medlineplus/hepatitisa.html Hepatitis B http://www.nlm.nih.gov/medlineplus/hepatitisb.html Hepatitis C http://www.nlm.nih.gov/medlineplus/hepatitisc.html Hepatitis C http://www.nlm.nih.gov/medlineplus/tutorials/hepatitiscloader.html

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Other guides Liver Diseases http://www.nlm.nih.gov/medlineplus/liverdiseases.html

Within the health topic page dedicated to hepatitis, the following was listed: ·

General/Overview Hepatitis http://www.4women.gov/faq/easyread/hepatitis-etr.htm Hepatitis A, B, and C: Learn the Differences Source: Immunization Action Coalition http://www.immunize.org/catg.d/p4075abc.htm

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Diagnosis/Symptoms Diagnosing and Treating Hepatitis Source: Hepatitis Foundation International http://www.hepfi.org/pages/liv_diagnosis.html Liver Biopsy Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/liverbiopsy/index.htm Liver Panel Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/liver_panel/glance.html

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Specific Conditions/Aspects Alcoholic Hepatitis Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ00200 Information to Live By: Hepatitis E Source: American Social Health Association http://www.ashastd.org/stdfaqs/hepe.html

Patient Resources

Two Cautions for Those Living with Hepatitis Source: Hepatitis Foundation International http://www.hepfi.org/pages/liv_two.html Viral Hepatitis and Injection Drug Users Source: National Center for HIV, STD, and TB Prevention http://www.cdc.gov/idu/hepatitis/viral_hep_drug_use.htm ·

Children Hepatitis Source: Nemours Foundation http://kidshealth.org/parent/infections/bacterial_viral/hepatitis.html Neonatal Hepatitis Source: American Liver Foundation http://www.liverfoundation.org/cgibin/dbs/articles.cgi?db=articles&uid=default&ID=1048&view_records=1

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From the National Institutes of Health Viral Hepatitis A to E and Beyond Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/viralhepatitis/index.htm

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Law and Policy Applying for Disability Source: Hepatitis Foundation International http://www.hepfi.org/pages/liv_disability.html

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Organizations American Liver Foundation http://www.liverfoundation.org/ Hepatitis Foundation International http://www.hepfi.org/ Immunization Action Coalition http://www.immunize.org/index.htm National Center for Infectious Diseases http://www.cdc.gov/ncidod/index.htm National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/ National Institute of Diabetes and Digestive and Kidney Diseases http://www.niddk.nih.gov/

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Prevention/Screening CDC Issues Recommendations Designed to Prevent Hepatitis Infections in Correctional Settings Source: Centers for Disease Control and Prevention http://www.cdc.gov/od/oc/media/pressrel/r030123.htm Preventing Hepatitis Source: Hepatitis Foundation International http://www.hepfi.org/pages/liv_preventing.html Right Way to Use a Condom Source: American Social Health Association http://www.ashastd.org/stdfaqs/condom_a.html

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Statistics Hepatitis and Liver Diseases in the United States Source: American Liver Foundation http://www.liverfoundation.org/cgibin/dbs/articles.cgi?db=articles&uid=default&ID=1008&view_records=1

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Teenagers How Hepatitis Can Hurt You Source: Nemours Foundation http://kidshealth.org/teen/infections/stds/hepatitis.html Imprisoned Youth at High Risk for Viral Hepatitis Source: National Center for Infectious Diseases http://www.cdc.gov/ncidod/diseases/hepatitis/spotlights/juvcorrections.htm

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on hepatitis. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: ·

Vaccinations for Adults with Hepatitis C Virus Infection Source: St. Paul, MN: Immunization Action Coalition. 1998. 1 p.

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Contact: Available from Immunization Action Coalition. 1573 Selby Avenue, St. Paul, MN 55104. (612) 647-9009. Fax (612) 647-9131. E-mail: [email protected]. Website: www.immunize.org. Price: Single copy free. Summary: Adults who have the hepatitis C virus (HCV) need to make sure they are fully vaccinated against other diseases. Seventy percent of people with HCV have chronic liver disease. These people have special needs, including pneumococcal vaccine and hepatitis A vaccine. This fact sheet contains a chart summarizing the recommendations for each of seven immunizations: hepatitis A; hepatitis B; pneumococcal; influenza; tetanus and diphtheria; measles, mumps and rubella; and varicella (for those who have never had chickenpox). For each vaccine, the chart lists the reasons for getting immunized and the common dosage schedule. Hepatitis A vaccine is recommended for people with chronic liver disease, as is the pneumococcal vaccine. While the influenza vaccine is not specifically recommended for persons with chronic liver disease, it can be given to anyone as a preventive. The fact sheet also provides hotline numbers to call for more information about hepatitis C and the Government's recommendations. ·

Hepatitis B and Adoption Information Source: St. Paul, MN: Immunization Action Coalition. 1997. 14 p. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Fax (612) 647-9131. PRICE: $1.00. Summary: Chronic hepatitis B is the most common serious infectious disease affecting children adopted internationally. This information packet provides guidelines about hepatitis B for parents who adopt children internationally. The packet includes five items: a fact sheet on myths about hepatitis B in children; a fact sheet about pre-adoption screening and its drawbacks; two articles from the Adoption Medical News newsletter on the diagnosis and medical management issues of chronic hepatitis B; and information on how to subscribe to Adoption Medical News. The information stresses that all children adopted from other countries, all U.S. newborns not screened during pregnancy, and all older children should be screened (preferably twice) for hepatitis B: at the time of arrival into the adoptive home and again after the maximum incubation period has passed (at six months). Tests done in the country of origin (except for Korea) are highly unreliable. The materials provide contact information for resource organizations and support groups.

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Chronic Hepatitis Source: Cedar Grove, NJ: American Liver Foundation. 1997. [2 p.]. Contact: Available from American Liver Foundation. Information and Distribution Center, 1425 Pompton Avenue, Suite 3, Cedar Grove, NJ 07009-1000. (800) GO-LIVER, ext. 234 or (888) 4HEP-ABC. Fax (973) 256-3214. E-mail: [email protected]. Website: www.liverfoundation.org. PRICE: $0.50 for single copy; bulk orders available; plus shipping and handling. Summary: Chronic hepatitis is ongoing injury to the cells of the liver with inflammation which continues for more than six months. There are many causes, including viruses, abnormalities of the immune system, medications, and the inability of the body to rid itself of copper. This fact sheet reviews chronic hepatitis. Written in a question and answer format, the fact sheet covers a definition of chronic hepatitis, the etiology (causes), diagnostic tests that can confirm and stage the condition, the symptoms of

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chronic hepatitis, and treatment options. The author concludes that an important aspect of treatment is supportive care, with a well balanced diet. The fact sheet concludes with the contact information for the American Liver Foundation, a nonprofit, national voluntary health organization (www.liverfoundation.org). ·

Hepatitis A Source: Cedar Grove, NJ: American Liver Foundation. 1999. [2 p.]. Contact: Available from American Liver Foundation. Information and Distribution Center, 1425 Pompton Avenue, Suite 3, Cedar Grove, NJ 07009-1000. (800) GO-LIVER, ext. 234 or (888) 4HEP-ABC. Fax (973) 256-3214. E-mail: [email protected]. Website: www.liverfoundation.org. PRICE: $0.50 for single copy; bulk orders available; plus shipping and handling. Summary: Hepatitis A is one of five known viruses that cause inflammation of the liver. This brief fact sheet reviews hepatitis A. Written in a question and answer format, the fact sheet covers the transmission of hepatitis A, risk factors for being infected with this virus, the symptoms of hepatitis A infection, complications of hepatitis A, diagnostic tests used to confirm hepatitis A, treatment options, and the vaccine for hepatitis A (including who should receive the vaccine). There is no specific treatment for hepatitis A. Most patients are told to rest for one to four weeks after the diagnosis is made, to avoid intimate contact, and to consume foods high in protein. People who have come into contact with the patient should be given temporary immunization with immune globulin, within two weeks of exposure. The fact sheet concludes with the contact information for the American Liver Foundation, a nonprofit, national voluntary health organization (www.liverfoundation.org).

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Hepatitis B Fast Facts: Or, Everything You Need to Know in 2 Minutes or Less! Source: Doylestown, PA: Hepatitis B Foundation. 2003. 2 p. Contact: Available from Hepatitis B Foundation. 700 East Butler Avenue, Doylestown, PA 18901-2697. (215) 489-4900 Fax: (215) 489-4920 Email: [email protected]. Website: www.hepb.org. PRICE: Full-text available online at no charge. Summary: Hepatitis B (a type of liver inflammation caused by a virus) is the world's most common, serious liver infection. Hepatitis B is caused by the hepatitis B virus (HBV), which can be transmitted through blood, sex, shared needles, and from an infected mother to her newborn during delivery. HBV is spreading because many chronic hepatitis B carriers are not aware that they have the virus and unknowingly pass it on to those who are in close contact with them. This fact sheet quickly reviews the basics of hepatitis B and its prevention in a bulleted, outline format. The fact sheet covers who is most at risk for contracting the virus, HVB transmission, and the role of vaccination against HBV. The fact sheet concludes with a brief list of resources, including the Hepatitis B Foundation (www.hepb.org). Simple graphics illustrate the fact sheet.

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Hepatitis B: Breaking the Cycle of Infection From Mother to Newborn Source: Cedar Grove, NJ: American Liver Foundation. 2001. [2 p.]. Contact: Available from American Liver Foundation. Information and Distribution Center, 1425 Pompton Avenue, Suite 3, Cedar Grove, NJ 07009-1000. (800) GO-LIVER, ext. 234 or (888) 4HEP-ABC. Fax (973) 256-3214. E-mail: [email protected].

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Website: www.liverfoundation.org. PRICE: $0.50 for single copy; bulk orders available; plus shipping and handling. Summary: Hepatitis B virus (HBV) infection is a serious liver infection caused by a virus and spread by contact with infected body fluids. One way that the virus is transmitted is during birth when virus in the blood and vaginal fluids of the mother readily expose the baby to the disease. This fact sheet explores strategies that can break the cycle of hepatitis B transmission from mothers to their newborns. The fact sheet covers the problem of hepatitis B, groups at high risk for hepatitis B, recommended hepatitis B screening, the risks to babies born of carrier mothers, the use of hepatitis B immune globulin and hepatitis B vaccine, the estimated number of hepatitis B carriers in pregnant women in the United States, the long term risks associated with hepatitis B (including increased liver cancer risk), and vaccine availability. The fact sheet concludes with the contact information for the American Liver Foundation, a nonprofit, national voluntary health organization (www.liverfoundation.org). ·

Preventing Hepatitis C Source: American Family Physician. 59(1): 91-92. January 1, 1999. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. Also available at http://familydoctor.org. Summary: Hepatitis C is a liver disease that is spread by contact with the blood of a person who has the infection. This fact sheet describes hepatitis C infection and how to avoid contracting it. Written in a question and answer format, the fact sheet is designed to be distributed to patients by their family physician. Topics include a definition of hepatitis C virus (HCV) and its effects, ways to prevent HCV infection (particularly sexual transmission), and ways that HCV infection is not transmitted, as well as how to know whether one already has hepatitis C, and who should be tested for the virus. The fact sheet focuses on high risk behaviors, such as the use of recreational intravenous drugs, the sharing of personal care articles, tattooing or body piercing, and occupational exposures (for health care workers). The fact sheet stresses that, people who have sex with more than one steady partner should use a latex condom correctly for each sexual episode to help protect them from hepatitis C and other sexually transmitted diseases. The fact sheet also encourages people at high risk for HCV infection to get tested so that they can learn how to protect their liver from further damage.

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Check Out the Facts About Hepatitis B and C (HBV and HCV) Source: Kenilworth, NJ: Schering Corporation. 1997. [2 p.]. Contact: Available from Schering Corporation. 2000 Galloping Hill Road, Kenilworth, NJ 07033. (800) 446-8766 or (908) 298-4000. Fax (908) 298-4490. Website: www.scheringplough.com. PRICE: Single copy free for patients; available to health professionals through local sales representatives. Summary: Hepatitis is an inflammation of the liver caused by a virus, drugs, or other factors. This fact sheet reviews basic information about hepatitis B virus (HBV) and hepatitis C virus (HCV). There are at present six types of viral hepatitis: A, B, C, D, E, and G. They differ in how they are transmitted as well as how long and how severely they affect the patient. Hepatitis A and E, milder forms, are spread through contaminated foods or water, while hepatitis B, C, and D (more serious forms) are spread through contact with human blood or by sexual activity. Hepatitis B and C have

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the greatest potential for long term liver damage. There is a vaccine to prevent hepatitis B, but not hepatitis C. Many people have few or no symptoms with HBV and HCV; blood tests may discover the infection. Liver function tests can then be performed to measure the severity of infection. Both hepatitis B and C are very common and can be either acute (short term, less than 6 months) or chronic (long term, more than 6 months) infections. The fact sheet stresses the important, varied roles of the liver, noting that a liver damaged by hepatitis cannot handle all these tasks very well. Hepatitis C can lead to permanent liver damage that may require a liver transplant. Almost one third of all liver transplants in the United States are needed because the patient had chronic hepatitis C. The fact sheet concludes by briefly reviewing prevention strategies for hepatitis B and C: never share needles or personal items that can hold blood (toothbrushes, razors), make sure that any tattooing or body piercing is done with sterile instruments, avoid multiple sex partners, and practice safer sex (use a latex condom). The fact sheet concludes with two toll free telephone hotlines where readers can get additional information: 800-GO-LIVER (465-4837) and 888-4HEP-ABC (443-7222). ·

AIDS, Hepatitis, and Dental Office Infection Control Contact: Academy of General Dentistry, Medical Information Systems, Incorporated, 2 Seaview Blvd, Port Washington, NY, 11050-4618, (516) 621-7200. Summary: In this teaching aid, part of a continuing dental education activity, 3 panelists discuss the Occupational Safety and Health Administration (OSHA), AIDS, hepatitis B (HBV), and infection control in the dental practice. The participants discuss the Centers for Disease Control and Prevention's (CDC) universal precautions for health care workers and the infection control regulations OSHA developed to protect employees' health and safety. They discuss treating an HIV-positive patient. One panelist describes the process of being inspected by an OSHA team. The participants discuss the Florida dental case of Dr. Acer, and conclude that the exact mode of transmission is still unknown. The panelists also discuss office procedures: providing the HBV vaccine for employees; handling accidental needle sticks; HIV and HBV testing; and OSHA regulations regarding educating employees about infection control. A day-to-day commitment to infection control based on an exposure control plan for the dental office is stressed.

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Pegylated Interferon Treatment for Hepatitis C Source: Cedar Grove, NJ: American Liver Foundation. 2001. 2 p. Contact: Available from American Liver Foundation. Information and Distribution Center, 1425 Pompton Avenue, Suite 3, Cedar Grove, NJ 07009-1000. (800) GO-LIVER, ext. 234 or (888) HEP-ABC. Fax (973) 256-3214. E-mail: [email protected]. Website: www.liverfoundation.org. PRICE: $0.50 for single copy; bulk orders available; plus shipping and handling. Summary: Interferon is a type of protein produced by the body's cells in response to viral hepatitis and other infections. Interferon stimulates the body's immune system to fight viral infections and affect the ability of viruses to divide in liver cells. In pegylation, one or more changes of polyethelene glycol (PEG, a gelatinous compound used to thicken food) are bonded to an interferon molecule. The PEG acts as a barrier to normal breakdown of the interferon molecule, working to keep the interferon in the body longer, without reducing efficacy. Whereas three injections are normally required with regular interferon treatment, only one injection of pegylated interferon is required per week. This fact sheet describes the use of pegylated interferon treatment for hepatitis

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C. The once weekly pegylated injection is prescribed for the treatment of chronic hepatitis C in patients who are at least 18 years of age, have not previously been treated with alpha interferon, and who are at greatest risk for progression to cirrhosis. Side effects can include flu like symptoms, such as fever, chills, headaches, muscle or joint aches, tiredness, and weakness. These side effects usually decrease in severity as treatment continues. Patients in some clinical trials reported less mental and physical fatigue with pegylated interferon compared to regular interferon therapy. Although not yet approved by the FDA, pegylated interferon shows great promise in research trials. The fact sheet includes the hotline numbers and website for the ALF (www.liverfoundation.org). ·

Role of Iron in Viral Hepatitis Source: idInsight. 2(2): 4. 1999. Contact: Available from Iron Disorders Institute. P.O. Box 2031, Greenville, SC 29602. (864) 241-0111. Fax (864) 244-2104. Website: www.irondisorders.org. Summary: More than 15 years ago, scientists began to notice elevated iron levels in those with chronic viral hepatitis. Some speculate that iron is released from liver cells injured by the presence of hepatitis virus. This brief newsletter article familiarizes patients and physicians with the role of iron in viral hepatitis. One of the researchers noted that patients on dialysis (whose serum ferritin, blood iron levels, were lower) cleared of infection sooner than those with elevated levels of ferritin. The levels of iron may also be correlated to which patients with hepatitis will respond to alpha interferon therapy; in one study, liver iron content in the 50 percent of patients who did not respond to treatment were twice as high as levels of iron in responders to interferon. In another study, it was noted that liver enzymes ALT were significantly reduced in response to interferon treatment when administered following a series of phlebotomies (removal of blood) to reduce ferritin. Patients with viral hepatitis are counseled to ask their attending physician to determine body iron status by measuring ferritine and transferrin iron saturation percentage. If elevated, reduction of ferritin levels may be considered for improved response to ongoing treatment. One chart summarizes the most common types of hepatitis, their transmission, risk factors, diagnostic tests, treatment, symptoms, anticipated recovery, and vaccination use. The article concludes with website addresses for readers wishing additional information; a suggested reading list for physicians is also provided. 1 table. 3 references.

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Neonatal Hepatitis Source: Cedar Grove, NJ: American Liver Foundation. 1997. 2 p. Contact: Available from American Liver Foundation. Information and Distribution Center, 1425 Pompton Avenue, Suite 3, Cedar Grove, NJ 07009-1000. (800) GO-LIVER, ext. 234 or (888) HEP-ABC. Fax (973) 256-3214. E-mail: [email protected]. Website: www.liverfoundation.org. PRICE: $0.50 for single copy; bulk orders available; plus shipping and handling. Summary: Neonatal hepatitis is inflammation of the liver that occurs only in early infancy, usually between one and two months after birth. This fact sheet from the American Liver Foundation (ALF) offers a brief overview of neonatal hepatitis. About 20 percent of infants with neonatal hepatitis were infected by their mother with a virus that caused the inflammation before birth or shortly after birth. These viruses include cytomegalovirus, rubella (measles), and hepatitis A, B, or C viruses. In the remaining 80 percent of the cases, no specific virus can be identified as the cause. Neonatal hepatitis

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presents with jaundice (yellow eyes and skin) that appears at one to two months of age, lack of weight gain and development, and enlarged liver and spleen. The infant cannot absorb vitamins for proper growth. Liver biopsy is often used for diagnosis, in part to differentiate neonatal hepatitis from biliary atresia. Patients with neonatal hepatitis caused by rubella or cytomegalovirus are at risk of developing an infection of the brain that could lead to mental retardation or cerebral palsy. Many of these infants will also have permanent liver disease from the destruction of liver cells and the resulting scarring (cirrhosis). Infants who develop cirrhosis ultimately will need a liver transplant. Chronic neonatal hepatitis will lead to the inability of the liver to eliminate toxins in the bile. This can cause itching, skin eruptions, and irritability. There is no specific treatment for neonatal hepatitis. Vitamin supplements are usually prescribed and many infants are given phenobarbital, a drug used to control seizures, but which also stimulates the liver to excrete additional bile. The fact sheet concludes with the contact information for ALF (800-GO-LIVER, www.liverfoundation.org). ·

[Hepatitis C, B and A Virus Infections.] Source: Cedar Grove, NJ: Hepatitis Foundation International. 2000. [1 p.]. Contact: Available from Hepatitis Foundation International. 30 Sunrise Terrace, Cedar Grove, NJ 07009-1423. (800) 891-0707. E-mail: [email protected]. Website: www.hepfi.org. PRICE: Single copy free. Summary: on hepatitis C virus infection (HCV), hepatitis B virus infection (HBV), and hepatitis A virus (HAV)infection. In regards to HCV, the fact sheet notes that about 36,000 Americans contract the disease each year, and an estimated 2.7 million Americans (about 1.8 percent of the population) are chronically infected with HCV. Between 60 and 85 percent of patients infected with the HCV will remain chronically infected and 8,000 to 10,000 people die in the United States of HCV related cirrhosis or liver cancer each year. Indeed, almost one third of all liver transplants are performed for HCV related chronic liver disease. An estimated 200,000 Americans are infected with HBV each year, with 70 percent of new cases occurring among people between the ages of 15 and 39. Every year, 5,000 Americans die from cirrhosis and 1,000 from liver cancer due to HBV infections. HBV is 100 times more infectious than HIV, and HBV can live on a dry surface for at least 7 days. However, hepatitis B vaccine can provide immunity in over 95 percent of young healthy adults. As for hepatitis A, each year an estimated 180,000 HAV infections occur in the United States. One third of all Americans have had HAV but now have immunity; approximately 100 Americans die each year from hepatitis A. The fact sheet also includes annual cost estimates for each of the diseases.

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Hepatitis B and the Health Care Worker Source: St. Paul, MN: Immunization Action Coalition. 1998. 1 p. Contact: Available from Immunization Action Coalition. 1573 Selby Avenue, St. Paul, MN 55104. (612) 647-9009. Fax (612) 647-9131. E-mail: [email protected]. PRICE: $1.00 per copy; available for free at www.immunize.org/catg.d/free.htm. Summary: Persons who have a reasonable expectation of being exposed to blood on the job should be offered hepatitis B vaccine. This fact sheet answers commonly asked questions about how to protect health care workers from hepatitis B. Written in a question and answer format, the fact sheet discusses appropriate sites for administering the vaccine, specific dosage and administration issues, the safety of vaccinating pregnant health care workers, the indications for serologic testings after receiving three doses of the vaccine, methods for dealing with nonresponders to hepatitis B vaccination,

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and the indications for ongoing testing for anti-HBs. The fact sheet reiterates that a health care worker who has been vaccinated does not need to be tested unless he or she has an exposure. Persons who perform invasive procedures should be treated the same as other health care workers with respect to anti-HBs testing. One table notes the guidelines for postexposure prophylaxis, to be consulted when a health care worker has an exposure (e.g., needlestick). 1 table. ·

Hepatitis B Clinical Trials: What You Need to Know Source: Doylestown, PA: Hepatitis B Foundation. 2003. 2 p. Contact: Available from Hepatitis B Foundation. 700 East Butler Avenue, Doylestown, PA 18901-2697. (215) 489-4900 Fax: (215) 489-4920 Email: [email protected]. Website: www.hepb.org. PRICE: Full-text available online at no charge. Summary: There are several promising new drugs that are being tested for hepatitis B treatment in the United States and around the world. This fact sheet, from the Hepatitis B Foundation, explains how clinical trials work and how volunteers can get involved in drug research studies. Topics include a definition of the four phases of clinical trials, guidelines to protect people who choose to participate in clinical trials, the advantages of being a participant in a clinical trial, informed consent, and tips to learn about clinical trials. The fact sheet includes a list of 12 questions to ask one's health care provider about clinical trials. The fact sheet notes that the Hepatitis B Foundation (www.hepb.org) maintains a list of HBV clinical trials on its website. For more information about clinical trials in general, readers are encouraged to visit the National Institutes of Health (NIH) clinical trials site (www.clinicaltrials.gov) or Center Watch (www.centerwatch.com). Simple graphics illustrate the fact sheet.

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Is Your Older Child Protected? : About Hepatitis B Shots Contact: Channing L. Bete Company Incorporated, 200 State Rd, South Deerfield, MA, 01373-0200, (800) 477-4776, http://www.channing-bete.com. Summary: This brochure advises parents about the hepatitis B virus (HBV) and why it is necessary for them to have their children and adolescents vaccinated against HVC despite the fact that it is primarily spread through needle sharing among injection drug users and unprotected sex. It provides the epidemiology of HBV among children and teens in the United States. The brochure describes the HBV vaccine and the side effects that one may experience. It advises the reader when to have one's child vaccinated, and examines how HBV is transmitted from person to person. It discusses what parents can do to help protect their children and adolescents from HBV.

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Hepatitis C : Treatment Alternatives Contact: National Institutes of Health : National Center for Complementary and Alternative Medicine Clearinghouse, PO Box 8218, Silver Spring, MD, 20907-8218, (888) 644-6226, http://www.nccam.nih.gov. Summary: This brochure discusses alternative therapies commonly used by individuals with the hepatitis C, which is caused by the hepatitis C virus (HCV). The brochure states that there has been little medical research done in this field and identifies the reasons why individuals with HCV undertake complementary therapies to aid them in their standard medical treatment. Information is provided for several herbs used in alternative therapy (i.e., milk thistle, licorice root, ginseng, ginger, and St. John's Wort). Specifically the brochure discusses how these herbs are expected to help, what their

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effects are according to studies performed on them, how these studies were conducted, and possible detrimental effects and their symptoms. Individuals with HCV should get an accurate diagnosis from their health care providers, tell their health care providers about all medications they are currently taking, consider being vaccinated for the hepatitis A virus (HAV) and the hepatitis B virus (HBV), and avoid treating the disease themselves, donating blood, engaging in substance abuse, o sharing needles for injection drug use. A list of organizations is provided for those seeking additional information. ·

Infectious Diseases in the School Setting: HIV/AIDS, Hepatitis B, and Other Common Infectious Diseases Contact: Feature Facts Incorporated, PO Box 2208, Merced, CA, 95344, (209) 383-1008. Summary: This brochure discusses diseases that a person could be exposed to in the classroom, with particular attention paid to Human immunodeficiency virus (HIV) and Hepatitis B. The brochure tells what HIV, the etiologic agent of Acquired immunodeficiency syndrome (AIDS), and Hepatitis are, and discusses ways in which they are spread and how transmission can be avoided. It also addresses new OSHA bloodborne pathogens regulations that are applicable to schools, an expanded Universal Precautions section, additional avoidance strategies, and information resources. Particular attention is given to prevention of all infections in the school setting.

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What Every Parent Should Know : Hepatitis B and Adolescents : Preteens/Teens : Vax : Prevent Hepatitis B Now Contact: SmithKline Beecham Pharmaceuticals, PO Box 7929, Philadelphia, PA, 19101, (800) 366-8900, http://www.sb.com/. Summary: This brochure discusses the hepatitis B virus (HBV) and vaccination, Vax, as a method of HBV prevention. The brochure describes HBV and the vaccination for infants and adolescents against the disease. It identifies the methods by which HBV is transmitted and describes the vaccination process. The brochure explains that HBV is a serious threat to children and adolescents and provides an epidemiological overview of the infection in the United States.

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Hepatitis B and Me : Straight Talk for Teens : I Got Vaxed : And You Should, Too : Preteens/Teens : Vax : Prevent Hepatitis B Now Contact: SmithKline Beecham Pharmaceuticals, PO Box 7929, Philadelphia, PA, 19101, (800) 366-8900, http://www.sb.com/. Summary: This brochure discusses the vaccine, Vax, for the hepatitis B virus (HBV). The brochure states the HBV is a very serious illness that can last for long periods of time, but can be easily prevented through vaccination. It explains the process involved in getting vaccinated for HBV, and also the ways that the virus is transmitted from person to person.

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Help Erase Hepatitis B : Find Out How to Reduce Your Risk Contact: Merck and Company, PO Box 4, West Point, PA, 19486-0004, (215) 652-5000, http://www.merck.com. Summary: This brochure explains the hepatitis B virus (HBV) and its prevention. The brochure defines HBV and methods of transmission from person to person. It identifies the high-risk behaviors that can put the readers at risk for HBV. The brochure also emphasizes that, while HBV is easier to contract than the human immunodeficiency

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virus (HIV)/acquired immune deficiency syndrome (AIDS), it is also easier to prevent. The brochure identifies the symptoms associated with HBV and explains that the HBV vaccine can prevent the infection. ·

Hepatitis C. Information for Inmates Contact: SIDA Nouveau Brunswick/AIDS New Brunswick, 65 Brunswick St, Fredericton, (506) 459-7518, http://www.aidsnb.com. Summary: This brochure for incarcerated persons provides information about hepatitis C through a question and answer format. The following topics are briefly addressed: transmission through blood, needle and syringe sharing, and sex; diagnosis; disease course; effects on the liver; treatment; occurrence in prison populations; prevention; and the difference between hepatitis B (HBV) and hepatitis C (HCV).

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Hepatitis A : Facts Every Parent Should Know Contact: SmithKline Beecham Pharmaceuticals, PO Box 7929, Philadelphia, PA, 19101, (800) 366-8900, http://www.sb.com/. Summary: This brochure for parents uses a question and answer format to provide information on hepatitis A and the preventive vaccine, Havrix, and includes recommendations from the Center for Disease Control and Prevention (CDC) on hepatitis A vaccination of children. Hepatitis A is an infectious disease of the liver caused by hepatitis A virus (HAV), which can lead to illness, hospitalization, and even death. It is most often spread through personal contact, childcare centers, international travel, and contaminated food or water. Day-care children may be at risk for infection with HAV, and adults and children traveling from the United States to high-risk areas should be vaccinated. The brochure includes a list of these high-risk areas. Symptoms of HAV infection may include fever, nausea, jaundice, fatigue, dark urine, or lack of appetite, or there may be no symptoms present. A laboratory test can identify HAV infection. The effects of HAV infection differ from person to person. In general, younger children's symptoms are not as severe as older persons' symptoms, but infected children without symptoms can still infect others. Symptoms usually last two months, and hospitalization of children due to hepatitis A is unusual. Adults with hepatitis A can lose work, be hospitalized, experience relapse, and have symptoms for up to six months. Havrix is a vaccine used to prevent HAV infection. Given as an injection, a single dose can protect children and adolescents for up to one year. A booster dose is recommended to extend protection. Havrix is licensed in more than 70 countries and is licensed for children in more than 50 countries. The most common side effects are headache and a little soreness in the arm. Detailed prescribing information for Havrix (i.e., description, clinical pharmacology, indications and usage, contraindications, warnings, precautions, adverse reactions, dosage and administration, storage, and how supplied) is included.

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If You Have Hepatitis C: Almost 4 Million Americans Have Been Infected With Hepatitis C Virus Contact: CDC National Prevention Information Network, PO Box 6003, Rockville, MD, 20849-6003, (800) 458-5231, http://www.cdcnpin.org. Summary: This brochure for the persons with hepatitis C provides information on the effects, treatment, transmission, and prevention of hepatitis C. Hepatitis C is a liver disease caused by the hepatitis C virus (HCV), which is spread by contact with blood of persons infected with the virus. Some persons carry hepatitis C and do not feel sick from the disease. Others with liver damage due to HCV may develop cirrhosis (scarring) of

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the liver and liver failure. Persons who test positive for HCV should contact their doctors, as additional tests may be needed. Many persons with hepatitis C have no symptoms and feel well, but should still see their doctors. To take care of their livers, persons with HCV should see their doctors regularly, not drink alcohol, tell their doctor about all medicines they are taking, and be vaccinated against hepatitis A if there is liver damage. Drugs are licensed for the treatment of long-term hepatitis C. However, there is no vaccination against hepatitis C. Hepatitis C may have been acquired if persons injected street drugs, were treated for clotting problems with a blood product made before 1987, received a blood transfusion or solid organ transplant from an infected donor, were ever on long-term kidney dialysis, were health care workers and had frequent contact with blood in the work place, had mothers who had hepatitis C, had sex with a person infected with HCV, or lived with someone who was infected with HCV and shared items that might have had blood on them. To prevent the spread of HCV, persons with hepatitis C should not donate blood, body organs, other tissue, or sperm; should not share personal care articles that might have blood on them; should cover cuts and open sores; and may consider using barrier precautions during sex, although there is a low chance of transmitting HCV to a partner through sexual activity. About five out of every 100 infants born to women with HCV become infected; there is no preventable treatment. HCV is not spread by breast feeding, casual contact, food or water, sneezing, coughing, or sharing eating utensils or drinking glasses. Injection drug users should seek treatment, use clean drug works, and get vaccinated against hepatitis A and B. Persons having sex with more than one partner can get other diseases, should use latex condoms, should be vaccinated against hepatitis B, and may want to consider abstinence from sex. ·

Hepatitis B : What School Personnel Need to Know Contact: SmithKline Beecham Pharmaceuticals, PO Box 7929, Philadelphia, PA, 19101, (800) 366-8900, http://www.sb.com/. Summary: This brochure informs educators and school personnel about how they can protect themselves against the hepatitis B virus (HBV). The brochure describes HBV, its transmitted, and its symptoms. It examines the curability rate for HBV and identifies those persons who are at the highest risk for contracting HBV. It explains that HBV can help to be prevented through vaccination and provides the readers with information about this vaccine. It recommends that school employees get vaccinated and that they follow universal precautions as set forth by the Occupational Safety and Health Administration (OSHA).

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Hepatitis B: 100 Times Easier to Catch than HIV! Source: St. Paul, MN: Immunization Action Coalition. 1997. 2 p. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Fax (612) 647-9131. PRICE: $1.00. Summary: This brochure informs readers about hepatitis B and how to prevent it. Hepatitis B is a sexually transmitted liver disease caused by the hepatitis B virus (HBV). The brochure warns that HBV is easier to catch than HIV because it is over 100 times more concentrated in an infected person's blood. Written in a question and answer format, the brochure discusses risk factors for HBV infection, how to prevent transmission, the role of vaccination, how HBV is spread, symptoms, carrier status and its complications, how to know if one has had hepatitis B, and where to get hepatitis B shots. The brochure features line drawings of two young men and is targeted at a gay

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and bisexual reader population. The brochure reiterates the importance of vaccinations and includes the contact information for the Hepatitis B Coalition. ·

Hepatitis B: The Other Virus Contact: Ireland Department of Health, Health Promotion Unit, Hawkins House, Dublin. Summary: This brochure presents basic information about hepatitis B, an infection of the liver that is prevalent among drug users, gay men, and sexual partners of high-risk individuals. The incidence and prevalence of hepatitis B in Ireland is addressed and transmission factors, symptoms, and treatment are reviewed. Safe sexual practices, safer drug use, and good hygiene methods are recommended.

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Merge With Caution : If You Think You Have an STD. Make Sure You're Vaccinated Against Hepatitis B Contact: SmithKline Beecham Pharmaceuticals, PO Box 7929, Philadelphia, PA, 19101, (800) 366-8900, http://www.sb.com/. Summary: This brochure presents information to the general public about the hepatitis B virus (HBV). The brochure describes HBV, its modes of transmission, and its symptoms. It describes the vaccination process for HBV and its effectiveness against the virus. The brochure identifies the high-risk behaviors including unprotected sexual intercourse, associated with the transmission of HBV and risk factors, such as previoulsy being infected with a sexually transmitted disease (STD), that can help to facilitate its spread.

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Hepatitis Basics Contact: International Health Awareness Center, HOPE Publications, 350 E Michigan Ave Ste 301, Kalamazoo, MI, 49007-9834, (616) 343-0770, http://www.hopepublications.com. Summary: This brochure provides general and prevention information concerning the hepatitis A virus (HAV), hepatitis B virus (HBV), and the hepatitis C virus (HCV). For HAV, HBV, and HCV the brochure discusses the methods of transmission, symptoms, and treatment options if ones is exposed to the viruses. For each type of hepatitis, the brochure identifies a number of prevention techniques and explaines the HAV and HBV vaccines.

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Hepatitis B--Stop the Spread Contact: Channing L. Bete Company Incorporated, 200 State Rd, South Deerfield, MA, 01373-0200, (800) 477-4776, http://www.channing-bete.com. Summary: This brochure provides information concerning the hepatitis B virus (HBV). The brochure explains that HBV is a disease that affects the liver and can have severe long term complications if left untreated. It identifies the ways that HBV can and cannot be spread from person to person, and identifies the symptoms of the infection. The brochure explains that the best protection against HBV is the HBV vaccine and lists those who should get vaccinated, especially pregnant women and their infants. Other ways of preventing HBV discussed include practicing safer sex through the use of a condom, avoiding injection drug use or sharing needles for such a purpose, cleaning needle works after every use, and avoiding sharing personal items that may contain blood.

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About Hepatitis A Contact: Channing L. Bete Company Incorporated, 200 State Rd, South Deerfield, MA, 01373-0200, (800) 477-4776, http://www.channing-bete.com. Summary: This brochure provides readers with information concerning the hepatitis A virus (HAV) and its prevention. The brochure describes HAV and its methods of transmission. It states that HAV can be prevented through vaccination, proper personal hygiene and sanitation. It discusses risk factors associated with children, contaminated food, travelers, health care workers, intercourse, and injection drug use. The brochure also discusses risk reduction and makes recommendations about available treatments for HAV.

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Hepatitis B : What Public Safety Workers Need to Know Contact: SmithKline Beecham Pharmaceuticals, PO Box 7929, Philadelphia, PA, 19101, (800) 366-8900, http://www.sb.com/. Summary: This brochure provides safety professionals with information concerning the hepatitis B virus (HBV) and prevention techniques for occupational settings. The brochure describes HBV, symptoms, and methods of transmission. It identifies the reasons that public safety workers are at high risk for HBV and explains what can be done to prevent the virus. The brochure examines the HBV vaccine, its effectiveness, side effects, and benefits for public safety workers.

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Facts About Hepatitis C : The Silent Epidemic Contact: Hazelden Foundation, Educational Materials, PO Box 176, Center City, MN, 55012-0176, (651) 213-4000, http://www.hazelden.org. Summary: This brochure provides the general public with information about the sexually transmitted disease (STD), hepatitis C. It discusses what hepatitis C is, its epidemiology, transmission, the course of infection, symptoms and complications, atrisk populations who should be tested, the meaning of a positive test result, curability, and transmission.

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The Hepatitis Information You Need to Know Contact: American Liver Foundation, 75 Maiden Ln Ste 603, New York, NY, 10038-4826, (973) 256-2550, http://www.liverfoundation.org. Summary: This brochure, for injection drug users (IDUs), discusses the serious liver disease, hepatitis C (HCV). It provides information on HCV transmission (e.g., by sharing needles, having unsafe sex, and unsanitary conditions); the importance of testing for HCV; how to prevent HCV; HCV symptoms; and two other forms of viral hepatitis, hepatitis A and B.

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The Hepatitis Information You Need to Know: The Impact of Viral Hepatitis in Our Community Contact: American Liver Foundation, 75 Maiden Ln Ste 603, New York, NY, 10038-4826, (973) 256-2550, http://www.liverfoundation.org. Summary: This brochure, for Native Americans, examines hepatitis A, B, and C. It provides information on the risk factors for contracting hepatitis A, B, and C; how to reduce one's risk of infection; methods of transmission; testing for and treating hepatitis; hepatitis A and B vaccines; dietary and alcohol considerations for individuals with the

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virus, and relevant epidemiological data. It provides information on the Digestive Health Initiative (DHI) Viral Hepatitis Education Campaign. ·

Getting Hip to Hep : What You Should Know About Hepatitis A, B, and C Contact: American Liver Foundation, 75 Maiden Ln Ste 603, New York, NY, 10038-4826, (973) 256-2550, http://www.liverfoundation.org. Summary: This brochure, for the general public, discusses hepatitis A, hepatitis B, and hepatitis C. The brochure explains how hepatitis infects the liver. For hepatitis A, the brochure provides information on the epidemiology, the means by which it is transmitted, and the groups of individuals who are at risk for this type of virus. For hepatitis B and hepatitis C, the brochure provides information regarding their epidemiology; the possible long-term effects if left untreated; those groups of individuals who are at risk for hepatitis B and hepatitis C; and the way these viruses are transmitted. Hepatitis B or C may be asymptomatic or may manifest the symptoms described in the brochure. The different tests available to determine the presence of these types of hepatitis are reviewed and recommendations are made about how to prevent each type of hepatitis, including vaccinations against hepatitis A and B.

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Every Week Thousands of Sexually Active People Are Infected With Hepatitis B Contact: Immunization Action Coalition, 1573 Selby Ave Ste 234, St Paul, MN, 55104, (651) 647-9009, http://www.immunize.org. Summary: This brochure, written for the general public, discusses the hepatitis B virus (HBV). Hepatitis B is a sexually transmitted liver disease, caused by HBV, which is much easier to contract than the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and can cause severe liver disease, scarring, and liver cancer. A quiz is supplied in the brochure for individuals to use to assess their risks for HBV. HBV can be spread through unprotected vaginal or anal sex, needle-sharing for injection drugs use, contact with open sores, and prolonged exposure to an individual with HBV. It can also be contracted through body piercing or tattooing with unsterile equipment, the sharing of personal products that may contain blood such as toothbrushes or razors, and human bites. Individuals can protect themselves from HBV through vaccination and by practicing safer sex. The symptoms of hepatitis B include loss of appetite, nausea, fever, dark-colored urine, jaundice, fatigue, joint pain, and a bloated and tender belly. Most people who get HBV will fully recover; however, a small percentage will carry the infection in their bodies for life. The only way for individuals to know if they have been infected with HBV is to get tested. The HBV vaccine will not protect individuals from the hepatitis A vaccine (HAV) or the hepatitis C virus (HCV). The HBV vaccine may be available at no charge through clinics or health departments.

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Does Your Patient Have Chronic Hepatitis B? Source: St. Paul, MN: Hepatitis B Coalition. 1997. 1 p. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Fax (612) 647-9131. PRICE: $1.00. Summary: This fact sheet answers common questions that health care providers may have about chronic hepatitis B virus (HBV) infection. Topics include how chronic HBV infection is diagnosed; the outcomes in a patient with chronic HBV infection, including the possibilities of liver cirrhosis and primary hepatocellular carcinoma (HCC, or liver cancer); the liver damage caused by HBV; the need for ongoing patient followup, even

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when test batteries indicate a lower infection rate; management of patients who are chronically infected with HBV; and the treatment modalities. Approximately 40 percent of suitable patients with chronic HBV with significant liver damage and ongoing viral replication benefit from treatment with interferon. Those who are most likely to respond to treatment for HBV are those who have evidence of liver damage and low HBV DNA levels. Because interferon may have significant risks and side effects associated with its use, treatment should be carried out by a gastroenterologist or hepatologist with experience in the antiviral treatment of chronic hepatitis. 1 table. (AA-M). ·

ABC's of Hepatitis Source: Silver Spring, MD: Hepatitis Foundation International. 2000. 1 p. Contact: Available from Hepatitis Foundation International. 504 Blick Drive, Silver Spring, MD 20904. (800) 891-0707 or (301) 622-4200. Fax: (301) 622-4702. E-mail: [email protected]. Website: www.hepfi.org. PRICE: Full-text available online at no charge; contact organization for print copies. Summary: This fact sheet consists of a chart detailing five different types of hepatitis: hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV, or delta virus), and hepatitis E virus (HEV). For each type, the chart lists a brief definition, the incubation, transmission, symptoms, treatment of chronic disease, vaccine (when available), risk factors, and prevention strategies. The fact sheet also includes the contact information for Hepatitis Foundational International (800-891-0707).

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Recommended Dosages and Schedules of Hepatitis A Vaccines. Recommended Dosages of Hepatitis B Vaccines Source: St. Paul, MN: Immunization Action Coalition. 1997. 1 p. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 234, St. Paul, MN 55104. (612) 647-9009. Fax (612) 647-9131. PRICE: $1.00. Summary: This fact sheet consists of two charts designed to guide clinic workers who are administering vaccinations. The first chart lists recommended dosages and schedules of hepatitis A vaccines; the second lists recommended dosages of hepatitis B vaccines. The first chart (hepatitis A) notes the vaccine brand, the group of patients in whom it is used, ages, dose, volume, number of doses, and schedule. Two vaccine brands are noted: Havrix (SmithKline Beecham) and VAQTA (Merck and Co.). The hepatitis B chart notes HBV risk group or age group and the dosages for two different brands: Engerix-B (SmithKline Beecham) and Recombivax HB (Merck and Co.). The chart reminds users that different vials contain different concentrations of vaccine. In addition, once one brand is started, the same brand should be used to complete the series. An end note provides recommendations for adult patients on dialysis.

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Universal Precautions for the Prevention of Human Immunodeficiency Virus, Hepatitis B Virus and Other Blood - Borne Diseases in the Medical Center Contact: US Department of Veterans Affairs, Central Texas Veterans Health Care System, Thomas T Connally Integrated Clinical Facility, 1016 Ward St, Marlin, TX, 76661, (254) 883-3511, http://www.va.gov/facilities. Summary: This fact sheet details the Veterans Administration Medical Center in Marlin, TX, policy on implementing universal precautions to prevent the transmission of the Human immunodeficiency virus (HIV), the Hepatitis B virus (HBV), and other

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bloodborne illnesses. The fact sheet outlines the policy of the center, and the responsibilities of the medical center director and medical center employees. ·

What is the Role of Prisons in HIV, Hepatitis, STD and TB Prevention? Contact: University of California San Francisco, Center for AIDS Prevention Studies, 74 New Montgomery St Ste 600, San Francisco, CA, 94105, (415) 597-9100, http://www.caps.ucsf.edu/capsweb. CDC National Prevention Information Network, PO Box 6003, Rockville, MD, 20849-6003, (800) 458-5231, http://www.cdcnpin.org. Summary: This fact sheet discusses the role of prisons in the prevention of the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), hepatitis, sexually transmitted diseases (STDs), and tuberculosis (TB). Rates of these diseases are higher for the incarcerated than for the total United States population. Although most inmates with infectious diseases come to jail or prison already infected, there is some evidence that infection also occurs during incarceration, especially TB and the hepatitis C virus (HCV) infection. Inmates are at risk due to injection drug use, other illicit drug use, unprotected sex, tattooing, and close quarters. Often problems that led to incarceration are also associated with increased risk for infection. The role of prisons in prevention is important because there are many opportunities for preventing, testing, and treating infectious diseases, and prisons provide a venue for drug treatment and education and STD screening. Obstacles to prevention include illegal activities that take place in prisons (e.g., sex, rape, drug use, tattooing), the prohibition against condom possession or distribution and needles and syringes in prisons, and risky celebratory behavior in which ex-prisoners may participate upon release. The fact sheet describes three prison programs that are addressing infectious disease prevention and recommends a collaboration among inmate service providers, prevention efforts that begin immediately upon the inmates detainment and continue upon release, substance abuse treatment, a change in laws regarding access to condoms and clean needles, and access to screening, testing, and treatment.

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Chronic Hepatitis C: Current Disease Management Source: Bethesda, MD: National Digestive Diseases Information Clearinghouse (NDDIC). 2001. 12 p. Contact: Available from National Digestive Diseases Information Clearinghouse (NDDIC). 2 Information Way, Bethesda, MD 20892-3570. (800) 891-5389 or (301) 6543810. Fax (301) 634-0716. E-mail: [email protected]. Website: www.niddk.nih.gov. PRICE: Full-text available online at no charge; single copy free; bulk copies available. Order number: DD-172. Summary: This fact sheet educates readers about current patient care management strategies for people with chronic hepatitis C, which can cause cirrhosis, liver failure, and liver cancer. Approximately 20 percent of patients develop cirrhosis within ten to twenty years of the onset of infection. Liver failure resulting from chronic hepatitis C is one of the most common reasons for liver transplants in the U.S. Men, alcoholics, cirrhosis patients, people over age 40, and those infected for 20 to 40 years are more likely to develop HCV-related liver cancer. The fact sheet outlines the risk factors and transmission of hepatitis C virus (including sexual transmission, maternal-infant transmission, and sporadic transmission); and the clinical signs and symptoms, including those for cirrhosis and the extra-hepatic (nonliver) manifestations. The fact sheet also explains diagnostic tests used to confirm and monitor HCV infection, including enzyme immunoassays, recombinant immunoblot assays, PCR amplification,

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quantification of HCV RNA in serum, genotyping and serotyping of HCV, normal serum ALT levels, liver biopsy, and immunostaining; differentiating between acute and chronic hepatitis C; treatment options, notably the use of alpha interferon and patient selection issues; patient education; options for patients who do not respond to treatment; and the side effects of treatment. The fact sheet concludes with a discussion of present and future efforts in hepatitis C research. A brief description of the National Digestive Diseases Information Clearinghouse is provided on the back page, along with the contact information for two other sources of patient education materials. 5 figures. 9 references. ·

Hepatitis A and B Vaccination Source: Cedar Grove, NJ: Hepatitis Foundation International. 2002. 1 p. Contact: Available from Hepatitis Foundation International. 504 Blick Drive, Silver Spring, MD 20904-2901. (301) 622-4200. Fax (301) 622-4702. E-mail: [email protected]. Website: www.hepatitisfoundation.org. PRICE: $2.00 for 5 copies; discounts available for bulk orders. Summary: This fact sheet from Hepatitis Foundation International reviews vaccination for hepatitis A and hepatitis B. The fact sheet presents brief information on the vaccines for each type of hepatitis, including recommendations for who should have the vaccines, and dosage and administration schedules. The publication also briefly explains the transmission of each of these viruses.

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Diet and Hepatitis C Source: New York, NY: American Liver Foundation. 1998. [3 p.]. Contact: Available from American Liver Foundation. 1425 Pompton Avenue, Suite 3, Cedar Grove, NJ 07009. (800) 465-4837. E-mail: [email protected]. Website: www.liverfoundation.org. PRICE: $0.50 for a single copy; bulk copies available; plus shipping and handling. Also available for free at gi.ucsf.edu/ALF/info/diethepc.html. Summary: This fact sheet from the American Liver Foundation reviews the relationship between diet and hepatitis C, a virus that infects the liver. General guidelines for individuals infected with HCV include maintaining a healthy lifestyle; eating a well balanced, low fat diet; and avoiding alcohol. A diet high in complex carbohydrates may be helpful in providing calories and maintaining weight. Adequate rest and moderate exercise can also contribute to a feeling of well being. Total avoidance of all alcohol intake is recommended, as alcohol is a potent toxin to the liver. Patients with chronic hepatitis C sometimes have an increase in the iron concentration in the liver, which can be very damaging; thus, they should avoid the use of iron supplements and monitor or restrict their intake of iron rich foods. Patients with chronic hepatitis C are advised to achieve and maintain normal weight, preferably in consultation with their physician. Adequate protein intake is important to build and maintain muscle mass and to assist in healing and repair. The fact sheet describes the complication of encephalopathy (impaired mental status), which may be related to protein intake; the fact sheet recommends vegetable protein consumption. Patients with hepatitis C who have ascites (fluid accumulation) must be on sodium restricted diets. The fact sheet concludes by reminding readers with chronic liver disease to be aware of the medications that they take; although they are not food, medications must pass through the liver to be metabolized.

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Hot Sheet: Listing of Useful Telephone Numbers and Homepage Addresses for Those Interested in Hepatitis B Source: Jenkintown, PA: Hepatitis B Foundation. 1997. 2 p. Contact: Available from Hepatitis B Foundation. 101 Greenwood Avenue, Suite 570, Jenkintown, PA 19046. (215) 884-8786. Fax (215) 887-1931. PRICE: Single copy free. Summary: This fact sheet lists telephone numbers and information for readers interested in hepatitis B virus (HBV). Sections provide information about the Hepatitis B Foundation; HBV vaccines, including brand names; support groups; resources; drug development; the three levels of infections from HBV; and a glossary of related medical terms. The drug development section briefly describes clinical trials underway on various drugs and includes reference(s) for additional information about each study.

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Hepatitis C Combination Therapy Source: Cedar Grove, NJ: American Liver Foundation. 1999. 2 p. Contact: Available from American Liver Foundation. Information and Distribution Center, 1425 Pompton Avenue, Suite 3, Cedar Grove, NJ 07009-1000. (800) GO-LIVER, ext. 234 or (888) HEP-ABC. Fax (973) 256-3214. E-mail: [email protected]. Website: www.liverfoundation.org. PRICE: $0.50 for single copy; bulk orders available; plus shipping and handling. Summary: This fact sheet lists the American Liver Foundation's (ALF) Helpline callers' most frequently asked questions about hepatitis C combination therapy, with brief answers for each question. The fact sheet notes that the combination of interferon (Intron A) and ribavirin (Rebetol) is the treatment that has been approved by the Food and Drug Administration (FDA) for hepatitis C patients who have never had any interferon therapy and for patients who have relapsed following interferon therapy. The combination therapy is marketed by Schering as Rebetron. The fact sheet reviews patient candidacy for this therapy, the percentage of success (approximately 40 percent), the dosage and duration of combination therapy, side effects associated with Rebetron, the success of combination therapy in previous nonresponders, and other treatment options for hepatitis C patients. The fact sheet concludes with a table of the FDA approved therapies for hepatitis C, categorized by patient type (first time therapy, prior treatment then relapse, and nonresponders). The ALF Helpline (888-4-HEP-USA) welcomes all questions from patients, family members, and health care professionals. The fact sheet includes the hotline numbers and website for the ALF (www.liverfoundation.org).

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Fact Sheet: Hepatitis, Liver and Gallbladder Diseases in the United States Source: New York, NY: American Liver Foundation. 1997. 2 p. Contact: Available from American Liver Foundation. 75 Maiden Lane, Suite 603, New York, NY 10038. (800) 465-4837. Fax: (212) 483-8179. E-mail: [email protected]. Website: www.liverfoundation.org. PRICE: $.50; discounts available for large orders. Summary: This fact sheet offers basic statistics about hepatitis (liver inflammation), liver, and gallbladder diseases in the United States. The fact sheet covers epidemiology, mortality (deaths), etiology (causes), transmission, chronic disease (hepatitis), costs, risk factors, ethnic groups, transplantation, and prevention. The fact sheet concludes with the contact information for the American Liver Foundation, a nonprofit, national

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voluntary health organization dedicated to the prevention, treatment, and cure of hepatitis and other liver diseases. (www.liverfoundation.org). ·

Vaccination for Hepatitis A and B Source: Bethesda, MD: National Digestive Diseases Information Clearinghouse (NDDIC). 2000. 2 p. Contact: Available from National Digestive Diseases Information Clearinghouse (NDDIC). 2 Information Way, Bethesda, MD 20892-3570. (800) 891-5389 or (301) 6543810. Fax (301) 634-0716. E-mail: [email protected]. Website: www.niddk.nih.gov. PRICE: Full-text available online at no charge; single copy free; bulk copies available. Summary: This fact sheet outlines vaccination recommendations for the prevention of hepatitis A and hepatitis B. The front side outlines vaccination for hepatitis A. Routine vaccination is recommended for children living in areas with high prevalence of hepatitis A and periodic outbreaks. The fact sheet lists high risk populations, including: travelers to developing countries, including Mexico; men who have sex with men; users of illegal injection drugs; people who work with hepatitis A virus in research settings; people who work with nonhuman primates; recipients of clotting factor concentrates; and people with chronic liver disease (because of risk of fulminant hepatitis A). The fact sheet then notes the recommended doses and schedules for HAVRIX (SmithKline Beecham) and VAQTA (Merck and Company). A final section describes postexposure prophylaxis. Immune globulin is more than 85 percent effective in preventing hepatitis A when given within 2 weeks of exposure to the hepatitis A virus. The reverse side of the fact sheet outlines vaccination for hepatitis B. Routine vaccination is recommended for all infants and for children age 11 to 12 years who have not been vaccinated previously. The fact sheet lists high risk populations, then notes the doses and schedules for Recombivax HB (Merck and Company) and for Energix-B (SmithKline Beecham). Prophylactic treatment for exposure to hepatitis B virus involves either hepatitis B immune globulin, hepatitis B vaccine, or a combination of both. 3 tables.

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Hepatitis Statistics Source: Cedar Grove, NJ: Hepatitis Foundation International. 2001. 2 p. Contact: Available from Hepatitis Foundation International. 504 Blick Drive, Silver Spring, MD 20904-2901. (301) 622-4200. Fax (301) 622-4702. E-mail: [email protected]. Website: www.hepatitisfoundation.org. PRICE: $2.00 for 5 copies; discounts available for bulk orders. Summary: This fact sheet presents statistics about hepatitis, primarily in the United States. An introductory section lists general statistics on incidence and mortality. Remaining sections list statistics on hepatitis A, hepatitis B, and hepatitis C and provide information on incidence and prevalence, transmission, risk factors, morbidity, mortality, and symptoms.

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Hepatitis B Toolbox Source: Needle Tips and the Hepatitis B Coalition News. 6(1): 16. January 1996. Contact: Available from Hepatitis B Coalition. Immunization Action Coalition, 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Fax (612) 647-9131. E-mail: [email protected]. WWW site: http://www.winternet.com/.

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Summary: This fact sheet provides a summary of information for health care providers on hepatitis B. Three sections outline groups at risk for hepatitis B virus infection, interpretation of the hepatitis B panel, and the laboratory diagnosis of chronic hepatitis B, C, and D. Brief information is included with the summary boxes. The fact sheet is designed to be posted as a reminder for health care providers. ·

Hepatitis A: GMHC Treatment Issues Fact Sheet. Translated title Contact: Gay Mens Health Crisis, 119 W 24th St Tisch Bldg, New York, NY, 10011-1995, (212) 367-1205, http://www.gmhc.org. Summary: This fact sheet provides basic information about Hepatitis A in both English and Spanish. The fact sheet defines Hepatitis A and explains that it is transmitted through direct or indirect contact with fecal material. Hepatitis A is common among gay men. Symptoms and prevention are described, including a discussion of a newlyapproved Hepatitis-A vaccine. While no specific treatment for Hepatitis A is available, the patient will benefit from bed rest and proper nutrition.

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Management of Chronic Hepatitis B in Children and Guidelines in Adults with Chronic Hepatitis B Source: St. Paul, MN: Hepatitis B Coalition. 1997. 2 p. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Fax (612) 647-9131. PRICE: $1.00. Summary: This fact sheet provides guidelines for the management of chronic hepatitis B in children and in adults. Topics in the first section include tests to be done once a child is found to be HBsAg positive, follow up in children, considerations for therapy in children, and vaccination indications for household members and close, frequent contacts of children with chronic hepatitis B. The author stresses that interferon has been shown to hasten the rates of remission in adults and children. All children with elevated serum liver enzymes (ALT, AST) more than 2 to 3 times the normal range, evidence of active viral replication, and evidence of active disease on liver biopsy should be considered candidates for interferon therapy. The section on adults with chronic hepatitis B emphasizes that all patients who are HBeAg positive with elevated liver enzymes for more than 6 months should be referred for liver biopsy. Treatment options include interferon, experimental trials with lamivudine (3TC) and famciclovir, and liver transplantation. Patients with evidence of cirrhosis and signs of decompensation of their liver disease should be evaluated for liver transplantation. (AA-M).

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Hepatitis. [Hepatitis] Contact: Project Inform, HIV Treatment Hotline, 205 13th St Ste 2001, San Francisco, CA, 94103, (415) 558-8669, http://www.projectinform.org. Summary: This fact sheet provides information on hepatitis A, B, and C, and their effects on persons with the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS). The fact sheet discusses symptoms, prevention (postexposure prevention for hepatitis A and B), and treatment. It provides information on experimental and alternative/supplemental therapies, new drugs in development, considerations for therapy, and multidrug-resistant TB.

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HIV/AIDS and Hepatitis C in Prisons: The Facts Contact: Canadian Public Health Association, Canadian HIV/AIDS Clearinghouse, 4001565 Carling Ave Ste 400, Ottawa, (613) 725-3434, http://www.cpha.ca. Summary: This fact sheet provides statistics on the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and the hepatitis C virus (HCV) in Canadian federal prisons (where offenders sentenced to terms of two years or more serve their terms), Canadian provincial prisons (where offenders sentenced to terms of less than two years serve their terms), and prisons worldwide. Statistics are tabulated by gender and geographic region. Rates of HIV-infection in inmate populations are closely related to two factors: the proportion of prisoners who injected drugs prior to imprisonment and the rate of HIV infection among injection drug users in the community. And while most HCV-positive inmates come to prison already infected, there is potential for further spread of the virus in the prison system.

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Diagnosis and Treatment of Viral Hepatitis Source: Cedar Grove, NJ: Hepatitis Foundation International. 2001. [2 p.]. Contact: Available from Hepatitis Foundation International. 504 Blick Drive, Silver Spring, MD 20904-2901. (301) 622-4200. Fax (301) 622-4702. E-mail: [email protected]. Website: www.hepatitisfoundation.org. PRICE: $0.75 for single copy; discounts available for bulk orders. Summary: This fact sheet reviews the diagnosis and treatment of viral hepatitis. The fact sheet describes each type of hepatitis separately, including hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV), hepatitis D (HDV), and hepatitis E (HEV). For each type, the fact sheet notes diagnostic tests and strategies, risk factors for transmission, treatment options, and prevention. For hepatitis A, 99 percent of those infected will recover without treatment. Individuals exposed to hepatitis A through household and close personal contact or who plan to travel to developing countries where sanitary conditions are poor can receive temporary immunity (less than 3 months) by having immune globulin (IG) administered intramuscularly. Vaccines to prevent HAV infection prior to exposure provide protection against the virus as early as 2 to 4 weeks after vaccination. While there is no treatment for acute hepatitis B, there are two approved treatments for chronic HBV: interferon alfa 2b and lamivudine. Patients with chronic HBV should be vaccinated against HAV. Safe and effective vaccines provide protection against hepatitis B for 15 years and possibly much longer. All children and adolescents should be vaccinated since most cases of HBV occur in sexually active young adults. Infection by the HCV can be determined by a blood test that detects HCV antibodies in the blood. Over 80 percent of HCV infections become chronic, which result in increased risk for end stage liver disease. Currently, there are three types of interferon and a combination of interferon and ribavirin used to treat hepatitis C. Treatment may be prolonged and given a second time to those who relapse after initial treatment. Anyone with hepatitis C should be vaccinated against hepatitis A and B and should not drink alcohol. The contact information for the Hepatitis Foundation International is provided (800-891-0707).

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Who's at Risk for Hepatitis C? Contact: Schering Corporation, 2000 Galloping Hill Rd, Kenilworth, NJ, 07033, http://www.schering.de/eng.index.html.

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Summary: This fact sheet, for adolescents and young adults, discusses hepatitis C, the leading cause for liver transplants in the United States, and reports the latest epidemiological data available for hepatitis C. It discusses risk factors for hepatitis C such as blood transfusions, hemodialysis, ear or body piercing, and tatoos. The fact sheet contains an exercise to help readers identify individuals if they are at high-risk for hepatitis C. ·

Hepatitis B : Facts for Health Professionals Contact: Washington State Department of Health Office of STD Services, PO Box 47842, Olympia, WA, 98504-7842, http://www.doh.wa.gov/cfh/STD/default.htm. Summary: This fact sheet, for health professionals, discusses the viral liver infection, hepatitis B. It discusses the risk factors, transmission, symptoms, prevention, incubation period, and treatment of hepatitis B. The fact sheet discusses a vaccine available to protect people from hepatitis B.

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If You Are a Hepatitis B Carrier. Contact: Immunization Action Coalition, 1573 Selby Ave Ste 234, St Paul, MN, 55104, (651) 647-9009, http://www.immunize.org. Summary: This fact sheet, for individuals with the hepatitis B virus (HBV), provides information about self-care and protecting others from HBV. Individuals with HBV should see their doctors at least once a year for a liver evaluation. It is recommended that HBV carriers discuss with their doctors if they are eligible for the medication, interferon alfa-2b, and get periodic tests to detect evidence of liver cancer. Individuals should talk with their physicians about the medications they are taking, should tell them if they are pregnant, and should avoid alcoholic beverages. If persons with HBV have advanced beyond being 'healthy carriers,' they should get an influenza and a hepatitis A virus (HAV) vaccine and should not eat raw oysters. HBV carriers can help to protect others from this disease by informing their sex partners and health care workers of their infection, making sure all household members see a physician, covering all cuts and sores with bandages, disposing of personal items that may contain blood, washing their hands after touching blood or body fluids, and cleaning up blood spills. To protect others from infection, individuals with HBV should not share personal products that may contain blood, share food that has been in their mouths, share needles or syringes, or donate blood or organs.

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Basic Knowledge About Hepatitis B Contact: Immunization Action Coalition, 1573 Selby Ave Ste 234, St Paul, MN, 55104, (651) 647-9009, http://www.immunize.org. Summary: This fact sheet, written for health care professionals, provides basic information about hepatitis B. Specifically it identifies moderate- and high-risk groups who should be vaccinated and who need serologic testing. The fact sheet also discusses interpretation of the hepatitis B panel and laboratory diagnosis of chronic hepatitis B, C, and D.

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Hepatitis C : Know the Facts Contact: Hepatitis Foundation International, 30 Sunrise Terr, Cedar Grove, NJ, 07009, (800) 857-0707.

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Summary: This fact sheet, written for the general public, discusses the modes by which the hepatitis C virus (HCV) is transmitted. HCV is not airborne, and it cannot be spread through sneezing, coughing, holding hands, closed mouth kissing or kissing on the cheek, sharing a bathroom, having someone over for dinner, or holding a child. HCV is in the blood of an infected person. HCV can be spread by using something with infected blood on it such as razors, nail clippers, scissors, toothbrushes, water pics, tattoo or body piercing needles, injection drug needles, tampons, or sanitary napkins. The virus must enter the body through the skin or mucous membrane. Many of the people who are infected with HCV are unaware that they have the virus. Anyone who has shared any of the items listed above in the past twenty years should get tested for HCV. ·

Preventing AIDS and Hepatitis B in the Workplace Contact: de'MEDICI Systems, 1047 El Camino Real Ste 202, Menlo Park, CA, 94025, (415) 326-1600. Summary: This information package describes a computer-assisted instruction, interactive software package designed to prevent hospital employee exposure to Hepatitis B and Human immunodeficiency virus (HIV), the etiologic agent of Acquired immunodeficiency syndrome (AIDS). The training program ensures that hospitals comply with occupational safety standards. A recordkeeping system tracks employee vaccinations and training sessions.

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Promote prevention: Hepatitis: Education and information for patients and professionals Source: Bethesda, MD: National Digestive Diseases Information Clearinghouse. ca. 1999. 7 items. Contact: Available from National Digestive Diseases Information Clearinghouse, 2 Information Way, Bethesda, MD 20892-3570. Telephone: (301) 654-3810 (800) 891-5389 / fax: (301) 907-8906 / e-mail: [email protected] / Web site: http://www.niddk.nih.gov. Available at no charge. Summary: This information package includes materials for use by health care professionals with their patients including three booklets describing Hepatitis A, B, and C; a booklet titled Chronic Hepatitis C: Current Disease Management; a fact sheet on vaccinations for hepatitis A; a list of professional and patient education publications; and an order form.

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Management of Chronic Hepatitis B in Children and Adults Source: St. Paul, MN: Hepatitis B Coalition. 1997. 12 p. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Fax (612) 647-9131. PRICE: $5.00. Summary: This information packet contains six fact sheets addressing common concerns that health care providers may have about chronic hepatitis B virus (HBV) infection in children and adults. The six fact sheets are: Does Your Patient Have Chronic Hepatitis B?; Management of the HBsAg Positive Patient; Management of Chronic Hepatitis B in Adults; Management of Chronic Hepatitis B in Children and Adults; and What the Physician Can Do to Help the Child Who is a Hepatitis B Carrier. Topics include how chronic HBV infection is diagnosed; the outcomes in a patient with chronic infection, including the possibilities of liver cirrhosis and primary hepatocellular carcinoma (HCC, or liver cancer); the liver damage caused by HBV; the need for ongoing patient

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followup, even when test batteries indicate a lower infection rate; the management of patients who are chronically infected with HBV; the treatment modalities available; the natural history of HBV; risk factors for transmission; indications for testing of sexual and household contacts; and diagnostic testing and followup in children. 2 figures. 2 tables. ·

Hepatitis C (HCV) Information Packet Contact: Hepatitis C Support Project, PO Box 427037, San Francisco, CA, 94142-7037, (415) 978-2400, http://www.hcvadvocate.org. Summary: This information packet, for the general public, provides information about the hepatitis C virus (HCV), which can cause chronic liver disease. It discusses the statistics of HCV incidents in the United States and it provides information on testing for HCV, its symptoms, treatment, and prevention. It discusses conditions linked to HCV, co-infection with HIV and HCV, and clinical trials. It presents treatment options from a western/conventional medicine and an alternative/complementary perspective. These treatments include interferon, rebetron, ribavirin, amantadine, infergen, pegylated (PEG), pegylated interferon, maxamine, ribozmes, new therapies, herbs, Traditional Chinese Medicine (TCM), acupuncture, and Qi Gong. The brochure provides information on managing HCV and discusses hepatitis A and B vaccines, nutrition, and additional self-care suggestions. For individuals interested in learning more about HCV, contact information for several organizations is provided.

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Hepatitis: Overview Contact: University of New Mexico School of Medicine, New Mexico AIDS Education and Training Center, New Mexico AIDS InfoNet, PO Box 810, Arroyo Seco, NM, 87514, (505) 776-8032, http://www.aidsinfonet.org. Summary: This information sheet discusses hepatitis, an inflammation of the liver, which can be caused by viruses; alcohol; drugs, including prescription medications; poisons; and opportunistic infections such as mycobacterium avium complex, or cytomegalovirus. Viral hepatitis can be caused by seven different viruses and can be acute or chronic. These viruses cause hepatitis A, B, C, D, E, F, and G. Hepatitis B is common among people with human immunodeficiency virus (HIV). The information sheet describes the symptoms; transmission; treatment (including alternative approaches); and prevention of hepatitis through good personal hygiene, vaccines against hepatitis A and B, avoiding close contact or contact with the blood of infected people, using proper sanitation, and using condoms.

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Frequently Asked Questions and Answers about Coinfection with HIV and Hepatitis C Virus Contact: CDC National Prevention Information Network, PO Box 6003, Rockville, MD, 20849-6003, (800) 458-5231, http://www.cdcnpin.org. Summary: This information sheet discusses problems of coinfection with both the human immunodeficiency virus (HIV) and the hepatitis C virus. The sheet explains which HIV positive individuals are most likely to be coinfected, the effects of coinfection on progression of both diseases, prevention suggestions, treatment options, and other disease management guidelines for persons living with HIV and hepatitis C. The information sheet also provides resources for further information.

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The HIV and Viral Hepatitis Co-Epidemics Contact: National Alliance of State and Territorial AIDS Directors, 444 N Capitol St NW Ste 339, Washington, DC, 20001-1512, (202) 434-8090, http://www.nastad.org. Summary: This information sheet examines the relationship between hepatitis and the human immunodeficiency syndrome (HIV)/acquired immunodeficiency syndrome (AIDS). The information sheet explains how hepatitis and HIV/AIDS are related, their joint impact on the public health care system, the relationship between hepatitis and HIV prevention, and how selected state governments and the Centers for Disease Control and Prevention (CDC) are addressing the hepatitis and HIV/AIDS coepidemics.

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Is Hepatitis C (HCV) Transmission Preventable? Contact: University of California San Francisco, Center for AIDS Prevention Studies, 74 New Montgomery St Ste 600, San Francisco, CA, 94105, (415) 597-9100, http://www.caps.ucsf.edu/capsweb. Summary: This information sheet presents information about hepatitis C prevention. The information sheet discusses who is at risk for hepatitis C, available treatments, and how this disease is similar to the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS). It provides information on hepatitis C coinfection in HIV-positive persons, current methods of prevention, and what needs to be done to further promote hepatitis C prevention.

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Resources on Hepatitis Source: Postgraduate Medicine. 107(2): 163-166. February 2000. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Summary: This listing of resources on hepatitis accompanies a four article symposium that provides a practical approach to the diagnosis and management of common hepatic disorders encountered by primary care physicians. The listing is divided into four categories: resources for physicians, resources for patients, publications about hepatitis, and resources on other liver disease topics. Organizations included are the American Association for the Study of Liver Diseases, the American Liver Foundation, the Centers for Disease Control and Prevention (CDC), CliniWeb International, TransWeb, CenterWatch, the C. Everett Koop Institute at Dartmouth, Children's Liver Association for Support Services, Hepatitis B Foundation, HIV and Hepatitis.com, Immunization Action Coalition, National Hepatitis C Coalition, the National Task Force on Hepatitis B Immunization (Focus on Asians and Pacific Islanders), National Cancer Institute, National Center for the Study of Wilson's Disease, Alpha1 Association, Iron Disorders Institute, and the Wilson's Disease Association. The entry for each organization includes the address and telephone numbers, Internet addresses and websites as available, and a short description of the activities and services offered.

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Hepatitis C: Treatment Alternatives Source: Gaithersburg, MD: National Center for Complementary and Alternative Medicine. 2000. 8 p. Contact: Available from National Center for Complementary and Alternative Medicine Clearinghouse. P.O. Box 7923, Gaithersburg, MD 20898. (888) 644-6226;

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INTERNATIONAL PHONE: (301) 519-3153; TTY: (866) 464-3615; FAX: (866) 464-3616; EMAIL: [email protected]. PRICE: Free. Publication Number: D004. Summary: This monograph discusses alternative treatments for hepatitis C. The most promising alternative treatment appears to be the herb commonly called milk thistle. Available evidence suggests that milk thistle does not cure liver disease, but it may improve the way the liver works in patients with cirrhosis. However, there is no evidence indicating that milk thistle directly affects hepatitis C virus (HCV). Licorice root and ginseng also may help reduce the damage to liver tissue caused by hepatitis. Ginger and St. John's wort have been used to treat some of the side effects of conventional treatment with interferon. This article provides the following information: (1) overview of hepatitis C; (2) a summary of evidence for the potential benefits of milk thistle and other herbs; (3) a glossary of terms; (4) practical suggestions for people with HCV infection; (5) a list of organizations for additional information; and (6) 21 references. ·

Hepatitis B: It Can't Be Cured, But It Can Be Prevented Contact: CDC National Prevention Information Network, PO Box 6003, Rockville, MD, 20849-6003, (800) 458-5231, http://www.cdcnpin.org. Summary: This pamphlet discusses hepatitis B, its transmission, symptoms, treatment, and prevention. The pamphlet explains how a pregnant women can protect her baby from the virus, who should be vaccinated for hepatitis B, and where the vaccination is available. It also provides telephone numbers for more information.

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Hepatitis C Contact: Project Inform, National HIV/AIDS Treatment Hotline, 205 13th St Ste 2001, San Francisco, CA, 94103, (415) 558-8669, http://www.projectinform.org. Summary: This pamphlet discusses hepatitis C and how it can affect individuals with the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). The pamphlet examines the relationship between HIV and hepatitis C as a coinfection; how hepatitis C is transmitted, diagnosed, and treated; and the possible drug interactions between those used to treat hepatitis C and those used in HIV treatment.

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Hepatitis C: Understanding the Risk Contact: Channing L. Bete Company Incorporated, 200 State Rd, South Deerfield, MA, 01373-0200, (800) 477-4776, http://www.channing-bete.com. Summary: This pamphlet discusses the facts about the sexually transmitted disease (STD), hepatitis C. The pamphlet explains hepatitis C, how it is transmitted, its effects on the body, what individuals can do to help to prevent its transmission, and what individuals should do if they contract this STD.

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Hepatitis C: Find Out If You're at Risk Contact: Schering Corporation, 2000 Galloping Hill Rd, Kenilworth, NJ, 07033, http://www.schering.de/eng.index.html. Summary: This pamphlet discusses the need to learn about hepatitis C, and describes the disease, the function of the liver, the three types of hepatitis (A, B, and C), their transmission, and how each affects the liver and the body in general. The pamphlet also discusses who is at risk for hepatitis C, who should be tested, and what to do if the test

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is positive. A list of resources that can give more information about hepatitis C and a hepatitis C risk quiz are included. ·

Hepatitis C : Viral Hepatitis Contact: Education Training and Research Associates, PO Box 1830, Santa Cruz, CA, 95061-1830, (800) 321-4407, http://www.etr.org. Summary: This pamphlet examines the transmission, diagnosis, symptoms, prevention, and management of hepatitis C. Hepatitis C is a viral disease that damages the liver. It is usually spread through contact with blood and body fluids by sharing needles or personal items and during sexual intercourse. The pamphlet examines the dangers associated with the disease, describes the symptom management program for people with hepatitis C, and explains how this disease can complicate the treatment of other illnesses.

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What I Need to Know About Hepatitis B Contact: US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, National Digestive Diseases Information Clearinghouse, 2 Information Way, Bethesda, MD, 20814, (301) 654-3810, http://www.niddk.nih.gov. Summary: This pamphlet informs the readers about the hepatitis B virus (HBV). HBV is a viral disease that affects the liver, and is transmitted through unprotected sex, needle sharing among injection drugs users (IDUs), the use of contaminated needles or other paraphernalia for piercings or tattoos, needle stick injuries, or the use of a toothbrush or razor of an infected person. Symptoms of HBV include fatigue, nausea, fever, loss of appetite, stomach pain, diarrhea, dark yellow urine, light-colored stools, and yellowing of the eyes and skin. Some individuals do not experience symptoms. HBV can be diagnosed by testing one's blood or through a liver biopsy. Treatment may involve a drug called interferon or long-term outcomes may include the need for surgery (i.e., a liver transplant). Readers can protect themselves against HBV by getting a vaccination, practicing safer sex with a condom, avoiding sharing drug needles with others, observing universal precautions if working in health or safety setting, avoiding sharing toothbrushes and razors, and insisting that clean needles and other paraphernalia are used when receiving a tattoo.

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About Viral Hepatitis Contact: Channing L. Bete Company Incorporated, 200 State Rd, South Deerfield, MA, 01373-0200, (800) 477-4776, http://www.channing-bete.com. Summary: This pamphlet presents general information about viral hepatitis. This disease, which damages liver cells, can spread easily and can be present in people without them knowing they have the disease. The pamphlet describes the various hepatitis viruses; explains how people are infected with hepatitis A, B, and C viruses; presents the symptoms of viral hepatitis; and discusses treatment for viral hepatitis. Other topics include how to handle possible exposure to viral hepatitis and how to prevent the spread of hepatitis. The pamphlet explains how health care workers can be accidentally infected with a hepatitis virus and presents the safety precautions they should follow to avoid infection. In addition, the pamphlet answers some questions about viral hepatitis.

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Stay Free From Hepatitis B Contact: Channing L. Bete Company Incorporated, 200 State Rd, South Deerfield, MA, 01373-0200, (800) 477-4776, http://www.channing-bete.com. Summary: This pamphlet presents information about the sexually transmitted disease (STD) hepatitis B. The pamphlet discusses hepatitis B, how it is transmitted, and how it affects the body. It explains what individuals can do to help to prevent this STD, including abstaining from sex, practicing safer sex by using condoms, and cleaning of needles by injecting drug users (IDUs).

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Prevent Hepatitis B: Get Vaccinated Summary: This pamphlet promotes prevention of hepatitis B virus (HBV) infection by getting vaccinated. The pamphlet explains the symptoms of HBV infection, the seriousness of the disease, the truth and myths about transmission, and various ways of preventing infection. It advises persons practicing high-risk behaviors, as well as everyone under nineteen years of age, to get vaccinated against HBV. Each year, thousands of people of all ages get hepatitis B and about 5,000 die of chronic (life-long) liver problems caused by HBV infection. HBV is spread by contact with the blood of an infected person or by having sex with an infected person, and a woman who has hepatitis B can spread the virus to her baby during birth. HBV is not spread through sneezing or coughing, kissing or hugging, the sharing of eating utensils, glasses, breast feeding, food or water, or casual contact. Only a blood test can tell for sure if an individual is infected with HBV. To prevent HBV infection, individuals should get vaccinated, practice "safer" sex, not share anything that might have blood on it, think about the health risks associated with getting a tattoo or body piercing, and follow standard precautions when working in healthcare settings. Most individuals do not need to get their blood tested after getting the vaccine. Individuals who should get a blood test one to two months after completing the vaccination series include those whose sex partner has chronic hepatitis B, whose immune system is not working well, or whose job exposes them to human blood.

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Hepatitis A--What You Should Know Contact: Channing L. Bete Company Incorporated, 200 State Rd, South Deerfield, MA, 01373-0200, (800) 477-4776, http://www.channing-bete.com. Summary: This pamphlet provides basic facts about hepatitis A. This viral liver infection is commonly spread by contact with infected feces. The pamphlet identifies other modes of transmission, including anal sex with an infected person; lists the signs of hepatitis A infection; and discusses ways to prevent and treat hepatitis A.

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Hepatitis A Virus Contact: Multicultural Health Communication Service, GPO Box 1614, Sydney, http://www.health.nsw.gov.au/health-public-affairs/mhcs. Summary: This pamphlet provides general information about hepatitis A virus (HAV). It describes the symptoms of HAV, explains how HAV is transmitted and how people with HAV can prevent transmission to others, and discusses a vaccine to prevent HAV. In addition, the pamphlet provides contact information for sexual health services in New South Wales, Australia.

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Hepatitis C and Inmates Contact: Channing L. Bete Company Incorporated, 200 State Rd, South Deerfield, MA, 01373-0200, (800) 477-4776, http://www.channing-bete.com. Summary: This pamphlet provides information, for incarcerated persons, about the sexually transmitted disease (STD), hepatitis C. The pamphlet discusses the importance of the liver and how hepatitis C affects it, lists the symptoms of hepatitis C, explains how it is transmitted, and identifies individuals at risk for this STD. The pamphlet makes recommendations for ways incarcerated individuals can help to prevent acquiring or spreading hepatitis C.

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What You Should Know About Hepatitis Contact: Health Edco, Division of WRS Group, Inc., PO Box 21207, Waco, TX, 767021207, (254) 776-6461. Summary: This pamphlet provides the general public with basic facts about hepatitis. This disease causes chronic inflammation of the liver. Hepatitis A, B, C, D, and E are the most common hepatitis viruses. The disease may also be caused by alcohol abuse, medications, or chemicals. Hepatitis B and D are transmitted more easily through sexual contact than other hepatitis viruses. The pamphlet discusses the symptoms, mode of transmission, prevention, and treatment of viral, alcoholic, and toxic hepatitis. It also offers advice for individuals living with hepatitis.

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News Breaking Story: Hepatitis A Outbreak!: Help Protect Yourself in Your Community During an Outbreak Contact: Merck and Company, PO Box 4, West Point, PA, 19486-0004, (215) 652-5000, http://www.merck.com. Summary: This pamphlet uses a news report of a fictionalized hepatitis A outbreak to provide basic information about the disease, including its transmission, symptoms, and prevention. The news report focuses on steps that managers of day care centers and restaurants can take to help prevent the spread of the disease, the importance of receiving treatment if exposure to heptatitis A is suspected, and the need for a vaccine for people traveling to or living in areas with high rates of infection.

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Facts About Hepatitis C: Learn Who's at Risk Contact: Schering Corporation, 2000 Galloping Hill Rd, Kenilworth, NJ, 07033, http://www.schering.de/eng.index.html. Summary: This pamphlet uses a question and answer format to help readers learn more about hepatitis A, B, and C. The pamphlet explains what hepatitis is, how the hepatitis virus is transmitted, the features of each type of hepatitis, the risk factors for hepatitis C, and what readers should do if they think they are at risk for hepatitis C. In addition, the pamphlet highlights the treatment options available for hepatitis C and identifies sources of additional information.

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Making Good Decisions: Tattoos and Body Piercing: Protecting Yourself From Hepatitis and HIV: Reducing Your Risk Contact: Journeyworks Publishing, PO Box 8466, Santa Cruz, CA, 95061-8466, (831) 4231400, http://www.promotehealth.com.

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Summary: This pamphlet, written for the general public, presents information on the relationship between body art (tattoos and body piercing) and the transmission of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), hepatitis B (HBV), hepatitis C (HCV), tuberculosis (TB), and tetanus. It discusses how unsterilized needles can lead to the transmission of these diseases and recommends that individuals consider the possible risks associated with body art, resist peer pressure to undergo such a procedure, and take steps to prevent HIV/hepatitis (i.e., by visiting a body art professional who sterilizes the equipment, uses new disposable needles for each customer, and does not use a piercing gun). It recommends that customers ask their body art professional a list of questions before getting a tattoo or piercing. ·

Coping with Hepatitis C: Alternative or Complementary Approaches Source: San Francisco, CA: National Hepatitis C Program, Department of Veterans Affairs Medical Center. 2002. 3 p. Contact: Available from National Hepatitis C Program. Department of Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121. (415) 750-2105. PRICE: Free. Summary: This patient education brochure from the Centers of Excellence in Hepatitis C Research and Education at the Veterans Administration provides information about complementary and alternative medicine (CAM) approaches for people who have hepatitis C. It lists three guidelines to follow if alternative treatments will be used, and gives important warnings about herbal remedies, supplements, vitamins, and other natural treatments. It also discusses several types of CAM treatments for hepatitis C, including aromatherapy, massage therapy, meditation and visualization, and yoga.

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When You Have Hepatitis C Source: American Family Physician. 59(2): 357. January 15, 1999. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. Summary: This patient education handout briefly reviews the recommendations for people who test positive for hepatitis C. A positive test for hepatitis C means that they are infected with the hepatitis C virus (HCV), an infection that causes a liver disease than can lead to liver failure. The handout notes that most people who get hepatitis C have the virus for the rest of their lives and end up with some liver damage. Some people don't feel sick from the liver damage for a long time and some get cirrhosis (liver scarring). The handout encourages readers to discuss the test results with their physician, noting that additional tests may be indicated to confirm the diagnosis and assess any liver damage. The handout also helps readers learn how to take care of the liver (to avoid additional damage), how to treat hepatitis C, how to avoid transmitting the virus to other people, and what are the risks that a mother can pass HCV to her baby at birth. Strategies to avoid transmission include refraining from donating blood, organs, tissue, or sperm; not sharing toothbrushes, razors, or other items that might have blood on them; keeping cuts and sores covered with bandages; and using condoms to lower the chance of transmission during sexual activity.

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Finding Out About Hepatitis C Source: American Family Physician. 55(8): 2759-2761. June 1997.

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Summary: This patient education handout provides information about hepatitis C, an inflammation of the liver caused by a virus (HCV). Written in a question and answer format, the handout defines hepatitis and then describes how hepatitis affects the liver, the chronic nature of hepatitis C, the transmission of hepatitis C, the importance of following a healthy lifestyle to reduce the complications of hepatitis C, and treatment options for hepatitis C, notably interferon. The handout notes that interferon does not cure hepatitis C, but it helps patients to feel better and may prevent future liver problems. However, interferon causes a common side effect that feels like having the flu. Some people taking interferon have fevers, body aches, headaches, fatigue, irritability, nausea, vomiting, sleep disturbance, or changes in their blood. The decision to use interferon therapy can be hard to make because of the expense (approximately $6,000 per year) and the side effects. The handout is designed to be duplicated and distributed by physicians to their patients. (AA-M). ·

Universal Precautions: AIDS and Hepatitis B Prevention for the Dental Health Team Contact: Medcom Incorporated, PO Box 6003, Cypress, CA, (800) 541-0253. Summary: This teaching aid, consisting of a videorecording and an accompanying study guide, teaches dental health professionals about universal precautions to prevent the transmission of the Human immunodeficiency virus (HIV) and the Hepatitis B virus (HBV). Users are asked to first take the pre-test and then to complete the five lessons, which consist of lesson from the study guide and a related video segment. Each lesson includes a summary and a list of videorecording key ideas. At the end of the five lessons, the user should take the post-test. The five lessons cover Hepatitis B infection, symptoms, and treatment; HIV infection, symptoms, and risk of infection through dental work; ways in which both viruses are and are not transmitted; using personal protective equipment; and working safely to avoid puncture wounds, contact with infectious waste, and blood spills.

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Hepatitis C: How Do You Diagnose It? Source: Kennilworth, NJ: Schering Corporation. 2000. [2 p.]. Contact: Available from Schering Corporation. 2000 Galloping Hill Road, Kenilworth, NJ 07033. (800) 446-8766 or (908) 298-4000. Fax (908) 298-4490. Website: www.scheringplough.com. PRICE: Single copy free for patients; available to health professionals through local sales representatives. Summary: This two-sided cardstock document reviews the diagnosis of hepatitis C. One side of the document lists the risk factors for hepatitis C: blood transfusions before 1992, including blood received during a Cesarean section; hemodialysis; ear or body piercing (using improperly sterilized equipment); exposure to blood as a health care worker or member of the military; tattoos (due to potentially contaminated needles or ink); IV (intravenous) drug use, even just once; snorting cocaine or other drugs (due to blood on shared straw or bill); and sharing a razor, toothbrush, or any item that could carry infected blood. The reverse side of the document offers a diagnosis algorithm (flow chart for decision making) for hepatitis C, based on whether or not the patient has or does not have risk factors for the disease. Diagnostic tests incorporated into the algorithm include ALT (alanine aminotransferase), EIA (ELISA, or enzyme linked immunoadsorbent assay), PCR (polymerase chain reaction), and RIBA (recombinant immunoblot assay). The disclaimer on the bottom of the factsheet reminds readers that all decisions on the diagnosis and management of hepatitis C rest in the hands of the

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individual physician, and should not be based solely on the material contained on this sheet.

The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “hepatitis” (or synonyms). The following was recently posted: ·

Chronic hepatitis B Source: American Association for the Study of Liver Diseases - Private Nonprofit Research Organization; 2001 December; 17 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3446&nbr=2672&a mp;string=hepatitis

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Diagnosis and treatment of autoimmune hepatitis Source: American Association for the Study of Liver Diseases - Private Nonprofit Research Organization; 2002 August; 19 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3447&nbr=2673&a mp;string=hepatitis

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Guidelines for laboratory testing and result reporting of antibody to hepatitis C virus Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2003 February 7; 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3620&nbr=2846&a mp;string=hepatitis

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Hepatitis C. Sexually transmitted diseases treatment guidelines 2002 Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1993 (revised 2002 May 10); 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3243&nbr=2469&a mp;string=hepatitis

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Management of hepatitis C: 2002 Source: National Institutes of Health (NIH) Consensus Development Panel on Management of Hepatitis C - Independent Expert Panel; 1997 March (revised 2002 August 26); 44 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3416&nbr=2642&a mp;string=hepatitis

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Prevention and control of infections with hepatitis viruses in correctional settings Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2003 January 24; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3596&nbr=2822&a mp;string=hepatitis

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Prevention of Hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP) Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1999 October 1; 39 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2139&nbr=1365&a mp;string=hepatitis

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Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1998 October; 40 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1518&nbr=744&am p;string=hepatitis

·

Recommendations to prevent hepatitis B virus transmission-United States-Update Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1999 January 22; 2 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1982&nbr=1208&a mp;string=hepatitis

Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: ·

Adolescent and School-Based Health: Hepatitis B in API Youth Summary: This article provides recommendations for increasing the vaccination rate for hepatitis B among Asian American and Pacific Islander youth. Source: National Alliance of State and Territorial AIDS Directors http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7364

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All Kids Need Hepatitis B Shots Source: Immunization Action Coalition http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7271

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Articles Related to Hepatitis B Concerns for APIs Summary: Links to articles, essays and journal reports on Hepatitis B concerns for APIs (Asian American and Pacific Islander), available online. Source: National Task Force on Hepatitis B: Focus on Asians and Pacific Islanders http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5260

·

Autoimmune Hepatitis Summary: Describes the symptoms, diagnosis, treatment, and side effects of treatment of autoimmune hepatitis. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6491

·

Chronic Hepatitis C: Current Disease Management Summary: This online health information document provides basic information about Hepatitis C. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2298

·

Coping With HCV (Hepatitis C) Infection: Alternative or Complementary Approaches Summary: A patient guide to usage of alternative therapies for hepatitis C (HCV) infection. Source: Department of Veterans Affairs http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5324

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Do You Have Chronic Hepatitis B? Source: Immunization Action Coalition http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3382

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Every Week Hundreds of Teens Are Infected with Hepatitis B: Get Vaccinated Against This Disease! Source: Immunization Action Coalition http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3378

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FAQ - About Hepatitis B Source: Immunization Action Coalition http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3386

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FAQs: Viral Hepatitis B Source: National Center for Infectious Diseases, Centers for Disease Control and Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6448

·

healthfinder® just for you: Asian Americans, Native Hawaiians, and Other Pacific Islanders Summary: This special section of healthfinder® provides reliable health information on key issues affecting these populations, including cardiovascular disease, cancer, hepatitis B, and tuberculosis. Source: U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7020

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Hepatitis A Vaccine Source: Immunization Action Coalition http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7360

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Hepatitis A Virus (HAV) Summary: Written for clinicians, this hepatitis A virus (HAV) fact sheet presents basic information about the disorder that includes diagnosis, epidemiology, disease management guidelines, and information Source: Educational Institution--Follow the Resource URL for More Information http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5317

·

Hepatitis B and the Vaccine: Questions and Answers Summary: Questions and answers about hepatitis B vaccine and its safety and side effects. Source: National Immunization Program, Centers for Disease Control and Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6574

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Hepatitis B Immunization Coverage Among Vietnamese-American Children 3 to 18 Years Old Summary: Persons with chronic hepatitis B virus (HBV) infection are at increased risk of chronic hepatitis, cirrhosis, and liver cancer. Source: American Academy of Pediatrics http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7366

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Hepatitis B in Asian Americans Source: Asian Liver Center at Stanford University http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6602

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Hepatitis B Information for Adults and Children from Endemic Areas Source: Immunization Action Coalition http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7315

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Hepatitis B Information for Asian and Pacific Islander Americans Summary: Hepatits B is a disease that is caused by a virus. This virus is common in many parts of the world includilng Asia and the Pacific Islands. Source: Immunization Action Coalition http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7449

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Hepatitis B Shots Are Recommended for All New Babies Source: Immunization Action Coalition http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7289

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Hepatitis B Vaccine Source: Immunization Action Coalition http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7361

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Hepatitis B Virus (HBV) Summary: Written for clinicians, this hepatitis B virus (HBV) fact sheet presents basic information about the disorder that includes diagnosis, epidemiology, disease management guidelines, data on risk groups, Source: Educational Institution--Follow the Resource URL for More Information http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5319

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Hepatitis C (HCV) Patient Education Materials Summary: This web site presents materials for patients with hepatitis C. Source: Department of Veterans Affairs http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5325

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Hepatitis C (HCV) Provider Education Materials Summary: Materials about hepatitis C (HCV), written especially for physicians. Source: Department of Veterans Affairs http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5327

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Hepatitis C Fact Sheet Summary: This fact sheet presents a general overview about hepatitis C including means of transmission, diagnosis, treatment, and prevention guideline. Source: World Health Organization http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4715

·

Hepatitis C Virus (HCV) Summary: Written for clinicians, this Hepatitis C Virus (HCV) fact sheet presents basic information about the disorder that includes diagnosis, epidemiology, disease management guidelines, data on risk Source: Educational Institution--Follow the Resource URL for More Information http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5316

·

Hepatitis C: New Treatment Helps Some, But Cure Remains Elusive Summary: This FDA Consumer magazine discusses Hepatitis C -- current treatment options, future options through clinical research, how patients are coping with the disease, and efforts at educating the medical Source: U.S. Food and Drug Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4430

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Hepatitis C: The Facts Source: Department of Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7478

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Hepatitis C: Treatment Alternatives Summary: This consumer health information brochure discusses research and research findings related to alternative therapy treatments for hepatitis C virus. Source: National Center for Complementary and Alternative Medicine, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5349

·

Hepatitis C: What Clinicians and Other Health Professionals Need to Know Summary: A web-based training course on hepatitis C virus (HCV) infection designed for primary care physicians, infectious disease specialists, blood bank employees, public health professionals and other Source: Division of Viral Hepatitis, National Center for Infectious Diseases http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5314

·

Hepatitis D Virus (HDV) Summary: Written for clinicians, this hepatitis D virus (HDV) fact sheet presents basic information about hepatitis D that includes diagnosis, epidemiology, disease management guidelines and data on risk Source: Educational Institution--Follow the Resource URL for More Information http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5321

·

Hepatitis E Virus (HEV) Summary: Written for clinicians, this hepatitis E virus (HEV) fact sheet presents basic information about hepatitis E that includes diagnosis, epidemiology, disease management guidelines and data on risk Source: Educational Institution--Follow the Resource URL for More Information http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5322

·

Hepatitis G Virus (HGV) Summary: Written for clinicians, this hepatitis G virus (HEV) fact sheet presents basic information about hepatitis G that includes diagnosis, epidemiology and disease management guidelines. Source: Educational Institution--Follow the Resource URL for More Information http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5323

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·

Model Programs for Hepatitis A, B, and C Prevention Summary: This web site presents programs across the United States that work to prevent hepatitis A, B, or C in people who are at risk for infection -- especially adults and adolescents. Source: Immunization Action Coalition http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6273

·

Needle Tips and the Hepatitis B Coalition News Summary: Readers can read the entire current issue in PDF format or choose only the sections they desire. Source: Immunization Action Coalition http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7140

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Prevention of Hepatitis A Virus (HAV) Infection - Vaccination Questions and Answers Summary: Guidelines for immunization against hepatitis A virus (HAV) infection. Source: Educational Institution--Follow the Resource URL for More Information http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5318

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Prevention of Hepatitis B Virus (HBV) - Vaccination Questions and Answers Summary: Guidelines for immunization against hepatitis B virus (HBV) infection. Source: Educational Institution--Follow the Resource URL for More Information http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5320

·

Reducing the Burden of Viral Hepatitis in American Indian and Alaska Native Communities Summary: This article outlines prevention strategies for hepatitis A, B, and C within American Indian and Alaska Native communities. Source: National Center for Infectious Diseases, Centers for Disease Control and Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6759

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The Johns Hopkins Center for Viral Hepatitis Website Summary: This web site links users to: a an interactive, question-and-answer forum where Viral Hepatitis specialists at the Johns Hopkins Center for Viral Hepatitis will respond to questions posted on the Source: Educational Institution--Follow the Resource URL for More Information http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4717

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Vaccine Information Statements - Centers for Disease Control and Prevention Summary: This web site provides links to general information on a variety of vaccines for the general public including chickenpox, diphtheria, HIB, measles, mumps, pertussis, polio, rubella, hepatitis and Source: National Immunization Program, Centers for Disease Control and Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=366

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Vaccines for Children Program Summary: The Vaccines for Children (VFC) program provides vaccines free of charge to eligible children, including hepatitis A and hepatitis B vaccines. The VFC Web site provides specifics. Source: National Immunization Program, Centers for Disease Control and Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6272

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Vietnamese Community Health Promotion Project Archives Summary: These booklets in Vietnamese provide information on cervical cancer, hepatitis B, breast cancer, smoking, and nutrition. Source: Vietnamese Community Health Promotion Project http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7416

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Viral Hepatitis - Resource Center Summary: This web site is a one-stop shopping center for information about Hepatitis, from A to E. Source: Division of Viral Hepatitis, National Center for Infectious Diseases http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3819

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Viral Hepatitis A - Information Summary: This web site provides access to information about Hepatitis A for both health professionals and the lay public. Source: Division of Viral Hepatitis, National Center for Infectious Diseases http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3813

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Viral Hepatitis B Information Summary: This web site provides access to information about Hepatitis B for both health professionals and the lay public. Source: Division of Viral Hepatitis, National Center for Infectious Diseases http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3814

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Viral Hepatitis C Information Summary: This web site provides access to fact sheets, pamphlets, advisories, alerts and reports about Hepatitis C for both health professionals and the lay public. Source: Division of Viral Hepatitis, National Center for Infectious Diseases http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3815

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Viral Hepatitis D (Delta) Information Summary: Visitors to this site can view a slide set presentation and technical notes on Hepatitis D. Source: Division of Viral Hepatitis, National Center for Infectious Diseases http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3816

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Viral Hepatitis E Information Summary: Visit this site to view a slide set presentation and technical notes on Hepatitis E (HEV). Source: Division of Viral Hepatitis, National Center for Infectious Diseases http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3817

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What I Need to Know About Hepatitis A Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2301

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What I Need to Know About Hepatitis B Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2299

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What I Need to Know About Hepatitis C Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2300

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What Is the Role of Prisons in HIV, Hepatitis, STD and TB Prevention? Source: Center for AIDS Prevention Studies http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3502

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The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to hepatitis. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.

Additional Web Sources

A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: ·

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/specific.htm

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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

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Med Help International: http://www.medhelp.org/HealthTopics/A.html

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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

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WebMDÒHealth: http://my.webmd.com/health_topics

Associations and Hepatitis The following is a list of associations that provide information on and resources relating to hepatitis: ·

Hepatitis B Foundation Telephone: (215) 489-4900 Fax: (215) 489-4920 Email: [email protected] Web Site: http://www.hepb.org Background: The Hepatitis B Foundation in a national non-profit organization dedicated to finding a cure and improving the quality of life for those affected by hepatitis B worldwide. Its commitment includes funding research, promoting disease awareness, supporting immunization and treatment initiatives, and serving as the primary source of information for patients and their families, the medical and scientific community and the general public. Hepatitis B is the most common serious liver infection in the world. It is caused by the hepatitis B virus (HBV) that attacks liver cells and can lead to liver failure, cirrhosis (scarring) or cancer of the liver. Materials provided by the Hepatitis B Foundation include the B Informed newsletter; videos in

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English, Chinese, Korean, and Vietnamese; brochures; and comprehensive informational packets. Interactive email and a telephone HelpLine are also available. ·

Hepatitis C Outreach Project Telephone: (503) 285-8712 Fax: (503) 737-0214 Email: [email protected] Web Site: http://www.hcop.org Background: The mission of the Hepatitis C Outreach Project is to inspire, support, and enhance community efforts toward prevention, awareness, education, and treatment of hepatitis C and to promote organ donation. This voluntary organization is committed to working with organizations, agencies, and professional individuals to develop partnerships resulting in quality programming and good public decision-making, based on accurate informaiton regarding hepatitis C. Hepatitis C is a viral infection of the liver, transmitted primarily through infected blood and blood products. It is estimated that 85 percent of those who have such an infection are not aware of it. Delayed diagnosis leaves people at risk for serious damage to the liver.

·

Hepatitis C Society of Canada Telephone: (416) 979-5855 Toll-free: (800) 652-4372 Fax: (416) 979-5856 Email: [email protected] Web Site: http://web.idirect.com/~hepc/ Background: The Hepatitis C Society of Canada (HeCSC) is a national voluntary nonprofit organization dedicated to providing comfort and support to those infected with the hepatitis C virus, their family members, and other concerned individuals; promoting public awareness of hepatitis C and its transmission, care, and prevention; seeking fair treatment of all people living with and affected by hepatitis C; and promoting research that will help to prevent, treat, and cure hepatitis C. Viral hepatitis is inflammatory liver disease caused by viral infection. There are several forms of viral hepatitis that may be caused by different viruses. The virus responsible for hepatitis C, known as HCV, travels in the blood to the liver where it invades liver cells, multiples, and damages or destroys liver cells. Symptoms, which may range from mild to severe, may include fatigue, abdominal pain, nausea with or without vomiting, fever, itchy skin, and yellowish discoloration of the skin, whites of the eyes, and mucous membranes (jaundice). The Hepatitis C Society of Canada was established in 1994 and currently has a network of over 20 support groups across Canada to promote mutual support and networking among affected individuals and family members. The Society also compiles and distributes information about hepatitis C to affected individuals and family members, the general public, the medical community, and policymakers and has established an ongoing dialogue with public health officials and government representatives to advocate for equality of access to disability pension plans, fair treatment from employers, and improvements in the security of Canada's blood supply. The Hepatitis C Society of Canada also offers local counseling, support, and referral services for affected individuals, family members, and friends via its 800 line; communicates on behalf of employees for fair treatment in the workplace; assists affected individuals in obtaining benefits from the disability pension plan; and provides

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representation at the Krever Commission Blood Inquiry on behalf of transfused carriers of hepatitis C. In addition, the Society conducts educational seminars, publishes a bimonthly newsletter, and maintains a web site on the Internet. ·

Hepatitis Foundation International Telephone: (301) 622-4200 Toll-free: (800) 891-0707 Fax: (301) 622-4702 Email: [email protected] Web Site: http://www.hepatitisfoundation.org Background: Hepatitis Foundation International (HFI) is a voluntary not-for-profit membership organization dedicated to increasing awareness of the worldwide problem of viral hepatitis and educating the public and health care providers about its prevention, diagnosis, and treatment. Viral hepatitis is inflammatory liver disease caused by viral infection. There are several different forms of viral hepatitis that may be caused by different viruses. Such forms of hepatitis include hepatitis A, hepatitis B, hepatitis C, hepatitis D, and hepatitis E. Depending upon the specific form of the disease and other factors, viral hepatitis may cause liver cell damage, associated scarring of the liver (cirrhosis), and, in some cases, an increased risk of liver cancer. In some cases, affected individuals may have no apparent symptoms. In other cases, some adults with hepatitis A may have dark urine and light stools and may experience fatigue, nausea, vomiting, fever, abdominal pain, and/or abnormal yellowing of the skin and the whites of the eyes (jaundice). Some individuals with hepatitis B, C, D, or E may have dark urine and light stools and experience mild flu-like symptoms, fatigue, fever, and/or jaundice. Hepatitis Foundation International was established in 1995 and currently consists of approximately 35,000 members. The Foundation focuses exclusively on bringing viral hepatitis under control by supporting research to find cures; providing educational programs and materials to inform health professionals, affected individuals, family members, and the public concerning new diagnostic and treatment methods; and offering a support network for those who are affected by viral hepatitis. Hepatitis Foundation International also engages in patient advocacy and lobbying, provides appropriate referrals, and has a registry. The Foundation offers a wide range of educational materials including brochures, posters, information sheets, booklets, a primer for teachers concerning hepatitis B and substance abuse prevention, a coloring book for children, and a regular newsletter entitled 'Hepatitis Alert.'.

·

Immunization Action Coalition/Hepatitis B Coalition Telephone: (651) 647-9009 Fax: (651) 647-9131 Email: [email protected] Web Site: http://www.immunize.org Background: The Immunization Action Coalition (IAC) is a nonprofit organization that works to prevent disease by creating and distributing educational materials for health professionals and the public that enhance delivery of safe and effective immunization services and increase their use. The Coalition also facilitates communication within the broad immunization community, including parents, concerning issues of safety, efficacy, and the use of vaccines. The Hepatitis B Coalition, a program of IAC, promotes hepatitis B vaccination for all children 0-18 years of age, HBsAg screening for all

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pregnant women, hepatitis B testing and vaccination for risk groups, and education and treatment for people who are chronically infected with hepatitis B. The IAC's educational materials include 3 print periodicals, NEEDLE TIPS and the Hepatitis B Coalition News, VACCINATE ADULTS!, and VACCINATE WOMEN. IAC also produces a weekly email news service containing current immunization information titled IAC EXPRESS. In addition, IAC creates and distributes print materials and audiovisual aids and maintains 4 websites, www.immunize.org, www.vaccineinformation.org, www.izcoalitions.org, and www.hepprograms.org.

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to hepatitis. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with hepatitis.

The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about hepatitis. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797.

Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “hepatitis” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information.

The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit

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your search to “Organizations” and “hepatitis”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “hepatitis” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “hepatitis” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.27

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

27

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)28: ·

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

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California: Gateway Health Library (Sutter Gould Medical Foundation)

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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

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Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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·

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

·

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

·

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

·

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

·

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

·

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

·

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

·

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

·

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

·

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

·

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

·

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

568 Hepatitis

·

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

·

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

·

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

·

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

·

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

·

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

·

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

·

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

·

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

·

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

·

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

·

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

·

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

·

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

·

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

·

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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569

·

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

·

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

·

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

·

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

·

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

·

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

570 Hepatitis

·

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

·

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

·

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

571

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: ·

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

·

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

·

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

·

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

·

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

·

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

·

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on hepatitis: ·

Basic Guidelines for Hepatitis Hepatitis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001154.htm Hepatitis A Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000278.htm Hepatitis A - vaccine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/005107.htm Hepatitis B Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000279.htm Hepatitis C Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000284.htm Hepatitis virus serology Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003558.htm

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·

Signs & Symptoms for Hepatitis Abdominal distention Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003122.htm Abdominal fullness, gaseous Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003124.htm Abdominal indigestion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003260.htm Abdominal pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003120.htm Abnormal taste Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003050.htm Abnormal urine color Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003139.htm Breast development in males Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003165.htm Clay colored stools Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003129.htm Dark urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003138.htm Depression Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm Difficulty breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Fainting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm Fatigue Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Headache Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003024.htm Indigestion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003260.htm Itching Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003217.htm

Online Glossaries 573

Jaundice Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003243.htm Leukemia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001299.htm Loss of appetite Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003121.htm Malaise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003089.htm Muscle aches Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003178.htm Nausea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Nausea and vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Nosebleed - symptom Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003106.htm Point tenderness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003273.htm Rash Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Yellow skin, jaundice Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003243.htm ·

Diagnostics and Tests for Hepatitis Bilirubin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003479.htm Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm Dialysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003421.htm

574 Hepatitis

ELISA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003332.htm Hepatitis A virus (HAV) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003558.htm Hepatitis serology Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003558.htm Hepatitis virus serology Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003558.htm IgA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003544.htm IgG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003544.htm IgM Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003544.htm Immunoelectrophoresis - serum Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003541.htm Liver biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003895.htm Liver function tests Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003436.htm Serology Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003511.htm Venipuncture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003423.htm ·

Background Topics for Hepatitis Acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002215.htm Antibodies Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002223.htm Antibody Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002223.htm Antigen Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002224.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm

Online Glossaries 575

Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Hepatitis B vaccine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002022.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Intravenous Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002383.htm Liver disease - support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002182.htm Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm Safer sex behaviors Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001949.htm Support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002150.htm Toxins Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002331.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: ·

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

·

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

·

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

·

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

577

HEPATITIS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [NIH] Absolute risk: The observed or calculated probability of an event in a population under study, as contrasted with the relative risk. [NIH] Acatalasia: A rare autosomal recessive disorder resulting from the absence of catalase activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Acute Disease: Disease having a short and relatively severe course. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature

578 Hepatitis

blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Deaminase: An enzyme that catalyzes the hydrolysis of adenosine to inosine with the elimination of ammonia. Since there are wide tissue and species variations in the enzyme, it has been used as a tool in the study of human and animal genetics and in medical diagnosis. EC 3.5.4.4. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenaline: A hormone. Also called epinephrine. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of

Dictionary 579

solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Aflatoxin B1: A potent hepatotoxic and hepatocarcinogenic mycotoxin produced by the Aspergillus flavus group of fungi. It is also mutagenic, teratogenic, and causes immunosuppression in animals. It is found as a contaminant in peanuts, cottonseed meal, corn, and other grains. The mycotoxin requires epoxidation to aflatoxin B1 2,3-oxide for activation. Microsomal monooxygenases biotransform the toxin to the less toxic metabolites aflatoxin M1 and Q1. [NIH] Aflatoxins: A group of closely related toxic metabolites that are designated mycotoxins. They are produced by Aspergillus flavus and A. parasiticus. Members of the group include aflatoxin B1, aflatoxin B2, aflatoxin G1, aflatoxin G2, aflatoxin M1, and aflatoxin M2. [NIH] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Age-Adjusted: Summary measures of rates of morbidity or mortality in a population using statistical procedures to remove the effect of age differences in populations that are being compared. Age is probably the most important and the most common variable in determining the risk of morbidity and mortality. [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Aggressiveness: The quality of being aggressive (= characterized by aggression; militant; enterprising; spreading with vigour; chemically active; variable and adaptable). [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] A-HA: First enzyme in the biosynthetic pathway of branched-chain amino acids. [NIH] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is

580 Hepatitis

produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Alanine Transaminase: An enzyme that catalyzes the conversion of L-alanine and 2oxoglutarate to pyruvate and L-glutamate. (From Enzyme Nomenclature, 1992) EC 2.6.1.2. [NIH]

Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alpha-fetoprotein: AFP. A protein normally produced by a developing fetus. AFP levels are usually undetectable in the blood of healthy nonpregnant adults. An elevated level of AFP suggests the presence of either a primary liver cancer or germ cell tumor. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alum: A type of immune adjuvant (a substance used to help boost the immune response to a vaccine). Also called aluminum sulfate. [NIH]

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Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Amantadine: An antiviral that is used in the prophylactic or symptomatic treatment of Influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake. [NIH] Amber: A yellowish fossil resin, the gum of several species of coniferous trees, found in the alluvial deposits of northeastern Germany. It is used in molecular biology in the analysis of organic matter fossilized in amber. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amputation: Surgery to remove part or all of a limb or appendage. [NIH] Anaemia: A reduction below normal in the number of erythrocytes per cu. mm., in the

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quantity of haemoglobin, or in the volume of packed red cells per 100 ml. of blood which occurs when the equilibrium between blood loss (through bleeding or destruction) and blood production is disturbed. [EU] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anaesthetic: 1. Pertaining to, characterized by, or producing anaesthesia. 2. A drug or agent that is used to abolish the sensation of pain. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anterior Cerebral Artery: Artery formed by the bifurcation of the internal carotid artery. Branches of the anterior cerebral artery supply the caudate nucleus, internal capsule, putamen, septal nuclei, gyrus cinguli, and surfaces of the frontal lobe and parietal lobe. [NIH] Anthrax: An acute bacterial infection caused by ingestion of bacillus organisms. Carnivores

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may become infected from ingestion of infected carcasses. It is transmitted to humans by contact with infected animals or contaminated animal products. The most common form in humans is cutaneous anthrax. [NIH] Anthropology: The science devoted to the comparative study of man. [NIH] Antiasthmatic: An agent that relieves the spasm of asthma. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibodies, Anticardiolipin: Antiphospholipid antibodies found in association with systemic lupus erythematosus (lupus erythematosus, systemic), antiphospholipid syndrome, and in a variety of other diseases as well as in healthy individuals. The antibodies are detected by solid-phase immunoassay employing the purified phospholipid antigen cardiolipin. [NIH] Antibodies, Antiphospholipid: Autoantibodies directed against phospholipids. These antibodies are characteristically found in patients with systemic lupus erythematosus, antiphospholipid syndrome, related autoimmune diseases, some non-autoimmune diseases, and also in healthy individuals. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidepressant: A drug used to treat depression. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH]

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Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiphospholipid Syndrome: The presence of antibodies directed against phospholipids (antibodies, antiphospholipid). The condition is associated with a variety of diseases, notably systemic lupus erythematosus and other connective tissue diseases, thrombopenia, and arterial or venous thromboses. In pregnancy it can cause abortion. Of the phospholipids, the cardiolipins show markedly elevated levels of anticardiolipin antibodies (antibodies, anticardiolipin). Present also are high levels of lupus anticoagulant (lupus coagulation inhibitor). [NIH] Antiproliferative: Counteracting a process of proliferation. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Antiviral Agents: Agents used in the prophylaxis or therapy of virus diseases. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. [NIH] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aplastic anemia: A condition in which the bone marrow is unable to produce blood cells. [NIH]

Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Archaea: One of the three domains of life (the others being bacteria and Eucarya), formerly called Archaebacteria under the taxon Bacteria, but now considered separate and distinct.

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They are characterized by: 1) the presence of characteristic tRNAs and ribosomal RNAs; 2) the absence of peptidoglycan cell walls; 3) the presence of ether-linked lipids built from branched-chain subunits; and 4) their occurrence in unusual habitats. While archaea resemble bacteria in morphology and genomic organization, they resemble eukarya in their method of genomic replication. The domain contains at least three kingdoms: crenarchaeota, euryarchaeota, and korarchaeota. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articular: Of or pertaining to a joint. [EU] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Aspartate: A synthetic amino acid. [NIH] Aspartate Transaminase: An enzyme of the transferase class that catalyzes the conversion of L-aspartate and 2-ketoglutarate to oxaloacetate and L-glutamate. EC 2.6.1.1. [NIH] Aspiration: The act of inhaling. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU]

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Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [NIH] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Audiovisual Aids: Auditory and visual instructional materials. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmune Hepatitis: A liver disease caused when the body's immune system destroys liver cells for no known reason. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autopsy: Postmortem examination of the body. [NIH] Avian: A plasmodial infection in birds. [NIH] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract

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infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Bed Rest: Confinement of an individual to bed for therapeutic or experimental reasons. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Bereavement: Refers to the whole process of grieving and mourning and is associated with a deep sense of loss and sadness. [NIH] Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Atresia: Atresia of the biliary tract, most commonly of the extrahepatic bile ducts. [NIH]

Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioassays: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard

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preparation. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [NIH] Biogenic Monoamines: Biogenic amines having only one amine moiety. Included in this group are all natural monoamines formed by the enzymatic decarboxylation of natural amino acids. [NIH] Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotypes: Causes septicemic and pneumonic pasteurellosis in cattle and sheep, usually in conjunction with a virus infection such as parainfluenza 3. Also recorded as a cause of acute mastitis in cattle. [NIH] Biphasic: Having two phases; having both a sporophytic and a gametophytic phase in the life cycle. [EU] Bladder: The organ that stores urine. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH]

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Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood transfusion: The administration of blood or blood products into a blood vessel. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Borne Pathogens: Infectious organisms in the blood, of which the predominant medical interest is their contamination of blood-soiled linens, towels, gowns, bandages, other items from individuals in risk categories, needles and other sharp objects, and medical and dental waste, all of which health workers are exposed to. This concept is differentiated from the clinical conditions of bacteremia, viremia, and fungemia where the organism is present in the blood of a patient as the result of a natural infectious process. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brain Infarction: The formation of an area of necrosis in the brain, including the cerebral hemispheres (cerebral infarction), thalami, basal ganglia, brain stem (brain stem infarctions), or cerebellum secondary to an insufficiency of arterial or venous blood flow. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Brain Stem Infarctions: Infarctions that occur in the brain stem which is comprised of the midbrain, pons, and medulla. There are several named syndromes characterized by their distinctive clinical manifestations and specific sites of ischemic injury. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH]

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Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bromine: A halogen with the atomic symbol Br, atomic number 36, and atomic weight 79.904. It is a volatile reddish-brown liquid that gives off suffocating vapors, is corrosive to the skin, and may cause severe gastroenteritis if ingested. [NIH] Bronchiseptica: A small, gram-negative, motile bacillus. A normal inhabitant of the respiratory tract in man, dogs, and pigs, but is also associated with canine infectious tracheobronchitis and atrophic rhinitis in pigs. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH] Cadaver: A dead body, usually a human body. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Campylobacter: A genus of bacteria found in the reproductive organs, intestinal tract, and oral cavity of animals and man. Some species are pathogenic. [NIH] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH]

Capsular: Cataract which is initiated by an opacification at the surface of the lens. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carboxy: Cannabinoid. [NIH] Carboxy-terminal: The end of any polypeptide or protein that bears a free carboxyl group. [NIH]

Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiolipins: Acidic phospholipids composed of two molecules of phosphatidic acid covalently linked to a molecule of glycerol. They occur primarily in mitochondrial inner membranes and in bacterial plasma membranes. They are the main antigenic components of the Wassermann-type antigen that is used in nontreponemal syphilis serodiagnosis. [NIH]

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Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiopathy: Any disorder or disease of the heart. In addition to heart disease of inflammatory origin, there are arteriosclerotic cardiopathy, due to arteriosclerosis; fatty cardiopathy, due to growth of fatty tissue; hypertensive cardiopathy, due to high blood pressure; nephropathic cardiopathy, due to kidney disease, thyrotoxic cardiopathy, due to thyroid intoxication; toxic cardiopathy, due to the effect of some toxin; and valvular cardiopathy, due to faulty valve action. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovirus: A genus of the family Picornaviridae causing encephalitis and myocarditis in rodents. Encephalomyocarditis virus is the type species. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carrier State: The condition of harboring an infective organism without manifesting symptoms of infection. The organism must be readily transmissable to another susceptible host. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catalase: An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. EC 1.11.1.6. [NIH] Catalyse: To speed up a chemical reaction. [EU] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH]

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Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [NIH] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Physiology: Characteristics and physiological processes of cells from cell division to cell death. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH]

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Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Centriole: A small body which plays a part in the cell division. It is found near the nucleus of a cell. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]

Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Cesarean Section: Extraction of the fetus by means of abdominal hysterotomy. [NIH] Check-up: A general physical examination. [NIH] Chemical Warfare: Tactical warfare using incendiary mixtures, smokes, or irritant, burning, or asphyxiating gases. [NIH] Chemical Warfare Agents: Chemicals that are used to cause the disturbance, disease, or death of humans during war. [NIH] Chemoembolization: A procedure in which the blood supply to the tumor is blocked surgically or mechanically, and anticancer drugs are administered directly into the tumor. This permits a higher concentration of drug to be in contact with the tumor for a longer period of time. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH]

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Chickenpox: A mild, highly contagious virus characterized by itchy blisters all over the body. [NIH] Child Care: Care of children in the home or institution. [NIH] Child Development: The continuous sequential physiological and psychological maturing of the child from birth up to but not including adolescence. It includes healthy responses to situations, but does not include growth in stature or size (= growth). [NIH] Chimeras: Organism that contains a mixture of genetically different cells. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chiropractic: A system of treating bodily disorders by manipulation of the spine and other parts, based on the belief that the cause is the abnormal functioning of a nerve. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Chloroform: A commonly used laboratory solvent. It was previously used as an anesthetic, but was banned from use in the U.S. due to its suspected carcinogenecity. [NIH] Cholangitis: Inflammation of a bile duct. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [NIH]

Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Cholic Acid: A major primary bile acid produced in the liver and usually conjugated with glycine or taurine. It facilitates fat absorption and cholesterol excretion. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromaffin Cells: Cells that store epinephrine secretory vesicles. During times of stress, the nervous system signals the vesicles to secrete their hormonal content. Their name derives from their ability to stain a brownish color with chromic salts. Characteristically, they are located in the adrenal medulla and paraganglia (paraganglia, chromaffin) of the sympathetic

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nervous system. [NIH] Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromic: Catgut sterilized and impregnated with chromium trioxide. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Chymopapain: A cysteine endopeptidase isolated from papaya latex. Preferential cleavage at glutamic and aspartic acid residues. EC 3.4.22.6. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary Body: A ring of tissue extending from the scleral spur to the ora serrata of the retina. It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal portion and the ciliary processes are in the epithelial portion. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Circumcision: Excision of the prepuce or part of it. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH] Climacteric: Physiologic period, characterized by endocrine, somatic, and psychic changes with the termination of ovarian function in the female. It may also accompany the normal diminution of sexual activity in the male. [NIH]

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Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical resistance: The failure of a cancer to shrink after treatment. [NIH] Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognitive restructuring: A method of identifying and replacing fear-promoting, irrational beliefs with more realistic and functional ones. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been

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used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Communicable disease: A disease that can be transmitted by contact between persons. [NIH] Community Health Services: Diagnostic, therapeutic and preventive health services provided for individuals in the community. [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Compassionate: A process for providing experimental drugs to very sick patients who have no treatment options. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments

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that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complement 1: The first complement component to act in the cytolysis reaction. It is a trimolecular complex held together with Ca ions and, when activated, has esterase activity which initiates the next step in the sequence. [NIH] Complement 4: The second component to react in the complement sequence. It is a betaglobulin with a sedimentation coefficient of 18.7, a molecular weight of 240,000 and a serum concentration of 430 micrograms/ml. It is activated by complement 1 and serves as a receptor for C2. [NIH] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computer-Assisted Instruction: A self-learning technique, usually online, involving interaction of the student with programmed instructional materials. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Condoms: A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. [NIH] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH]

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Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Diseases: A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried

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by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Coumarins: Synthetic or naturally occurring substances related to coumarin, the deltalactone of coumarinic acid. Coumarin itself occurs in the tonka bean. The various coumarins have a wide range of proposed actions and uses including as anticoagulants, pharmaceutical aids, indicators and reagents, photoreactive substances, and antineoplastic agents. [NIH] Cowpox: A mild, eruptive skin disease of milk cows caused by cowpox virus, with lesions occurring principally on the udder and teats. Human infection may occur while milking an infected animal. [NIH] Cowpox Virus: A species of orthopoxvirus that is the etiologic agent of cowpox. It is closely related to but antigenically different from vaccina virus. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cryoglobulinemia: A condition characterized by the presence of abnormal or abnormal quantities of cryoglobulins in the blood. They are precipitated into the microvasculature on exposure to cold and cause restricted blood flow in exposed areas. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH]

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Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytostatic: An agent that suppresses cell growth and multiplication. [EU] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Day Care: Institutional health care of patients during the day. The patients return home at night. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Death Certificates: Official records of individual deaths including the cause of death certified by a physician, and any other required identifying information. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH]

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Deception: The act of deceiving or the fact or condition of being deceived. [NIH] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Decompensation: Failure of compensation; cardiac decompensation is marked by dyspnea, venous engorgement, and edema. [EU] Decontamination: The removal of contaminating material, such as radioactive materials, biological materials, or chemical warfare agents, from a person or object. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]

Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Assistants: Individuals who assist the dentist or the dental hygienist. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dental Staff: Personnel who provide dental service to patients in an organized facility, institution or agency. [NIH] Dental Waste: Any waste product generated by a dental office, surgery, clinic, or laboratory including amalgams, saliva, and rinse water. [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Deoxyguanosine: A nucleoside consisting of the base guanine and the sugar deoxyribose. [NIH]

Depigmentation: Removal or loss of pigment, especially melanin. [EU] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermatosis: Any skin disease, especially one not characterized by inflammation. [EU]

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Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [NIH] Dextran Sulfate: Long-chain polymer of glucose containing 17-20% sulfur. It has been used as an anticoagulant and also has been shown to inhibit the binding of HIV-1 to CD4+ Tlymphocytes. It is commonly used as both an experimental and clinical laboratory reagent and has been investigated for use as an antiviral agent, in the treatment of hypolipidemia, and for the prevention of free radical damage, among other applications. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Foot: Ulcers of the foot as a complication of diabetes. Diabetic foot, often with infection, is a common serious complication of diabetes and may require hospitalization and disfiguring surgery. The foot ulcers are probably secondary to neuropathies and vascular problems. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialysate: A cleansing liquid used in the two major forms of dialysis--hemodialysis and peritoneal dialysis. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dilatation: The act of dilating. [NIH] Dilated cardiomyopathy: Heart muscle disease that leads to enlargement of the heart's chambers, robbing the heart of its pumping ability. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Diphtheria: A localized infection of mucous membranes or skin caused by toxigenic strains of Corynebacterium diphtheriae. It is characterized by the presence of a pseudomembrane at the site of infection. Diphtheria toxin, produced by C. diphtheriae, can cause myocarditis, polyneuritis, and other systemic toxic effects. [NIH]

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Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disease Susceptibility: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. [NIH] Disease Transmission: The transmission of infectious disease or pathogens. When transmission is within the same species, the mode can be horizontal (disease transmission, horizontal) or vertical (disease transmission, vertical). [NIH] Disease Transmission, Horizontal: The transmission of infectious disease or pathogens from one individual to another in the same generation. [NIH] Disease Transmission, Vertical: The transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disinfection: Rendering pathogens harmless through the use of heat, antiseptics, antibacterial agents, etc. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Distention: The state of being distended or enlarged; the act of distending. [EU] Disulphide: A covalent bridge formed by the oxidation of two cysteine residues to a cystine residue. The-S-S-bond is very strong and its presence confers additional stability. [NIH] Docetaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [NIH]

Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for

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its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dosage schedule: A scheme set up to determine and regulate size, frequency and number of doses. [EU] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Doxycycline: A synthetic tetracycline derivative with a range of antimicrobial activity and mode of action similar to that of tetracycline, but more effective against many species. Animal studies suggest that it may cause less tooth staining than other tetracyclines. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Drug Toxicity: Manifestations of the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques. It does not include accidental or intentional poisoning for which specific headings are available. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysentery: Any of various disorders marked by inflammation of the intestines, especially of the colon, and attended by pain in the abdomen, tenesmus, and frequent stools containing blood and mucus. Causes include chemical irritants, bacteria, protozoa, or parasitic worms. [EU]

Dyspepsia: Impaired digestion, especially after eating. [NIH]

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Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electron microscope: A microscope (device used to magnify small objects) that uses electrons (instead of light) to produce an enlarged image. An electron microscopes shows tiny details better than any other type of microscope. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Electroporation: A technique in which electric pulses of intensity in kilovolts per centimeter and of microsecond-to-millisecond duration cause a temporary loss of the semipermeability of cell membranes, thus leading to ion leakage, escape of metabolites, and increased uptake by cells of drugs, molecular probes, and DNA. Some applications of electroporation include introduction of plasmids or foreign DNA into living cells for transfection, fusion of cells to prepare hybridomas, and insertion of proteins into cell membranes. [NIH] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH]

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Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emergency Medical Services: Services specifically designed, staffed, and equipped for the emergency care of patients. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [NIH] Encephalomyocarditis Virus: The type species of cardiovirus causing encephalomyelitis and myocarditis in rodents, pigs, and monkeys. Infection in man has been reported with CNS involvement but without myocarditis. [NIH] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the

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body. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endotoxemia: A condition characterized by the presence of endotoxins in the blood. If endotoxemia is the result of gram-negative rod-shaped bacteria, shock may occur. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [NIH] Enterovirus: A genus of the family Picornaviridae whose members preferentially inhabit the intestinal tract of a variety of hosts. The genus contains many species. Newly described members of human enteroviruses are assigned continuous numbers with the species designated "human enterovirus". [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers:

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1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

ERV: The expiratory reserve volume is the largest volume of gas that can be expired from the end-expiratory level. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythropoietin: Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excrete: To get rid of waste from the body. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH]

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Expiratory Reserve Volume: The extra volume of air that can be expired with maximum effort beyond the level reached at the end of a normal, quiet expiration. Common abbreviation is ERV. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] Facial Expression: Observable changes of expression in the face in response to emotional stimuli. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatal Outcome: Death resulting from the presence of a disease in an individual, as shown by a single case report or a limited number of patients. This should be differentiated from death, the physiological cessation of life and from mortality, an epidemiological or statistical concept. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Fatty Liver: The buildup of fat in liver cells. The most common cause is alcoholism. Other causes include obesity, diabetes, and pregnancy. Also called steatosis. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated

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from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fetoprotein: Transabdominal aspiration of fluid from the amniotic sac with a view to detecting increases of alpha-fetoprotein in maternal blood during pregnancy, as this is an important indicator of open neural tube defects in the fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fine-needle aspiration: The removal of tissue or fluid with a needle for examination under a microscope. Also called needle biopsy. [NIH] Flaviviridae: A family of RNA viruses, some formerly classified under Togoviridae, many of which cause disease in humans and domestic animals. The three genera are Flavivirus, Pestivirus, and Hepatitis C-like viruses. [NIH] Flavivirus: A genus of Flaviviridae, also known as Group B arbovirus, containing several subgroups and species. Most are arboviruses transmitted by mosquitoes or ticks. The type species is yellow fever virus. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds

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with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Foot Ulcer: Lesion on the surface of the skin of the foot, usually accompanied by inflammation. The lesion may become infected or necrotic and is frequently associated with diabetes or leprosy. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH] Fulminant Hepatic Failure: Liver failure that occurs suddenly in a previously healthy person. The most common causes of FHF are acute hepatitis, acetaminophen overdose, and liver damage from prescription drugs. [NIH] Fungemia: The presence of fungi circulating in the blood. Opportunistic fungal sepsis is seen most often in immunosuppressed patients with severe neutropenia or in postoperative patients with intravenous catheters and usually follows prolonged antibiotic therapy. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Galactosemia: Buildup of galactose in the blood. Caused by lack of one of the enzymes needed to break down galactose into glucose. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma irradiation: A type of radiation therapy that uses gamma radiation. Gamma radiation is a type of high-energy radiation that is different from x-rays. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gangrenous: A circumscribed, deep-seated, suppurative inflammation of the subcutaneous tissue of the eyelid discharging pus from several points. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH]

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Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastroenterologist: A doctor who specializes in diagnosing and treating disorders of the digestive system. [NIH] Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] General practitioner: A medical practitioner who does not specialize in a particular branch of medicine or limit his practice to a specific class of diseases. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetic transcription: The process by which the genetic information encoded in the gene,

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represented as a linear sequence of deoxyribonucleotides, is copied into an exactly complementary sequence of ribonucleotides known as messenger RNA. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germfree: Free from all living micro-organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] Ginger: Deciduous plant rich in volatile oil (oils, volatile). It is used as a flavoring agent and has many other uses both internally and topically. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucosidases: Enzymes that hydrolyze O-glucosyl-compounds. (Enzyme Nomenclature, 1992) EC 3.2.1.-. [NIH]

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Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]

Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycogen Storage Disease: A group of inherited metabolic disorders involving the enzymes responsible for the synthesis and degradation of glycogen. In some patients, prominent liver involvement is presented. In others, more generalized storage of glycogen occurs, sometimes with prominent cardiac involvement. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Gonadal: Pertaining to a gonad. [EU] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]

Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions.

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[NIH]

Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granule: A small pill made from sucrose. [EU] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanine: One of the four DNA bases. [NIH] Habitat: An area considered in terms of its environment, particularly as this determines the type and quality of the vegetation the area can carry. [NIH] Haemodialysis: The removal of certain elements from the blood by virtue of the difference in the rates of their diffusion through a semipermeable membrane, e.g., by means of a haemodialyzer. [EU] Haemorrhage: The escape of blood from the vessels; bleeding. Small haemorrhages are classified according to size as petechiae (very small), purpura (up to 1 cm), and ecchymoses (larger). The massive accumulation of blood within a tissue is called a haematoma. [EU] Handwashing: The act of cleansing the hands with water or other liquid, with or without the inclusion of soap or other detergent, for the purpose of removing soil or microorganisms. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH]

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Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Behavior: Behaviors expressed by individuals to protect, maintain or promote their health status. For example, proper diet, and appropriate exercise are activities perceived to influence health status. Life style is closely associated with health behavior and factors influencing life style are socioeconomic, educational, and cultural. [NIH] Health Policy: Decisions, usually developed by government policymakers, for determining present and future objectives pertaining to the health care system. [NIH] Health Promotion: Encouraging consumer behaviors most likely to optimize health potentials (physical and psychosocial) through health information, preventive programs, and access to medical care. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Helicobacter: A genus of gram-negative, spiral-shaped bacteria that is pathogenic and has been isolated from the intestinal tract of mammals, including humans. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hematopoietic growth factors: A group of proteins that cause blood cells to grow and mature. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemochromatosis: A disease that occurs when the body absorbs too much iron. The body stores the excess iron in the liver, pancreas, and other organs. May cause cirrhosis of the liver. Also called iron overload disease. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobin A: Normal adult human hemoglobin. The globin moiety consists of two alpha

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and two beta chains. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemophilia: Refers to a group of hereditary disorders in which affected individuals fail to make enough of certain proteins needed to form blood clots. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepadnaviridae: A family of hepatotropic DNA viruses which contains double-stranded DNA genomes and causes hepatitis in humans and animals. There are two genera: Avihepadnavirus and Orthohepadnavirus. Hepadnaviruses include hepatitis B virus, duck hepatitis B virus, heron hepatitis B virus, ground squirrel hepatitis virus, and woodchuck hepatitis B virus. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatitis Antigens: Antigens from any of the hepatitis viruses including surface, core, and other associated antigens. [NIH] Hepatitis B: Hepatitis caused by hepatitis B virus. It may be transmitted by transfusion of contaminated blood or blood products. [NIH] Hepatitis C: A form of hepatitis, similar to type B post-transfusion hepatitis, but caused by a virus which is serologically distinct from the agents of hepatitis A, B, and E, and which may persist in the blood of chronic asymptomatic carriers. Hepatitis C is parenterally transmitted and associated with transfusions and drug abuse. [NIH] Hepatitis D: Hepatitis caused by the hepatitis delta virus in association with hepatitis B. It is endemic in some European countries and is seen in drug users, hemophiliacs, and polytransfused persons. [NIH] Hepatitis Delta Virus: A defective virus, containing particles of RNA nucleoprotein in virion-like form, present in patients with acute hepatitis B and chronic hepatitis. Officially this is classified as a subviral satellite RNA. [NIH] Hepatitis E: An acute form of hepatitis caused by a virus serologically distinct from the agents of hepatitis A, B, and C. Hepatitis E is associated with fecally-contaminated water, is enterically transmitted, and is commonly found in tropical or subtropical countries. [NIH] Hepatitis Viruses: Any of the viruses that cause inflammation of the liver. They include both DNA and RNA viruses as well viruses from humans and animals. [NIH] Hepatitis, Chronic: A collective term for a clinical and pathological syndrome which has

Dictionary 619

several causes and is characterized by varying degrees of hepatocellular necrosis and inflammation. Specific forms of chronic hepatitis include autoimmune hepatitis, chronic hepatitis B, chronic hepatitis C, chronic hepatitis D, indeterminate chronic viral hepatitis, cryptogenic chronic hepatitis, and drug-related chronic hepatitis. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocyte: A liver cell. [NIH] Hepatologist: A doctor who specializes in liver diseases. [NIH] Hepatology: The field of medicine concerned with the functions and disorders of the liver. [NIH]

Hepatoma: A liver tumor. [NIH] Hepatomegaly: Enlargement of the liver. [NIH] Hepatorenal Syndrome: Renal failure in those with liver disease, usually liver cirrhosis or obstructive jaundice. Historically called Heyd disease, urohepatic syndrome, or bile nephrosis. [NIH] Hepatotoxic: Toxic to liver cells. [EU] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes virus: A member of the herpes family of viruses. [NIH] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterogenic: Derived from a different source or species. Also called heterogenous. [NIH] Heterogenous: Derived from a different source or species. Also called heterogenic. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] HIV: Human immunodeficiency virus. Species of lentivirus, subgenus primate lentiviruses, formerly designated T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). It is acknowledged to be the agent responsible for the acute infectious manifestations, neurologic disorders, and immunologic abnormalities linked to the acquired immunodeficiency syndrome. [NIH]

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Home Infusion Therapy: Use of any infusion therapy on an ambulatory, outpatient, or other non-institutionalized basis. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] Hospitals, Public: Hospitals controlled by various types of government, i.e., city, county, district, state or federal. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Housekeeping: The care and management of property. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydration: Combining with water. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that

Dictionary 621

readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperbaric: Characterized by greater than normal pressure or weight; applied to gases under greater than atmospheric pressure, as hyperbaric oxygen, or to a solution of greater specific gravity than another taken as a standard of reference. [EU] Hyperbaric oxygen: Oxygen that is at an atmospheric pressure higher than the pressure at sea level. Breathing hyperbaric oxygen to enhance the effectiveness of radiation therapy is being studied. [NIH] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hyperreflexia: Exaggeration of reflexes. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hysterotomy: An incision in the uterus, performed through either the abdomen or the vagina. [NIH] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Immune adjuvant: A drug that stimulates the immune system to respond to disease. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH]

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Immune Tolerance: The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunization Programs: Organized services to administer immunization procedures in the prevention of various diseases. The programs are made available over a wide range of sites: schools, hospitals, public health agencies, voluntary health agencies, etc. They are administered to an equally wide range of population groups or on various administrative levels: community, municipal, state, national, international. [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunocompetence: The ability of lymphoid cells to mount a humoral or cellular immune response when challenged by antigen. [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunocompromised Host: A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]

Immunodominant Epitopes: Subunits of the antigenic determinant that are most easily recognized by the immune system and thus most influence the specificity of the induced antibody. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogen: A substance that is capable of causing antibody formation. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunomodulator: New type of drugs mainly using biotechnological methods. Treatment of cancer. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such

Dictionary 623

as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Indolent: A type of cancer that grows slowly. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant Mortality: Perinatal, neonatal, and infant deaths in a given population. [NIH] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infection Control: Programs of disease surveillance, generally within health care facilities, designed to investigate, prevent, and control the spread of infections and their causative

624 Hepatitis

microorganisms. [NIH] Infectious Diarrhea: Diarrhea caused by infection from bacteria, viruses, or parasites. [NIH] Infectious Mononucleosis: A common, acute infection usually caused by the Epstein-Barr virus (Human herpesvirus 4). There is an increase in mononuclear white blood cells and other atypical lymphocytes, generalized lymphadenopathy, splenomegaly, and occasionally hepatomegaly with hepatitis. [NIH] Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix

Dictionary 625

glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon Alfa-2b: A recombinant alfa interferon consisting of 165 amino acid residues with arginine in position 23 and histidine in position 34. It is used extensively as an antiviral and antineoplastic agent. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interferon-beta: One of the type I interferons produced by fibroblasts in response to stimulation by live or inactivated virus or by double-stranded RNA. It is a cytokine with antiviral, antiproliferative, and immunomodulating activity. [NIH] Interleukin-8: A cytokine that activates neutrophils and attracts neutrophils and Tlymphocytes. It is released by several cell types including monocytes, macrophages, Tlymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to platelet factor 4. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervention Studies: Epidemiologic investigations designed to test a hypothesized causeeffect relation by modifying the supposed causal factor(s) in the study population. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intrahepatic: Within the liver. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intramuscular injection: IM. Injection into a muscle. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH]

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Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Involution: 1. A rolling or turning inward. 2. One of the movements involved in the gastrulation of many animals. 3. A retrograde change of the entire body or in a particular organ, as the retrograde changes in the female genital organs that result in normal size after delivery. 4. The progressive degeneration occurring naturally with advancing age, resulting in shrivelling of organs or tissues. [EU] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irrigation: The washing of a body cavity or surface by flowing solution which is inserted and then removed. Any drug in the irrigation solution may be absorbed. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isocitrate Dehydrogenase: An enzyme of the oxidoreductase class that catalyzes the conversion of isocitrate and NAD+ to yield 2-ketoglutarate, carbon dioxide, and NADH. It occurs in cell mitochondria. The enzyme requires Mg2+, Mn2+; it is activated by ADP, citrate, and Ca2+, and inhibited by NADH, NADPH, and ATP. The reaction is the key ratelimiting step of the citric acid (tricarboxylic) cycle. (From Dorland, 27th ed) (The NADP+ enzyme is EC 1.1.1.42.) EC 1.1.1.41. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]

Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH]

Dictionary 627

Kava: Dried rhizome and roots of Piper methysticum, a shrub native to Oceania and known for its anti-anxiety and sedative properties. Heavy usage results in some adverse effects. It contains alkaloids, lactones, kawain, methysticin, mucilage, starch, and yangonin. Kava is also the name of the pungent beverage prepared from the plant's roots. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratoconjunctivitis: Simultaneous inflammation of the cornea and conjunctiva. [NIH] Keratoconjunctivitis Sicca: Drying and inflammation of the conjunctiva as a result of insufficient lacrimal secretion. When found in association with xerostomia and polyarthritis, it is called Sjogren's syndrome. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Ketoprofen: An ibuprofen-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Kidney Transplantation: The transference of a kidney from one human or animal to another. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU] Lacrimal: Pertaining to the tears. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH]

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Lamivudine: A reverse transcriptase inhibitor and zalcitabine analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Lassitude: Weakness; exhaustion. [EU] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] LDL: Low-density lipoprotein. Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lentivirus: A genus of the family Retroviridae consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species. [NIH] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lethal: Deadly, fatal. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Dictionary 629

Lice: A general name for small, wingless, parasitic insects, previously of the order Phthiraptera. Though exact taxonomy is still controversial, they can be grouped in the orders Anoplura (sucking lice), Mallophaga (biting lice), and Rhynchophthirina (elephant lice). [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipid Peroxides: Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]

Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver Neoplasms: Tumors or cancer of the liver. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive

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substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Local Government: Smallest political subdivisions within a country at which general governmental functions are carried-out. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [NIH] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along

Dictionary 631

lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphadenitis: Inflammation of the lymph nodes. [NIH] Lymphadenopathy: Disease or swelling of the lymph nodes. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lymphotoxin: Soluble substance released by lymphocytes activated by antigens or T-cell mitogens, that is cytotoxic to other cells. It is involved in allergies and chronic inflammatory diseases. Lymphotoxin is antigenically distinct from tumor necrosis factor-alpha (tumor necrosis factor), though they both share a common receptor, biological activities, and significant amino acid sequences. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macrophage Activation: The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune response-

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associated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malaise: A vague feeling of bodily discomfort. [EU] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Malondialdehyde: The dialdehyde of malonic acid. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen

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with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Assistance: Financing of medical care provided to public assistance recipients. [NIH] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] Medical Waste: Blood, mucus, tissue removed at surgery or autopsy, soiled surgical dressings, and other materials requiring special disposal procedures. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fusion: The adherence of cell membranes, intracellular membranes, or artifical membrane models of either to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight

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200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Methanol: A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU]

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Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milk Thistle: The plant Silybum marianum in the family Asteraceae containing the bioflavonoid complex silymarin. For centuries this has been used traditionally to treat liver disease. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate mitogen-activated protein kinases and are themselves phosphorylated by MAP kinase kinase kinases. JNK kinases (also known as SAPK kinases) are a subfamily. EC 2.7.10.- [NIH] Mitogen-Activated Protein Kinases: A superfamily of protein-serine-threonine kinases that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by mitogen-activated protein kinase kinases which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP kinase kinase kinases). Families of these mitogen-activated protein kinases (MAPKs) include extracellular signal-regulated kinases (ERKs), stress-activated protein kinases (SAPKs) (also known as c-jun terminal kinases (JNKs)), and p38-mitogen-activated protein kinases. EC 2,7,1.- [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mode of Transmission: Hepatitis A [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]

Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Evolution: Multiple rounds of selection, amplification, and mutation leading to molecules with the desired properties. [NIH] Molecular Probes: A group of atoms or molecules attached to other molecules or cellular structures and used in studying the properties of these molecules and structures. Radioactive DNA or RNA sequences are used in molecular genetics to detect the presence of a complementary sequence by molecular hybridization. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH]

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Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Monokines: Soluble mediators of the immune response that are neither antibodies nor complement. They are produced largely, but not exclusively, by monocytes and macrophages. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multidose: Occurring in, or using multiple doses. [EU] Multiple Organ Failure: A progressive condition usually characterized by combined failure of several organs such as the lungs, liver, kidney, along with some clotting mechanisms, usually postinjury or postoperative. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous

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chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH] Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables. [NIH] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Mutagen: Any agent, such as X-rays, gamma rays, mustard gas, TCDD, that can cause abnormal mutation in living cells; having the power to cause mutations. [NIH] Mutagenic: Inducing genetic mutation. [EU] Myalgia: Pain in a muscle or muscles. [EU] Mycobacterial disease: Any disease caused by Mycobacterium other than M. tuberculosis, M. bovis, and M. avium. [NIH] Mycobacteriosis: Any disease caused by Mycobacterium other than M. tuberculosis, M. bovis, and M. avium. [NIH] Mycobacterium: A genus of gram-positive, aerobic bacteria. Most species are free-living in soil and water, but the major habitat for some is the diseased tissue of warm-blooded hosts. [NIH]

Mycobacterium avium: A bacterium causing tuberculosis in domestic fowl and other birds. In pigs, it may cause localized and sometimes disseminated disease. The organism occurs occasionally in sheep and cattle. It should be distinguished from the M. avium complex, which infects primarily humans. [NIH] Mycobacterium avium Complex: A complex that includes several strains of M. avium. M. intracellulare is not easily distinguished from M. avium and therefore is included in the complex. These organisms are most frequently found in pulmonary secretions from persons with a tuberculous-like mycobacteriosis. Strains of this complex have also been associated with childhood lymphadenitis and AIDS. M. avium alone causes tuberculosis in a variety of birds and other animals, including pigs. [NIH] Mycophenolate mofetil: A drug that is being studied for its effectiveness in preventing graft-versus-host disease and autoimmune disorders. [NIH] Mycotoxins: Toxins derived from bacteria or fungi. [NIH] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelitis: Inflammation of the spinal cord. Relatively common etiologies include infections; autoimmune diseases; spinal cord; and ischemia (see also spinal cord vascular diseases). Clinical features generally include weakness, sensory loss, localized pain, incontinence, and other signs of autonomic dysfunction. [NIH] Myelodysplastic syndrome: Disease in which the bone marrow does not function normally. Also called preleukemia or smoldering leukemia. [NIH] Myeloid Cells: Cells which include the monocytes and the granulocytes. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU]

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Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myoglobin: A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Needle biopsy: The removal of tissue or fluid with a needle for examination under a microscope. Also called fine-needle aspiration. [NIH] Needle Sharing: Usage of a single needle among two or more people for injecting drugs. Needle sharing is a high-risk behavior for contracting infectious disease. [NIH] Needlestick Injuries: Penetrating stab wounds caused by needles. They are of special concern to health care workers since such injuries put them at risk for developing infectious disease. [NIH] Needs Assessment: Systematic identification of a population's needs or the assessment of individuals to determine the proper level of services needed. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal Hepatitis: Irritation of the liver with no known cause. Occurs in newborn babies. Symptoms include jaundice and liver cell changes. [NIH] Neonatal period: The first 4 weeks after birth. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephrologist: A doctor who treats patients with kidney problems or hypertension. [NIH] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH]

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Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural tube defects: These defects include problems stemming from fetal development of the spinal cord, spine, brain, and skull, and include birth defects such as spina bifida, anencephaly, and encephalocele. Neural tube defects occur early in pregnancy at about 4 to 6 weeks, usually before a woman knows she is pregnant. Many babies with neural tube defects have difficulty walking and with bladder and bowel control. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurosecretory Systems: A system of neurons that has the specialized function to produce and secrete hormones, and that constitutes, in whole or in part, an endocrine organ or system. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxins: Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutralization: An act or process of neutralizing. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Nevirapine: A potent, non-nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for treatment of HIV infection and AIDS. [NIH] Nipples: The conic organs which usually give outlet to milk from the mammary glands. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14.

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Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Non-nucleoside: A member of a class of compounds, including delavirdine, loviride and nevirapine, that acts to directly combine with and block the action of HIV's reverse transcriptase. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleocapsid: A protein-nucleic acid complex which forms part or all of a virion. It consists of a capsid plus enclosed nucleic acid. Depending on the virus, the nucleocapsid may correspond to a naked core or be surrounded by a membranous envelope. [NIH] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleoprotein: Chromosomes consist largely of nuclei acids and proteins, joined here as complexes called nucleoproteins. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nursing Care: Care given to patients by nursing service personnel. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Occupational Exposure: The exposure to potentially harmful chemical, physical, or biological agents that occurs as a result of one's occupation. [NIH]

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Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Oesophagitis: Inflammation of the esophagus. [EU] Office Management: Planning, organizing, and administering activities in an office. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oligo: Chemical and mineral elements that exist in minimal (oligo) quantities in the body, in foods, in the air, in soil; name applied to any element observed as a microconstituent of plant or animal tissue and of beneficial, harmful, or even doubtful significance. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Manifestations: Disorders of the mouth attendant upon non-oral disease or injury. [NIH]

Orf: A specific disease of sheep and goats caused by a pox-virus that is transmissible to man and characterized by vesiculation and ulceration of the lips. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organ Transplantation: Transference of an organ between individuals of the same species

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or between individuals of different species. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxaloacetate: An anionic form of oxaloacetic acid. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]

Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] P53 gene: A tumor suppressor gene that normally inhibits the growth of tumors. This gene is altered in many types of cancer. [NIH] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or

Dictionary 643

concerned with paediatrics. [EU] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Papain: A proteolytic enzyme obtained from Carica papaya. It is also the name used for a purified mixture of papain and chymopapain that is used as a topical enzymatic debriding agent. EC 3.4.22.2. [NIH] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [NIH] Paraganglia, Chromaffin: Small bodies containing chromaffin cells occurring outside of the adrenal medulla, most commonly near the sympathetic ganglia and in organs such as the kidney, liver, heart and gonads. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paramedic: An emergency medical technician (EMT) who received further training for the delivery of some aspects of advanced life support (ALS) care. [NIH] Parapoxvirus: A genus of the family Poxviridae, subfamily Chordopoxvirinae, which infect ungulates and may infect humans. Orf virus is the type species. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural

644 Hepatitis

and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Advocacy: Promotion and protection of the rights of patients, frequently through a legal process. [NIH] Patient Care Management: Generating, planning, organizing, and administering medical and nursing care and services for patients. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pediatric Dentistry: The practice of dentistry concerned with the dental problems of children, proper maintenance, and treatment. The dental care may include the services provided by dental specialists. [NIH] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pentoxifylline: A methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Library: A collection of cloned peptides, or chemically synthesized peptides, frequently consisting of all possible combinations of amino acids making up an n-amino acid peptide. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation

Dictionary 645

and ending 7 to 28 days after birth. [EU] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Pertussis: An acute, highly contagious infection of the respiratory tract, most frequently affecting young children, usually caused by Bordetella pertussis; a similar illness has been associated with infection by B. parapertussis and B. bronchiseptica. It is characterized by a catarrhal stage, beginning after an incubation period of about two weeks, with slight fever, sneezing, running at the nose, and a dry cough. In a week or two the paroxysmal stage begins, with the characteristic paroxysmal cough, consisting of a deep inspiration, followed by a series of quick, short coughs, continuing until the air is expelled from the lungs; the close of the paroxysm is marked by a long-drawn, shrill, whooping inspiration, due to spasmodic closure of the glottis. This stage lasts three to four weeks, after which the convalescent stage begins, in which paroxysms grow less frequent and less violent, and finally cease. Called also whooping cough. [EU] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmacists: Those persons legally qualified by education and training to engage in the practice of pharmacy. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH]

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Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280400 mm. There are two main types : photoallergy and photoxicity. [EU] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physicians, Family: Those physicians who have completed the education requirements specified by the American Academy of Family Physicians. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Picornavirus: Any of a group of tiny RNA-containing viruses including the enteroviruses and rhinoviruses. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Plana: The radiographic term applied to a vertebral body crushed to a thin plate. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of

Dictionary 647

proteins. [EU] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet Count: A count of the number of platelets per unit volume in a sample of venous blood. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pneumococcal Infections: Infections with bacteria of the species Streptococcus pneumoniae. [NIH]

Pneumococcal Vaccines: Vaccines or candidate vaccines used to prevent infections with Streptococcus pneumoniae. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Poliomyelitis: An acute viral disease, occurring sporadically and in epidemics, and characterized clinically by fever, sore throat, headache, and vomiting, often with stiffness of the neck and back. In the minor illness these may be the only symptoms. The major illness, which may or may not be preceded by the minor illness, is characterized by involvement of the central nervous system, stiff neck, pleocytosis in the spinal fluid, and perhaps paralysis. There may be subsequent atrophy of groups of muscles, ending in contraction and permanent deformity. The major illness is called acute anterior p., infantile paralysis and Heine-Medin disease. The disease is now largely controlled by vaccines. [EU] Polyarthritis: An inflammation of several joints together. [EU] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

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Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polyneuritis: Inflammation of several peripheral nerves at the same time. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyvalent: Having more than one valence. [EU] Population Dynamics: The pattern of any process, or the interrelationship of phenomena, which affects growth or change within a population. [NIH] Porphyria: A group of disorders characterized by the excessive production of porphyrins or their precursors that arises from abnormalities in the regulation of the porphyrin-heme pathway. The porphyrias are usually divided into three broad groups, erythropoietic, hepatic, and erythrohepatic, according to the major sites of abnormal porphyrin synthesis. [NIH]

Porphyria Cutanea Tarda: A form of hepatic porphyria (porphyria, hepatic) characterized by photosensitivity resulting in bullae that rupture easily to form shallow ulcers. This condition occurs in two forms: a sporadic, nonfamilial form that begins in middle age and has normal amounts of uroporphyrinogen decarboxylase with diminished activity in the liver; and a familial form in which there is an autosomal dominant inherited deficiency of uroporphyrinogen decarboxylase in the liver and red blood cells. [NIH] Porphyria, Hepatic: Porphyria in which the liver is the site where excess formation of porphyrin or its precursors is found. Acute intermittent porphyria and porphyria cutanea tarda are types of hepatic porphyria. [NIH] Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. [NIH] Portal Hypertension: High blood pressure in the portal vein. This vein carries blood into the liver. Portal hypertension is caused by a blood clot. This is a common complication of cirrhosis. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postherpetic Neuralgia: Variety of neuralgia associated with migraine in which pain is felt in or behind the eye. [NIH]

Dictionary 649

Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predictive factor: A situation or condition that may increase a person's risk of developing a certain disease or disorder. [NIH] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Pregnancy Tests: Tests to determine whether or not an individual is pregnant. [NIH] Preleukemia: Conditions in which the abnormalities in the peripheral blood or bone marrow represent the early manifestations of acute leukemia, but in which the changes are not of sufficient magnitude or specificity to permit a diagnosis of acute leukemia by the usual clinical criteria. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Preoperative: Preceding an operation. [EU] Prepuce: A covering fold of skin; often used alone to designate the preputium penis. [EU] Presumptive: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Preventive Health Services: Services designed for promotion of health and prevention of

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disease. [NIH] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [NIH] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Primary Sclerosing Cholangitis: Irritation, scarring, and narrowing of the bile ducts inside and outside the liver. Bile builds up in the liver and may damage its cells. Many people with this condition also have ulcerative colitis. [NIH] Private Sector: That distinct portion of the institutional, industrial, or economic structure of a country that is controlled or owned by non-governmental, private interests. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Programmed Instruction: Instruction in which learners progress at their own rate using workbooks, textbooks, or electromechanical devices that provide information in discrete steps, test learning at each step, and provide immediate feedback about achievement. (ERIC, Thesaurus of ERIC Descriptors, 1996). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Progressive disease: Cancer that is increasing in scope or severity. [NIH] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Promyelocytic leukemia: A type of acute myeloid leukemia, a quickly progressing disease

Dictionary 651

in which too many immature blood-forming cells are found in the blood and bone marrow. [NIH]

Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protective Clothing: Clothing designed to protect the individual against possible exposure to known hazards. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Engineering: Procedures by which nonrandom single-site changes are introduced into structural genes (site-specific mutagenesis) in order to produce mutant genes which can be coupled to promoters that direct the synthesis of a specifically altered protein, which is then analyzed for structural and functional properties and then compared with the predicted and sought-after properties. The design of the protein may be assisted by computer graphic technology and other advanced molecular modeling techniques. [NIH] Protein Folding: A rapid biochemical reaction involved in the formation of proteins. It begins even before a protein has been completely synthesized and proceeds through discrete intermediates (primary, secondary, and tertiary structures) before the final structure (quaternary structure) is developed. [NIH] Protein Kinase C: An enzyme that phosphorylates proteins on serine or threonine residues in the presence of physiological concentrations of calcium and membrane phospholipids. The additional presence of diacylglycerols markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by phorbol esters

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and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. EC 2.7.1.-. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors. EC 2.7.10. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Proteome: The protein complement of an organism coded for by its genome. [NIH] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]

Prothrombin Time: Measurement of clotting time of plasma recalcified in the presence of excess tissue thromboplastin. Factors measured are fibrinogen, prothrombin, and factors V, VII, and X. It is used for monitoring anticoagulant therapy with coumarins. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoan: 1. Any individual of the protozoa; protozoon. 2. Of or pertaining to the protozoa; protozoal. [EU] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Proxy: A person authorized to decide or act for another person, for example, a person having durable power of attorney. [NIH] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other

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psychological or behavioral functions. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psyllium: Dried, ripe seeds of Plantago psyllium, P. indica, and P. ovata (Plantaginaceae). Plantain seeds swell in water and are used as demulcents and bulk laxatives. [NIH] Public Assistance: Financial assistance to impoverished persons for the essentials of living through federal, state or local government programs. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Fibrosis: Chronic inflammation and progressive fibrosis of the pulmonary alveolar walls, with steadily progressive dyspnea, resulting finally in death from oxygen lack or right heart failure. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyrazinamide: A pyrazine that is used therapeutically as an antitubercular agent. [NIH] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH]

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Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quiescent: Marked by a state of inactivity or repose. [EU] Rabies: A highly fatal viral infection of the nervous system which affects all warm-blooded animal species. It is one of the most important of the zoonoses because of the inevitably fatal outcome for the infected human. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even

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numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Rape: Unlawful sexual intercourse without consent of the victim. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Reentry: Reexcitation caused by continuous propagation of the same impulse for one or more cycles. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a

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straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]

Reinfection: A second infection by the same pathogenic agent, or a second infection of an organ such as the kidney by a different pathogenic agent. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Reminder Systems: Systems used to prompt or aid the memory. The systems can be computerized reminders, color coding, telephone calls, or devices such as letters and postcards. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Remission Induction: Therapeutic act or process that initiates a response to a complete or partial remission level. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Replicon: In order to be replicated, DNA molecules must contain an origin of duplication and in bacteria and viruses there is usually only one per genome. Such molecules are called replicons. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Response Elements: Nucleotide sequences, usually upstream, which are recognized by

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specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [NIH]

Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retinyl palmitate: A drug being studied in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retreatment: The therapy of the same disease in a patient, with the same agent or procedure repeated after initial treatment, or with an additional or alternate measure or follow-up. It does not include therapy which requires more than one administration of a therapeutic agent or regimen. Retreatment is often used with reference to a different modality when the original one was inadequate, harmful, or unsuccessful. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Reverse Transcriptase Inhibitors: Inhibitors of reverse transcriptase (RNA-directed DNA polymerase), an enzyme that synthesizes DNA on an RNA template. [NIH] Rheology: The study of the deformation and flow of matter, usually liquids or fluids, and of the plastic flow of solids. The concept covers consistency, dilatancy, liquefaction, resistance to flow, shearing, thixotrophy, and viscosity. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although

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infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Rhinovirus: A genus of Picornaviridae inhabiting primarily the respiratory tract of mammalian hosts. It includes the human strains associated with common colds. [NIH] Ribavirin: 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. [NIH] Ribonuclease: RNA-digesting enzyme. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Rimantadine: An RNA synthesis inhibitor that is used as an antiviral agent in the prophylaxis and treatment of influenza. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Risk-Taking: Undertaking a task involving a challenge for achievement or a desirable goal in which there is a lack of certainty or a fear of failure. It may also include the exhibiting of certain behaviors whose outcomes may present a risk to the individual or to those associated with him or her. [NIH] Rituximab: A type of monoclonal antibody used in cancer detection or therapy. Monoclonal antibodies are laboratory-produced substances that can locate and bind to cancer cells. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rotavirus: A genus of Reoviridae, causing acute gastroenteritis in birds and mammals, including humans. Transmission is horizontal and by environmental contamination. [NIH] Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Rubella: An acute, usually benign, infectious disease caused by a togavirus and most often affecting children and nonimmune young adults, in which the virus enters the respiratory tract via droplet nuclei and spreads to the lymphatic system. It is characterized by a slight cold, sore throat, and fever, followed by enlargement of the postauricular, suboccipital, and cervical lymph nodes, and the appearances of a fine pink rash that begins on the head and spreads to become generalized. Called also German measles, roetln, röteln, and three-day measles, and rubeola in French and Spanish. [EU] Rubella Virus: The type (and only) species of Rubivirus causing acute infection in humans, primarily children and young adults. Humans are the only natural host. A live, attenuated vaccine is available for prophylaxis. [NIH] Rural Population: The inhabitants of rural areas or of small towns classified as rural. [NIH] Safe Sex: Sex behavior that prevents or decreases the spread of sexually transmitted

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diseases or pregnancy. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salmonella: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that utilizes citrate as a sole carbon source. It is pathogenic for humans, causing enteric fevers, gastroenteritis, and bacteremia. Food poisoning is the most common clinical manifestation. Organisms within this genus are separated on the basis of antigenic characteristics, sugar fermentation patterns, and bacteriophage susceptibility. [NIH] Sanitary: Relating or belonging to health and hygiene; conductive to the restoration or maintenance of health. [NIH] Sanitation: The development and establishment of environmental conditions favorable to the health of the public. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Secretory Vesicles: Vesicles derived from the golgi apparatus containing material to be released at the cell surface. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU]

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Sediment: A precipitate, especially one that is formed spontaneously. [EU] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensory loss: A disease of the nerves whereby the myelin or insulating sheath of myelin on the nerves does not stay intact and the messages from the brain to the muscles through the nerves are not carried properly. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Septicaemia: A term originally used to denote a putrefactive process in the body, but now usually referring to infection with pyogenic micro-organisms; a genus of Diptera; the severe type of infection in which the blood stream is invaded by large numbers of the causal. [NIH] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serial Passage: Inoculation of a series of animals or in vitro tissue with an infectious bacterium or virus, as in virulence studies and the development of vaccines. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Seroconversion: The change of a serologic test from negative to positive, indicating the development of antibodies in response to infection or immunization. [EU] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serologic Tests: Diagnostic procedures involving immunoglobulin reactions. [NIH]

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Serology: The study of serum, especially of antigen-antibody reactions in vitro. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serotypes: A cause of haemorrhagic septicaemia (in cattle, sheep and pigs), fowl cholera of birds, pasteurellosis of rabbits, and gangrenous mastitis of ewes. It is also commonly found in atrophic rhinitis of pigs. [NIH] Serrata: The serrated anterior border of the retina located approximately 8.5 mm from the limbus and adjacent to the pars plana of the ciliary body. [NIH] Serrated: Having notches or teeth on the edge as a saw has. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Behavior: Sexual activities of humans. [NIH] Sexual Partners: Married or single individuals who share sexual relations. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [NIH] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [NIH] Shigella: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that ferments sugar without gas production. Its organisms are intestinal pathogens of man and other primates and cause bacillary dysentery. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Sicca: Failure of lacrimal secretion, keratoconjunctivitis sicca, failure of secretion of the salivary glands and mucous glands of the upper respiratory tract and polyarthritis. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH]

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Silymarin: A mixture of flavonoids extracted from seeds of the milk thistle, Silybum marianum. It consists primarily of three isomers: silicristin, silidianin, and silybin, its major component. Silymarin displays antioxidant and membrane stabilizing activity. It protects various tissues and organs against chemical injury, and shows potential as an antihepatoxic agent. [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smallpox: A generalized virus infection with a vesicular rash. [NIH] Smiling: A facial expression which may denote feelings of pleasure, affection, amusement, etc. [NIH] Smoldering leukemia: Disease in which the bone marrow does not function normally. Also called preleukemia or myelodysplastic syndrome. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Security: Government sponsored social insurance programs. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Socialization: The training or molding of an individual through various relationships, educational agencies, and social controls, which enables him to become a member of a particular society. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle

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displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spasmodic: Of the nature of a spasm. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Vascular Diseases: Hypoxic-ischemic and hemorrhagic disorders of the spinal cord. Arteriosclerosis, emboli, and vascular malformations are potential causes of these conditions. [NIH] Spirochete: Lyme disease. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenomegaly: Enlargement of the spleen. [NIH] Spondylitis: Inflammation of the vertebrae. [EU] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Standardize: To compare with or conform to a standard; to establish standards. [EU] State Government: The level of governmental organization and function below that of the national or country-wide government. [NIH] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Steatosis: Fatty degeneration. [EU]

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Stellate: Star shaped. [NIH] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Sterilization: The destroying of all forms of life, especially microorganisms, by heat, chemical, or other means. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulants: Any drug or agent which causes stimulation. [NIH] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]

Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Street Drugs: Drugs obtained and often manufactured illegally for the subjective effects they are said to produce. They are often distributed in urban areas, but are also available in suburban and rural areas, and tend to be grossly impure and may cause unexpected toxicity. [NIH]

Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stress management: A set of techniques used to help an individual cope more effectively with difficult situations in order to feel better emotionally, improve behavioral skills, and often to enhance feelings of control. Stress management may include relaxation exercises, assertiveness training, cognitive restructuring, time management, and social support. It can be delivered either on a one-to-one basis or in a group format. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU]

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Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sulfates: Inorganic salts of sulfuric acid. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Sulfuric acid: A strong acid that, when concentrated is extemely corrosive to the skin and mucous membranes. It is used in making fertilizers, dyes, electroplating, and industrial explosives. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's

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response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Tetani: Causal agent of tetanus. [NIH] Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild

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condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thimerosal: A topical antiseptic used on skin and mucous membranes. It is also used as a preservative in pharmaceuticals. [NIH] Thioacetamide: A crystalline compound used as a laboratory reagent in place of hydrogen sulfide. It is a potent hepatocarcinogen. [NIH] Thioredoxin: A hydrogen-carrying protein that participates in a variety of biochemical reactions including ribonucleotide reduction. Thioredoxin is oxidized from a dithiol to a disulfide during ribonucleotide reduction. The disulfide form is then reduced by NADPH in a reaction catalyzed by thioredoxin reductase. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombopenia: Reduction in the number of platelets in the blood. [NIH] Thromboplastin: Constituent composed of protein and phospholipid that is widely distributed in many tissues. It serves as a cofactor with factor VIIa to activate factor X in the extrinsic pathway of blood coagulation. [NIH] Thromboses: The formation or presence of a blood clot within a blood vessel during life. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymosin: A family of heat-stable, polypeptide hormones secreted by the thymus gland.

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Their biological activities include lymphocytopoiesis, restoration of immunological competence and enhancement of expression of T-cell characteristics and function. They have therapeutic potential in patients having primary or secondary immunodeficiency diseases, cancer or diseases related to aging. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroiditis: Inflammation of the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tic: An involuntary compulsive, repetitive, stereotyped movement, resembling a purposeful movement because it is coordinated and involves muscles in their normal synergistic relationships; tics usually involve the face and shoulders. [EU] Ticks: Blood-sucking arachnids of the order Acarina. [NIH] Time Management: Planning and control of time to improve efficiency and effectiveness. [NIH]

Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Titre: The quantity of a substance required to produce a reaction with a given volume of another substance, or the amount of one substance required to correspond with a given amount of another substance. [EU] Tobacco Mosaic Virus: The type species of tobamovirus which causes mosaic disease of tobacco. Transmission occurs by mechanical inoculation. [NIH] Tobamovirus: A genus of plant viruses in which the virion is a rigid filament. Transmission is by mechanical inoculation or seed. The type species is tobacco mosaic virus. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonicity: The normal state of muscular tension. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxic Hepatitis: Hepatitis with inflammatory changes around small bile ducts causing

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obstructive jaundice; the disease may be due to intoxication by certain chemical substances, e. g. manganese. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Toxoid: The material resulting from the treatment of toxin in such a way that the toxic properties are inactivated whilst the antigenic potency remains intact. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transaminase: Aminotransferase (= a subclass of enzymes of the transferase class that catalyse the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally 2-keto acid). Most of these enzymes are pyridoxal-phosphate-proteins. [EU]

Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Translating: Conversion from one language to another language. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH]

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Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] TYPHI: The bacterium that gives rise to typhoid fever. [NIH] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH]

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Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Universal Precautions: Prudent standard preventive measures to be taken by professional and other health personnel in contact with persons afflicted with a communicable disease, to avoid contracting the disease by contagion or infection. Precautions are especially applicable in the diagnosis and care of AIDS patients. [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]

Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Uroporphyrinogen Decarboxylase: One of the enzymes active in heme biosynthesis. It catalyzes the decarboxylation of uroporphyrinogen III to coproporphyrinogen III by the conversion of four acetic acid groups to four methyl groups. EC 4.1.1.37. [NIH] Uterine Contraction: Contraction of the uterine muscle. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH]

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Vaccine adjuvant: A substance added to a vaccine to improve the immune response so that less vaccine is needed. [NIH] Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. [NIH] Vaccinia Virus: The type species of Orthopoxvirus, related to cowpox virus, but whose true origin is unknown. It has been used as a live vaccine against smallpox. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of vaccinia virus. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Varicella: Chicken pox. [EU] Variola: A generalized virus infection with a vesicular rash. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venoms: Poisonous animal secretions forming fluid mixtures of many different enzymes, toxins, and other substances. These substances are produced in specialized glands and secreted through specialized delivery systems (nematocysts, spines, fangs, etc.) for disabling prey or predator. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villous: Of a surface, covered with villi. [NIH] Vinyl Chloride: A gas that has been used as an aerosol propellant and is the starting material for polyvinyl resins. Toxicity studies have shown various adverse effects,

Dictionary 673

particularly the occurrence of liver neoplasms. [NIH] Viraemia: The presence of virus in blood or blood plasma. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Hepatitis: Hepatitis caused by a virus. Five different viruses (A, B, C, D, and E) most commonly cause this form of hepatitis. Other rare viruses may also cause hepatitis. [NIH] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Viral Proteins: Proteins found in any species of virus. [NIH] Viral Regulatory Proteins: Proteins which regulate the rate of transcription of viral structural genes. [NIH] Viral Structural Proteins: Viral proteins that do not regulate transcription. They are coded by viral structural genes and include nucleocapsid core proteins (gag proteins), enzymes (pol proteins), and membrane components (env proteins). Transcription of viral structural genes is regulated by viral regulatory proteins. [NIH] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Viremia: The presence of viruses in the blood. [NIH] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Virus Activation: The mechanism by which latent viruses, such as genetically transmitted tumor viruses or prophages of lysogenic bacteria, are induced to replicate and are released as infectious viruses. It may be effected by various endogenous and exogenous stimuli, including B-cell lipopolysaccharides, glucocorticoid hormones, halogenated pyrimidines, ionizing radiation, ultraviolet light, and superinfecting viruses. [NIH] Virus Diseases: A general term for diseases produced by viruses. [NIH] Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of proteins, nucleic acids, and sometimes lipids, and their assembly into a new infectious particle. [NIH] Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Voluntary Health Agencies: Non-profit organizations concerned with various aspects of

674 Hepatitis

health, e.g., education, promotion, treatment, services, etc. [NIH] War: Hostile conflict between organized groups of people. [NIH] Waste Management: Disposal, processing, controlling, recycling, and reusing the solid, liquid, and gaseous wastes of plants, animals, humans, and other organisms. It includes control within a closed ecological system to maintain a habitable environment. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yellow Fever: An acute infectious disease primarily of the tropics, caused by a virus and transmitted to man by mosquitoes of the genera Aedes and Haemagogus. [NIH] Yellow Fever Virus: The type species of the Flavivirus genus. Principal vector transmission to humans is by Aedes spp. mosquitoes. [NIH] Zalcitabine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chainterminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy. [NIH] Zoonosis: Disease of animals, e. g. rabies, that can be transmitted to humans. A risk in major disasters; any disease and/or infection which is likely to be naturally transmitted from animals to man; disease caused by animal parasites. [NIH] Zoster: A virus infection of the Gasserian ganglion and its nerve branches, characterized by discrete areas of vesiculation of the epithelium of the forehead, the nose, the eyelids, and the cornea together with subepithelial infiltration. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

675

INDEX A Abdomen, 577, 588, 589, 605, 609, 621, 625, 629, 644, 645, 663, 664, 667 Abdominal Pain, 62, 377, 443, 560, 561, 577, 613, 671 Aberrant, 223, 577 Abortion, 57, 577, 584 Abscess, 57, 250, 577, 660 Absolute risk, 6, 577 Acatalasia, 577, 591 Acceptor, 577, 629, 642, 669 Acetaminophen, 577, 612 Acetylcholine, 577, 594, 639 Acidity, 577, 645 Acquired Immunodeficiency Syndrome, 422, 438, 467, 542, 543, 577, 619 Acrylonitrile, 577, 658 Acute Disease, 4, 353, 372, 414, 471, 577 Acute myeloid leukemia, 577, 650 Acute renal, 578, 618 Acyl, 403, 578 Adaptability, 578, 592 Adaptation, 380, 578 Adenine, 578, 653 Adenocarcinoma, 578, 619 Adenosine, 92, 97, 578, 646 Adenosine Deaminase, 92, 97, 578 Adenovirus, 94, 135, 143, 182, 208, 267, 578 Adipocytes, 578, 628 Adjunctive Therapy, 17, 454, 578 Adjustment, 24, 578 Adjuvant, 42, 105, 219, 288, 401, 578 Adolescence, 578, 594 Adrenal Cortex, 578, 600, 650 Adrenal Medulla, 403, 578, 591, 594, 609, 640, 643 Adrenaline, 403, 578 Adrenergic, 578, 605, 609, 666, 670 Adsorption, 177, 349, 578 Adsorptive, 579 Adverse Effect, 6, 16, 18, 52, 105, 286, 302, 443, 454, 579, 605, 627, 661, 672 Aerobic, 579, 635, 637 Aerosol, 579, 672 Afferent, 579, 628 Affinity, 359, 369, 389, 410, 579, 585, 662 Aflatoxin B1, 130, 270, 276, 579

Aflatoxins, 112, 579 Age Groups, 15, 579 Age of Onset, 579, 670 Age-Adjusted, 54, 579 Aged, 80 and Over, 579 Aggressiveness, 14, 579 Agonist, 407, 579, 605 A-HA, 342, 579 Alanine Transaminase, 44, 369, 448, 449, 580 Albumin, 113, 580, 646 Algorithms, 580, 588 Alimentary, 12, 29, 261, 291, 301, 580, 643 Alkaline, 374, 411, 580, 581, 590 Alkaline Phosphatase, 374, 411, 580 Alkaloid, 580, 596 Alleles, 74, 80, 90, 443, 580 Allogeneic, 196, 256, 580, 616 Allograft, 7, 46, 102, 122, 191, 226, 356, 580 Allylamine, 580, 581 Alopecia, 296, 580 Alpha Particles, 580, 654 Alpha-1, 399, 490, 497, 580 Alpha-fetoprotein, 66, 196, 580, 611 Alternative medicine, 274, 280, 302, 481, 580 Alum, 105, 362, 580, 596 Aluminum, 580, 581 Amantadine, 351, 449, 454, 541, 581 Amber, 97, 581 Ameliorating, 378, 581 Amine, 406, 581, 588 Amino Acid Sequence, 92, 350, 368, 382, 399, 410, 581, 583, 613, 631 Amino Acid Substitution, 210, 364, 581 Amino-terminal, 218, 377, 581 Ammonia, 578, 581, 671 Amphetamines, 581, 596 Amplification, 44, 70, 99, 130, 132, 136, 144, 168, 169, 173, 363, 371, 375, 533, 581, 635 Ampulla, 581, 594, 607 Amputation, 400, 581 Anaemia, 240, 581 Anaerobic, 582, 659, 661 Anaesthesia, 582, 623 Anaesthetic, 201, 582

676 Hepatitis

Anal, 49, 162, 297, 484, 531, 545, 582, 608, 630, 637 Analgesic, 577, 582, 621, 627, 641 Analog, 65, 121, 176, 345, 582, 628 Analogous, 582, 605, 669 Analytes, 516, 582 Anaphylatoxins, 582, 598 Anatomical, 437, 582, 594, 623, 634, 659 Anemia, 7, 8, 10, 34, 53, 342, 418, 449, 582, 632, 667 Angiogenesis, 582, 632 Animal model, 17, 69, 75, 78, 87, 97, 103, 104, 106, 112, 118, 123, 125, 424, 582 Anionic, 366, 582, 642 Anions, 580, 582, 626, 665 Annealing, 582, 648 Anorexia, 32, 67, 377, 443, 581, 582, 613, 671 Anterior Cerebral Artery, 582, 593 Anthrax, 365, 582 Anthropology, 124, 583 Antiasthmatic, 402, 583 Antibacterial, 583, 604, 663 Antibiotic, 583, 590, 612, 644, 663, 667 Antibodies, Anticardiolipin, 583, 584 Antibodies, Antiphospholipid, 583, 584 Anticholinergic, 351, 583 Anticoagulant, 47, 583, 584, 603, 651, 652 Antidepressant, 402, 403, 583 Antigen-Antibody Complex, 583, 597 Antigen-presenting cell, 583, 602 Anti-infective, 583, 620, 626 Anti-inflammatory, 229, 293, 378, 402, 577, 583, 585, 592, 614, 621, 627, 643, 649 Anti-Inflammatory Agents, 378, 583, 585, 592 Antimetabolite, 584, 658 Antimicrobial, 179, 210, 299, 440, 584, 603, 605 Antineoplastic, 584, 600, 625 Antioxidant, 85, 98, 111, 227, 584, 585, 642, 662 Antiphospholipid Syndrome, 130, 298, 583, 584 Antiproliferative, 584, 625 Antipyretic, 577, 584, 627 Antiseptic, 584, 667 Antiviral Agents, 65, 73, 80, 81, 121, 348, 364, 375, 387, 411, 417, 424, 450, 584 Anuria, 584, 627 Anus, 582, 584, 586, 589, 597 Anxiety, 150, 192, 293, 584, 627

Aplastic anemia, 256, 584 Apolipoproteins, 584, 629 Apoptosis, 95, 116, 117, 176, 205, 216, 258, 288, 296, 584, 591 Applicability, 37, 49, 584 Aqueous, 295, 373, 584, 587, 601, 620, 628 Archaea, 584, 634 Arginine, 582, 585, 625 Arterial, 274, 280, 580, 584, 585, 589, 593, 594, 621, 652, 666 Arteries, 400, 585, 589, 599, 628, 630, 634, 637 Arterioles, 585, 589, 634 Arteriosclerosis, 585, 591, 663 Artery, 448, 582, 585, 600, 606, 643, 653, 659 Articular, 585, 629, 642 Ascorbic Acid, 271, 277, 585, 621 Aseptic, 31, 474, 585, 641, 664 Aspartate, 7, 20, 44, 264, 361, 369, 394, 585 Aspartate Transaminase, 44, 369, 585 Aspiration, 585, 611 Aspirin, 449, 585 Astrocytes, 585, 634, 636 Asymptomatic, 7, 8, 21, 22, 23, 30, 53, 55, 58, 59, 83, 163, 176, 289, 345, 353, 373, 398, 455, 459, 464, 480, 482, 505, 531, 577, 585, 618, 643 Atmospheric Pressure, 585, 621 Atopic, 219, 396, 585 Atresia, 77, 85, 111, 586, 587 Atrophy, 586, 647 Attenuation, 209, 586 Atypical, 369, 370, 586, 624 Audiovisual Aids, 562, 586 Autoantibodies, 67, 161, 186, 265, 370, 443, 452, 583, 586 Autoantigens, 179, 586 Autodigestion, 586, 643 Autoimmune disease, 63, 379, 395, 396, 404, 443, 583, 586, 636, 637 Autoimmunity, 63, 179, 207, 255, 265, 586 Autologous, 148, 341, 396, 586 Autonomic, 577, 586, 637, 640, 645, 665 Autopsy, 6, 206, 586, 633 Avian, 69, 153, 377, 395, 586 Axonal, 235, 586, 674 B Bacillus, 582, 586, 590 Bacteremia, 586, 589, 659 Bacterial Physiology, 578, 586 Bactericidal, 370, 586, 609

Index 677

Bacteriophage, 313, 586, 659, 669 Bacterium, 176, 586, 618, 637, 660, 670 Bacteriuria, 586, 671 Base, 81, 208, 445, 578, 587, 601, 602, 613, 627, 647, 666, 671 Basement Membrane, 587, 610, 627 Basophils, 587, 616, 628 Bed Rest, 537, 587 Benign, 8, 58, 587, 612, 616, 638, 658 Bereavement, 461, 587 Beta-Thromboglobulin, 587, 625 Bilateral, 185, 587, 657 Bile Acids, 587, 664, 666 Bile Acids and Salts, 587 Bile duct, 12, 21, 85, 88, 203, 587, 594, 650, 668 Bile Pigments, 587, 626 Biliary, 76, 85, 111, 258, 270, 276, 399, 449, 451, 452, 456, 524, 587, 594, 643 Biliary Atresia, 76, 85, 111, 258, 399, 524, 587 Biliary Tract, 587, 643 Bilirubin, 44, 60, 573, 580, 587, 621 Binding Sites, 29, 236, 587 Bioassays, 112, 587 Bioavailability, 109, 406, 407, 588 Bioavailable, 17, 588 Biochemical reactions, 588, 667 Biogenic Monoamines, 403, 588 Biological Markers, 355, 588 Biological response modifier, 588, 625 Biological therapy, 588, 616 Biomarkers, 81, 112, 117, 211, 588 Biopsy specimen, 193, 588 Biotechnology, 128, 178, 215, 217, 223, 273, 274, 279, 280, 291, 301, 432, 440, 481, 495, 588 Biotypes, 384, 588 Biphasic, 5, 215, 588 Bladder, 304, 588, 598, 623, 636, 639, 651, 671 Bloating, 588, 623 Blood Coagulation, 589, 590, 667 Blood Glucose, 589, 617, 624 Blood Platelets, 589, 661, 667 Blood pressure, 460, 573, 589, 591, 621, 636, 648, 662 Blood transfusion, 7, 8, 33, 37, 57, 59, 294, 358, 429, 445, 450, 463, 470, 528, 539, 548, 589 Blood-Borne Pathogens, 101, 106, 501, 589 Blood-Brain Barrier, 589, 628

Body Mass Index, 21, 217, 589 Bone Marrow, 208, 256, 378, 454, 578, 584, 589, 601, 609, 613, 616, 622, 631, 637, 649, 651, 662, 664 Bone Marrow Transplantation, 208, 378, 589 Bowel, 369, 396, 582, 589, 603, 608, 624, 625, 639, 664, 671 Bowel Movement, 589, 603, 664 Brain Infarction, 403, 404, 589 Brain Stem, 589, 593 Brain Stem Infarctions, 589 Branch, 424, 431, 470, 503, 569, 589, 601, 613, 631, 643, 653, 663, 667 Breakdown, 37, 522, 589, 603, 612 Breeding, 83, 590 Broad-spectrum, 73, 590 Bromine, 366, 590 Bronchiseptica, 590, 645 Bronchitis, 590, 595 Buccal, 590, 630, 664 C Cachexia, 378, 396, 590 Cadaver, 200, 590 Calcium, 180, 360, 590, 595, 597, 632, 651, 652, 661 Campylobacter, 457, 590 Capsid, 125, 149, 153, 155, 171, 176, 357, 381, 388, 391, 590, 640, 673 Capsular, 121, 401, 590 Capsules, 326, 337, 354, 590 Carbohydrate, 220, 354, 590, 615, 648, 660 Carboxy, 382, 395, 412, 590 Carboxy-terminal, 395, 412, 590 Carcinogen, 112, 590, 637 Carcinogenesis, 15, 88, 134, 242, 590 Carcinogenic, 110, 432, 590, 624, 641, 650, 664 Cardiac, 341, 404, 449, 580, 590, 602, 609, 615, 638, 664 Cardiolipins, 584, 590 Cardiomyopathy, 591 Cardiopathy, 402, 403, 591 Cardiovascular, 407, 552, 591, 661 Cardiovascular disease, 552, 591 Cardiovirus, 591, 607 Carnitine, 226, 335, 591 Carrier State, 59, 142, 398, 456, 591 Case report, 198, 206, 208, 233, 251, 254, 301, 504, 591, 596, 610 Case series, 39, 53, 591, 596 Case-Control Studies, 80, 591, 608

678 Hepatitis

Caspase, 299, 591 Catalase, 370, 577, 591 Catalyse, 386, 591, 669 Catecholamine, 591, 604 Catheterization, 57, 591, 626 Cathode, 591, 592 Cations, 479, 592, 626 Causal, 63, 483, 592, 608, 618, 625, 660, 666 Cause of Death, 320, 592, 601 Celecoxib, 287, 592 Celiac Disease, 461, 592 Cell Adhesion, 592, 625 Cell Death, 76, 116, 355, 584, 592, 614 Cell Differentiation, 592, 661 Cell Division, 586, 592, 593, 601, 616, 633, 635, 646, 651, 660 Cell membrane, 356, 592, 602, 606, 633, 646 Cell Physiology, 450, 592 Cell proliferation, 79, 396, 585, 592, 661 Cell Respiration, 592, 635, 656 Cell Size, 592, 611 Cell Survival, 111, 316, 592, 616 Cell Transplantation, 252, 592 Cellulose, 592, 646 Central Nervous System Infections, 592, 616 Centrifugation, 593, 634 Centriole, 223, 593 Cerebellum, 589, 593 Cerebral, 298, 402, 403, 435, 524, 582, 589, 593, 609, 612, 632 Cerebral hemispheres, 589, 593 Cerebral Infarction, 402, 403, 589, 593 Cerebral Palsy, 524, 593 Cerebrospinal, 72, 166, 593 Cerebrospinal fluid, 72, 593 Cerebrovascular, 591, 593 Cerebrum, 593 Cervical, 193, 379, 557, 593, 658 Cervix, 577, 593 Cesarean Section, 57, 593 Check-up, 325, 336, 342, 593 Chemical Warfare, 593, 602 Chemical Warfare Agents, 593, 602 Chemoembolization, 274, 280, 593 Chemotactic Factors, 593, 598 Chemotherapy, 12, 179, 196, 208, 210, 238, 290, 292, 296, 299, 300, 301, 361, 379, 479, 593 Chickenpox, 519, 557, 594 Child Care, 28, 457, 594

Child Development, 460, 594 Chimeras, 70, 75, 177, 385, 594 Chin, 189, 193, 199, 244, 248, 273, 279, 290, 300, 594, 633 Chiropractic, 465, 594 Chlorine, 317, 366, 594 Chloroform, 136, 594 Cholangitis, 182, 369, 370, 399, 449, 594 Cholera, 594, 661 Cholestasis, 12, 77, 85, 237, 286, 594 Cholesterol, 187, 304, 400, 460, 587, 594, 595, 600, 628, 629, 630, 633, 664 Cholesterol Esters, 594, 629 Cholic Acid, 402, 594 Choline, 283, 594 Chorioretinitis, 594, 657 Choroid, 594, 657 Chromaffin Cells, 403, 594, 643 Chromaffin System, 595, 607 Chromatin, 207, 356, 584, 595, 608, 639 Chromic, 594, 595 Chromosomal, 581, 595, 647, 659 Chromosome, 410, 595, 616, 629, 659, 660 Chronic Fatigue Syndrome, 396, 595 Chronic Obstructive Pulmonary Disease, 404, 595 Chronic renal, 67, 202, 595, 671 Chylomicrons, 595, 629 Chymopapain, 595, 643 Ciliary, 595, 661 Ciliary Body, 595, 661 Circulatory system, 285, 595, 607 Circumcision, 57, 595 CIS, 157, 595 Citric Acid, 595, 626 Citrus, 585, 595 Cleave, 97, 595 Climacteric, 402, 403, 595 Clinical Medicine, 399, 596, 649 Clinical resistance, 95, 596 Clinical study, 109, 290, 596, 599 Clone, 70, 75, 116, 157, 160, 175, 176, 183, 374, 387, 596 Cloning, 70, 91, 92, 102, 103, 126, 130, 349, 361, 392, 420, 588, 596 Coagulation, 5, 317, 356, 584, 589, 596, 618, 646, 667 Coca, 596 Cocaine, 14, 115, 548, 596 Codon, 208, 391, 596, 613 Coenzyme, 585, 596 Cofactor, 59, 75, 596, 652, 667

Index 679

Cognitive restructuring, 596, 664 Cohort Studies, 15, 27, 50, 80, 153, 596, 608 Colchicine, 118, 596 Colitis, 171, 369, 370, 597 Collagen, 379, 400, 581, 587, 597, 599, 610, 611, 632, 647, 650 Collapse, 589, 597 Colloidal, 580, 597, 606 Colon, 38, 304, 597, 605, 624, 628, 671 Communicable disease, 482, 597, 671 Community Health Services, 78, 597 Comorbidity, 82, 597 Compassionate, 4, 597 Complement, 70, 90, 99, 183, 293, 295, 404, 582, 597, 598, 613, 625, 632, 636, 646 Complement 1, 598 Complement 4, 295, 598 Complementary and alternative medicine, 41, 285, 286, 295, 312, 547, 598 Complementary medicine, 286, 598 Complete remission, 598, 656 Complete response, 325, 598 Compliance, 13, 42, 105, 204, 386, 453, 501, 598 Computational Biology, 86, 495, 598 Computed tomography, 190, 598 Computer-Assisted Instruction, 540, 598 Computerized tomography, 598 Conception, 138, 577, 598, 611, 664 Concomitant, 6, 35, 142, 598 Condoms, 472, 528, 533, 541, 545, 547, 598 Confounding, 10, 12, 113, 177, 598 Conjugated, 587, 594, 599, 601, 638 Conjunctiva, 599, 624, 627 Connective Tissue, 584, 585, 589, 597, 599, 611, 612, 630, 657, 666 Connective Tissue Diseases, 584, 599 Consciousness, 582, 599, 602, 604, 652 Constipation, 460, 599 Constitutional, 599, 657 Constriction, 599, 626, 659 Consultation, 51, 189, 329, 450, 457, 474, 534, 599 Consumption, 3, 18, 23, 40, 50, 54, 58, 110, 183, 233, 245, 599, 603, 613, 656 Contamination, 3, 137, 316, 348, 463, 589, 599, 618, 619, 658 Continuum, 81, 599 Contraindications, ii, 49, 52, 443, 449, 473, 527, 599 Control group, 24, 99, 331, 599, 650, 654

Controlled clinical trial, 16, 270, 276, 599, 655 Controlled study, 251, 291, 599 Conventional therapy, 599 Conventional treatment, 418, 443, 543, 599 Coordination, 593, 599, 636 Cornea, 599, 627, 674 Coronary, 448, 591, 599, 600, 634, 637 Coronary heart disease, 591, 599 Coronary Thrombosis, 600, 634, 637 Cortical, 600, 660 Corticosteroids, 10, 11, 16, 49, 77, 161, 443, 600, 614, 649 Cortisol, 119, 580, 600 Cortisone, 600, 649 Coumarins, 600, 652 Cowpox, 600, 672 Cowpox Virus, 600, 672 Cranial, 593, 600, 616, 641, 645 Craniocerebral Trauma, 600, 616 Creatinine, 11, 600, 627, 671 Crossing-over, 600, 655 Cross-Sectional Studies, 600, 608 Cryoglobulinemia, 10, 24, 55, 93, 205, 233, 600 Crystallization, 383, 600 Curative, 85, 600, 667 Cutaneous, 395, 396, 583, 600, 630, 646, 672 Cyclic, 386, 600, 646, 648 Cyclin, 196, 600 Cyclosporine, 16, 601 Cystine, 601, 604 Cytochrome, 179, 352, 407, 601 Cytogenetics, 601, 659 Cytokine, 76, 88, 95, 96, 104, 107, 123, 128, 154, 233, 317, 404, 451, 601, 625, 644 Cytomegalovirus, 72, 302, 361, 369, 394, 405, 456, 507, 523, 541, 601 Cytoplasm, 370, 372, 584, 587, 592, 601, 608, 639, 658 Cytosine, 157, 403, 601, 654 Cytoskeleton, 601, 625 Cytostatic, 601, 637 Cytotoxic, 92, 94, 103, 138, 139, 141, 154, 160, 165, 177, 191, 372, 406, 601, 631, 661 Cytotoxicity, 262, 291, 372, 406, 580, 601 D Data Collection, 84, 601 Day Care, 43, 63, 546, 601 De novo, 191, 202, 273, 279, 401, 413, 601 Deamination, 98, 601, 636, 671

680 Hepatitis

Death Certificates, 6, 601 Decarboxylation, 588, 601, 671 Deception, 215, 602 Decision Making, 548, 602 Decompensation, 39, 51, 81, 537, 580, 602 Decontamination, 424, 501, 602 Defense Mechanisms, 150, 602, 625 Degenerative, 602, 618, 642, 657 Deletion, 78, 148, 171, 208, 584, 602, 613 Delusions, 602, 653 Dementia, 73, 402, 403, 577, 602 Denaturation, 602, 648 Dendrites, 602, 639 Dendritic, 79, 112, 129, 187, 202, 602 Dendritic cell, 79, 112, 187, 202, 602 Density, 92, 93, 133, 401, 589, 593, 602, 611, 629, 641, 647, 663 Dental Assistants, 44, 602 Dental Care, 602, 644 Dental Staff, 454, 602 Dental Waste, 589, 602 Dentists, 44, 434, 602 Deoxyguanosine, 99, 112, 143, 602 Depigmentation, 602, 673 Depolarization, 602, 661 Dermatosis, 237, 602 Detergents, 459, 603 Detoxification, 13, 603 Developed Countries, 21, 26, 603 Developing Countries, 69, 79, 536, 538, 603 Dextran Sulfate, 359, 389, 603 Diabetes Mellitus, 14, 40, 261, 317, 603, 614, 617 Diabetic Foot, 400, 603 Diagnostic procedure, 347, 352, 481, 603, 660 Dialysate, 47, 603 Dialyzer, 47, 603, 617 Diarrhea, 62, 374, 384, 457, 460, 544, 603, 624 Diastolic, 603, 621 Digestion, 399, 580, 587, 589, 603, 605, 623, 625, 629, 664, 672 Digestive system, 346, 460, 603, 613 Digestive tract, 62, 459, 603, 662 Dilatation, 577, 603, 650 Dilated cardiomyopathy, 270, 275, 603 Dilution, 136, 603 Diphtheria, 43, 204, 401, 519, 557, 603 Diploid, 604, 646 Discrete, 105, 604, 630, 650, 651, 674

Disease Susceptibility, 119, 604 Disease Transmission, 424, 445, 498, 604 Disease Transmission, Horizontal, 604 Disease Transmission, Vertical, 604 Disinfectant, 315, 366, 604, 609 Disinfection, 317, 464, 469, 501, 604 Dissociation, 579, 604, 626 Distal, 586, 604, 652 Distention, 572, 604 Disulphide, 401, 604 Docetaxel, 292, 604 Dopa, 604, 628 Dopamine, 351, 581, 596, 604, 628, 636, 639, 645 Dosage schedule, 519, 605 Double-blind, 291, 331, 340, 605 Double-blinded, 291, 331, 340, 605 Doxycycline, 289, 605 Drug Design, 82, 411, 413, 489, 490, 605 Drug Interactions, 30, 33, 73, 198, 489, 543, 605 Drug Resistance, 65, 160, 162, 605 Drug Tolerance, 605, 668 Drug Toxicity, 16, 605 Duct, 12, 581, 591, 605, 609, 659 Duodenum, 587, 605, 607, 664 Dura mater, 605, 633, 642 Dyes, 587, 605, 611, 639, 665 Dysentery, 605, 661 Dyspepsia, 605, 623 Dysplasia, 225, 379, 606 Dyspnea, 602, 606, 653 E Edema, 602, 606, 637, 671 Effector, 104, 121, 178, 415, 577, 597, 606, 646 Ejaculation, 606, 660 Elastic, 606, 615, 662, 665 Elastin, 597, 599, 606, 610 Elective, 38, 253, 606 Electrocardiogram, 324, 326, 327, 328, 329, 330, 334, 335, 337, 606 Electrocoagulation, 596, 606 Electrolysis, 582, 592, 606 Electrolyte, 606, 627, 662, 671 Electron microscope, 382, 606 Electrophoresis, 369, 606 Electroporation, 87, 606 Elementary Particles, 606, 631, 639, 652 Emaciation, 577, 606 Emboli, 298, 606, 663 Embolus, 606, 623

Index 681

Embryo, 577, 592, 607, 623 Emergency Medical Services, 497, 499, 607 Emphysema, 595, 607 Empirical, 119, 607 Encapsulated, 354, 607 Encephalitis, 126, 379, 591, 607 Encephalitis, Viral, 607 Encephalomyelitis, 166, 607 Encephalomyocarditis Virus, 186, 607 Encephalopathy, 66, 356, 448, 496, 534, 607 Endemic, 32, 38, 39, 69, 83, 127, 133, 141, 165, 166, 173, 201, 217, 230, 244, 274, 280, 553, 594, 607, 618, 632, 663 Endocrine Glands, 607 Endocrine System, 24, 607 Endocytosis, 93, 200, 401, 607 Endogenous, 96, 262, 586, 604, 607, 642, 669, 673 Endopeptidases, 607, 651 Endoscope, 607 Endoscopic, 20, 200, 607 Endoscopy, 57, 607 Endothelial cell, 186, 234, 356, 589, 608, 625, 667 Endotoxemia, 270, 276, 608 Endotoxin, 164, 608, 670 End-stage renal, 595, 608 Energy balance, 608, 628 Enhancer, 148, 175, 177, 608, 657 Enterocolitis, 165, 608 Enterovirus, 380, 608 Environmental Exposure, 80, 109, 588, 608 Environmental Health, 266, 494, 496, 608 Enzymatic, 145, 152, 180, 385, 397, 581, 588, 590, 597, 608, 633, 643, 648 Enzyme Inhibitors, 375, 386, 608, 646 Enzyme-Linked Immunosorbent Assay, 164, 168, 608 Eosinophils, 608, 616, 628 Epidemiologic Studies, 127, 588, 608 Epidermis, 608, 627, 653 Epigastric, 609, 643 Epinephrine, 578, 594, 604, 609, 639, 640, 670 Epithelial, 225, 250, 578, 595, 609, 627 Epithelial Cells, 609, 627 Epithelium, 587, 609, 674 Epitope, 75, 138, 168, 177, 194, 350, 363, 364, 382, 395, 409, 609 ERV, 106, 294, 609, 610

Erythrocytes, 116, 581, 582, 589, 609, 618, 655 Erythropoietin, 7, 240, 609 Esophagus, 586, 603, 609, 613, 617, 641, 645, 664 Estrogen, 504, 609 Ethanol, 98, 111, 370, 379, 609, 611 Ethnic Groups, 15, 460, 535, 609 Eukaryotic Cells, 126, 361, 609, 623, 640, 642 Evacuation, 599, 609 Excipient, 105, 609 Excitation, 581, 609, 611, 639 Excrete, 524, 584, 609, 627 Exhaustion, 265, 609, 628, 632 Exocrine, 609, 643 Exogenous, 94, 274, 279, 372, 396, 399, 406, 579, 607, 609, 670, 673 Expiratory, 609, 610 Expiratory Reserve Volume, 609, 610 Extensor, 610, 652, 673 Extracellular, 64, 151, 413, 585, 599, 607, 610, 611, 624, 632, 635, 662 Extracellular Matrix, 64, 599, 610, 611, 624, 632 Extracellular Matrix Proteins, 610, 632 Extracellular Space, 610 Extraction, 136, 178, 201, 248, 315, 593, 610 Extrapyramidal, 581, 604, 610 Extravasation, 47, 610 Extremity, 400, 610 Eye Infections, 578, 610 F Facial, 610, 643, 662 Facial Expression, 610, 662 Family Planning, 495, 610 Fat, 399, 460, 534, 578, 587, 589, 594, 600, 606, 610, 628, 629, 636, 657, 662, 665 Fatal Outcome, 32, 610, 654 Fatty acids, 580, 610, 615, 629 Fatty Liver, 20, 50, 239, 399, 610 Feces, 138, 459, 484, 545, 599, 610, 664 Fermentation, 611, 659 Ferritin, 29, 523, 611 Fetoprotein, 123, 611 Fetus, 32, 456, 457, 577, 580, 593, 609, 611, 622, 649, 671 Fibrin, 356, 589, 611, 667 Fibrinogen, 611, 646, 652, 667 Fibroblasts, 611, 625 Filtration, 317, 366, 611, 627 Fine-needle aspiration, 611, 638

682 Hepatitis

Flaviviridae, 73, 93, 103, 149, 381, 384, 392, 398, 410, 607, 611 Flavivirus, 75, 79, 156, 387, 611, 674 Flow Cytometry, 128, 611 Fluorescence, 151, 370, 611 Fluorescent Dyes, 611 Fold, 38, 54, 68, 93, 337, 398, 612, 649 Foot Ulcer, 400, 603, 612 Forearm, 589, 612 Free Radicals, 584, 604, 612 Frontal Lobe, 582, 593, 612 Fructose, 612, 615 Fulminant Hepatic Failure, 419, 424, 612 Fungemia, 589, 612 Fungi, 579, 610, 612, 634, 637, 674 G Galactosemia, 399, 612 Gallbladder, 200, 448, 449, 535, 577, 587, 603, 612, 613 Gamma irradiation, 124, 612 Gamma Rays, 612, 637, 654 Ganglia, 577, 589, 612, 638, 643, 645, 665 Ganglion, 612, 641, 674 Gangrenous, 612, 661 Gas, 581, 594, 609, 612, 620, 623, 637, 640, 661, 665, 672 Gastric, 586, 591, 612, 617 Gastrin, 613, 620 Gastroenteritis, 426, 433, 590, 613, 658, 659 Gastroenterologist, 60, 532, 613 Gastrointestinal, 60, 88, 98, 228, 394, 443, 444, 445, 457, 461, 609, 613, 632, 661, 665, 670 Gastrointestinal tract, 60, 88, 443, 444, 445, 609, 613, 661, 670 Gene Deletion, 250, 613 Gene Expression, 70, 76, 86, 87, 95, 105, 111, 131, 160, 412, 613 Gene Therapy, 184, 202, 354, 451, 578, 613 General practitioner, 355, 613 Genetic Code, 613, 640 Genetic Engineering, 588, 596, 613 Genetic Markers, 334, 613 Genetic testing, 613, 648 Genetic transcription, 613, 650, 669 Genetics, 90, 322, 578, 601, 614, 635 Genital, 115, 456, 614, 626, 671 Genitourinary, 179, 614, 671 Genomics, 77, 86, 614 Germfree, 88, 165, 614 Gestation, 128, 614, 644 Giant Cells, 614, 659

Ginger, 525, 543, 614 Ginseng, 525, 543, 614 Gland, 578, 595, 600, 614, 630, 632, 643, 651, 659, 664, 667, 668 Glomerular, 614, 627, 656 Glomeruli, 614 Glomerulonephritis, 10, 24, 55, 63, 202, 335, 356, 614 Glomerulus, 614, 638 Glottis, 614, 645 Glucocorticoid, 614, 649, 673 Glucose, 212, 585, 589, 592, 603, 612, 614, 615, 617, 624, 659 Glucose Intolerance, 603, 614 Glucosidases, 114, 614 Glutamate, 580, 585, 615 Glutathione Peroxidase, 98, 394, 615, 660 Gluten, 592, 615 Glycerol, 590, 615, 646 Glycerophospholipids, 615, 646 Glycine, 581, 587, 594, 615, 639, 660 Glycogen, 399, 615 Glycogen Storage Disease, 399, 615 Glycoside, 402, 615, 659 Glycosylation, 387, 409, 615 Goats, 615, 641 Gonadal, 615, 664 Gout, 596, 615 Governing Board, 615, 649 Gp120, 615, 644 Grade, 48, 50, 460, 615 Grading, 68, 206, 323, 497, 615 Graft, 36, 37, 46, 102, 181, 197, 228, 455, 616, 620, 623, 637 Graft Rejection, 616, 623 Graft-versus-host disease, 181, 616, 637 Gram-negative, 590, 608, 616, 617, 659, 661 Gram-positive, 616, 637 Granule, 616, 658 Granulocyte, 38, 616 Granuloma, 176, 616 Growth factors, 256, 616, 634 Guanine, 602, 616, 653 H Habitat, 616, 637 Haemodialysis, 246, 263, 265, 374, 616 Haemorrhage, 577, 616 Handwashing, 446, 616 Haploid, 616, 646 Haptens, 579, 616 Headache, 377, 527, 572, 616, 617, 624, 647 Headache Disorders, 616, 617

Index 683

Health Behavior, 221, 460, 617 Health Policy, 66, 617 Health Promotion, 442, 460, 465, 529, 557, 617 Health Services, 78, 82, 89, 545, 617 Health Status, 82, 329, 617 Heart attack, 7, 591, 617 Heart failure, 617, 653 Heartburn, 617, 623 Helicobacter, 88, 134, 150, 165, 171, 173, 355, 617 Hematology, 84, 156, 256, 301, 364, 384, 431, 453, 617 Hematopoietic growth factors, 34, 617 Heme, 587, 601, 617, 638, 648, 671 Hemochromatosis, 399, 617 Hemodialysis, 7, 14, 18, 30, 47, 139, 141, 149, 153, 170, 213, 243, 262, 288, 369, 447, 539, 548, 603, 617, 627 Hemoglobin, 37, 582, 609, 617, 618, 648, 667 Hemoglobin A, 617, 648 Hemoglobinopathies, 613, 618 Hemolysis, 17, 37, 53, 618 Hemolytic, 10, 53, 136, 342, 618, 667 Hemophilia, 5, 91, 254, 304, 340, 418, 454, 618 Hemorrhage, 73, 600, 606, 616, 618, 653, 664 Hemostasis, 618, 625, 661 Hepadnaviridae, 395, 618 Hepatitis Antigens, 362, 456, 618 Hepatitis, Chronic, 371, 457, 618 Hepatocyte, 76, 80, 86, 88, 95, 96, 117, 124, 140, 164, 171, 175, 215, 245, 594, 619 Hepatologist, 464, 532, 619 Hepatoma, 123, 250, 272, 277, 358, 361, 373, 619 Hepatomegaly, 88, 619, 624 Hepatorenal Syndrome, 66, 619 Hepatotoxic, 579, 619 Hepatotoxicity, 3, 98, 619 Hepatovirus, 618, 619 Hereditary, 599, 615, 618, 619, 667 Heredity, 613, 614, 619 Herpes, 220, 243, 292, 379, 435, 456, 464, 619 Herpes virus, 379, 619 Herpes Zoster, 619 Heterodimers, 186, 619, 624 Heterogeneity, 27, 55, 75, 131, 149, 153, 411, 579, 619

Heterogenic, 619 Heterogenous, 370, 619 Histidine, 619, 625 Histology, 21, 38, 48, 58, 59, 111, 136, 228, 271, 277, 443, 449, 452, 455, 619, 643 Home Infusion Therapy, 30, 620 Homeostasis, 87, 355, 620 Homogeneous, 370, 599, 620 Homologous, 70, 75, 179, 359, 382, 383, 389, 401, 580, 600, 613, 620, 636, 660, 666 Hormonal, 586, 594, 620 Hormone, 124, 403, 578, 587, 588, 600, 609, 613, 620, 624, 626, 628, 650, 658, 661, 668 Horseradish Peroxidase, 608, 620 Hospitals, Public, 620, 622 Housekeeping, 498, 620 Humoral, 74, 79, 87, 103, 104, 128, 156, 391, 396, 616, 620, 622 Humour, 620 Hybrid, 87, 136, 357, 389, 596, 620 Hybridization, 144, 150, 169, 173, 174, 248, 375, 620, 635 Hybridomas, 606, 620 Hydration, 105, 620 Hydrogen Peroxide, 591, 615, 620, 629, 665 Hydrolysis, 365, 578, 620, 646, 652 Hydrophilic, 603, 620 Hydrophobic, 401, 603, 615, 621, 629 Hydroxylysine, 597, 621 Hydroxyproline, 581, 597, 621 Hyperbaric, 290, 621 Hyperbaric oxygen, 290, 621 Hyperbilirubinemia, 621, 626 Hyperlipidemia, 426, 448, 621 Hyperplasia, 88, 621 Hyperreflexia, 621, 666 Hypersensitivity, 621, 658 Hypertension, 504, 591, 616, 621, 638, 648, 671 Hypertrophy, 621 Hypoxia, 407, 621 Hysterotomy, 593, 621 I Ibuprofen, 621, 627 Id, 282, 303, 391, 427, 516, 549, 550, 559, 568, 570, 621 Idiopathic, 85, 107, 621, 659 Immune adjuvant, 580, 621 Immune function, 23, 114, 119, 322, 330, 621 Immune Sera, 621, 622

684 Hepatitis

Immune Tolerance, 110, 156, 622 Immunization Programs, 59, 467, 622 Immunoassay, 130, 132, 135, 140, 145, 151, 153, 163, 169, 172, 230, 238, 381, 496, 583, 608, 622 Immunocompetence, 410, 622 Immunocompromised, 50, 62, 66, 373, 396, 424, 622 Immunocompromised Host, 424, 622 Immunodominant Epitopes, 79, 622 Immunofluorescence, 369, 622 Immunogen, 357, 388, 413, 622 Immunogenic, 103, 350, 357, 368, 370, 382, 385, 388, 395, 409, 412, 622 Immunoglobulin, 33, 134, 141, 153, 158, 160, 163, 169, 176, 252, 263, 583, 622, 636, 660 Immunomodulator, 395, 396, 622 Immunosuppressive, 16, 272, 278, 443, 455, 614, 622, 623, 666 Immunosuppressive therapy, 16, 272, 278, 443, 455, 622, 623 Immunotherapy, 79, 156, 379, 588, 623 Impairment, 67, 187, 321, 594, 610, 623, 633, 653 In situ, 29, 70, 93, 211, 623 In Situ Hybridization, 70, 93, 623 Incision, 621, 623, 626 Incontinence, 623, 637 Incubation, 32, 161, 380, 456, 457, 464, 484, 519, 532, 539, 623, 628, 645 Incubation period, 32, 380, 456, 457, 464, 519, 539, 623, 628, 645 Indicative, 426, 623, 643, 672 Indigestion, 572, 623 Indolent, 125, 623 Induction, 11, 47, 87, 89, 94, 105, 110, 117, 122, 158, 161, 168, 222, 254, 356, 373, 404, 623 Infancy, 80, 128, 206, 523, 623 Infant Mortality, 460, 623 Infant, Newborn, 579, 623 Infarction, 402, 404, 593, 623 Infection Control, 7, 28, 193, 223, 240, 294, 434, 464, 466, 497, 500, 505, 522, 623 Infectious Diarrhea, 457, 624 Infectious Mononucleosis, 427, 456, 624 Infertility, 407, 624 Infiltration, 614, 624, 674 Inflammatory bowel disease, 356, 369, 370, 395, 396, 624

Influenza, 34, 78, 138, 351, 386, 455, 519, 539, 581, 624, 658 Informed Consent, 32, 499, 525, 624 Infusion, 14, 181, 329, 395, 396, 620, 624, 669 Ingestion, 25, 147, 254, 286, 288, 369, 484, 582, 624, 634, 647 Inhalation, 33, 241, 579, 624, 647 Initiation, 4, 17, 37, 43, 126, 150, 273, 279, 624, 650, 669 Inorganic, 354, 365, 366, 624, 636, 665 Inotropic, 605, 624 Inpatients, 13, 624 Insight, 52, 104, 105, 111, 624 Insulator, 624, 636 Insulin, 14, 624, 670 Insulin-dependent diabetes mellitus, 624 Integrins, 234, 624 Interferon Alfa-2b, 5, 58, 199, 345, 419, 539, 625 Interferon-beta, 274, 280, 301, 625 Interleukin-8, 117, 143, 625 Intermittent, 39, 625, 630, 645, 648 Interstitial, 79, 273, 279, 296, 610, 625, 626, 633, 638, 656 Intervention Studies, 23, 625 Intestinal, 353, 402, 403, 590, 592, 608, 617, 625, 632, 661 Intestinal Mucosa, 592, 608, 625 Intestine, 401, 587, 589, 625, 628 Intoxication, 591, 625, 669, 674 Intracellular Membranes, 625, 633 Intrahepatic, 75, 76, 88, 126, 159, 176, 187, 244, 262, 625 Intramuscular, 128, 144, 625, 643 Intramuscular injection, 128, 625 Intravascular, 356, 625 Intrinsic, 73, 579, 587, 626 Intubation, 591, 626 Invasive, 57, 117, 127, 223, 355, 498, 501, 525, 622, 626, 631 Involuntary, 626, 638, 662, 663, 668 Involution, 176, 626 Iodine, 366, 626 Ionization, 133, 366, 626 Ionizing, 580, 608, 626, 673 Ions, 577, 587, 598, 604, 606, 620, 626, 652 Irradiation, 626 Irrigation, 180, 626 Ischemia, 404, 407, 586, 626, 637 Isocitrate Dehydrogenase, 369, 626

Index 685

J Joint, 235, 329, 504, 505, 523, 531, 542, 585, 626, 642, 666 K Kava, 150, 287, 293, 294, 308, 627 Kb, 409, 494, 627 Keratinocytes, 625, 627 Keratoconjunctivitis, 627, 661 Keratoconjunctivitis Sicca, 627, 661 Keto, 627, 669 Ketoprofen, 222, 627 Kidney Failure, 329, 608, 627 Kidney Failure, Acute, 627 Kidney Failure, Chronic, 627 Kidney Transplantation, 36, 45, 46, 229, 250, 447, 627 Kinetics, 50, 71, 112, 159, 170, 199, 207, 224, 225, 266, 388, 627 L Labile, 597, 627 Laceration, 627, 666 Lacrimal, 627, 661 Laminin, 64, 587, 610, 627 Large Intestine, 603, 625, 628, 655, 662 Lassitude, 448, 628 Latent, 108, 504, 628, 649, 673 LDL, 93, 400, 401, 628, 630 Least-Squares Analysis, 628, 656 Lectin, 232, 292, 360, 628 Lens, 590, 628, 656 Lentivirus, 619, 628 Leprosy, 379, 612, 628 Leptin, 206, 628 Lethal, 586, 628, 637 Leucocyte, 580, 628 Leukemia, 454, 573, 578, 613, 628, 649 Leukocytes, 115, 317, 404, 587, 589, 593, 608, 625, 628, 639, 670 Levodopa, 351, 604, 628 Library Services, 568, 628 Lice, 475, 629 Life cycle, 97, 364, 374, 450, 588, 612, 629 Life Expectancy, 45, 446, 629 Ligaments, 599, 629 Ligands, 117, 120, 357, 388, 401, 624, 629 Ligation, 97, 629 Likelihood Functions, 629, 656 Linear Models, 629, 655 Linkage, 106, 613, 629 Lipid, 58, 98, 116, 362, 391, 406, 584, 585, 594, 615, 624, 627, 629, 636, 642 Lipid Peroxidation, 98, 116, 629, 642

Lipid Peroxides, 99, 629 Lipopolysaccharide, 160, 243, 291, 301, 616, 629 Lipoprotein, 93, 360, 401, 616, 628, 629, 630, 673 Liver Neoplasms, 629, 673 Liver scan, 321, 629 Liver Transplantation, 7, 9, 10, 23, 26, 31, 36, 46, 52, 53, 54, 61, 66, 77, 85, 86, 92, 102, 117, 121, 123, 125, 141, 149, 163, 179, 191, 196, 197, 205, 206, 208, 209, 211, 213, 219, 228, 237, 259, 337, 351, 361, 368, 398, 421, 423, 424, 443, 455, 458, 464, 467, 468, 483, 496, 503, 537, 630 Lobe, 582, 593, 630 Local Government, 630, 653 Localized, 237, 409, 603, 607, 623, 627, 630, 636, 637, 646, 666, 670 Locomotion, 630, 646 Logistic Models, 630, 656 Longitudinal Studies, 23, 600, 630 Longitudinal study, 115, 630 Long-Term Care, 123, 630 Loop, 152, 350, 395, 412, 413, 630 Low-density lipoprotein, 400, 628, 629, 630 Lucida, 627, 630 Luciferase, 374, 411, 630 Lupus, 356, 404, 583, 584, 630, 666 Lymph, 79, 593, 595, 608, 619, 620, 624, 630, 631, 658, 659 Lymph node, 79, 593, 630, 631, 658, 659 Lymphadenitis, 631, 637 Lymphadenopathy, 619, 624, 631 Lymphatic, 623, 630, 631, 658, 662, 663, 668 Lymphatic system, 630, 631, 658, 662, 663, 668 Lymphocyte, 138, 141, 165, 181, 191, 257, 372, 381, 406, 577, 583, 631, 633 Lymphocyte Count, 577, 631 Lymphoid, 21, 72, 93, 112, 121, 157, 166, 170, 300, 583, 600, 622, 628, 631 Lymphokines, 631 Lymphoma, 24, 80, 109, 243, 301, 313, 329, 631 Lymphoproliferative, 230, 631 Lymphotoxin, 262, 631 Lytic, 293, 372, 631, 660 M Macrophage, 38, 73, 76, 124, 158, 161, 165, 631

686 Hepatitis

Macrophage Activation, 76, 165, 631 Magnetic Resonance Imaging, 631 Magnetic Resonance Spectroscopy, 73, 631 Maintenance therapy, 53, 231, 251, 631 Major Histocompatibility Complex, 162, 166, 179, 262, 631 Malabsorption, 305, 592, 632 Malaise, 377, 393, 573, 632 Malaria, 121, 378, 435, 632 Malaria, Falciparum, 632 Malaria, Vivax, 632 Malignancy, 12, 286, 632 Malignant, 78, 109, 353, 577, 578, 584, 629, 632, 638 Malnutrition, 98, 113, 580, 586, 590, 632 Malondialdehyde, 227, 632 Mammary, 632, 639 Manic, 632, 653 Manic-depressive psychosis, 632, 653 Manifest, 397, 531, 586, 632 Mastitis, 588, 632, 661 Matrix metalloproteinase, 203, 632 Meat, 139, 479, 632 Mediate, 102, 133, 182, 374, 401, 409, 604, 632 Mediator, 261, 604, 632, 661 Medical Assistance, 181, 633 Medical Records, 6, 12, 324, 633, 657 Medical Staff, 605, 633 Medical Waste, 468, 633 Medicament, 379, 633 MEDLINE, 59, 64, 66, 495, 633 Meiosis, 633, 637, 666 Melanin, 602, 633, 645, 670 Membrane Fusion, 80, 360, 633 Membrane Lipids, 633, 646 Memory, 128, 159, 178, 183, 202, 224, 233, 582, 602, 633, 656 Meninges, 592, 600, 605, 633 Meningitis, 378, 633 Mental Disorders, 89, 346, 633, 650, 652, 653 Mental Health, iv, 34, 69, 77, 82, 106, 346, 494, 508, 633, 650, 653 Mental Processes, 604, 633, 653 Mental Retardation, 524, 633 Mentors, 104, 633 Mercury, 611, 633 Meta-Analysis, 10, 289, 634 Metabolic disorder, 58, 615, 634 Metabolite, 634, 650

Metastasis, 632, 634 Methanol, 377, 634 Methionine, 49, 273, 279, 634, 665 MI, 137, 141, 167, 209, 210, 244, 256, 397, 529, 575, 634 Microbe, 634, 669 Microcirculation, 629, 634 Microglia, 585, 634, 636 Microorganism, 596, 634, 643, 673 Micro-organism, 614, 634, 660 Microscopy, 369, 587, 620, 634, 640 Microsomal, 161, 579, 634 Migration, 404, 631, 635 Milk Thistle, 286, 309, 310, 525, 543, 635, 662 Milliliter, 27, 635 Mitochondria, 87, 626, 635, 642 Mitogen-Activated Protein Kinase Kinases, 635 Mitogen-Activated Protein Kinases, 151, 635 Mitosis, 584, 635 Mitotic, 223, 604, 635 Mobility, 74, 173, 635 Mode of Transmission, 38, 392, 420, 456, 497, 522, 546, 635 Modeling, 56, 69, 86, 112, 605, 635, 651 Modification, 14, 23, 58, 81, 111, 388, 425, 581, 613, 635, 654, 674 Modulator, 81, 635 Molecular Evolution, 162, 264, 635 Molecular Probes, 606, 635 Monoamine, 403, 636, 670 Monoamine Oxidase, 403, 636, 670 Monoclonal, 80, 93, 155, 161, 168, 169, 179, 194, 368, 400, 408, 409, 490, 620, 626, 636, 654, 658 Monoclonal antibodies, 80, 400, 408, 409, 636, 658 Monocyte, 96, 272, 277, 636 Monokines, 356, 636 Mononuclear, 74, 91, 138, 148, 149, 159, 164, 210, 387, 616, 624, 636, 670 Monophosphate, 17, 636 Morphological, 70, 88, 607, 636 Morphology, 475, 585, 617, 631, 636 Motion Sickness, 636, 638 Mucins, 636, 659 Mucosa, 228, 630, 636, 664 Mucus, 605, 633, 636, 671 Multidose, 240, 636 Multiple Organ Failure, 378, 636

Index 687

Multiple sclerosis, 213, 378, 483, 636 Multivalent, 103, 357, 388, 401, 636 Multivariate Analysis, 68, 637 Mustard Gas, 365, 637 Mutagen, 73, 81, 637 Mutagenic, 236, 579, 637 Myalgia, 624, 637 Mycobacterial disease, 379, 637 Mycobacteriosis, 637 Mycobacterium, 121, 541, 628, 637 Mycobacterium avium, 541, 637 Mycobacterium avium Complex, 541, 637 Mycophenolate mofetil, 16, 298, 637 Mycotoxins, 579, 637 Myelin, 636, 637, 660 Myelitis, 198, 637 Myelodysplastic syndrome, 256, 637, 662 Myeloid Cells, 369, 637 Myocardial infarction, 6, 587, 600, 634, 637 Myocarditis, 126, 591, 603, 607, 637 Myocardium, 634, 637, 638 Myoglobin, 638, 648 N Naive, 63, 83, 87, 128, 151, 171, 222, 272, 278, 339, 638 Nasal Mucosa, 624, 638 NCI, 1, 83, 336, 345, 493, 595, 638 Needle biopsy, 206, 611, 638 Needle Sharing, 99, 470, 525, 544, 638 Needlestick Injuries, 7, 638 Needs Assessment, 314, 422, 638 Neonatal, 77, 85, 110, 111, 128, 138, 237, 258, 517, 523, 623, 638 Neonatal Hepatitis, 77, 85, 111, 258, 517, 523, 638 Neonatal period, 128, 638 Neoplasia, 638 Neoplasm, 638 Neoplastic, 415, 620, 631, 638 Nephritis, 355, 404, 638 Nephrologist, 447, 638 Nephropathy, 402, 403, 627, 638 Nephrosis, 619, 638 Nerve, 403, 578, 586, 594, 602, 612, 632, 636, 638, 639, 641, 643, 649, 659, 664, 669, 674 Nervous System, 171, 315, 577, 579, 580, 581, 592, 594, 596, 612, 628, 632, 634, 636, 638, 639, 641, 645, 647, 654, 661, 665, 666, 670 Networks, 124, 639 Neural, 579, 611, 620, 634, 636, 639

Neural tube defects, 611, 639 Neurologic, 37, 619, 639 Neurology, 108, 185, 235, 244, 248, 291, 639 Neuronal, 72, 639 Neurons, 596, 602, 612, 628, 639, 665, 666 Neuropathy, 63, 185, 244, 639, 674 Neuroretinitis, 639, 657 Neurosecretory Systems, 607, 639 Neurotoxic, 639 Neurotoxins, 72, 639 Neurotransmitter, 577, 578, 581, 604, 615, 639, 640, 661, 665, 670 Neutralization, 87, 167, 360, 409, 639 Neutrons, 580, 626, 639, 654 Neutrophils, 138, 369, 370, 616, 625, 628, 639 Nevirapine, 478, 639, 640 Nipples, 38, 639 Nitrogen, 580, 581, 610, 627, 639, 670 Non-nucleoside, 639, 640 Norepinephrine, 578, 604, 639, 640 Nosocomial, 28, 164, 240, 341, 640 Nuclear, 122, 161, 164, 175, 184, 233, 240, 247, 271, 276, 352, 369, 609, 612, 640, 671 Nuclei, 372, 580, 582, 613, 631, 635, 639, 640, 641, 652, 658 Nucleic Acid Hybridization, 620, 640 Nucleocapsid, 110, 125, 133, 138, 154, 350, 357, 389, 395, 412, 413, 640, 673 Nucleolus, 640, 658 Nucleoprotein, 110, 618, 640 Nursing Care, 23, 640, 644 O Observational study, 164, 167, 640 Occult, 39, 164, 196, 208, 241, 640 Occupational Exposure, 28, 30, 231, 232, 257, 424, 469, 499, 504, 521, 640 Ocular, 216, 641 Odds Ratio, 10, 43, 641, 656 Oesophagitis, 185, 641 Office Management, 457, 641 Ointments, 641, 643 Oligo, 374, 641 Oliguria, 627, 641 Oncogenic, 625, 628, 641 Opacity, 602, 641 Operon, 641, 650, 656 Opiate, 13, 129, 641 Opium, 641 Opportunistic Infections, 100, 541, 577, 641

688 Hepatitis

Optic Nerve, 639, 641, 642, 657 Oral Health, 214, 216, 454, 641 Oral Manifestations, 454, 641 Orf, 220, 380, 641, 643 Organ Culture, 641, 668 Organ Transplantation, 67, 369, 641 Organelles, 593, 601, 642 Osmosis, 366, 642 Osmotic, 580, 642 Osteoarthritis, 305, 378, 627, 642 Outpatient, 24, 60, 260, 329, 342, 620, 642 Overdose, 612, 642 Ovum, 614, 629, 642, 650 Oxaloacetate, 585, 642 Oxidants, 49, 642 Oxidation, 230, 577, 584, 601, 604, 615, 629, 642 Oxidation-Reduction, 642 Oxidative Stress, 29, 76, 98, 111, 112, 115, 233, 642 P P53 gene, 80, 109, 642 Pachymeningitis, 633, 642 Paediatric, 66, 251, 642 Palate, 643, 664 Palliative, 378, 643, 667 Pancreas, 207, 448, 449, 577, 588, 603, 613, 617, 624, 643, 670 Pancreatic, 272, 278, 591, 643 Pancreatitis, 254, 305, 404, 643 Papain, 271, 277, 315, 643 Paraffin, 193, 643 Paraganglia, Chromaffin, 594, 643 Paralysis, 402, 403, 643, 647 Paramedic, 424, 643 Parapoxvirus, 220, 379, 380, 643 Parasitic, 605, 629, 643 Parenteral, 9, 33, 67, 113, 115, 148, 167, 242, 299, 365, 439, 497, 643 Parkinsonism, 628, 643 Parotid, 643, 659 Paroxysmal, 617, 643, 645, 674 Partial remission, 643, 656 Pathogen, 7, 97, 367, 377, 623, 643 Pathogenesis, 9, 26, 58, 62, 69, 71, 73, 76, 85, 86, 87, 90, 92, 94, 95, 96, 97, 102, 103, 104, 107, 111, 114, 117, 118, 119, 123, 125, 133, 135, 164, 234, 243, 316, 362, 414, 419, 420, 427, 431, 440, 445, 447, 457, 503, 643 Pathologic, 21, 44, 64, 243, 584, 588, 599, 621, 643, 644, 652

Pathologic Processes, 584, 644 Pathophysiology, 111, 447, 448, 644 Patient Advocacy, 561, 644 Patient Care Management, 533, 644 Patient Education, 14, 54, 443, 459, 466, 473, 518, 534, 540, 547, 548, 554, 566, 568, 575, 644 Patient Selection, 17, 31, 534, 644 Pediatric Dentistry, 454, 644 Pelvis, 577, 644, 671 Penicillin, 504, 644 Penis, 598, 606, 644, 649 Pentoxifylline, 49, 644 Peptide Library, 79, 644 Peptide T, 265, 644 Percutaneous, 9, 26, 27, 84, 101, 442, 644 Perfusion, 621, 644 Pericardium, 644, 666 Perinatal, 8, 47, 85, 110, 142, 226, 264, 419, 446, 469, 471, 472, 483, 484, 623, 644 Peripheral blood, 72, 74, 91, 93, 96, 159, 210, 274, 279, 387, 625, 645, 649 Peripheral Nervous System, 639, 645, 665 Peripheral stem cells, 616, 645 Peritoneal, 603, 645 Peritoneal Dialysis, 603, 645 Pertussis, 43, 204, 315, 338, 401, 402, 557, 645, 674 Petroleum, 643, 645 PH, 135, 161, 190, 251, 262, 295, 645 Phagocyte, 642, 645 Phagocytosis, 408, 634, 645 Pharmacists, 34, 645 Pharmacokinetic, 73, 319, 645 Pharmacologic, 23, 275, 280, 645, 669 Pharynx, 624, 645 Phenotype, 75, 121, 129, 178, 207, 588, 613, 645 Phenylalanine, 645, 670 Phosphodiesterase, 644, 646 Phospholipases, 646, 661 Phospholipids, 360, 583, 584, 590, 610, 629, 633, 646, 651 Phosphorus, 590, 646 Phosphorylated, 109, 596, 635, 646 Phosphorylation, 122, 158, 166, 175, 376, 635, 646, 652 Photocoagulation, 596, 646 Photosensitivity, 646, 648 Physical Examination, 25, 321, 322, 324, 326, 327, 328, 329, 330, 334, 335, 338, 593, 646

Index 689

Physicians, Family, 423, 646 Physiologic, 93, 286, 579, 595, 604, 646, 655 Physiology, 9, 110, 465, 468, 471, 588, 613, 617, 646 Picornavirus, 380, 646 Pilot study, 6, 32, 67, 274, 280, 301, 351, 646 Plana, 646, 661 Plants, 78, 580, 590, 594, 595, 596, 614, 615, 628, 636, 639, 640, 646, 659, 669, 670, 674 Plasma cells, 583, 646 Plasma protein, 580, 646, 652 Plasmapheresis, 321, 647 Plasmid, 105, 370, 647, 672 Platelet Activation, 647, 661 Platelet Aggregation, 582, 644, 647 Platelet Count, 20, 185, 647 Platelets, 73, 321, 587, 647, 667 Platinum, 630, 647 Pneumococcal Infections, 338, 647 Pneumococcal Vaccines, 338, 647 Pneumonia, 404, 599, 647 Pneumonitis, 273, 279, 296, 647 Point Mutation, 93, 240, 647 Poisoning, 605, 613, 625, 634, 638, 647, 659 Poliomyelitis, 126, 386, 647 Polyarthritis, 627, 647, 661 Polyethylene, 58, 68, 327, 647 Polymerase Chain Reaction, 13, 39, 62, 157, 180, 183, 194, 240, 294, 445, 496, 548, 648 Polymorphism, 140, 204, 222, 648 Polyneuritis, 603, 648 Polysaccharide, 338, 401, 583, 592, 648 Polyvalent, 194, 357, 389, 648 Population Dynamics, 84, 112, 648 Porphyria, 24, 55, 399, 648 Porphyria Cutanea Tarda, 24, 55, 399, 648 Porphyria, Hepatic, 648 Porphyrins, 354, 648 Portal Hypertension, 20, 393, 648 Portal Vein, 648 Posterior, 582, 593, 594, 643, 648 Postherpetic Neuralgia, 581, 648 Postnatal, 128, 264, 649, 664 Postoperative, 259, 612, 636, 649 Postsynaptic, 649, 661 Post-translational, 381, 649 Potentiates, 182, 649 Potentiation, 649, 661 Practicability, 649, 670 Practice Guidelines, 43, 427, 508, 549, 649

Preclinical, 17, 104, 166, 375, 649 Precursor, 239, 363, 381, 594, 604, 606, 608, 628, 640, 645, 649, 650, 652, 670 Predictive factor, 207, 245, 419, 420, 649 Predisposition, 399, 649 Prednisolone, 649 Prednisone, 504, 649 Pregnancy Tests, 327, 649 Preleukemia, 637, 649, 662 Prenatal, 264, 453, 469, 607, 649 Preoperative, 14, 649 Prepuce, 595, 649 Presumptive, 60, 649 Preventive Health Services, 504, 597, 649 Primary Biliary Cirrhosis, 270, 276, 322, 399, 449, 497, 650 Primary endpoint, 107, 650 Primary Prevention, 28, 650 Primary Sclerosing Cholangitis, 218, 369, 370, 497, 650 Private Sector, 498, 650 Probe, 24, 80, 136, 160, 174, 359, 375, 389, 650 Prodrug, 108, 367, 368, 650 Progesterone, 650, 664 Prognostic factor, 45, 239, 464, 466, 650 Programmed Instruction, 598, 650 Progressive disease, 456, 650 Projection, 295, 602, 640, 641, 650 Proline, 597, 621, 650 Promoter, 39, 51, 88, 94, 96, 161, 177, 185, 210, 212, 223, 248, 261, 363, 370, 650 Promotor, 51, 650, 657 Promyelocytic leukemia, 184, 650 Prone, 498, 501, 651 Prophase, 637, 651, 666 Proportional, 608, 651 Prospective Studies, 53, 56, 109, 341, 651 Prospective study, 13, 35, 109, 163, 195, 236, 630, 651 Prostate, 588, 651, 670 Protease Inhibitors, 73, 314, 332, 364, 374, 397, 405, 406, 407, 411, 651 Protective Clothing, 469, 651 Protein C, 116, 377, 534, 580, 581, 584, 586, 596, 611, 629, 651, 652, 671, 673 Protein Conformation, 581, 651 Protein Engineering, 395, 413, 651 Protein Folding, 388, 651 Protein Kinase C, 635, 651 Protein S, 82, 86, 151, 316, 361, 382, 440, 584, 588, 613, 651, 652, 658, 667

690 Hepatitis

Protein-Serine-Threonine Kinases, 635, 652 Proteinuria, 63, 652 Proteolytic, 580, 597, 611, 643, 652 Proteome, 81, 652 Prothrombin, 20, 185, 652, 667 Prothrombin Time, 20, 185, 652 Protocol, 105, 111, 119, 145, 234, 294, 320, 328, 341, 450, 472, 652 Protons, 580, 620, 626, 631, 652, 654 Protozoan, 592, 632, 652 Proximal, 604, 652, 660 Proxy, 479, 652 Pruritus, 12, 652, 671 Psoriasis, 287, 404, 637, 652, 657 Psychiatric, 9, 37, 209, 225, 246, 249, 252, 256, 322, 329, 588, 633, 652 Psychiatry, 71, 106, 244, 246, 291, 652 Psychic, 595, 633, 652, 660 Psychoactive, 18, 652, 674 Psychology, 124, 604, 653 Psychosis, 260, 653 Psyllium, 310, 653 Public Assistance, 37, 633, 653 Public Policy, 495, 653 Pulmonary, 107, 404, 589, 594, 599, 627, 637, 653, 665, 672 Pulmonary Artery, 589, 653, 672 Pulmonary Edema, 594, 627, 653 Pulmonary Fibrosis, 107, 653 Pulse, 105, 636, 653 Purifying, 359, 365, 366, 389, 603, 653 Purines, 653, 660 Purpura, 288, 616, 653 Purulent, 577, 653 Pyogenic, 653, 660 Pyrazinamide, 504, 653 Pyridoxal, 653, 669 Pyrimidines, 654, 660, 673 Q Quality of Life, 23, 35, 46, 49, 82, 107, 108, 121, 225, 286, 329, 425, 433, 464, 559, 654, 665 Quaternary, 651, 654 Quiescent, 38, 654, 673 R Rabies, 654, 674 Race, 24, 33, 66, 103, 323, 604, 635, 654 Radiation, 285, 606, 608, 611, 612, 621, 622, 626, 654, 673, 674 Radiation therapy, 612, 621, 626, 654

Radioactive, 602, 620, 626, 629, 635, 636, 640, 641, 654, 666, 671 Radiological, 644, 654 Random Allocation, 654 Randomization, 273, 279, 298, 654 Randomized clinical trial, 336, 654 Randomized Controlled Trials, 11, 64, 654 Rape, 533, 655 Reactivation, 12, 39, 205, 290, 300, 301, 451, 479, 655 Reactive Oxygen Species, 87, 98, 112, 404, 655 Reagent, 355, 594, 603, 630, 655, 667 Reality Testing, 653, 655 Receptor, 80, 92, 93, 101, 102, 110, 118, 120, 137, 141, 163, 176, 195, 203, 208, 230, 249, 258, 260, 271, 272, 274, 276, 277, 280, 359, 388, 389, 400, 404, 410, 413, 478, 578, 583, 598, 604, 615, 631, 644, 652, 655, 661 Recombinant Proteins, 381, 655 Recombination, 105, 174, 201, 613, 655 Reconstitution, 446, 655 Rectum, 584, 589, 597, 603, 612, 623, 624, 628, 651, 655 Recurrence, 36, 121, 141, 199, 259, 272, 278, 455, 632, 655 Red blood cells, 37, 609, 618, 648, 655, 659 Reductase, 655, 667 Reentry, 90, 655 Refer, 1, 362, 590, 597, 612, 619, 630, 638, 639, 640, 653, 655, 669 Refraction, 655, 663 Refractory, 11, 350, 480, 606, 655 Regeneration, 147, 297, 655 Regimen, 5, 13, 25, 34, 54, 150, 326, 332, 409, 446, 450, 480, 504, 606, 655, 657 Regression Analysis, 21, 655 Reinfection, 13, 33, 52, 121, 156, 197, 222, 656 Relapse, 13, 16, 38, 41, 46, 52, 58, 148, 228, 328, 348, 351, 368, 451, 527, 535, 538, 656 Relative risk, 577, 656 Reliability, 20, 152, 170, 173, 499, 656 Reminder Systems, 127, 656 Remission, 11, 16, 52, 61, 67, 298, 443, 537, 631, 632, 655, 656 Remission Induction, 16, 656 Renal failure, 231, 449, 619, 656 Replicon, 81, 94, 123, 182, 197, 200, 235, 272, 277, 278, 479, 656 Repressor, 78, 641, 656

Index 691

Resection, 199, 274, 280, 656 Resolving, 45, 142, 656 Respiration, 636, 656 Respiratory distress syndrome, 404, 656 Response Elements, 271, 276, 656 Response rate, 4, 5, 8, 9, 11, 13, 20, 22, 23, 31, 40, 45, 53, 58, 91, 102, 103, 120, 351, 448, 657 Restoration, 655, 657, 659, 668, 674 Retina, 594, 595, 628, 639, 641, 657, 658, 661 Retinitis, 108, 657 Retinoids, 657 Retinol, 128, 657 Retinopathy, 271, 277, 400, 646, 657 Retinyl palmitate, 128, 657 Retreatment, 41, 143, 223, 239, 249, 251, 299, 419, 422, 454, 657 Retrograde, 626, 657 Retrospective, 6, 56, 158, 251, 294, 505, 657 Retrospective study, 294, 657 Retroviral vector, 613, 657 Reverse Transcriptase Inhibitors, 332, 657 Rheology, 644, 657 Rheumatism, 396, 404, 621, 657 Rheumatoid, 63, 93, 291, 305, 378, 379, 395, 396, 627, 642, 657 Rheumatoid arthritis, 63, 378, 379, 395, 396, 627, 657 Rhinitis, 590, 658, 661 Rhinovirus, 126, 658 Ribonuclease, 92, 658 Ribose, 578, 658 Ribosome, 75, 129, 152, 186, 221, 260, 275, 281, 317, 658, 669 Rigidity, 643, 646, 658 Rimantadine, 454, 658 Risk patient, 117, 658 Risk-Taking, 99, 658 Rituximab, 205, 329, 658 Rod, 586, 608, 658, 659, 661 Rotavirus, 457, 658 Rubber, 577, 658 Rubella, 130, 351, 519, 523, 557, 658 Rubella Virus, 130, 351, 658 Rural Population, 221, 658 S Safe Sex, 465, 658 Saliva, 115, 119, 163, 321, 602, 659 Salivary, 127, 601, 603, 659, 661 Salivary glands, 601, 603, 659, 661 Salmonella, 120, 365, 457, 613, 659

Sanitary, 538, 540, 659 Sanitation, 63, 530, 541, 659 Saponins, 659, 664 Sarcoidosis, 237, 396, 659 Satellite, 368, 465, 500, 618, 659 Schizoid, 659, 674 Schizophrenia, 659, 674 Schizotypal Personality Disorder, 659, 674 Sclerosis, 585, 636, 659 Screening, 25, 26, 27, 31, 47, 54, 57, 66, 80, 82, 84, 89, 106, 109, 117, 127, 130, 139, 171, 200, 204, 210, 220, 240, 251, 288, 301, 322, 327, 330, 342, 355, 358, 360, 363, 366, 374, 376, 393, 397, 411, 417, 418, 420, 425, 445, 448, 451, 452, 453, 465, 469, 470, 485, 496, 497, 500, 501, 502, 507, 519, 521, 533, 561, 596, 659, 671 Secretory, 239, 594, 659 Secretory Vesicles, 594, 659 Sedative, 327, 335, 627, 659 Sediment, 660, 671 Sedimentation, 317, 593, 598, 660 Segregation, 587, 655, 660 Seizures, 209, 524, 643, 660 Selenium, 98, 283, 660 Self Care, 23, 660 Semen, 112, 138, 321, 606, 651, 660 Senile, 402, 403, 660 Sensory loss, 637, 660 Sepsis, 404, 612, 660 Septal, 48, 582, 660 Septic, 378, 585, 660 Septicaemia, 182, 660, 661 Sequence Analysis, 135, 136, 138, 140, 151, 172, 173, 314, 359, 372, 389, 406, 660 Sequence Homology, 401, 644, 660 Sequencing, 24, 70, 81, 92, 141, 150, 153, 165, 194, 648, 660 Serial Passage, 124, 660 Serine, 47, 175, 292, 364, 374, 405, 607, 635, 651, 652, 660 Seroconversion, 21, 35, 36, 39, 44, 51, 58, 83, 84, 99, 154, 158, 166, 181, 451, 660 Serologic Tests, 47, 64, 660 Serology, 44, 89, 447, 465, 500, 571, 574, 661 Serotonin, 403, 636, 639, 661, 670 Serotypes, 121, 661 Serrata, 307, 595, 661 Serrated, 661 Sex Behavior, 575, 661 Sexual Partners, 14, 321, 464, 467, 529, 661

692 Hepatitis

Shedding, 115, 485, 661 Shigella, 457, 661 Shock, 378, 608, 661, 670 Sicca, 55, 661 Signal Transduction, 92, 94, 122, 147, 661 Signs and Symptoms, 329, 425, 456, 533, 656, 661, 671 Silymarin, 635, 662 Skeleton, 626, 662 Skull, 600, 639, 662, 666 Small intestine, 595, 605, 620, 625, 662 Smallpox, 662, 672 Smiling, 465, 662 Smoldering leukemia, 637, 662 Smooth muscle, 233, 255, 404, 580, 581, 582, 662, 663, 665 Sneezing, 528, 540, 545, 645, 661, 662 Social Environment, 654, 662 Social Security, 655, 662 Social Support, 662, 664 Socialization, 84, 662 Sodium, 29, 352, 534, 615, 662 Soft tissue, 589, 662 Solid tumor, 454, 582, 662 Solvent, 373, 406, 594, 609, 615, 634, 642, 662 Somatic, 578, 595, 620, 633, 635, 645, 662 Sound wave, 334, 662 Spasm, 583, 663 Spasmodic, 645, 663 Specialist, 60, 321, 447, 464, 562, 663 Specificity, 66, 98, 187, 194, 350, 388, 579, 607, 622, 649, 663 Spectrum, 20, 57, 91, 103, 109, 130, 255, 270, 276, 419, 456, 459, 634, 663 Sperm, 359, 389, 528, 547, 595, 663 Spinal cord, 585, 589, 592, 593, 594, 605, 607, 612, 633, 637, 638, 639, 642, 645, 663, 665 Spinal Cord Vascular Diseases, 637, 663 Spirochete, 663, 666 Spleen, 524, 601, 631, 659, 663 Splenomegaly, 624, 663 Spondylitis, 379, 663 Sporadic, 27, 83, 140, 166, 248, 256, 361, 371, 414, 533, 648, 663 Stabilization, 94, 315, 663 Staging, 68, 206, 323, 355, 399, 497, 663 Standard therapy, 4, 16, 120, 445, 480, 663 Standardize, 15, 120, 663 State Government, 542, 663 Statistically significant, 24, 47, 56, 663

Steatosis, 20, 50, 199, 267, 610, 663 Stellate, 50, 76, 106, 664 Stem cell transplantation, 196, 256, 454, 664 Stem Cells, 609, 645, 664 Sterile, 34, 69, 99, 501, 522, 585, 664 Sterility, 624, 664 Sterilization, 464, 664 Steroid, 4, 301, 378, 404, 587, 600, 659, 664 Stimulants, 614, 664 Stimulus, 605, 609, 625, 664, 667 Stomach, 544, 577, 586, 603, 609, 612, 613, 620, 638, 645, 662, 663, 664 Stomatitis, 103, 141, 664 Stool, 597, 623, 628, 664 Strand, 73, 124, 159, 171, 176, 376, 380, 381, 409, 648, 664 Street Drugs, 528, 664 Stress management, 418, 425, 664 Stroke, 346, 403, 460, 494, 591, 664 Stromal, 203, 664 Styrene, 658, 664 Subacute, 379, 448, 623, 664 Subarachnoid, 616, 664 Subclinical, 48, 52, 454, 459, 623, 660, 665 Subcutaneous, 59, 168, 228, 578, 606, 612, 643, 665 Subspecies, 663, 665, 672 Substance P, 19, 634, 655, 659, 665 Substrate, 292, 374, 383, 411, 608, 665, 670 Suction, 611, 665 Sulfates, 504, 665 Sulfur, 603, 610, 628, 634, 665 Sulfuric acid, 665 Superoxide, 116, 665 Superoxide Dismutase, 116, 665 Supplementation, 128, 303, 665 Support group, 423, 425, 461, 464, 519, 535, 560, 575, 665 Supportive care, 85, 520, 665 Suppression, 12, 36, 65, 96, 113, 122, 135, 144, 147, 151, 161, 229, 274, 279, 324, 665 Suppressive, 301, 396, 665 Surfactant, 366, 665 Survival Rate, 27, 36, 39, 46, 443, 665 Sympathetic Nervous System, 595, 665, 666 Sympathomimetic, 605, 609, 640, 666, 670 Symptomatic, 5, 31, 37, 176, 286, 373, 581, 643, 666 Symptomatic treatment, 581, 666 Synaptic, 639, 661, 666

Index 693

Synergistic, 40, 98, 195, 257, 351, 666, 668 Syphilis, 57, 435, 590, 666 Systemic lupus erythematosus, 63, 378, 404, 583, 584, 666 Systolic, 621, 666 T Tacrolimus, 16, 666 Taurine, 311, 587, 594, 666 Technetium, 258, 666 Temporal, 71, 83, 617, 666 Teratogenic, 579, 666 Terminator, 596, 666, 674 Tetani, 402, 666 Tetanic, 666 Tetanus, 43, 128, 204, 401, 519, 547, 666 Tetracycline, 174, 605, 667 Thalassemia, 460, 667 Therapeutics, 12, 29, 73, 104, 108, 261, 291, 301, 319, 354, 356, 413, 427, 489, 636, 667 Thermal, 365, 366, 604, 639, 648, 667 Thimerosal, 483, 667 Thioacetamide, 243, 667 Thioredoxin, 243, 667 Thorax, 577, 667 Threonine, 635, 644, 651, 652, 660, 667 Threshold, 621, 667 Thrombin, 611, 647, 651, 652, 667 Thrombocytes, 647, 667 Thrombocytopenia, 227, 667 Thrombomodulin, 651, 667 Thrombopenia, 584, 667 Thromboplastin, 652, 667 Thromboses, 584, 667 Thrombosis, 63, 175, 259, 356, 587, 625, 652, 664, 667 Thrombus, 600, 623, 647, 667 Thymosin, 11, 67, 270, 271, 274, 275, 276, 279, 280, 331, 340, 414, 490, 667 Thymus, 176, 311, 622, 631, 667, 668 Thyroid, 63, 67, 591, 626, 668, 670 Thyroid Gland, 668 Thyroiditis, 24, 668 Thyroxine, 580, 645, 668 Tic, 80, 668 Ticks, 611, 668 Time Management, 664, 668 Tissue Culture, 78, 87, 95, 103, 114, 375, 668 Titre, 497, 668 Tobacco Mosaic Virus, 168, 668 Tobamovirus, 668

Tolerance, 48, 104, 107, 110, 147, 373, 443, 453, 578, 614, 668 Tomography, 342, 343, 598, 631, 668 Tonicity, 618, 668 Tooth Preparation, 578, 668 Topical, 609, 620, 643, 667, 668 Torsion, 623, 668 Toxic Hepatitis, 290, 292, 295, 297, 546, 668 Toxicity, 30, 38, 54, 100, 111, 114, 128, 176, 179, 198, 345, 399, 605, 634, 664, 669, 672 Toxicology, 109, 287, 496, 669 Toxin, 286, 534, 579, 591, 603, 608, 666, 668, 669 Toxoid, 128, 401, 669 Trachea, 645, 668, 669 Transaminase, 16, 447, 669 Transcriptase, 87, 137, 153, 154, 159, 169, 349, 364, 376, 377, 386, 628, 639, 640, 657, 669, 674 Transcription Factors, 87, 657, 669 Transduction, 92, 122, 661, 669 Transfection, 105, 588, 606, 613, 669 Transfer Factor, 622, 669 Transferases, 615, 669 Translating, 363, 669 Translation, 17, 71, 126, 129, 135, 186, 229, 359, 390, 581, 669 Translational, 76, 81, 123, 129, 669 Transmitter, 577, 585, 604, 632, 640, 669, 670 Transplantation, 16, 17, 18, 23, 28, 36, 53, 54, 66, 67, 86, 102, 123, 125, 191, 197, 200, 206, 208, 226, 228, 229, 237, 251, 252, 263, 266, 271, 277, 368, 398, 424, 443, 452, 455, 471, 535, 537, 595, 622, 631, 670 Trauma, 404, 643, 670 Treatment Failure, 443, 670 Treatment Outcome, 9, 24, 64, 91, 480, 670 Trees, 581, 658, 670 Tropism, 101, 102, 147, 670 Tryptophan, 597, 661, 670 Tumor marker, 588, 670 Tumor Necrosis Factor, 92, 151, 160, 404, 631, 670 Tumor suppressor gene, 109, 642, 670 Tunica, 636, 670 Type 2 diabetes, 14, 58, 670 TYPHI, 120, 670 Typhoid fever, 670 Tyramine, 636, 670

694 Hepatitis

Tyrosine, 122, 158, 180, 604, 670 U Ulcer, 305, 400, 670, 671 Ulceration, 641, 671 Ulcerative colitis, 369, 370, 378, 396, 461, 624, 650, 671 Unconscious, 602, 621, 671 Universal Precautions, 7, 31, 424, 467, 469, 497, 500, 501, 522, 526, 528, 532, 544, 548, 671 Uraemia, 643, 671 Uranium, 666, 671 Urea, 404, 627, 671 Uremia, 627, 656, 671 Urethra, 644, 651, 671 Urinalysis, 328, 671 Urinary, 304, 586, 614, 623, 641, 671 Urogenital, 614, 671 Uroporphyrinogen Decarboxylase, 648, 671 Uterine Contraction, 577, 671 Uterus, 577, 593, 621, 650, 671, 672 V Vaccine adjuvant, 451, 672 Vaccinia, 91, 131, 170, 380, 415, 672 Vaccinia Virus, 131, 170, 415, 672 Vacuoles, 607, 642, 672 Vagina, 593, 621, 672 Vaginal, 162, 521, 531, 672 Varicella, 315, 519, 672 Variola, 672 Vascular, 63, 73, 399, 400, 580, 594, 603, 617, 623, 629, 634, 663, 667, 668, 672 Vasculitis, 63, 88, 227, 299, 329, 643, 672 Vasodilator, 605, 672 VE, 93, 161, 246, 435, 465, 672 Vector, 121, 355, 367, 370, 669, 672, 674 Vein, 321, 327, 329, 625, 640, 643, 648, 659, 672 Venereal, 666, 672 Venoms, 639, 672 Venous, 584, 587, 589, 593, 602, 647, 652, 672 Venous blood, 589, 593, 647, 672 Ventricle, 653, 666, 672 Venules, 589, 634, 672 Vertebrae, 663, 672 Vesicular, 103, 141, 619, 634, 662, 672 Veterinary Medicine, 495, 672

Villous, 592, 672 Vinyl Chloride, 257, 672 Viraemia, 67, 251, 265, 361, 673 Viral Proteins, 71, 126, 250, 377, 393, 450, 673 Viral Regulatory Proteins, 673 Viral Structural Proteins, 377, 391, 673 Viral vector, 415, 673 Virion, 97, 210, 618, 640, 668, 673 Virulence, 89, 156, 177, 660, 669, 673 Virus Activation, 202, 208, 673 Virus Diseases, 584, 673 Vitiligo, 10, 24, 673 Vitro, 69, 81, 87, 94, 95, 96, 98, 102, 103, 109, 112, 120, 123, 124, 126, 130, 157, 159, 167, 175, 200, 263, 271, 272, 277, 278, 288, 292, 295, 301, 316, 353, 363, 374, 383, 396, 397, 411, 613, 623, 648, 660, 661, 666, 668, 673 Vivo, 71, 75, 79, 80, 81, 88, 94, 96, 102, 105, 109, 112, 114, 119, 126, 151, 157, 158, 159, 175, 194, 202, 220, 273, 278, 316, 353, 359, 383, 613, 623, 629, 642, 666, 673 Voluntary Health Agencies, 622, 673 W War, 437, 441, 472, 474, 475, 593, 637, 674 Waste Management, 501, 674 Weight Gain, 524, 674 White blood cell, 322, 324, 329, 334, 583, 616, 624, 628, 631, 636, 646, 674 Whooping Cough, 645, 674 Windpipe, 645, 668, 674 Withdrawal, 10, 16, 34, 37, 674 Wound Healing, 625, 632, 674 X Xenograft, 582, 674 X-ray, 321, 322, 324, 326, 327, 328, 329, 330, 334, 335, 337, 591, 598, 611, 612, 626, 637, 640, 654, 674 Y Yeasts, 612, 645, 674 Yellow Fever, 374, 456, 611, 674 Yellow Fever Virus, 611, 674 Z Zalcitabine, 628, 674 Zoonosis, 70, 674 Zoster, 315, 674 Zymogen, 651, 674

Index 695

696 Hepatitis

Hepatitis - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Hepatitis A Vaccine: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Hepatitis C Virus: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Hepatitis B Virus - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References