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

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

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HEPATITIS B 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 ©2004 by ICON Group International, Inc. Copyright ©2004 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 B: 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: 0-597-83979-4 1. Hepatitis B-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 B. 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 B .............................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Hepatitis B .................................................................................. 32 E-Journals: PubMed Central ....................................................................................................... 88 The National Library of Medicine: PubMed .............................................................................. 125 CHAPTER 2. NUTRITION AND HEPATITIS B .................................................................................. 173 Overview.................................................................................................................................... 173 Finding Nutrition Studies on Hepatitis B ................................................................................. 173 Federal Resources on Nutrition ................................................................................................. 179 Additional Web Resources ......................................................................................................... 180 CHAPTER 3. ALTERNATIVE MEDICINE AND HEPATITIS B............................................................ 181 Overview.................................................................................................................................... 181 National Center for Complementary and Alternative Medicine................................................ 181 Additional Web Resources ......................................................................................................... 201 General References ..................................................................................................................... 203 CHAPTER 4. DISSERTATIONS ON HEPATITIS B.............................................................................. 205 Overview.................................................................................................................................... 205 Dissertations on Hepatitis B ...................................................................................................... 205 Keeping Current ........................................................................................................................ 207 CHAPTER 5. CLINICAL TRIALS AND HEPATITIS B ........................................................................ 209 Overview.................................................................................................................................... 209 Recent Trials on Hepatitis B ...................................................................................................... 209 Keeping Current on Clinical Trials ........................................................................................... 221 CHAPTER 6. PATENTS ON HEPATITIS B......................................................................................... 223 Overview.................................................................................................................................... 223 Patents on Hepatitis B ............................................................................................................... 223 Patent Applications on Hepatitis B ........................................................................................... 249 Keeping Current ........................................................................................................................ 282 CHAPTER 7. BOOKS ON HEPATITIS B ............................................................................................ 283 Overview.................................................................................................................................... 283 Book Summaries: Federal Agencies............................................................................................ 283 Book Summaries: Online Booksellers......................................................................................... 286 The National Library of Medicine Book Index ........................................................................... 290 Chapters on Hepatitis B ............................................................................................................. 291 CHAPTER 8. MULTIMEDIA ON HEPATITIS B ................................................................................. 297 Overview.................................................................................................................................... 297 Video Recordings ....................................................................................................................... 297 Audio Recordings....................................................................................................................... 299 Bibliography: Multimedia on Hepatitis B.................................................................................. 300 CHAPTER 9. PERIODICALS AND NEWS ON HEPATITIS B .............................................................. 303 Overview.................................................................................................................................... 303 News Services and Press Releases.............................................................................................. 303 Newsletters on Hepatitis B ........................................................................................................ 307 Newsletter Articles .................................................................................................................... 308 Academic Periodicals covering Hepatitis B................................................................................ 310 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 311 Overview.................................................................................................................................... 311 U.S. Pharmacopeia..................................................................................................................... 311 Commercial Databases ............................................................................................................... 312

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Researching Orphan Drugs ....................................................................................................... 313 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 317 Overview.................................................................................................................................... 317 NIH Guidelines.......................................................................................................................... 317 NIH Databases........................................................................................................................... 319 Other Commercial Databases..................................................................................................... 326 The Genome Project and Hepatitis B ......................................................................................... 326 APPENDIX B. PATIENT RESOURCES ............................................................................................... 331 Overview.................................................................................................................................... 331 Patient Guideline Sources.......................................................................................................... 331 Associations and Hepatitis B ..................................................................................................... 357 Finding Associations.................................................................................................................. 358 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 361 Overview.................................................................................................................................... 361 Preparation................................................................................................................................. 361 Finding a Local Medical Library................................................................................................ 361 Medical Libraries in the U.S. and Canada ................................................................................. 361 ONLINE GLOSSARIES................................................................................................................ 367 Online Dictionary Directories ................................................................................................... 370 HEPATITIS B DICTIONARY...................................................................................................... 371 INDEX .............................................................................................................................................. 451

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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 B 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 B, 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 B, 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 B. 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 B, 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 B. 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 B Overview In this chapter, we will show you how to locate peer-reviewed references and studies on hepatitis B.

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 B, 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 B” (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: •

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

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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. •

Hepatitis B Vaccine Recommended for All Children Source: FDA Consumer. 25(5): 2-3. June 1991. Summary: All children should be vaccinated against hepatitis B, according to the Immunization Practices Advisory Committee of the U.S. Public Health Service. Immunization experts made this recommendation in February 1991, after strategies to vaccinate adults at high risk for hepatitis B failed to achieve sufficient coverage. This brief article reviews the reasons behind this decision and the potential benefits of universal immunization. 2 references. (AA-M).

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Risk Factors for Viral Hepatitis B and C Help Identify Disease Source: Practical Gastroenterology. 22(1): 10-12, 19-22, 25-26. January 1998. Contact: Available from Shugar Publishing, Inc. 99B Main Street, Westhampton Beach, NY 11978. (631) 288-4404. Fax (631) 288-4435. E-Mail: [email protected]. Summary: An estimated 200,000 to 300,000 people in the US become infected each year with the hepatitis B virus, and 150,000 become infected with the hepatitis C virus. Identification of the modes of transmission is of primary importance in efforts to curtail the spread of these infections. This article reviews the risk factors, both common and rare, that have been identified to date. The authors note that, in individual cases, knowledge of risk factors for transmission helps physicians to identify and counsel patients at risk, to identify those whose history indicates the possibility of infection, and, for those who are seropositive, to determine how and when infection occurred, which may have implications for prognosis and treatment. Topics include sexual contact, household and other social contacts, risks of HBV transmission in institutional settings, the maternal-fetal interface, blood and blood product transfusions, hemodialysis, transplantation associated risk, physicians as a risk to their patients, transmission from medical devices, occupational risk factors, social and recreational transmission, intravenous drug abuse, cosmetic transmission (ear piercing, tattooing, barber shop shaving, manicurists), the risk factor associated with certain sports, and insect-borne infection. 2 figures. 4 tables. 28 references. (AA-M).

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Prevention of Hepatitis B Virus in Athletic Training Source: Journal of Athletic Training. 29(2): 107-112. June 1994.

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Summary: Because of exposure to blood-borne pathogens and potentially infectious materials, athletic training is an allied health care profession with an increased risk of exposure to hepatitis B virus (HBV). This article considers the prevention of HBV in athletic training. Topics include the pathogenesis and epidemiology of HBV; signs and symptoms; transmission; and preventive measures, including immunization, protective equipment, housekeeping, and sharps. The authors stress the importance of information dissemination about prevention of HBV in the athletic training setting to all athletic training staff and students, through in-service training sessions, symposia, and lectures. 1 table. 11 references. (AA-M). •

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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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),

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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. •

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. 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.

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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 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

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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. •

New Treatment Strategies in Hepatitis B and C: Natural History of Chronic Hepatitis B and C Source: Journal of Gastroenterology and Hepatology. 14(Supplement): S1-S5. May 1999. 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) affects more than 300 million individuals worldwide, and in the United States approximately 1.25 million individuals are chronic carriers of HBV. This article reviews the natural history of chronic hepatitis B and C. The risk of becoming a chronic hepatitis B virus surface antigen carrier is dependent upon the mode of acquisition of infection as well as the age of the individual at the time of infection. For those individuals with high levels of virus replication, chronic active hepatitis (CAV) with progression to cirrhosis, liver failure and hepatocellular carcinoma (HCC, liver cancer) is common. Liver transplantation is an excellent treatment option for patients with end stage liver disease from HBV. Patients with chronic HBV infection should be screened periodically for hepatoma, although screening strategies have not been proven to prolong survival. Newer antiviral agents for the treatment of HBV are potent inhibitors of HBV DNA and their long term effect on the natural history of HBV is yet to be proven. The natural history of hepatitis C virus (HCV) infection is less well defined than that of chronic HBV. Certain patients who are chronic carriers of HCV may never develop extensive fibrosis, whereas others will progress to CAV with cirrhosis, HCC, and end stage liver disease. Factors that influence the progression of HCV are those related to the host, including the age at acquisition of infection, gender, and immune status; the disease process is accelerated in patients who consume regular amounts of alcohol. Hepatocellular carcinoma develops frequently in patients with HCV infection and its overall incidence is increasing due to this chronic viral disease. Patients with HCV cirrhosis should be screened regularly for hepatoma and liver transplantation is an effective treatment option for those with end stage disease. The author concludes that the impact of antiviral therapy on the natural history of HCV is still to be determined and should be the focus of large clinical trials. 4 tables. 30 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

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Hepatitis B

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 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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Occult Hepatitis B Virus Infection in Patients with Chronic Hepatitis C Liver Disease Source: New England Journal of Medicine. 341(1): 22-26. July 1, 1999. Summary: Hepatitis B virus (HBV) infections in patients who lack detectable hepatitis B surface antigen (HBsAg) are called occult infections. Although such infections have been identified in patients with chronic hepatitis C liver disease, their prevalence and clinical significance are not known. This article reports on a study that searched for HBV DNA in liver and serum samples from 200 HBsAg negative patients with hepatitis C virus (HCV) liver disease (147 with chronic hepatitis, 48 with cirrhosis, and 5 with minimal histologic changes). Of the patients, 100 had detectable antibodies to the HBV core antigen; 100 were negative for all HBV markers. Some patients (n = 83) were treated with interferon alfa. The study also included 50 patients with liver disease who were negative both for HBsAg and for HCV markers. Sixty six of the 200 patients with chronic hepatitis C liver disease (33 percent) had HBV sequences, as did 7 of the 50 patients with liver disease unrelated to hepatitis C. Among the 66 patients, 46 were anti HBc positive and 20 were negative for all HBV markers. Twenty two of these 66 patients (33 percent) had cirrhosis, as compared with 26 of the 134 patients with hepatitis C infection but no HBV sequences (19 percent). HBV sequences were detected in 26 of the 55 patients in whom interferon therapy was ineffective and 7 of the 28 patients in whom interferon therapy was effective. The authors conclude that occult hepatitis B infection occurs

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frequently in patients with chronic hepatitis C liver disease and may have clinical significance for these patients. 4 tables. 45 references. •

Chronic Hepatitis B and C Source: Postgraduate Medicine. 92(4): 75-80, 82. September 15, 1992. Summary: In this article, the author discusses the results of studies conducted to evaluate therapy with alpha, beta, and gamma interferon as well as with other agents, such as ribavirin, thymosin, and ursodeoxycholic acid. The author notes that at the time this article was written, interferon alfa-2b (Intron-A) is not approved for both indications; however, interferon is not without significant side effects and costs. 2 figures. 1 table. 32 references. (AA-M).

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Hepatic Failure and Lactic Acidosis Due to Fialuridine (FIAU), an Investigational Nucleoside Analogue for Chronic Hepatitis B Source: New England Journal of Medicine. 333(17): 1099-1105. October 26, 1995. Summary: In this article, the authors describe severe and unexpected multisystem toxicity that occurred during a study of the antiviral nucleoside analogue fialuridine (FIAU) as therapy for chronic hepatitis B virus infection. Fifteen patients with chronic hepatitis B were randomly assigned to receive fialuridine at a dose of either 0.10 or 0.25 mg per kilogram of body weight per day for 24 weeks. They were monitored every 1 to 2 weeks by means of a physical examination, blood tests, and testing for hepatitis B virus markers. During the 13th week, lactic acidosis and liver failure suddenly developed in 1 patient. The study was terminated on an emergency basis, and all treatment with fialuridine was discontinued. Seven patients were found to have severe hepatotoxicity, with progressive lactic acidosis, worsening jaundice, and deteriorating hepatic synthetic function, despite the discontinuation of fialuridine. Of these seven patients, five died and two survived after liver transplantation. The authors conclude that the toxic reaction was probably caused by widespread mitochondrial damage and may occur infrequently with other nucleoside analogues. 5 figures. 1 table. 43 references. (AA-M).

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Is Vaccination Against Hepatitis B Efficient? A Review of World Literature Source: Health Economics. 3(1): 25-37. January-February 1994. Contact: Available from John Wiley and Sons Limited. Subscriptions Department, 605 Third Avenue, New York, NY 10157-0228. (212) 850-6000. Summary: In this article, the authors report on the result of a study aimed at assessing the variability of assumptions upon which economic models for the introduction of vaccination against hepatitis B are based. They discuss the conclusions reached and define a minimum set of methodological standards upon which future economic studies on vaccines should be based. The literature review identified 116 published and unpublished works by Medline literature searches, consulting private databases, and corresponding with all authors and researchers active in the economic evaluation of vaccines. All works were assessed, but only the 90 studies that were original economic analyses are reviewed. The authors found profound variability on main parameters of the efficiency equation, including disease incidence, costing methods, use of marginal theory, discounting and study timespan, sensitivity analysis, and reporting methods. They caution against decisions made on biased evidence because of poor research

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methodology and call for the standardization of study methods and procedures. 6 tables. 121 references. (AA-). •

Hampering Hepatitis B Transmission Through Neonatal Therapy Source: National Medical Association News. May-June 1992. p. 3. Summary: In this interview article, Dr. Neil S. Silverman explains his views on hampering hepatitis B transmission through neonatal therapy. He proposes drug screening as a marker for increased risk of HBsAg positivity and empiric initiation of hepatitis B immune globulin (HBIG) prophylaxis for infants born to unregistered women with positive results of urine drug screening whose infants' HBsAg results are unavailable within 12 hours of delivery. In this interview, Dr. Silverman discusses the relationship between hepatitis B prevalence and the unregistered prenatal population; the incidence of hepatitis B in the population of women that use drugs; problems with legalities of a drug screening policy; specific advantages of prenatal testing; risks involved with immunoglobulin administration; statistics on the proposed numbers of hepatitis B cases that could be prevented annually; morbidity for children who become hepatitis carriers; the likelihood of a plan for hepatitis B prophylaxis being implemented; and problems created by the ongoing and increasing substance abuse situation.

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Hepatitis B Virus Mutant Associated with an Epidemic of Fulminant Hepatitis B Source: Liver Update. 5(1): 7-8. Spring 1991. Contact: Available from American Liver Foundation. 1425 Pompton Avenue, Cedar Grove, NJ 07009. (201) 256-2550 or (800) 223-0179. Summary: Infection with hepatitis B virus (HBV) leads to a wide spectrum of liver injury. Fulminant hepatitis B is a rare disease, but carries a high mortality. This brief article reports on a nosocomial outbreak of five cases of fulminant hepatitis B that occurred in Israel. Investigations by the author suggest that the five patients with fulminant hepatitis were infected by the same virus derived from a common source while a subclinical case was infected by another HBV strain at the same time. This study points to a role for naturally occurring viral mutations in the emergence of HBV viral strains capable of producing more severe liver injury.

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Potential for the Use of Modified Hepatitis Delta Virus in the Therapy of Chronic Hepatitis B Virus Infections Source: Viral Hepatitis Reviews. 1(1): 47-52. September 1995. Contact: Available from Journals Subscriptions Department, Harcourt Brace and Company Ltd. High Street, Foots Cray, Sidcup, Kent DA14 5HP UK. Telephone +181 300 3322. Summary: Infections by hepatitis B virus (HBV) continue to be a major source of chronic liver disease, despite the great advancements in our understanding of HBV infections and the widespread availability of an effective vaccine. Once a patient has become chronically infected with HBV, the currently available therapies are not particularly effective, and there is a high risk that infection will proceed to cirrhosis and hepatocellular carcinoma. This article evaluates the potential of a novel therapy: the application of modified forms of hepatitis delta virus (HDV) as part of an antiviral strategy for individuals with chronic hepatitis B virus infections. 3 figures. 31 references. (AA-M).

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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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Review: Hepatitis B and Liver Transplantation Source: Journal of Gastroenterology and Hepatology. 13(3): 217-223. March 1997. Contact: Available from Blackwell Science Pty Ltd. P.O. Box 378, Carlton, Victoria 3053, Australia. Phone: 61 3 9347 0300; Fax: 61 3 9347 5001; Web site: http://www.blacksci.co.uk. Summary: Liver transplantation in hepatitis B virus (HBV) infected patients is very commonly followed by recurrence of infection in the transplanted liver. This review article focuses on new strategies for the prevention and treatment of disease recurrence after transplantation. Most recipients with HBV recurrence will develop chronic hepatitis that follows a more aggressive course than is seen in nonimmunocompromised subjects; this frequently results in graft failure. The presence of hepatitis B e antigen or significant levels of HBV-DNA in the serum is highly predictive of recurrence and this has led to the view that patients, whose serum is positive for these conventional markers of replication, should be excluded from transplantation. The key to improving the results of transplantation in patients with HBV infection lies in the development of effective strategies to prevent reinfection. High dose anti-HBs immunoglobulin is effective in patients who are coinfected with hepatitis D, those transplanted for fulminant hepatitis, and cirrhotic patients who have very low levels of viral replication prior to transplantation. Unfortunately, immunoprophylaxis does not seem to influence the outcome in those patients with higher levels of replication. There are several new orally active nucleoside analogues that are potent inhibitors of hepatitis B replication that may be effective for both the prevention and treatment of recurrent disease. The most promising are lamivudine and famciclovir. Both agents have been extensively evaluated in animal models of HBV and have been shown to rapidly suppress viral replication. The author concludes that the initial experience with these agents in liver transplant recipients has been promising and a number of studies are currently under way to determine whether these drugs, used alone or in combination with immunoprophylaxis, are able to prevent recurrence in those patients at highest risk of posttransplant HBV recurrence. 1 table. 59 references. (AA-M).

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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.

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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: 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. •

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.

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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: 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 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. •

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.

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Injections Given in Healthcare Settings as a Major Source of Acute Hepatitis B in Moldova Source: International Journal of Epidemiology. 28(4): 782-786. August 1999.

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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: Reported rates of acute hepatitis B are high in many former Soviet Union republics and modes of transmission are not well defined. This article reports on two case control studies that were undertaken in Moldova to identify risk factors for acute hepatitis B in people aged 2 to 15 years (children) and older than 15 years (adults). Serologically confirmed acute hepatitis B cases occurring between January 1994 and August 1995 were matched on age, sex, and district of residence to three potential control groups who were tested for hepatitis B markers to exclude the immune. In multivariate analysis, compared with the 175 controls, the 70 adult cases (mean age 25 years, 66 percent male) were more likely to report receiving injections in the 6 months before illness during a dental visit, a hospital visit, or a visit to the polyclinic. Among children, receiving injections during a hospital visit was the only exposure reported significantly more often by the 19 cases (mean age 8 years, 68 percent male) compared with the 81 controls. These results, along with reported unsafe injection practices in Moldova, suggest that injections are a major source of hepatitis B virus transmission and highlight the importance of proper infection control procedures in preventing transmission of blood borne infections. 3 tables. 25 references. •

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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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

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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 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

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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. •

Impact of Hepatitis B and C Virus on Kidney Transplantation Outcome Source: Hepatology. 29(1): 257-263. January 1999. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: The impact of hepatitis B (HBV) and C (HCV) on patient survival after kidney transplantation is controversial. This article reports on a study undertaken to assess the independent prognostic values of hepatitis B surface antigen (HBsAg) and anti-HCV in a large renal transplant population. The study also compared infected and noninfected patients matched for factors possibly associated with graft and patient survival and assessed the prognostic value of biopsy proven cirrhosis. A total of 834 transplanted patients were included: 128 with positive HBsAg (group I), 216 with positive anti-HCV (group II), and 490 without serological markers of HBV and HCV (group III). Fifteen percent of patients were HBsAg positive, and 29 percent were antiHCV positive. Ten year survival of group I (55 percent) and group II (65 percent) were significantly lower than survival of group III (80 percent). At 10 years, among all 834 patients, 4 variables had independent prognostic values in patient survival: age at transplantation, year of transplantation, biopsy proven cirrhosis, and presence of HCV antibodies. In the case control study, comparison of infected patients with their matched controls showed that age at transplantation and anti-HCV were independent prognostic factors. HCV, biopsy proven cirrhosis, and age are independent prognostic factors of 10 year survival in patients with kidney grafts. The authors conclude that a routine liver histological analysis in infected patients would improve selection of patients for renal transplantation. 4 figures. 5 tables. 34 references. (AA-M).

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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. 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

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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. •

Detection of Hepatitis B Virus (HBV) in HBsAG Negative Individuals with Primary Liver Cancer Source: Digestive Diseases and Sciences. 36(8): 1122-1129. August 1991. Summary: The importance of chronic hepatitis B virus (HBV) infection in the development of primary liver cancer has been established by epidemiological studies. This article discusses the detection of HBV in HBsAG negative individuals with primary liver cancer. The authors report the use of the polymerase chain reaction to detect HBV DNA in the serum and liver of these patients. This technique allows both for the detection and cloning of HBV variants. The authors contend that the laboratory values obtained with this technique reinforce the role of HBV in the pathogenesis of this tumor. 5 figures. 39 references. (AA-M).

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Benefit-Cost Analysis of Hepatitis B Vaccine Programs for Occupationally Exposed Workers Source: Journal of Occupational Medicine. 33(6): 691-698. June 1991. Summary: The Occupational Safety and Health Administration proposed a vaccination program for workers exposed to the hepatitis B virus 12 or more times per year. This article reports on a benefit-cost analysis of the proposed regulation and an expanded rule that covers all at-risk workers, regardless of the number of exposures. The authors estimated the dollar benefit of the program using two methods. The first estimates the avoided cost of medical care, prophylaxis, and lost productivity at $124 million annually. The second approach includes the value of avoided pain and suffering from hepatitis B, thus increasing the total dollar benefit to $679 million. Although both methods indicate benefits are greater than program costs, the valuation of avoided pain and suffering substantially increases net benefits. Furthermore, providing the vaccine to all exposed workers is cost-effective if one or more cases of hepatitis B are avoided per 6500 workers annually. 1 figure. 7 tables. 12 references. (AA).

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Chronic Hepatitis B Infection in Eastern Europe and the Middle East Source: Viral Hepatitis Review. 6(1-4): 111-128. 2000. Contact: Available from Harcourt Brace and Company Ltd. Journals Subscriptions Department, High Street, Foots Cray, Sidcup, Kent DA14 5HP UK. Telephone +181 300 3322. Summary: The World Health Organization estimates that about 350 million chronic carriers of hepatitis B exist worldwide; many carriers develop cirrhosis (liver scarring) or hepatocellular carcinoma (HCC, liver cancer) over the course of their lives. Although infection poses a substantial public health burden in many parts of the world, the magnitude of this burden is often unclear (because available information is not readily accessible). This report summarizes the available information from multiple sources for two geographic regions: Eastern Europe and the Middle East. To estimate the hepatitis B burden in the two regions, the authors collated existing information from published literature, organizations with health care data, the Internet, and the Global Burden of

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Disease and Injury Series. Published literature provided the most extensive information about the occurrence of hepatitis B infection and was more available for Middle Eastern countries than for Eastern European countries. In both regions, most countries with prevalence data had an intermediate or high prevalence of carriers, but there was considerable heterogeneity within regions. Population subgroups within countries had different prevalences. Compared with the Middle East, relatively few Eastern European countries had infant immunization programs. The availability of information varies from country to country across the regions, and data comparisons are problematic. The low frequency of infant immunization programs in Eastern Europe constitutes an important missed opportunity for an effective public health intervention. Information about hepatitis B prevalence in population subgroups could be especially useful for identifying people who have the greatest need for intervention. 1 appendix. 2 figures. 4 tables. 69 references. •

Public Health Service Inter-Agency Guidelines for Screening Donors of Blood, Plasma, Organs, Tissues, and Semen for Evidence of Hepatitis B and Hepatitis C Source: MMWR. Morbidity and Mortality Weekly Report. 40(RR-4): 1-17. April 19, 1991. Summary: These guidelines address the use of tests for the hepatitis B and C viruses to screen donations of blood and plasma collected for transfusion or further manufacture into injectable products, as well as to screen donors of organs, tissues, and semen. These guidelines are intended to serve as a resource to individuals and organizations involved in testing, counseling, and evaluating donors tested for these viruses, and are based on currently available knowledge. 76 references. (AA).

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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 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.

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Family Physician Acceptance of Universal Hepatitis B Immunization of Infants Source: Journal of Family Practice. 36(2): 153-157. February 1993. Summary: This article describes a study that assessed the effectiveness of the Centers for Disease Control's (CDC) dissemination of a new immunization recommendation to family physicians; the effect of the new recommendation on clinical practice; and the degree to which noneconomic barriers may affect adoption of universal hepatitis B immunization. A random sample of 300 family physicians in North Carolina was surveyed by mail; a response rate of 78 percent was obtained. Overall, 48 percent of family physicians were aware of the new hepatitis B vaccine recommendation; however, only 17 percent agreed that it was warranted for all newborns in their practice. The authors conclude that the CDC does not have an effective mechanism for disseminating information to all physicians who care for children. Additionally, practical concerns of physicians and their patients regarding multiple injections and other practice-relevant issues must be considered when formulating new immunization recommendations. 4 tables. 6 references. (AA-M).

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Hepatitis B Infection and Liver Transplantation Source: Canadian Journal of Gastroenterology. 11(5): 462-468. July-August 1997. Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. Summary: This article discusses liver transplantation in patients with hepatitis B. Patients with chronic hepatitis B virus (HBV) infection have historically high rates of allograft reinfection from extrahepatic (outside the liver) reservoirs of HBV, with worse long term outcome compared with that of transplant recipients without HBV infection. As a result, chronic HBV infection has been considered a contraindication for transplantation. However, prophylaxis against HBV recurrence, in the form of passive immunization with high dose hepatitis B hyperimmunoglobulin and the antiviral agent lamivudine, has recently been demonstrated to decrease the risk of reinfection. The author summarizes past experience and current status of HBV infection and transplantation, with emphasis on the issues surrounding prophylaxis. The author concludes that with appropriate prophylaxis, liver transplantation can be a viable proposition for patients with HBV infection. The main obstacles to high dose HBIG prophylaxis are the continued availability of the product, practicality of administration, and the cost and long term duration of treatment. 2 tables. 60 references. (AA-M).

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Hepatitis B Virus Source: Scientific American. 264(4): 116-123. April 1991. Summary: This article discusses the hepatitis B virus (HBV) which causes liver diseases and a common form of cancer. During the past decade, evolving understanding of the molecular biology of HBV has found medical applications, particularly for preventing the infection. Mass vaccinations with the recombinant vaccine, the first vaccine for human use ever developed by recombinant DNA technology, will go far in controlling hepatitis B. The authors stress that such a campaign of vaccination would prevent not only the acute liver illness but also the associated cancer. This article emphasizes the epidemiology of hepatitis, the genetic structure and activity of HBV, and genetic engineering techniques used to develop a medical response to HBV. 6 figures. 5 references.

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Treatment of Chronic Hepatitis B and Hepatitis C with Interferon Alfa-2b Source: American Family Physician. 54(5): 1598-1602. October 1996. Summary: This article discusses the treatment of chronic hepatitis B and hepatitis C with interferon alfa-2b. Interferon alfa-2b is the only agent currently approved by the U.S. Food and Drug Administration for the treatment of chronic hepatitis B and C. The authors note that initial enthusiasm for this therapy has waned with the realization that response rates are low and relapses are common. Recent studies, however, provide evidence of improved response rates with higher doses of interferon alfa-2b. Improved response is also being obtained with the use of interferon alfa-2b in combination with iron reduction therapy consisting of repeated phlebotomies. The research has enabled the identification of predictors of an increased likelihood of response to interferon alfa2b therapy. The application of these predictors to patient selection may improve the cost-benefit ratio for this treatment. Research data have documented a significant reduction in the cost of health care and an increased life expectancy with interferon alfa2b therapy in patients who have chronic hepatitis C, particularly young patients without fibrosis. A patient care algorithm for the management of chronic hepatitis C with interferon alfa-2b is provided. 1 figure. 22 references. (AA-M).

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Hepatitis B Vaccination: Dosing Alternatives, Current Guidelines Source: Modern Medicine. 59(Supplement A): 6-10. 1991. Summary: This article explores the current guidelines for hepatitis B vaccination and offers suggestions for alternative dosing schedules. The author stresses that a national vaccination program will be necessary to prevent HBV infection in the general population and in specific high-risk groups. The use of an accelerated dosing schedule offers an alternative for patients who must develop immunity quickly, or who may be unable to comply with the longer conventional schedule. Other topics include booster doses, managing poor responses to the vaccine, safety issues, and routes of administration. 2 tables. 4 references.

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Hepatitis B: Immunising Health Workers and Patients Source: Nursing Times. 91(36): 29-31. September 6, 1995. Summary: This article familiarizes readers with current recommendations regarding hepatitis B immunizations for health care workers and patients. The author describes the disease process and the implications for people working in at-risk occupations in the hope of increasing the awareness of the need for, and subsequent use of, vaccination programs. Topics include the consequences of hepatitis B infection; the incidence and prevalence of hepatitis B; the main routes of transmission of hepatitis B virus (HBV); groups at higher risk of HBV infection; and signs and symptoms. The article also includes a brief glossary of related terms. 1 figure. 4 tables. 10 references. (AA-M).

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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. 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.

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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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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.

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

Hepatitis B: Virology, Epidemiology, Disease, and Prevention, and an Overview of Viral Hepatitis Source: American Journal of Preventive Medicine (Immunization in Medical Education Supplement). 10(supplement): 45-55. 1994. Contact: Available from Oxford University Press. 2001 Evans Road, Cary, NC 27513. Summary: This article presents an overview of viral hepatitis, with a focus on the virology, epidemiology, disease, and prevention of hepatitis B. The article also covers hepatitis A, delta hepatitis, hepatitis C, and hepatitis E. Other topics include the incidence and prevalence of hepatitis B virus (HBV) worldwide; the history of HBV isolation; HBV structure and infection nomenclature; the disease burden of HBV in the United States; modes of transmission; the clinical features of HBV infection; the outcome of HBV infection; diagnostic tests used to confirm the disease; the management of acute and chronic HBV infection; the prevention of HBV infection, notably the HBV vaccine, its safety and efficacy; and current recommendations for vaccination. 1 appendix. 9 figures. 1 table. 72 references.

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Hepatitis B Vaccination in Hospital Personnel and Medical Students Source: Journal of Clinical Gastroenterology. 28(4): 317-322. June 1999. Contact: Available from Lippincott-Raven Publishers. P.O. Box 1550, Hagerstown, MD 21741. (800) 638-3030 or (301) 714-2300. Summary: This article reports on a project undertaken to determine the prevalence of hepatitis B markers and the compliance to hepatitis B vaccination at University Hospital of Santa Maria, Lisbon. The program was begun in 1989 for all hospital personnel and students of the medical school. The screening included 2,360 health care workers and 1,153 students: 57 percent of hospital personnel and 41 percent of medical students appeared for vaccination. The prevalence of hepatitis B markers was 16.8 percent for hospital personnel and 5.5 percent for students; 0.95 percent of the hospital personnel

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and 0.3 percent of students were chronic carriers. The departments with the highest prevalence were the Biochemical Laboratory (7 out of 11 people, or 64 percent), Surgery (13 out of 31 people, 42 percent), Pulmonary (9 out of 23 people, 39 percent), Emergency (7 out of 24 people, 29 percent), Hematology Laboratory (7 out of 24 people, 29 percent), and Orthopedics (10 out of 35 people, 29 percent). The prevalence was higher in students in the last 3 years of medical school than those in the first 3 years (12.2 percent versus 7.2 percent, respectively). Adverse affects from vaccination occurred in 14.5 percent, with local pain the most frequent in 8.6 percent. The serologic efficacy was 95 percent. A nonresponse was observed in male workers: 13 percent compared with 5 percent for women. Older employees also showed higher nonresponse. The authors conclude that hepatitis B vaccination is safe and effective. This study shows the need for a more aggressive approach to the vaccination of health care workers because a significant percentage of them are not protected. 5 figures. 1 table. 32 references. (AAM). •

Prevalence of HIV, Hepatitis B, and Hepatitis C in People with Severe Mental Illness Source: American Journal of Public Health. 91(1): 31-37. 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 assessed seroprevalence (as determined by blood test) of HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) among individuals with severe mental illness. Participants in the study (n = 913) were patients undergoing inpatient or outpatient treatment in Connecticut, Maryland, New Hampshire, or North Carolina. The prevalence of HIV infection in this sample (3.1 percent) was approximately 8 times that estimated in the United States population, but lower than rates reported in previous studies of people with severe mental illness. Prevalence rates of HBV (23.4 percent) and HCV (19.6 percent) were approximately 5 and 11 times the overall estimated population rates for these infections, respectively. Although routes of transmission were not ascertained in this study, the high rates of substance use disorder, particularly injection drug use among women, are likely to contribute to increased risk. The authors conclude that elevated rates of all three infections were found in this population. Of particular concern are the high rates of HCV infection, which are frequently undetected. Individuals with HCV infection commonly fail to receive appropriate treatment to limit liver damage and unknowingly may be a source of infection to others. Greater efforts at prevention, screening, and treatment for HIV, HBV, and HCV are important. There is a lack of information and concern about HCV on the part of both providers and patients with severe mental illness. For example, a great majority of clients in this study who were infected with HIV were aware of their condition, but most of those with HCV were not. Previous experience with this population suggests that a cornerstone of successful intervention will be integrated dual diagnosis in the context of intensive case management. 3 tables. 35 references.

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Attitudes and Educational Practices of Obstetric Providers Regarding Infant Hepatitis B Vaccination Source: Obstetrics and Gynecology. 89(1): 61-64. January 1997. Summary: This article reports on a study to survey the current knowledge, attitudes, and practices of obstetric providers regarding the education of pregnant women about

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infant hepatitis B vaccination. A questionnaire was mailed to 264 physicians providing obstetric services in San Francisco; of these, 113 were confirmed to be providing prenatal care and 76 obstetric providers returned completed questionnaires. Among these respondents, 79 percent believed that hepatitis B vaccine should be administered to all infants at birth, and 92 percent believed that it is feasible to educate all expectant mothers about infant hepatitis B vaccination. However, only 53 percent of respondents provided such education to all their pregnant patients. Only 23 percent provided education about other routine childhood immunizations. The authors conclude that obstetric providers in San Francisco are willing to educate pregnant patients about hepatitis B vaccination but are not always doing so. Providing education in a consistent manner may improve infant hepatitis B vaccination rates and may increase coverage with other childhood vaccines. 3 tables. 18 references. (AA-M). •

Hepatitis B Carriage Explains the Excess Rate of Hepatocellular Carcinoma for Maori, Pacific Island and Asian People Compared to Europeans in New Zealand Source: International Journal of Epidemiology. 28(2): 204-210. April 1999. 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: This article reports on a study undertaken to determine the prevalence of hepatitis B surface antigen (HBsAg) carriers among cases of hepatocellular carcinoma (HCC), and the population attributable risk of HBsAg carriage for HCC, by ethnicity in New Zealand. The authors reviewed the hospital notes of HCC cases registered with the New Zealand Cancer Registry for the years 1987 to 1994. The HBsAg status was determined for 193 cases of HCC. The HBsAg carrier prevalence for non Europeans with HCC was markedly higher than that for Europeans (76.7 percent for Maori, 80.0 percent for Pacific Island people, and 88.5 percent for Asians, compared to 6.0 percent for Europeans). In addition to the effect of ethnicity, HCC cases younger than 60 years were more likely to be HBsAg carriers than those older than 60. The estimated population attributable risk of HBsAg for HCC, within each ethnic group, was only marginally less than the HBsAg prevalence due to the high relative risk of HBsAg carriage for HCC. The standardized incidence rate ratios of HCC for Maori, Pacific Island people, and Asians compared to Europeans were 9.6, 20.4, and 22.3, respectively. HCC attributable to HBsAg carriage explained 79 percent, 83 percent, and 92 percent of the excess standardized rate for Maori, Pacific Islanders, and Asians, respectively. The authors conclude that their data predict that 75 to 90 percent of the cases of HCC that will occur in the target population (subpopulations of New Zealand) will occur among HBsAg carriers and are therefore potentially detectable by ongoing screening. 5 tables. 28 references. (AA-M).

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Worldwide Immunization Program Targets Hepatitis B and Liver Cancer Source: Journal of the National Cancer Institute. 83(10): 666-668. May 15, 1991. Summary: This article reports on the worldwide immunization program that targets hepatitis B and liver cancer. Three doses of hepatitis B vaccine have been shown to be 95 percent effective in preventing chronic hepatitis B virus (HBV) infection, the cause of over four-fifths of the world's primary liver cancers. The article details the work of the International Task Force on Hepatitis B Immunization, an independent body of health professionals from eight countries that was created in 1986. A major accomplishment of the Task Force has been to foster more international acceptance of the hepatitis B vaccine

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and the concept of universal childhood immunization, even in areas with a relatively low prevalence for HBV, such as the United States. 1 figure. •

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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Treatment of Hepatitis B: Current Practice Source: Comprehensive Therapy. 20(4): 239-243. 1994. Contact: Available from American Society of Contemporary Medicine and Surgery. 233 East Erie Street, Suite 710, Chicago, IL 60611. (800) 621-4002 or (312) 951-1400. Summary: This article reviews current practice for treatment of hepatitis B. Topics include the use of interferon A, an immune modulator; typical chronic hepatitis; acute hepatitis B; mild chronic hepatitis B; decompensated cirrhosis due to hepatitis B; atypical serology in hepatitis B; immunosuppressed hosts with hepatitis B; thymosins; other immune modulators; antivirals, including ara-A and ara-AMP; and other antiviral agents. The author stresses the great strides made in the treatment of chronic hepatitis B. Interferon A is now widely employed and, although far from a perfect treatment, a significant number of patients are benefiting from its availability. 24 references.

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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

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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. •

Hepatitis B: Diagnosis and Treatment Source: Southern Medical Journal. 90(9): 866-870. September 1997. Contact: Available from Southern Medical Association. 35 Lakeshore Drive, Birmingham, AL 35209. (205) 945-1840. Summary: This article reviews the current methods of diagnosis and treatment of hepatitis B virus (HBV) infection. Physicians are now able to accurately diagnose acute and chronic hepatitis infection, though the understanding of viral quantitation and its impact on disease course and treatment response is evolving. The author notes that hepatitis B must now be considered a preventable disease, since acute infection can be effectively prevented by either passive or active immunization. However, when acute infection does occur, it evolves into chronic hepatitis or a chronic infectious carrier state in a variable proportion of cases, depending on the age and underlying immune competence of the patient. Chronic infection can be treated, though the effectiveness of available antiviral and immunomodulatory agents is less than complete. Finally, the author notes that variants of the HBV are being recognized and coinfection with the defective viroid known as hepatitis D has been described. 5 figures. 15 references. (AAM).

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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

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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 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. •

Chronic Hepatitis B: What You Need to Know Source: IM. Internal Medicine. 20(9): 32-34, 44-46. September 1999. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Summary: This article reviews the current thinking regarding the transmission, pathogenesis, diagnosis, prevention, and treatment of hepatitis B virus (HBV). In geographic areas such as the United States, with a low prevalence of HBV infection, sexual contact is the most common mode of transmission of the virus. The illegal use of injection drugs, particularly among those who share unsterilized needles, accounts for 23 percent of cases of HBV transmission in the United States. Health care workers are a recognized HBV risk group because of their exposure to needles, syringes, and other objects contaminated with blood, bodily fluids, or other secretions from infected individuals. The host immune response appears to be more important than viral factors in the pathogenesis of HBV infection. The serologic hallmark of chronic HBV infection is the presence of hepatitis B surface antigen (HBsAg) for a period of more than 6 months. Immunocompromised adults and those who are infected with HBV in early childhood are at 50 percent risk of developing chronic infection. Measures that reduce the risk of exposure to HBV include sexual behavior changes and need exchange programs for injection drug users. Vaccination is now recommended for high risk groups and for all children. The authors discuss treatment options, including postexposure prophylaxis, lamivudine therapy, and other strategies, notably immunomodulator and antiviral drugs. One sidebar briefly reviews the epidemiology of HBV worldwide. 1 figure. 4 tables. 13 references.

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High-Risk Groups for Hepatitis B and Interpretation of the Hepatitis B Profile Source: Hepatitis B Coalition News. 2(3): 5. April 1992. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Summary: This brief article presents a listing of groups at high risk for hepatitis B, noting that most people in these groups should be vaccinated with or without prior testing, depending on individual risk factors. The latter half of the article consists of a chart designed to help the reader understand the hepatitis B profile of diagnostic tests, including HBsAg, anti-HBc, anti-HBs, and HBeAg. For various results of each of these tests, the chart indicates the interpretation and recommendation as per vaccination.

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Brief Introduction to Hepatitis B for Parents of Adopted Children Source: Hepatitis B Coalition News. p. 6. September 1994.

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Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Summary: This brief article provides an overview of hepatitis B. Written to encourage parents of adopted children to have the children tested for hepatitis B, the article addresses hepatitis B infection in general; what tests should be done for children adopted from areas where hepatitis B is common; and what to do if the child is infected with hepatitis B. The article concludes with a list of resource organizations through which parents can obtain additional information. •

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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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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Public's Health Unprotected: Reversing a Decade of Underutilization of Hepatitis B Vaccine (editorial) Source: JAMA. Journal of the American Medical Association. 274(15): 1242-1243. October 18, 1995. Summary: This editorial highlights and praises the progress that has been made in hepatitis B vaccination in the United States, while examining why it takes so long to apply safe, effective, and low-cost preventive modalities to improve public health. The author first reviews a success story in which, in an extremely high incidence area, HBV transmission has all but been eliminated. The author then discusses the findings of two other articles from this issue of the journal that also document advances in this area. The remainder of the editorial focuses on the length of time required to institute an aggressive vaccination program and how leaders in the biomedical, public health, and political arenas must become more cognizant of the need for vaccination programs. The author concludes with a challenge to physicians to help eliminate hepatitis B. 15 references.

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Variants of Hepatitis B Virus Associated with Fulminant Liver Disease Source: New England Journal of Medicine. 324(24): 1737-1739. June 13, 1991. Summary: This editorial, which serves as an introduction for two other articles, considers variants of hepatitis B virus (HBV) that are associated with fulminant liver disease. The author reviews the current literature in this area, with an emphasis on examining the role of host immune responses in the activity and severity of liver disease. The author concludes that the current findings represent a major advance in the understanding of the pathogenesis of fulminant HBV infection and may ultimately lead to new therapeutic strategies to prevent its consequences. 22 references.

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Spring-Loaded Finger-Stick Device Transmits Hepatitis B Source: Hepatitis B Coalition of Minnesota News. 2(3): 3. April 1992. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Summary: This newsletter article summarizes two reports regarding the transmission of hepatitis B with a spring-loaded finger-stick device of the type used by people with diabetes. This article briefly reports on articles in the Morbidity and Mortality Weekly Report and the New England Journal of Medicine, and notes that the Food and Drug Administration is issuing a safety alert concerning the use of all spring-loaded fingerstick devices. The editor notes that many medical offices continue to use these devices when checking hemoglobin and blood glucose levels, and they do not change or sterilize the platforms between patients.

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Is Hepatitis A More Severe in Patients with Chronic Hepatitis B and Other Chronic Liver Diseases? Source: American Journal of Gastroenterology. 90(2): 201-205. February 1995. Summary: This review article analyzes published literature on the clinical course and outcome of acute hepatitis A in patients with chronic hepatitis B virus (HBV) infection and other chronic liver diseases, to determine if hepatitis A is more severe in these patients. The author reviews epidemics and large case series; small case series and case reports; and hepatitis A in other chronic liver diseases. The author concludes that the

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data seem to suggest that acute hepatitis A superimposed on chronic HBV infection is associated with higher peak laboratory abnormalities, more severe disease, including fulminant hepatic failure, and a higher case fatality rate. These conclusions, however, are not supported by all case series or case reports. 1 table. 17 references. (AA-M). •

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 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.

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Interferon in the Management of Chronic Hepatitis B Source: Digestive Diseases and Sciences. 38(4): 577-593. April 1993. Contact: Available from Plenum Publishing Corporation. 233 Spring Street, New York, NY 10013. (800) 221-9369 or (212) 620-8000. Summary: This review article discusses the use of interferon in the management of chronic hepatitis B. The author reviews the importance of chronic hepatitis B as a health problem, as well as the mechanisms of action, benefits, and adverse effects associated with interferon. Particular emphasis is given to the safety and efficacy data for recombinant interferon alfa-2b. The article reviews the magnitude and medical significance of hepatitis B; populations at risk; potential populations for treatment; the immunopathogenesis of chronic hepatitis B and the potential role for interferon; predictors of response and selection of patients; interferon trials; the combination of recombinant interferon alfa-2b with prednisone pretreatment; the adverse affects of interferon; guidelines for monitoring and dose modification; short-term and long-term benefits of therapy; and patient groups for further study. 5 tables. 116 references. (AAM).

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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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Hepatitis B Virus Infection in Asian Americans Source: Gastroenterology Clinics of North America. 23(3): 523-536. September 1994. Contact: Available from W.B. Saunders Company, Periodicals Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 654-2452. Summary: This review article summarizes studies on hepatitis B in the Asian American population. The authors include prevalence rates among different Asian subgroups, routes of transmission, and sequelae of both perinatal and childhood-acquired hepatitis B virus infection. The article also covers the rationale for the use of hepatitis B immune globulin and hepatitis B vaccine for Asian infants, and vaccine for children and seronegative adults. The authors review chronic hepatitis B, cirrhosis, and primary hepatocellular carcinoma in adults and screening for early detection of liver cancer. 4 tables. 48 references. (AA-M).

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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 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

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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.

Federally Funded Research on Hepatitis B The U.S. Government supports a variety of research studies relating to hepatitis B. 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 B. 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 B. The following is typical of the type of information found when searching the CRISP database for hepatitis B: •

Project Title: A RANDOMIZED TRIAL OF VACCINE ADHERENCE IN YOUNG IDU Principal Investigator & Institution: Lum, Paula J.; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): We propose a study to examine strategies to deliver a promising preventive HIV vaccine candidate-employing a surrogate hepatitis B vaccine-to a cohort of high-risk young injection drug users (IDU) and young male IDU that have sex with men (MSM-IDU). We will screen 750 IDU aged 29 or less in San Francisco and over sample MSM-IDU, who have very high rates of HIV seroconversion. We expect that about 50% of those screened will meet eligibility criteria for prospective study and of those, that 80% will enroll. We will follow this cohort of 300 individuals for one year, administering a combined hepatitis A virus (HAV) inactivated and hepatitis B virus (HBV) recombinant vaccine (Twinrix() to study medical management and implementation issues, including: (1) adherence to multi-dose immunization schedules, (2) novel methods to minimize losses to follow-up, and (3) physiologic and behavioral

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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factors that may alter vaccine effectiveness. The primary purpose of the study is to efficiently compare interventions to improve vaccine series adherence. In particular, we propose a randomized trial using a factorial design to compare the effects of clinical setting (syringe exchange program vs. immunization clinic) and outreach worker support (outreach vs. none) in enhancing adherence to a multiple dose immunization schedule. We have three secondary objectives. The first focuses on transience, one of the major causes of attrition in cohort studies of often-homeless IDU and other disenfranchised populations. For subjects who leave San Francisco during the study period, we will use novel technology to map their travel and achieve immunizations remotely. Secondly, we will compare vaccine effectiveness between HCV-infected and uninfected young IDU. We will measure protective antibody levels after immunizations. Finally, given the potential for reduced vaccine effectiveness in the setting of continued high-risk behavior, we will measure changes in behavior and vaccine attitudes. By testing strategies for delivering a multi-dose schedule of hepatitis vaccine and developing models for improving future HIV vaccine adherence and effectiveness, we can advance HIV vaccine development for young adult high-risk injection drug users. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ADJUVANTED DNA VACCINE FOR IMMUNOTHERAPY HIV INFECTION Principal Investigator & Institution: Haynes, Joel R.; Powderject Vaccines, Inc. 585 Science Dr Madison, Wi 53711 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-MAR-2004 Summary: The goal of this program is the optimization and evaluation of an adjuvanted therapeutic DNA vaccine strategy for AIDS using the rhesus monkey/SIV model system. In addition, a graduated clinical evaluation approach is planned to introduce this technology into the clinic in a stepwise manner. The DNA vaccine to be employed will encode the full length gag, pol, and env products of SIV as well as a series of defined CTL epitopes fused to an immunogenic carrier protein. The novelty of our approach centers on the inclusion of an adjuvant vector encoding the A and B subunits of cholera toxin (CT) or the E. coli heat labile enterotoxin (LT) to augment antigenspecific Th1 immunity and systemic and mucosal CTL responses. The adjuvanted DNA vaccine will be formulated onto microscopic gold particles and delivered to the skin as a therapeutic vaccine using a clinical "gene gun" device. Elucidation of the mechanism of adjuvant action will be assisted by the analysis of chemokine involvement and the activation and trafficking of dendritic cells. Justification of the proposed approach is based on three important findings from our laboratories: 1, Human clinical evaluation of a "gene gun"-based DNA vaccine for hepatitis B resulted in the induction of vigorous antigen-specific, Th1 and cytotoxic cellular immune responses in humans, confirming the clinical effectiveness of this means of DNA vaccine delivery. 2, The induction of SIVspecific CTL responses via gene gun-based DNA vaccination in the rhesus/SIV model provides measurable protection from challenge with pathogenic SIVdeltaB670. 3, The formulation of DNA vaccines with vectors encoding eith4r CT or LT results in marked and surprising enhancements of Th1 and CTL responses without any evidence of local or systemic toxicity in small and large animals. Clinical development of the adjuvanted DNA vaccine approach will take place in a graduated manner involving initial evaluation of a single HIV therapeutic DNA vaccine vector in a small phase I/II trial. A second clinical trial attempting to establish clinical proof of concept of the adjuvanted DNA vaccine approach will follow. The later trial will include the addition of a vector encoding CT or LT.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ADULT AIDS CLINICAL TRIALS UNIT Principal Investigator & Institution: Goldman, Mitchell; Medicine; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 01-JAN-2000; Project End 31-DEC-2004 Summary: (adapted from application's abstract): The Indiana University proposes to build upon the following in the renewal application: (1) scientific and administrative contributions. The Indiana ACTU ranks among the top 20 percent of ACTUs scientifically; (2) cost efficient accrual into AACTG trials. Indiana ranked third in cost weighed accrual; and (3) recruitment of women and minorities. The ACTU ranked second in recruitment of African- Americans and third in women. The long-term objectives of this site are to: expand scientific and administrative contributions through recruitment of additional investigators; increase accrual potential for women and minorities by expansion of the Wishard Hospital subunit; and increase the patient base by establishing a subunit at Community Hospital of Indianapolis. The first specific aim of the Indiana University ACTU is to contribute scientifically through submission of concept proposals and memberships on AACTG protocol teams and committees. Currently, Indiana investigators hold 32 positions on protocol teams. Concepts are proposed for: (a) salvage therapy for efavirenz failures; (b) evolution of anal dysplasia and the role of HPV in patients on HAART; (c) the role of gp 120 in HIV induced apoptosis of neurological cells in pathogenesis of dementia; (d) the role of GM-CSF and CD4 ligand on immunity to H. Capsulatum and HIV-1; (e) use of in vitro assays for drug interactions with protease inhibitors; and (f) the role of intestinal metabolism and bioavailability of antiretroviral drugs. The second specific aim is to expand the patient base, including women and minorities, though increased support for subunits at Wishard Hospital and Community Hospital. The work proposed in this application will be implemented through conduct of clinical trials as a member the AACTG, using an infrastructure that has been refined during 12 years as an ACTU. Specialized immunology, virology, and pharmacology laboratories will support this work. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AFB1 AND P53 CARCINOGENESIS IN HBSAG TRANSGENIC MICE Principal Investigator & Institution: Sell, Stewart; Professor; Pathology and Lab Medicine; Albany Medical College of Union Univ Union University Albany, Ny 12208 Timing: Fiscal Year 2001; Project Start 15-DEC-1998; Project End 30-NOV-2002 Summary: The interaction and mechanisms of the major risk factors for human hepatocellular carcinoma (HCC) will be analyzed in an animal model. World- wide HCC is arguable the tumor that causes the highest cancer mortality. HCCs occurring in high-risk areas of the world are associated with hepatitis B(HBV) infection and aflatoxin (AFB1) exposure, and these tumors have a high frequency of mutations in the tumor suppressor gene p53 at codon 249 (p53ser249). In specific Aim 1, the effect of expression of p53, HBV injury and AFB1 exposure on development of pre-neoplastic lesions and HCC development will be studied using F1s of p53 null mice X HBsAg transgenic lineage 50-4 mice. In specific aim 2, the effect of p53 mutation will be determined using a newly established mutant p53ser246 (equivalent to human p53ser249) mouse lineage. In specific aim 3 the mechanisms for effects of loss on p53, p53 mutation and AFB1 exposure on hepatocyte proliferation during carcinogenesis will be examined by analysis of specific cell cycle events and expression or reactivity to liver growth factors.

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In specific aim 4 HCCs arising in this model will be tested for chromosomal changes and cell cycle alterations and related to those in pre-neoplastic livers. These studies should lead to an understanding of how each of these risk factors affect hepatocyte proliferation and how these effects contribute to AFB1 hepatocarcinogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTIGEN SPECIFIC MODULATION OF T CELL RESPONSES Principal Investigator & Institution: Schneck, Jonathan P.; Associate Professor; Pathology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: Using Ig as a molecular scaffold, we have developed a general approach to making soluble divalent analogs of MHC class I and II molecules (MHC-I/Ig and MHCII/Ig). The divalent nature of these molecules effectively increased the affinity of these analogs for their cognate ligands, antigen specific T cells. Peptide loaded divalent high affinity MHC analogs (pepMHC/Ig) can be used to directly visualize antigen specific T cells by flow cytometry. The goals of the current application are to selectively modulate and monitor antigen-specific T cell responses in murine models using pepMHC/Ig complexes. Our first specific aim will focus on defining the mechanism of in vitro CTL modulation by pepMHC-I/Ig complexes. We will determine if pepMHC/Ig complexes inhibit 2C CTL by competitive inhibition, induction of anergy, or induction of apoptosis. The second specific aim will analyze the effects of pepMHC-I/Ig complexes on T cells in vivo using two model systems: peptide- specific 2C CTL and a Hepatitis B specific CTL, 6C2. The influence of pepMHC-I/Ig on both trafficking and modulation of CTL responses in vivo will be defined. Initial experiments will be aimed at optimizing platform development for homogeneously loading MHC-I/Ig complexes with the peptides of interest. Trafficking studies on 2C CTL will be studied using B6 animals injected with P815 tumor cells and suppression will be studied in a 2C-mediated model of diabetes. We will analyze the effects of HepBLd/Ig on Hepatitis B specific CTL by characterizing the ability of HepBLd/Ig complexes to: bind to HepB specific CTL, inhibit HepB specific CTL mediated lysis of target cells in vitro, and modulate hepatocellular necrosis in HBsAg transgenic mice injected with 6C2, HepB specific CTL in vivo. Should the direct modulation of specific CTL in vivo prove ineffective, the ability of pepMHC-I/Ig coupled to a fungal toxin, ricin, to specifically kill T cells in vitro and in vivo will be analyzed. To analyze the ability of pepMHC/Ig complexes to selectively regulate class II-restricted immune responses, we will study the ability of pepMHC-II/Ig compounds to modulate class II-restricted, immune responses. The model system to be analyzed will be the effects of MCCI-Ek/Ig on cytochrome-specific immune responses. Analysis of the effects of soluble divalent class II MHC molecules will reveal several interesting and unique features about regulation of class II-restricted immune responses. The first part of this specific aim we will analayze modulation of in vitro immune responses by MHC-II/Ig complexes and also address the ability of soluble divalent analogs of peptide antagonists complexed to the I-Ek/Ig molecule to modulate in vitro immune responses. In the second part of this specific aim we will study the ability of MHC-II/Ig complexes to modulate in vivo immune responses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ANTIVIRALS AGAINST HBV Principal Investigator & Institution: Otto, Michael J.; Pharmasset, Inc. 1860 Montreal Rd Tucker, Ga 30084

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Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant): The global magnitude of hepatitis B viral (HBV) infection warrants development of efficient treatment strategies to combat the virus. These treatment protocols will also aid in minimizing the protracted long-term effects of HBV infection namely cirrhosis and hepatocellular carcinoma. The short-term benefits of the currently available treatment protocols are greatly offset by the emergence of the resistant phenotype in the case of Lamivudine therapy and adverse side effects in the case of alpha-interferon. As a consequence of this, the goal of maintaining low viral loads cannot be achieved. The generation of a panel of potent antivirals against HBV would be a valuable addition to existing treatments. Novel combinations of anti-HBV drugs would greatly minimize the chances of development of resistance and provide sustained reduction in viral loads. A number of 2'-fluoro-2',3'-unsaturated D- and Lnucleosides (2'-F-D4N) showed potent anti-HBV activity with no appreciable toxicity in a number of cell lines. These compounds also demonstrated anti-HIV activity in vitro. In the proposed Phase I study, these compounds will be further characterized with respect to their anti-HBV activity in combination treatments, mechanisms of action, mitochondrial toxicity, and efficacy of inhibition of HBV viral polymerase. Crossresistance of these active nucleosides against the Lamivudine-resistant mutants will be determined. Pharmacokinetics of molecules with antiviral activity and no appreciable cellular and mitochondrial toxicity will be conducted. At the conclusion of the Phase I study, it should be possible to identify one or two best candidate molecules for detailed studies in animal models, preclinical studies and further development. Detailed studies for phase II studies which will include in vivo efficacy and sub chronic toxicology of the compounds. PROPOSED COMMERCIAL APPLICATION: There is an urgent need for therapies for the treatment and management of HBV worldwide. Limited success of the Lamivudine monotherapy and development of clinical resistance to Lamivudine have made the researchers as well as clinicians aware of the fact that alternate modalities of treatment have to be in place to tackle HBV infections successfully. Novel anti-HBV agents, hence, would have a much broader market as new combinations of drugs can be formulated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLIN. & HISTOLOGIC SPECTRUM OF HCV LIVER DISEASE IN IDU Principal Investigator & Institution: Edlin, Brian R.; Associate Professor of Medicine and Publ; Family and Community Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2002 Summary: Injection drug users (IDUs) have the highest hepatitis C (HCV) infection rates of any risk group in the United States; fully 70-96 percent of IDUs have been infected. Natural history studies of transfusion recipients have suggested that HCV infection represents a slowly progressive disease culminating in cirrhosis and liver cancer after decades. But while active IDUs represent the largest single group of persons infected with HCV, there are no studies to date describing the prevalence and severity of HCVrelated liver disease among street-recruited, actively injecting IDUs. Because most IDUs acquired HCV when they began injecting decades ago, many are at imminent risk for life-threatening complications. We propose a cross-sectional study of 1000 active, streetrecruited IDUs who test positive for HCV antibody in the Urban Health Study's ongoing program of HIV and hepatitis testing in inner-city neighborhoods in San Francisco. Indepth epidemiological, clinical and laboratory evaluations of HCV-positive participants will be conducted to assess signs, symptoms, and correlates of liver disease. A subset of

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200 HCV-positive participants will undergo liver biopsies. Specifically, this study aims to: 1) to describe the clinical and laboratory spectrum of HCV-related liver disease among 1000 active, street-recruited IDUs in San Francisco, 2) to determine the correlates of advanced liver disease among active IDUs, including demographic factors, injection and other behaviors, comorbidities, and viral markers. Advanced liver disease will be defined as Child-Pugh score B or greater, 3) to describe the histologic spectrum of HCVrelated liver disease in a subset of 200 active IDUs who will undergo liver biopsy, and 4) to determine the correlates of progressive liver disease among the 200 IDUs who undergo biopsy. Progressive liver disease will be defined as fibrosis stage 3 or 4 on liver biopsy. In addition, contact information will be collected so that this cross-sectional study can serve as a baseline for future cohorts to examine the incidence of clinical and histological disease in this cohort. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLINICAL AND CELLULAR EFFECTS OF INTERFERON ALFA 1 Principal Investigator & Institution: Borden, Ernest C.; Director; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: Using a preparation that was in limited supply, we previously assessed Interferon-alpha 1 (IFN-alpha 1) clinically in a randomized, double blind comparison to IFN-alpha 2. The frequency of side effects was much less with IFN-alpha1 (p less than 0,01). Yet effects of IFN-alpha 1 on granulocyte counts, NK cell cytotoxicity, and an ISG were comparable to IFN-alpha2. These findings suggest that IFN-alpha 1 might be given with better tolerance and or higher doses than IFN-alpha 2. Recombinant DNA produced IFN-alpha 1 has now come available in adequate supply through a collaboration with the Ministry of Public Health in Shanghai. In randomized, multicenter clinical trials in China, IFN-alpha 1 has proven effective for chronic hepatitis B and C. Data from China also suggests IFN-alpha 1 is better tolerated than IFN-alpha 2. IFN-alpha 1, together with IFN-alpha 2, is a predominant IFN-alpha species generally characteristic of an IFN. However, IFN-alpha 1 has differing receptor binding affinities and differing cross species antiviral activity differences in the transcription factor complexes activated in response to IFN-alpha 1 as compared to IFN-alpha 2. In addition to expected IFN antiproliferative and gene stimulatory (ISG) effects, we have also identified an increase in STAT1 protein expression and induction of apoptosis in myeloma cells by IFN-alpha 1. Studies of IFN-alpha have been designed with the following goals: a) confirm good clinical tolerance and define the dose response characteristics of ISG induction in patients, b) compare the signal transducing and gene modulatory activity to those of IFN-alpha 2 by oligonucleotide gene array and assessment of transcription activating factors, c) study apoptosis and gene induction in myeloma and renal carcinoma to confirm clinical antitumor activity. Since expanded clinical use of IFN- alpha 2 has increasingly been limited by side effects, IFN-alpha 1 may be particularly important in extending clinical leads provided by LFN-alpha 2. Finally, results will further confirm the postulate that antiviral specific activity in vitro does not predict for other biological and clinical effects of IFN. In addition, if the pattern of novel gene induction and cellular effects are expanded, IFN-alpha 1 could have a broader spectrum of responsive clinical tumor types. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CLINICAL TRIAL OF SHORT COURSE VS. INH FOR LTBI IN JAIL Principal Investigator & Institution: White, Mary C.; Community Health Systems; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Tuberculosis (TB) in incarcerated populations is a serious problem, due to the large proportion of inmates who are at high risk of having latent tuberculosis infection (LTBI) and developing active disease. Completion of treatment of LTBI has not been successful in jails, mainly because inmates are frequently released before finishing a 6-9 month course of standard therapy with daily isoniazid (INH), and because they have low rates of completing therapy in the community. Effective treatment of LTBI is complicated by length of therapy and toxicity of the drugs used against L TBI. Short-course therapies for LTBI may address this problem but they have not been studied adequately to answer questions about side effects, completion rates, and overall cost. We propose a two arm, open label randomized trial to test the effects of a short-course therapy for LTBI in jailed inmates; rifampin given daily for 4 months as compared to INH given twice weekly for 9 months. A sample of 972 consented and enrolled participants will be administered directly observed therapy (DOT) in jail. The study protocol includes links to the TB Clinic for post-release DOT, and close clinical and laboratory monitoring throughout the course of therapy. Participants will be followed, in jail and after release, for one year after enrollment, to measure three outcomes: toxicity, adherence, and cost-effectiveness. Toxicity leading to stopping drug will be analyzed by study group, and other predictors will be examined, such as age, alcohol use and hepatitis B and C. Adherence, measured by completion of therapy, will be compared by study group, and other predictors will be examined, including sociodemographic variables, intent to adhere, and stability of housing. Costeffectiveness will be compared by study group and will be calculated using direct costs of administering and monitoring care and costs of re-starting care in this population with a high rate of re-arrest, measured against the cost of prevented cases of TB. Short course regimens are promising in the inmate population to treat LTBI and eliminate risk of progression to active disease. This study will answer questions about the safety of rifampin compared directly to INH. Analysis of completion of therapy and costeffectiveness of this regimen will provide important information for policy change in the way L TBI is managed in jail. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COST-EFFECTIVE SCREENING IN INTERNATIONAL ADOPTEES Principal Investigator & Institution: Mandalakas, Anna M.; Pediatrics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 04-SEP-2001; Project End 30-JUN-2006 Summary: (provided by applicant): The candidate is a junior academic clinician, trained in pediatrics and epidemiology, whose long-term career goals are to conduct patient oriented research that will improve health care delivery to vulnerable children in the US and in the developing world. The proposed training program was designed to enable the candidate to transition from novice to independent researcher in epidemiology with expertise in international child heath. The specific objectives are to obtain maundered practical experience in patient oriented research and rigorous methodological training in decision analytic methods with an experienced team of mentors and national experts. The training plan describes activities (advanced degree coursework, independent study and patient oriented research) focused on further developing skills in epidemiology

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with immediate applications to cost- effective screening in internationally adopted (IA) children. Two complementary studies are proposed that address the clinical and costeffectiveness of hepatitis B virus (HBV) and tuberculosis (TB) screening in IA children. These studies are based on the hypothesis that focused, rational screening can provide a cost-effective means for improving the long-term health outcomes of immigrant children and is consonant with public health imperatives. Each study involves primary collection of new data that address important gaps regarding the prevalence and risk factors for infectious diseases in IA children, and the utility of markers (skin tests and immunization history) to predict infection, disease or protective immunity. This will provide new information regarding the infectious disease burden, and its expression, in the growing group of IA children in the US. These new data also will provide estimates necessary for cost-effectiveness analyses that will be developed to assess the utility of alternative approaches for immunization and TB screening. The proposal addresses important knowledge gaps about the health of children immigrating to the US from resource-poor environments and may provide important new data for rational and costeffective screening in IA children. The cohort of children developed in this proposal may be followed in future research designed to answer challenging questions with respect to the long-term impact of early screening and preventive TB therapy. Finally, the proposal will provide a key training opportunity to foster the candidate s career development as an epidemiologist with a commitment to patient oriented research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COUPLES HIV INTERVENTION RANDOMIZED CONTROLLED TRIAL Principal Investigator & Institution: Mcmahon, James M.; National Development & Res Institutes Research Institutes, Inc. New York, Ny 10010 Timing: Fiscal Year 2003; Project Start 26-SEP-2003; Project End 30-JUN-2007 Summary: The broad, long-term objective of the proposed research is to establish primary preventive interventions to reduce human immunodeficiency virus (HIV) risk behavior among drug-using minority women. Recent studies indicate that high rates of sexual risk behavior occur within drug-using minority women's primary heterosexual relationships. Based on an integrated theory of HIV risk behavior, it is predicted that a) interventions administered to couples rather than to women only, and b) interventions that focus on relationship dynamics in the context of HIV risk, will result in a reduction of sexual risk behavior among drug-using women and their primary partners. This fouryear study will employ a randomized controlled trial (RCT) 3-group design to test the efficacy of HIV intervention modality (couples versus women-only) and intervention content (relationship-focused versus standard HIV counseling and testing) on crack, cocaine and heroine (injected and noninjected) using women's sexual risk with primary partners. A total of 390 women drug-users and their partners will be recruited from the streets of East Harlem, New York City. Participants will be randomly assigned to one of three HIV intervention conditions: a) couples, relationship-focused; b) women-only, relationship-focused; or, c) women-only standard HIV-CT (control). All subjects will be administered baseline, 3-month, and 9-month follow-up assessments using a combination of computerassisted personal interview (CAPI) and computer-assisted self interview (CASI) techniques. In addition to sociodemographic characteristics, the interview will measure drug-use patterns, HIV risk behavior, and dyadic- and individual-level variables operationalized to test specific hypotheses of women's HIV risk behavior and behavior change. In addition to testing the effectiveness of the experimental interventions, data analyses will determine the theory-driven psychosocial

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mechanisms that act to mediate and moderate any observed association between intervention treatment and subsequent risk reduction. Incremental cost-effectiveness analyses will also be performed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIETARY FACTORS IN THE ETIOLOGY OF CANCER IN SHANGHAI Principal Investigator & Institution: Ross, Ronald K.; Professor; Preventive Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2001; Project Start 01-APR-1987; Project End 30-JUN-2002 Summary: (Adapted from the Applicant's Abstract): We are requesting continued support for an ongoing cohort study of 18,244 men, ages 45-64, living in a geographically defined area of metropolitan Shanghai, Peoples Republic of China. All cohort members have completed detailed diet and medical histories and have blood and urine samples. Questionnaires have been edited and computerized and blood and urine samples have been processed, aliquoted, and continuously stored at both -20_C and 70_C. The cohort was fully established in 1989. Follow-up of the cohort is proceeding through cancer registration by the population-based Shanghai Cancer Registry, by routine ascertainment of death certificates, and by annual recontact of all cohort members. As of March 1994, 606 have developed cancer and 989 have died. The leading cancers include lung, stomach, liver, and colorectal cancers, while stroke is the number one cause of death. Major accomplishments achieved through this cohort to date include: (1) the first direct evidence linking aflatoxin ingestion to human hepatocellular carcinoma (HCC); (2) strong evidence of synergy between aflatoxin biomarkers and chronic infection with hepatitis B virus in establishing risk of HCC; (3) failure to find an association between H. pylori serology and stomach cancer risk; (4) the absence of an inverse association between antioxidants and fatal stroke; and (5) the first comprehensive and systematic evaluations of smoking-related cancer incidence and mortality in China. We propose to continue to follow this cohort for an additional five years. We will continue to evaluate risk factors for major health outcomes in the cohort, building on previous observations and continuing to exploit the serum and urine banks available for biomarker studies. Although we did not collect buffy coats for genetic studies on cohort members, we have demonstrated that the stored serum samples contain sufficient cells for conducting selected PCR-based genetic studies. Among the scientific goals for the next five years are: (1) to continue to evaluate the aflatoxin/HCC association and to assess the impact of sequence variations in genes involved in aflatoxin metabolism (GSTM1 and EPHX) in modifying risk; (2) to continue to assess the role of H. pylori in gastric cancer etiology in Shanghai, and to assess the possible protective effect of tea polyphenols on risk; and (3) to better understand the complex interrelationships among carotenoids, smoking, and lung cancer and to assess the possible risk modifying impact of genes involved in metabolism of smoking-related carcinogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ELECTROCHEMICAL ENZYME IMMUNOASSAY TO TEST BLOOD HBV Principal Investigator & Institution: Henkens, Robert W.; Alderon Biosciences, Inc. 2810 Meridian Pky, Ste 152 Durham, Nc 27713 Timing: Fiscal Year 2001; Project Start 15-APR-2000; Project End 30-JUN-2003

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Summary: (provided by applicant):Millions of Americans are infected by the hepatitis B virus (HBV)-many of whom have no reason to believe they are infected. There is a need to track down America's millions of HBV victims-as well as a corresponding need for innovative technology to test blood for HBV. HBV is clearly a national medical priority. The overall goal of this project is to further develop and then integrate core sensor and enzyme immunoassay technologies into a novel technique for the rapid and accurate measurement of HBV levels in blood. We are targeting diagnostic (detection) applications as well as quantitative measurement needs (to monitor viral levels and treatment efficacy). The feasibility of our approach was clearly demonstrated during Phase I. The Phase II goal is to demonstrate/validate/optimize the integration of a unique electrochemical measurement method with proprietary electrochemical enzyme immunoassay architecture to produce a new diagnostic/monitoring capability for "real time," cost-effective HBV assessment in an outpatient setting. The product we envision is a disposable HBV test strip that can be read by an inexpensive, small (hand-held) instrument. It would represent a key development in medical diagnostics that would address major domestic and international market needs for low-cost HBV screening and monitoring. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENHANCED T AND B CELL RESPONSES VIA RECOMBINANT PROTEINS Principal Investigator & Institution: Gosselin, Edmund; Assistant Member; Alld Health Education Programs; Albany Medical College of Union Univ Union University Albany, Ny 12208 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2004 Summary: (Adapted from Applicant's Abstract) A safe and successful vaccine against HIV will likely require the simultaneous priming of both cellular and humoral immune responses, and will preferentially involve the use of recombinant proteins. Targeting immunogens to Fc gamma receptor type I (FcgRI) on antigen presenting cells (APC) significantly enhances T cell activation in vitro, and antibody production in vivo. In addition, it can also lead to simultaneous priming of both cytotoxic and helper T cell responses. Furthermore, by combining the administration of antigen with cytokines, T cell activation can be further enhanced, and T cell subset development modulated. It has also been demonstrated that targeting antigen (Ag) to FcgRI on APC can eliminate the need for traditional adjuvant, easing difficulties associated with vaccine preparation and distribution. Therefore, developing a strategy which facilitates antigen targeting to APC, and the use of cytokines in vaccines, is likely to have a significant impact on current vaccine technology, in particular as it applies to HIV. We propose to utilize molecular techniques, and FcgRI-specific constructs, to create and test the ability of a prototype two component (modular) immune targeting system to stimulate enhanced humoral, CD4 helper T cell, and CD8 cytotoxic T cell responses in vitro and in vivo. Components will consist of a humanized divalent FcgRI-specific biotin-binding targeting element, and biotinylated functional elements including Hepatitis B Ag, gp120 Ag, and IL-2. The ability of the two component immunogens to modulate human CD4 and CD8 T cell responses in vitro, and murine B cell, CD4 T cell, and CD8 T cell responses in vivo, will be examined. In the latter instance, transgenic mice that express human FcgRI will be immunized with two component immunogens. Following immunization, CD4 and CD8 T cell responses, as well as the generation of Ag-specific antibody will be measured. These studies will provide a novel and safe approach for simultaneously priming humoral and cellular responses in vivo using recombinant proteins. This approach will

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not only provide an effective means for controlling the spread of HIV, but many other infectious organisms as well. 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 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

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Project Title: GROWTH HEPATOCYTES

CONTROL

OF

NORMAL

AND

CIRRHOTIC

Principal Investigator & Institution: Behrns, Kevin E.; Associate Professor of Surgery; Surgery; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Hepatocytes are unique parenchymal cells that divide and regenerate the liver in response to major injury. This regenerative capacity, however, leads to disordered hepatocyte growth in the chronically injured, cirrhotic liver. Hepatocytes in the cirrhotic liver respond differently to growth control signals. Most hepatocellular carcinomas arise in a cirrhotic liver, providing evidence that cirrhotic hepatocytes have altered growth control behavior. Cirrhosis is a major worldwide health problem that is expected to increase in prevalence because of

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increasing alcohol abuse and dissemination of the hepatitis B and C viruses, all major causes of cirrhosis. In an earlier proposal (K08), we hypothesized that cirrhotic hepatocytes would be less sensitive to apoptosis. Indeed, studies confirmed that cirrhotic hepatocytes are less responsive to multiple apoptotic agents including tumor necrosis factor a (TNFalpha), transforming growth factor beta (TGFbeta), and ultraviolet-C irradiation (UV-C). The resistance to TGFbeta-induced apoptosis is of special interest because this cytokine is a known inhibitor of hepatocyte growth, and it is present in high concentrations in the cirrhotic liver. The mechanisms by which TGFR induces hepatocyte apoptosis are not well known, but our studies in primary normal mouse hepatocytes suggest that this occurs through a caspase-8 dependent mechanism that requires the generation of reactive oxygen species, depolarization of the mitochondria with cytochrome c release, and caspase-3 activation. This is the first demonstration of caspase-8 dependence. The mechanisms that inhibit this pathway in cirrhotic hepatocytes are unknown, but may involve other TGFR-activated pathways such as the Smad signaling pathway. We hypothesize that the Smad signaling pathway is necessary for hepatocyte apoptosis, and that defects in this pathway are present in cirrhotic hepatocytes. Alterations in the Smad signaling pathway may alter pro- or antiapoptotic factors that govern the cellular balance between survival and death. In this proposal, we aim to determine if the Smad signal transduction pathway is necessary for TGFbeta-induced hepatocyte apoptosis. In addition, because cirrhotic hepatocytes exhibit resistance to apoptosis that may be due to changes in expression of pro-and antiapoptotic factors, we hypothesize that normal and cirrhotic hepatocytes differ in their gene expression profiles. We propose to identify and characterize differences in gene expression profiles between normal and cirrhotic hepatocytes in response to apoptotic stimuli. Examination of these hypotheses will allow our laboratory to growth both in depth and in breadth, because we will use new microarray technology provided within the UNC Genomics Core and Microarray Facility. We will continue to seek counsel from our K08 mentors (Drs. David Brenner and Lola Reid) and use liberally the UNC Center for Gastrointestinal Biology and Disease for core facilities such as the Molecular Imaging Core. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HAWAII ACTU - ADULT THERAPEUTIC CLINICAL TRIALS PROGRAM Principal Investigator & Institution: Shikuma, Cecilia M.; Associate Professor of Medicine; Family Practice & Cmty Health; University of Hawaii at Manoa Honolulu, Hi 96822 Timing: Fiscal Year 2001; Project Start 01-JAN-1996; Project End 31-DEC-2004 Summary: (adapted from the application's abstract): The HACTU is part of the HIV clinical research arm of the University of Hawaii's program in Retrovirology. The HACTU has been a formal unit of the AACTG since 1990 with funding received under a minority institution initiative. The site brings to the AACTG: (1) an established clinical trials unit within the AACTG with a record in clinical trial management, currently meeting all ACTG standards for site operations; (2) access to Hawaii's ethnically diverse population, having previously contributed 41 percent of all ACTG's enrollees of Asian/Pacific Islander descent; (3) a unit with wide community, state governmental and university support for its operations as the only HIV/AIDS clinical research program in Hawaii; (4) a continued commitment to participate as broadly as feasible not only in AACTG's main antiretroviral trials but also in specialized areas of HIV immunology and complication research targeted at areas of special importance by the AACTG leadership;

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Hepatitis B

and (5) a minority unit with a record of increasing scientific contributions to the ACTG over the past five years and a commitment to contribute to the AACTG's scientific agenda in the next five years. The areas of pathogenesis/treatment of HIV/Hepatitis B and C co-infection; HIV-associated interest include metabolic complications; role of insertional mutagenesis and macrophages in the pathogenesis of HIV- associated malignancies; central nervous system (CNS) disease; and the impact of menopause and female replacement hormonal therapy on HIV-1 activity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HBV DIPSTICK FOR RESOURCE-LIMITED BLOOD BANKS Principal Investigator & Institution: Lee, Helen H.; Diagnostics for the Real World, Ltd 50 Mounds Rd, Unit 512 San Mateo, Ca 94402 Timing: Fiscal Year 2002; Project Start 16-SEP-2002; Project End 31-AUG-2003 Summary: (provided by applicant): According to WHO statistics on blood safety, 80 percent of the world's population has access to 20 percent of the world's safe blood supply. However, more than 20 percent (13,000,000 units) of the world blood supply is not tested for the three major transfusion-transmissible infections: HIV, HBV and HCV. Transfusion of unsafe blood accounts for 8-16 million hepatitis B virus infections. If inexpensive, rapid, improved dipsticks with sensitivity comparable to EIA were developed for blood screening, it would greatly improve the safety of the blood supply in developing countries.The overall aim of the project is to develop a HBsAg dipstick assay with high sensitivity, designated as the reflex diagnostic. The test can be used in developed countries under circumstances where an immediate result is required. For the developing countries, we propose that this test be integrated into a triplex test (HBV, HIV & HCV) and used as the initial step of pre-donation screening in high prevalence countries. The associated second step is to use the HBsAg reflex diagnostic test in order to identify the agent responsible for the positive Triplex test result.The specific aims of Phase I are to optimize the reagents in order to produce a prototype with sub-nanogram sensitivity and to evaluate the assay in 50 HBV-positive samples. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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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 •

Project Title: HBV PREVENTION FOR HOMELESS AT-RISK FOR HBV/HCV/HIV Principal Investigator & Institution: Nyamathi, Adeline M.; Professor and Associate Dean; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Nationwide, homeless populations are at risk for HIV infection due to disproportionate use of injection drugs, unprotected sexual activity, prostitution and victimization. Infection with the Hepatitis B Virus (HBV) and the Hepatitis C Virus (HCV) is high among homeless adults as they share risk factors with HIV. Hepatitis A Virus (HAV) is also high among populations vulnerable to HBV, HCV, and HIV as modes of transmission for HAV overlap with those of HBV, HCV, and HIV. Thus, education and screening programs for HAV, HBV, HCV, and HW, combined with vaccination programs for HAV and HBV, can significantly decrease Hepatitisrelated morbidity and mortality. However, homeless persons, many of whom may be contending with drug and alcohol abuse and unemployment, and live in a disorganized world with little access to health and social services, are often non-compliant. In this prospective two group quasi-experimental design, we will evaluate with approximately 1000 sheltered men and women in the Skid Row area of Los Angeles, the effectiveness of a theoretically-based HAV/HBV vaccination intervention focused primarily on completion of the combined Twinrix HAV/HBV vaccination series and secondarily on risk reduction of HAV, HBV, HCV, and HIV. We will also collect data on the relative cost of each of these programs in terms of completion of HAV/HBV vaccination, the cost effectiveness of improving vaccination completion, the cost per sero-protected case, and the cost per infection prevented. Once determined eligible, participants will be randomized by shelter into one of two programs: a Nurse Case Managed Plus Incentive and Tracking (NCMIT) program and a Standard Plus Incentive and Tracking (SIT) program. The proposed study is innovative in that the comparison of the SIT and NCMIT programs will allow us to look at the effect of a standard intervention combining brief education, incentives and tracking with that of a similar intervention that also includes nurse case management on completion of the HAV/HBV vaccination. Participants in the two programs will receive the 3-series vaccination by trained research nurses at the study clinic over six months, along with either the NCMIT, or the SIT program. All participants will be assessed at baseline and six- and twelve-month followup using a battery of psychosocial, behavioral, health and physical status, as well as HAV, HBV, HCV, and HIV sero-status measurements. This proposed study supports the National Drug Abuse Research Initiative as it is focused on assessing the effectiveness of intervention programs promoting the prevention of medical consequences of HAB, HBV, HCV, and HIV in homeless and drug abusing populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

46

Hepatitis B

•

Project Title: HBV, HCV, CMV & HHV-8 IN HIV POSITIVE WOMEN IN THAILAND Principal Investigator & Institution: Lallemant, Marc J.; Immunology/Infections Diseases; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-JUL-2003 Summary: (adapted from abstract) The Harvard School of Public Health's Perinatal HIV Prevention Trial, Thailand study (PHPT) and Thailand's recently established National Data Center for AIDS Vaccine Development (NDCAVD) at Mahidol University's Institute for Population and Social Research have combined efforts to strengthen Thailand's research capacity in the areas of data management and statistics within the context of clinical trials. The specific aims of this proposal are to investigate the epidemiology of four viral infections -- Hepatitis B (HBV), Hepatitis C (HCV), Cytomegalovirus (CMV), and Human Herpes Virus-8 (HHV-8) -- in relation to HIV among a large representative sample of pregnant Thai women. These viruses were chosen for their public health importance or their theoretical/known associations with HIV. This study plans to: 1) determine the seroprevalence of each infection and associated risk factors in HIV+ and HIV- pregnant women; 2) determine the rates of transmission of these viruses and risk factors for transmission in HIV+ women who are not breast feeding; 3) explore the relationship of perinatal HIV transmission to these other viruses; and 4) determine whether co-infection by these viruses are prognostic risk factors for progression of HIV disease in mothers and children. The sera from 35,000 women screened for HIV within the PHPT are available for testing. All HIV-positive women, as well as a randomly selected group of HIV-negative (stratified by urban/rural residence and age), will be screened for these four viruses. All infants born to coinfected (HIV and another virus) mothers will also be tested for the corresponding virus. Sociodemographic and behavioral data from all women, the HIV status of the infants and progression data from HIV-infected children are available from the PHPT. NDCAVD will perform all necessary data management and collaborate in the analysis and interpretation. As a retrospective substudy, this project will provide appropriate training for NDCAVD researchers in the data management of clinical trials, as well as answer some important questions regarding the association of these viruses with HIV and perinatal transmission. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HCV GENOMIC VARIABILITY IN HIV INFECTED HEMOPHILIACS Principal Investigator & Institution: Sherman, Kenneth E.; Associate Professor; Internal Medicine; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2005 Summary: Hemophiliacs with symptomatic disease are multiply exposed to blood products including factor concentrates to correct the Internet clotting factor deficiencies. Prior to routine use of heat inactivation and screening of donor blood for specific viral pathogens, hemophilia patients were routinely exposed to, and infected with, viruses such as hepatitis B (HBV), hepatitis C (HCV) and human immunodeficiency virus (HIV). Cohort studies in hemophiliacs suggest several clinically and scientifically important findings that warrant further detailed investigation including; a) Liver disease progression may be altered in hemophiliacs infected with HCV with more rapid progression to liver failure and death; b) The source of infection from large pools of concentrate that were potentially infected by multiple discreet donors leads to a high

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risks of mixed infection represented by both genotype and quasi species heterogeneity; c) The HIV coinfected hemophiliacs may have different clinical outcomes and an altered immune response may facilitate our understanding of the underlying process of mutant virus selection, and the associated clinical outcomes. The overall goals of this proposal include the study and characterization of the genomic RNA of HCV in infected hemophilic patients with and without confection with HIV. In the retrospective Phase 1, we utilize the NCI Multi center Hemophiliac Cohort Study serum bank database to study the relationship between progression to decompensated liver disease and quasi species variability in the viral envelope hyper variable and core domain. Heteroduplex analysis will be used to rapidly screen samples from index patients and matched controls using samples longitudinally collected over a 10 year or longer period of time. Peptides will be produced from unique quasi species and these peptides will be evaluated for their function as CTL epitomes. Phase 2 involves the initiation and performance of a clinical intervention trial designed to determine variable kinetic response rates to PEG-interferon+ribavirin between hemophiliacs with HCV alone vs HCV/HIV coinfected subjects. Quasi species populations will be modified/cloned, sequencing will be performed to generate families of closely related core peptides that will be studied for their ability to bind and stimulate an immune response. Treatment nonresponders will be followed in a prospective cohort study for up to 3 additional years so that the evolution of the virus, and its associated immune response in this group can be evaluated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HCV IN ALCOHOLICS Principal Investigator & Institution: Wands, Jack R.; Professor of Medicine; Rhode Island Hospital (Providence, Ri) Providence, Ri 02903 Timing: Fiscal Year 2003; Project Start 01-DEC-1993; Project End 30-JUN-2007 Summary: (provided by applicant): Chronic hepatitis C (HCV) infections are common in alcoholics with or without liver disease contributing to significant morbidity and mortality. The reasons for high rates of persistent viral hepatitis infection are unknown but may partially relate to the effects of alcohol on the humoral and cellular immune response to viral structural and nonstructural proteins. We established an animal model system of HCV specific antibody stimulation, CD4+ proliferative response, and CD8+ CTL activity in the context of genetic immunization to test this hypothesis. We plan to do the following: Specific Aim #1 - Further establish the differential effects of ethanol on the immune response(s) to HCV structural and nonstructural proteins in the context of genetic immunization with respect to: a. Assess variations in CD4+ T cell proliferative activity particularly against HCV core, NS3, NS3 helicase, NS4, NS5A and NS5B proteins. b. Evaluate Th1 and Th2 responses to determine if ethanol consumption shifts the immune response from the Th1 to Th2 phenotype. c. Characterize CD8+ CTL precursor frequency and function including possible differential effects of ethanol at the epitope level. d. Examine CTL activity in vivo against HCV derived peptides using an animal model of tumor growth. e. Determine the duration and reversibility of ethanol effects on CD4+ and CD8+ T-cell responses by crossover feeding studies with an isocaloric control diet. Specific Aim #2 - Develop approaches to augment and/or amplify humoral and cellular immune responses generated by DNA immunization in the setting of chronic ethanol administration, a. Explore whether systemic administration (murine and human IFN-a2, or pegylated IFN- a2) is more effective than local administration of cytokine expression construct (IL-2, GM-CSF, IL-12) at the site of gene delivery with respect to augmentation of the humoral and cellular immune

48

Hepatitis B

response(s) to HCV structural/nonstructural proteins. b. Determine the value of coimmunization with CpG motifs as an enhancer of the host B and T cell immune responses. c. Employ chimeric constructs to assess their possible role as a stimulant of virus specific B and T cell activities. Thus, principle long term goals of this application are to develop: a clinical DNA vaccine approach, effective alone or in combination with other antiviral agents (IFN-2a, etc.), to enhance the host immune response in an attempt to eradicate persistent viral infection from the liver in alcoholics; and obtain a clearer understanding of ethanol's effects on the immune response to HCV structural and nonstructural proteins in an experimental animal model system thereby generating principles applicable to chronic alcoholics 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 B SUBUNIT ORAL VACCINE IN TRANSGENIC PLANTS Principal Investigator & Institution: Thanavala, Yasmin; Professor; Roswell Park Cancer Institute Corp Buffalo, Ny 14263 Timing: Fiscal Year 2003; Project Start 30-SEP-1998; Project End 30-NOV-2007

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Summary: (provided by applicant): The proposal describes a series of experiments designed to target and track antigen following oral delivery via edible transgenic plants. The overall objective is to enhance both systemic and mucosal immune responses to orally delivered antigen. During the previous grant period we have demonstrated that mice fed potatoes expressing HBsAg make both primary and secondary antibodies responses in serum and anti-HBs IgA responses in mucosal secretions. We have provided transmission electron microscopic evidence that the transgenic potato cells harbored unusual membrane-bound bodies that contained circular structures that are approximately 17 nm in diameter. These structures are very similar to the virus-like particles (VLP) found in the serum samples of HBV infected patients and the distended ER vesicles are similar to those produced in yeast expressing HBsAg. These images provide the first ever evidence that in transgenic plants antigen is refined within vesicular structures. We also performed a successful double-blind placebo controlled Phase 1 trial to evaluate the safety and immunogenicity of the edible plant vaccine. None of the volunteers who ate nontransgenic potatoes showed changes in anti-HBs antibody titer. However, after volunteers ate transgenic potatoes, serum antibody titers increased in 62% who ate three doses and 53% who ate two doses of transgenic potatoes. Buffering of the stomach pH was not performed nor was any mucosal adjuvant used. This trial firmly establishes that oral vaccination via edible plant vaccines is possible for a non-enteric antigen such as HBsAg. Taken together, these data form a very solid foundation for the studies proposed in this application. In the current application we propose four specific aims designed (1) to improve the expression of HBsAg in transgenic plants, (2) target antigen to M cells in the gut, (3) to track the immune response elicited and (4) to potentiate the immune response to orally administered antigen by use of nontoxic mucosal adjuvants. We have provided significant new preliminary data and we believe that these provide strong documentation of the likelihood of continued success. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEPATITIS B VIRUS E ANTIGEN EXPRESSION Principal Investigator & Institution: Tong, Shuping; Rhode Island Hospital (Providence, Ri) Providence, Ri 02903 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Hepatitis B virus (HBV) infects nearly 1/10th of the world population and causes severe liver diseases including cancer. The e antigen (HBeAg) is a secreted soluble protein that promotes immune tolerance during perinatal infection and buffers immunity against HBcAg. The corresponding anti-HBe immune response plays a critical role in the clearance of HBV infection. Therefore, following seroconversion from HBeAg antigenemia to anti-HBe, HBV escape mutants with reduced or no HBeAg production often replace wild-type HBV genomes. The core promoter mutants have various nucleotide changes around positions 1750 -1770 of the HBV genome, and the most common mutations at 1762 and 1764 are known to reduce HBeAg expression at the transcriptional level. The precore mutants have nonsense or frameshift mutations in the HBeAg coding sequence and terminate HBeAg expression at the translational level. Considering the critical importance of HBeAg and anti-HBe in shaping the outcome of HBV infection, we wish to uncover novel regulatory mechanisms for HBeAg expression. In this regard, perinatally infected South African patients seroconvert from HBeAg to anti-HBe at a much accelerated pace than similarly infected Asian patients. Interestingly, the South African HBV variants often harbor two or three point mutations near the precore initiation codon. We plan to verify whether

50

Hepatitis B

the mutations cause leaky scanning to reduce HbeAg translation. Second, HBeAg maturation requires double proteolytic cleavage events in the secretory pathway. The first cleavage occurs in endoplasmic reticulum to remove the N-terminal signal peptide of 19 residues. A Val to Phe missense mutation at residue 17 is frequently detected in HBV genomes isolated from seroconverted patients. Since an aromatic residue at the -3 position of cleavage site is forbidden, we will test whether this mutation impairs HBeAg cleavage and secretion. Third, we recently identified several naturally occurring core promoter mutants with wild-type level of HBeAg production. Based on the results of preliminary mapping experiments, we will determine whether the number and position of core promoter mutations influence the level of HBeAg expression, and whether missense mutations in the HBeAg coding sequence also regulate HBeAg level. This study promises to verify and identify novel mechanisms regulating HBeAg expression, which has a major impact on the outcome of HBV infection. 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 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 casecontrol 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

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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

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Hepatitis B

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 •

Project Title: HIV DISEASE OUTCOMES IN DRUG USERS IN CLINICAL PRACTICE Principal Investigator & Institution: Moore, Richard D.; Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): In 1998, we were awarded an RO-1 (DA11602) from NIDA to conduct a longitudinal study in HIV-infected persons who have a history of illicit drug use (DU). The major aims of that study were to develop a longitudinal cohort of HIV-infected patients in medical care in order to characterize utilization of the new highly active antiretroviral drug therapies (HAART), and assess the effect of these therapies on HIV disease progression in DUs. We established a comprehensive longitudinal clinic-based cohort of over 4600 HIV infected persons; half of who have a history of DU. Our research suggests that DUs have not received the same level of benefit from HAART as non-DUs. Prior to HAART, there was little difference between DUs and non-DUs in HIV progression. Our research has shown that active DU is a barrier to receiving and adhering to HAART, and achieving effective viral and immunologic improvement on HAART. We hypothesize that the early differences that have emerged between DUs and non-DUs will substantially widen over the next 5 years as HIV resistance to current drugs increases, toxicity limits the use of therapy, and viral hepatitis along with other medical consequences of DU further increase the burden of

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morbidity. Because of HAART, HIV is now a chronic illness, and DUs have numerous barriers to stable, chronic disease management. We are optimally situated to assess the core factors that impede successful HIV management as the HAART era matures over the next 5 years, and are submitting a new proposal for a competitive continuing RO-I. We propose the following aims, consistent with our overarching goal of improving the outcomes of HIV infection in DUs: 1) Evaluate virologic, immunologic and clinical HIV disease progression for up to 10 years, 2) Assess the impact of viral hepatitis coinfection, 3) Assess other medical consequences of DU including bacterial infection and STDs, 4) Assess adverse effects of HIV therapy. We offer a productive resource to address our aims that is unique in scope and size, cost-efficient in conducting research, highly relevant to the HIV epidemic as it effects DUs, and fully operational from our prior R01. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

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), 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

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Hepatitis B

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: HIV/INFECTIOUS DISEASE TEST/TREATMENT IN SUBSTANCE ABUSE Principal Investigator & Institution: Lally, Michelle A.; Miriam Hospital Providence, Ri 02906 Timing: Fiscal Year 2001; Project Start 25-SEP-2000; Project End 31-AUG-2005 Summary: (Applicant's Abstract) Phase I of the proposed project will examine barriers to comprehensive HIV and other infectious disease testing and follow-up care among substance abusers at a short term (detox) substance abuse treatment center. In Phase II an intervention that includes comprehensive testing, counseling, medical deferral, and practical strategies to overcome barriers to follow up care will be designed and pilot tested. During Phase III, the intervention will be evaluated against the standard of care of offering HIV testing done through a randomized controlled trial. Three hundred and forty-four participants will be randomized to receive either the comprehensive testing and facilitated referral intervention which will offer testing for HIV, hepatitis B and C, and the STDs gonorrhea and chlamydia (and trichomonas for women only) or standard of care HIV testing alone and referral for further hepatitis and STD testing. Primary endpoints will be the number of tests performed, the number of test results received, and the degree of follow up medical care obtained for the two groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HOMELESS YOUTH: STREET CULTURE/SOCIAL NETWORKS/HIVRISK Principal Investigator & Institution: Auerswald, Colette L.; Pediatrics; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 11-JUN-2001; Project End 31-DEC-2005 Summary: (Adapted from applicant's description): Rates of risky behaviors in homeless youths are persistently high, resulting in high rates of morbidity, including seropositivity for HIV and Hepatitis B and C. Interventions based on risk-reduction in this population have had limited effectiveness. Recent research emphasizes that removal from the street should be a primary focus of HIV risk-reduction for homeless youths. Studies of risky behaviors in non-homeless youths and in at-risk adults strongly suggest that a better understanding of the relationships within which risk behaviors take place and of the meaning of the risky behaviors to the actors will lead to more effective interventions. The applicant is a pediatrician and specialist in adolescent medicine who has expertise in the ethnographic study of marginalized youths and experience in quantitative behavioral studies of risky behavior in adolescents. The candidate's career objective is to improve the health of marginalized youths, including homeless youths, through multidisciplinary research on the behavioral determinants of the health- related behaviors and barriers to care in this population. In the training phase of the award the applicant will have four primary development objectives: a) to develop further skills in patient-oriented qualitative research, b) to learn to follow longitudinal cohorts of hardto-reach populations, c) to gain additional expertise in the integration of qualitative and quantitative methodologies in the study of adolescent health-related behavior, and d) to learn to analyze social network data in the study of risky behavior. She will pursue her objectives through mentored research experiences. These will be complemented by

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focused course work offered by the K-30 funded Advanced Training in Clinical Research program at the University of California, San Francisco. The objective of the research phase of the award will be to conduct a joint ethnographic-epidemiologicalsocial network study to test the findings of her preliminary research. These findings, based on a street-based ethnographic study of youths, suggest that youths pass through stages of a life cycle of homelessness, each of which is characterized by different levels of acculturation to the street and different compositions of their social networks. By demonstrating in a large street-based longitudinal sample that youths in each stage differ according to acculturation and social networks and that these differences are correlated with rates of risky behaviors, we may have a powerful tool for designing interventions. An approach to intervention based on an understanding of these stages has practical implications, including new screening tools, the designing of stage- based services, and the development of intensive programs for the youths who are most susceptible to removal from the street. An understanding of how social network connections promote and prevent risky behaviors would also have significant implications for the designing of interventions with this population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HOST AND VIRAL GENETIC VARIABILITY IN HBV CARRIERS Principal Investigator & Institution: Evans, Alison A.; Assistant Member; Fox Chase Cancer Center Philadelphia, Pa 19111 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2006 Summary: Chronic carriers of hepatitis B virus (HBV) are at increased risk for hepatocellular carcinoma (HCC). Worldwide, however, the risk of HCC and other adverse outcomes varies substantially both between and within populations of HBV carriers. The reasons for these differences in the natural history of infection are not known. Our analysis of cohort studies in three endemic populations have suggested that the long term maintenance of high-titer viremia (i.e., equal to or > 1 pg/ml) is an important predictor of HCC. The mechanism behind the maintenance of viremia is, however, not well understood although it is clear that the host immune response plays a key role. In this application, we focus on molecular variants of the virus itself and polymorphisms of human immunoregulatory genes as potential predictive or explanatory factors in maintenance of viremia. We will draw upon established prospective cohorts of chronic HBV carriers in China, West Africa, and AsianAmericans. Our preliminary data support a relationship between deletions in the C ORF of HBV and clearance of active viral replication. In the proposed project we will test this hypothesis and extend our studies of molecular variation of HBV by application of novel statistical methods to sequence data. We will also test the hypothesis that maintenance of HBV viremia is associated with polymorphisms of the vitamin D receptor (VDR) and tumor necrosis factor alpha (TNFalpha) promoter. Allele frequencies for polymorphisms of lesser-studied immunomodulatory genes in our cohorts will be estimated in order to develop hypotheses about their relationship to maintenance of viremia in HBV carriers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: 'IMMATURE SECRETION' VARIANTS OF HUMAN HEPATITIS B VIRUS Principal Investigator & Institution: Shih, Chiaho; Professor; Pathology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555

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Hepatitis B

Timing: Fiscal Year 2001; Project Start 04-FEB-2000; Project End 31-JAN-2005 Summary: Our long-term goal is to understand the pathobiology of viral hepatitis. Hepatitis B virus (HBV) is the 4th most common infectious agent in humans worldwide. Chronic infection with HBV is tightly associated with the development of liver cancer. The mechanism of how HBV chronic infection is established and its pathogenesis remains to be fully explored. Recently, there has been increasing evidence that HBV chronicity may be influenced by the presence of genetic variants that evolve in patients as liver disease progresses. Since the invention of polymerase chain reaction technology, many HBV sequence variants have been reported. However, a common frustration in the research of HBV variants is that the majority of these reported sequence variants has no known functional significance and does not exhibit a strong phenotype distinctively different from the wild type virus. The most frequent missense mutation found in the HBV core antigen occurs at codon 97 in chronic carriers worldwide (in 83 percent hepatoma patients). Our recent functional characterization of this mutant uncovered a novel and strong phenotype, dubbed an "immature secretion" phenotype. Unlike wild type HBV, the secreted Dane particles of codon 97 mutants contain predominantly the immature form (lower molecular weight) of the HBV DNA genome. In this application, we propose 1) to extend our observation of the "immature secretion" phenomenon from tissue culture to patients and animal models. We also attempt to extend the "immature secretion" phenotype to other viral subtypes prevalent in different geographic locations. 2) to investigate the mechanism of "immature secretion" by both genetic and biochemical approaches. One of the several hypotheses to be tested is that "immature secretion" could be caused by hyper-efficient interactions between wild type envelope and mutant core proteins. 3) Finally, we will compare the infectivity of the highly frequent codon 97 mutants and wild type HBV via in vitro infection assays. Successful completion of this work will help understand the fundamental rules governing HBV morphogenesis and virion secretion, in addition to the important implications for chronic viral hepatitis as well as many other chronic progressive viral diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNE REGULATION OF CNS VIRAL RECRUDESCENCE Principal Investigator & Institution: Bergmann, Cornelia C.; Associate Professor; Neurology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 15-MAY-2001; Project End 31-MAR-2006 Summary: (provided by applicant): A variety of human viruses, including herpes viruses, hepatitis B virus and HIV, produce acute infections followed by persistence or recrudescence. However, the mechanism(s) regulating persistence and recrudescence depend on a balance between viral replication and the host immune response. Viral tropism and antigenic load provide additional determinants in this complex scheme. This proposal examines the contribution of cell mediated and humoral immunity in controlling recrudescence of a neurotropic virus following initial clearance. Infection of immunocompetent mice induces an acute encephalomyelitis, followed by persistence without infectious virus. During acute infection cell mediated immunity, predominantly the CD8+ T cells, are crucial in controlling virus replication within the central nervous system (CNS). However, in the absence of B cells, these effector functions do not suffice to suppress virus to undetectable levels, thereby allowing virus reactivation. Importantly, transfer of anti-viral antibody (Ab) prevents virus reactivation, implicating a crucial role for Ab and/or B cells in controlling persistence. However, analysis of virus specific T cells using class I tetramet technology revealed that the percentage of virus

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specific CD8+ T cells in the CNS is reduced compared to immunocompetent mice. In addition, there is no increase in virus specific T cells during reactivation. These data suggested that CD8+ T cells may be functionally impaired or exhausted due to increased antigen load. This proposal distinguishes between the requirement(s) for potent CD8+ T cell function vs Ab in controlling virus reactivation in a persistently infected host. The contribution of both neutralizing and non neutralizing Ab, Fc receptor (FcR) activity and complement are examined by Ab transfers and using mice deficient in FeR. These experiments will determine the mechanism of Ab mediated prevention of virus reactivation in an Ab deficient milieu. The possibility that the absence of Ab and/or B cells results in defective CD8+ T cell priming, ultimately leading to exhaustion during recrudescence is tested by functional and phenotypic analysis of CD8+ T cells during priming and recrudescence. Intervention via transfer of protective Ab or CD8+ T cells activated in vitro will determine if functionally impaired CD8+ T cells can be overcome. These experiments may have direct implications for therapeutic interventions during persistent viral infections. Finally, virus reactivation will be tested in an Ab deficient mouse with a normal B cell compartment. These experiments will distinguish between the possibilities of an Ab independent effect of B cells and a CD8+ T cell defect related to the absence of B cells. This proposal will provide insight into the immunological regulation of both virus recrudescence and the CNS as a target organ. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INITIATION OF HEPATITIS B VIRUS REPLICATION Principal Investigator & Institution: Mclachlan, Alan; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Hepatitis B virus (HBV) infection is a worldwide health problem. It is estimated that there are 200 to 500 million HBV chronic carriers in the world for whom, to date, there is no reliable treatment. HBV causes both acute and chronic liver disease and the estimated relative risk of primary hepatocellular carcinoma (PHC) in chronic HBV carriers is approximately 100 times greater than in uninfected individuals. Therefore, effective treatments for chronic HBV infection are required. In these studies, the mechanism(s) regulating the initial steps in the synthesis of hepatitis B virus (HBV) DNA will be investigated. HBV DNA synthesis is initiated by binding of the viral polymerase to a stem-loop structure, epsilon, located at the 5'-end of the HBV pregenomic RNA. Initially, the first three nucleotides of HBV minus-strand DNA are synthesized utilizing the amino-terminal domain of the polymerase as a primer and the bulge region of epsilon as a template. The HBV polymerase with the covalently attached trinucleotide sequence is subsequently translocated to the DR1 sequence at the 3'-end of the pregenomic RNA. HBV minus-strand DNA synthesis then proceeds by the reverse transcription of the pregenomic RNA. The mechanism(s) regulating the translocation step are unknown. Recently, a regulatory sequence element, phi, located immediately upstream of the DR1 sequence at the 3'-end of the pregnomic RNA that is important for efficient viral replication and is complementary to the 5'-half of epsilon was identified. This finding suggests that the translocation of the minus-strand primer from epsilon to DR1 might be mediated by a conformational change in the pregenomic RNA that brings the primer into proximity with the DR1 sequence at the 3'-end of the pregenomic RNA. The conservation of the complementarity between epsilon and phi in the woodchuck hepatitis virus (WHV) and the duck hepatitis B virus (DHBV) genomes also supports this contention. Therefore, the role of the complementarity between epsilon and phi in regulating HBV replication will be examined directly by mutational analysis of these

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Hepatitis B

sequence elements. This approach is aimed at identifying possible targets for therapeutic intervention in chronic HBV infection. 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 •

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

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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: INTERNATIONAL CONFERENCE ON HEPATITIS B VIRUSES Principal Investigator & Institution: Slagle, Betty L.; Assistant Professor; Molecular Virology & Microbiol; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2002 Summary: (provided by applicant): Infection with Hepatitis B virus (HBV) is still a serious public health problem, with an estimated 300 million chronic carriers worldwide. In recent years, substantial progress has been made in establishing the molecular basis of individual steps in the replication of the virus, revealing its unique status among retroelements. However, immense experimental difficulties, including the lack of appropriate in vivo and experimental, infection systems, have hampered a similarly detailed analysis of the early steps of infection. The limitations have further hindered the fundamental understanding the complex interplay between virus and host and its effects on pathogenicity. This conference is distinct from clinically oriented meetings, and is intended to gather scientists studying different aspects of HBV and related animal model viruses, for joint discussion of the latest conceptual and technical advances. The meeting is organized by Drs. Betty Slagle and Michael Roggendorf, who are assisted by a panel of expert HBV scientists acting as chairpersons for 12 lecture and 2 poster sessions. In addition, it is planned to have a workshop on controversial issues. Session topics will include: transcription; replication; structural proteins and receptors; regulatory proteins; hepatocellular carcinoma; HBV variants and hepatitis delta virus; and persistence, pathogenesis, and immunology. Each session will comprise 4-8 talks, selected from submitted abstracts that are peer-reviewed by the session chairpersons. In the tradition of previous meetings of this series, in addition to the attendance and presentations by senior investigators, graduate students and postdoctoral fellows will be particularly encouraged to participate in the lecture and poster sessions. HBV research is

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Hepatitis B

a major topic in the research mission of NIAID, and this is the only annual HBV meeting of its kind. 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, 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

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Project Title: INTERVENTIONS TO INCREASE HBV VACCINATION IN STD CLINICS Principal Investigator & Institution: Zimet, Gregory D.; Associate Professor; Pediatrics; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 05-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The objective of this study is to evaluate interventions to increase acceptance of, and follow through with, hepatitis B virus (HBV) immunization among patients attending sexually transmitted disease (STD) clinics in Chicago, IL and Indianapolis, IN. This research will have implications for the

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design of interventions that may increase HBV vaccine uptake in at-risk groups. The interventions may also be applicable to other STD vaccines as they become available. The first specific aim is to assess the effect of message framing on vaccine acceptance. Prospect theory will be used to guide the development of the message-framing interventions. This theory suggests that positively framed messages (i.e., benefits of getting vaccine) are more effective than negatively framed messages (i.e., dangers of not getting vaccine) in stimulating preventive health behaviors. Research on Prospect Theory and engagement in health behaviors suggests also that the effects may be moderated by other attitudinal factors, including perceived risk of the behavior and degree of involvement in the message. The second aim is to evaluate the effect of provider-based interventions. Prior research suggests that recommendations by health providers are very important in patients' decisions regarding acceptance of healthcare procedures. The third aim is to examine the effect of the interventions on follow-through with the second and third recommended vaccination. During Year 1 of the proposed plan, the message framing interventions will be developed and pilot tested and healthcare providers in Chicago and Indianapolis will be trained in the provider-based interventions. During Years 1-5, 3,344 patients (18 years and older) will be recruited and followed from Chicago and Indianapolis STD clinics during routine medical visits. An audio computer-assisted self-interview (A-CASI) will cover demographics, risk behaviors, and perceived risk associated with vaccination. Subjects then will be randomized to receive a gain-framed, loss-framed, or information only message regarding HBV immunization (also delivered by A-CASI). Upon completion of the message-framing intervention, subjects will be complete additional attitude questions via A-CASI, then will be randomly assigned to one of two provider intervention conditions: 1. vaccine-offered or 2. vaccine-recommended. For both conditions free HBV immunization will be provided by a nurse practitioner. Debriefing interviews will be carried out. Subsequently, postcard reminders will be sent and phone call reminders made for follow-up appointments for those receiving the first and second doses of vaccine. Outcome measures of interest include: (1) acceptance vs. rejection; (2) compliance with two doses vs. one dose only; and (3) completion of immunization vs. two doses only. The relationships of the interventions, socio-demographics, attitudes and behaviors to the outcome measures will be assessed with multiple logistic regression (MLR) and path analysis via structural equation modeling. 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.

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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 •

Project Title: LIVER CANCER CONTROL AMONG NORTH AMERICAN CHINESE Principal Investigator & Institution: Taylor, Victoria C.; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2003; Project Start 25-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Little is known about the disease prevention behavior of Chinese in North America, and few studies have addressed cancer control in this group. However, Chinese American men and women are four times more likely to be diagnosed with liver cancer than their non-Latino White counterparts. This excess risk is attributable to high rates of hepatitis B virus (HBV) infection combined with low levels of hepatitis B vaccination coverage. The goal of this research is to increase the proportion of less acculturated Chinese adults who have been tested for HBV (and, therefore, either have been vaccinated, are screened for liver cancer, or know they are immune to the disease). Objectives are to: obtain qualitative and quantitative information about the liver cancer prevention behavior of Chinese Americans and Canadians; develop a culturally and linguistically appropriate outreach intervention targeting hepatitis B and liver cancer among Chinese; and conduct a randomized controlled trial to evaluate the effectiveness, feasibility, and acceptability of the intervention program. To increase the generalizability of our findings, the research will be conducted in two cities: Seattle, Washington and Vancouver, British Columbia. The project will emphasize community involvement. PRECEDE and qualitative methods (i.e., forty in-depth interviews and eight focus groups) will be used to develop a quantitative survey instrument as well as intervention components. Six hundred Chinese men and women aged 18-64 who have not been serologically tested for HBV will be identified from a community-based survey of 1,200 individuals, and randomized to intervention or control status. Individuals in the experimental group will receive an outreach worker intervention (which will include a home visit and follow-up telephone call, tailored counseling and logistic assistance, and the use of audiovisual and print materials). Outcome evaluation will be based on data from a follow-up survey as well as medical record verification. If effective, our outreach intervention could be used by health care facilities and community organizations serving less acculturated Chinese in North America. 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 B Principal Investigator & Institution: Van Poelje, Paul D.; Metabasis Therapeutics, Inc. 9390 Towne Centre Dr, Ste 200 San Diego, Ca 921213026 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2002 Summary: (provided by applicant): The synthesis and characterization of novel prodrugs of the antiviral nucleosides acyclovir, penciclovir, and lamivudine are proposed with the purpose of identifying an agent with improved efficacy in the treatment of hepatitis B. The proposed prodrugs are designed to target the nucleosides selectively to the liver in their monophosphate form, and to enhance significantly the formation of the corresponding nucleoside triphosphates (NTP's), which are potent inhibitors of hepatitis B virus (HBV) polymerase. Enhanced hepatic NTP formation is likely to confer more rapid and complete suppression of HBV replication, and consequently to prevent the emergence of drug resistance, a major problem with current therapies. Studies are planned that will address (a) prodrug activation by a liver-specific enzyme (b) prodrug activation and phosphorylation in isolated hepatocytes and (c) prodrug pharmacokinetics and hepatic NTP generation in the rat. A key indicator for the success of the prodrug approach and its therapeutic potential is the temporal profile of hepatic NTP levels in vivo relative to parent nucleoside. A favorable profile will provide the impetus for additional studies envisaged for phase II of the proposal: the assessment of efficacy in animal models of HBV and the toxicological evaluations necessary to support clinical development. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MEASLES VIRUSES WITH ADDED VACCINE SPECIFICITIES Principal Investigator & Institution: Cattaneo, Roberto; Professor of Biochemistry & Molecular Bi; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2004; Project Start 01-DEC-2003; Project End 30-NOV-2007 Summary: (provided by applicant): The live attenuated measles vaccine has an outstanding efficiency and safety record and induces enduring immunity. We hypothesize that a currently used measles virus (MV) vaccine strain is an ideal platform for the development of pediatric vaccines eliciting immunity against other pathogens. We will test two propositions of this hypothesis: first that vectored MVs can protect against infection with another pathogen. Second, that they can elicit a strong immune response against other human pathogens whilst maintaining vaccine function against measles. To test the first proposition we will complete the production of a panel of vectored MV with the potential of inducing strong humoral and/or cellular immune responses to a mouse pathogen. We will take advantage of the detailed knowledge of the determinants of the immune response against the Daniels strain of the picornavirus Theiler. Proteins or peptides of this virus will be expressed in MV vectors with different scopes: induction of high neutralizing antibody titers, of specific cytotoxic T lymphocytes, or of both. The quality and strength of the immune response and the efficiency of protection against challenge with Theiler virus will then be measured in genetically modified mice permissive for MV infection. The correlates of vaccine efficiency will be established. To test the second proposition we will produce recombinant MVs with the potential of eliciting strong and sustained immune responses against two human pathogens for which an inexpensive vaccine requiring a single immunization is highly desirable. Recombinant MV expressing the surface antigen of

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the hepatitis B virus at different levels will be used to define the expression strategy most effective in inducing a strong humoral immune response. Recombinant MV expressing different proteins and CTL-inducing peptides of the hepatitis C virus will also be produced, and the strength of the induced humoral and cellular immune responses measured. Those viruses inducing the strongest immune response against hepatitis B and hepatitis C virus components in genetically modified mice will be inoculated into juvenile macaques. Their efficacy in protecting these primates against wild type measles infection and in inducing an immune response against the additional pathogen will be measured. 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: REPLICATION

MECHANISMS

OF

HEPADNAVIRUS

ASSEMBLY

AND

Principal Investigator & Institution: Hu, Jianming; Assistant Professor; Microbiology; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2001; Project Start 15-FEB-1999; Project End 31-JAN-2004 Summary: Hepadnaviruses, or hepatitis B viruses, are small, hepatotropic DNA viruses that replicate through an RNA intermediate (the pregenomic RNA or pgRNA) by reverse transcription. A critical early step in viral replication is the assembly of a ribonucleoprotein (RNP) complex comprised of the viral reverse transcriptase (RT) and

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pgRNA, which triggers both the assembly of nucleocapsids, the site of viral DNA synthesis, and the initiation of reverse transcription, which is primed by RT itself (the protein priming reaction). Through a complex multi- step reverse transcription pathway, the pgRNA is subsequently converted, within the context of the nucleocapsids, into the characteristic, relaxed circular DNA genome which can then exit the cell. The broad, long term objective of this proposal is to elucidate the molecular mechanisms of hepadnavirus replication, focusing on the virus-cell interactions critical for viral assembly and replication. The first specific aim is to identify host factors required for the interaction between RT and pgRNA and for protein priming. A combined approach based on physical association with RT, pgRNA and viral particles and biochemical fractionation and reconstitution will be used for this purpose, taking advantage of an established cell-free system that can recapitulate these early events in viral replication. The second aim is to elucidate the determinants on both RT and pgRNA responsible for specific RNA-protein interaction. Optimal conditions for RTbinding and crosslinking will be sought. The RT and contact sites in the RNP complex will then be identified through protein and RNA sequence analyses. This will, in turn, guide further mutagenesis studies to elucidate the specific requirements of RT and pgRNA for RNP formation. The third aim is to determine the requirements for individual steps of the viral reverse transcription pathway, using a recently developed synchronized viral replication system. Nucleocapsids from every stage of reverse transcription will be isolated to determine their structural changes, which accompany, and may be required for, the progression of viral DNA synthesis. Furthermore, specific host factors required for the different steps of reverse transcription will be identified by (1) carrying out viral DNA synthesis with the isolated nucleocapsids under cell-free reconstitution conditions and (2) treating virus-producing cells, at different stages of reverse transcription, with agents that target candidate host factors. The accomplishment of these goals should reveal novel cellular, as well as viral, targets for developing effective antivirals which is urgently needed for the treatment of over 300 million patients worldwide infected with the hepatitis B virus, who are at great risk of developing hepatic failure and hepatocellular carcinoma. In addition, studies on how host factors facilitate viral replication will also provide important insights into the normal cellular functions of these factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MIAMI ADULT AIDS CLINICAL TRIALS GROUP, AACTG Principal Investigator & Institution: Fischl, Margaret A.; Associate Professor; Medicine; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2001; Project Start 01-APR-1992; Project End 31-DEC-2004 Summary: (adapted from application's abstract): The Miami ACTU has been a member of the AACTG since its inception and has contributed to a number of AACTG studies that led to the approval of seven antiretroviral drugs and numerous HIV treatment strategies including lower and alternative dosing schedules for all three classes of antiretroviral agents, early treatment intervention, combination therapies with dual NRTIs and triple-drug therapy. The Miami ACTU has also actively participated in the Virology Laboratory Subcommittee working groups with an active role in the standardization of a PBMC culture assay for determining drug susceptibility, the assessment of interlaboratory concordance of DNA sequencing analysis of HIV RT, and the development of a consensus sequencing protocol to detect drug resistant mutations. This unit has also been involved with the Surrogate Markers Subcommittee with an active role in the assessment of plasma cytokines and soluble markers, cytotoxic T-

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lymphocyte activity, lymphocyte proliferation and advanced flow cytometry, and defining and validating immunologic markers as surrogate markers independent of CD4 and HIV RNA. Finally, this unit has contributed to the Pharmacology Committee with the evaluation of targeted- concentration control studies and the correlation of drug exposure with treatment response and failure parameters. The Miami ACTU will actively participate in HIV Disease RAC efforts and provide expertise to address study treatment strategies for initial therapy, treatment options for virologic failure and utilization of phenotypic and genotypic assessments to direct subsequent therapy and treatment intensification. The Miami ACTU will also bring expertise in the areas of hepatitis B and C pathogenesis and treatment, metabolic complications of HIV-1 protease inhibitor pathogenesis and treatment, HIV dementia pathogenesis and treatment and peripheral neuropathy pain assessment, Kaposi sarcoma (KS) pathogenesis, intensive immunologic monitoring and definition, and validation of immunologic determinants of treatment response. The Miami ACTU plans to enroll 100 subjects per year across AACTG studies and 70 patients into AACTG substudies, including but limited to Compartmental, Virology, Viral Dynamics, Pharmaceuticals, Metabolic, Neurologic, Women's Health and Adherence and Outcomes substudies. With a support system in place for the long-term follow-up of patients, the Miami ACTU anticipates to enroll approximately 80 patients into the ALLRT study (ACTG 5001) over a 2-year period. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

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 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

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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: CARCINOMA

MOLECULAR

EPIDEMIOLOGY

OF

HEPATOCELLULAR

Principal Investigator & Institution: London, W. Thomas.; Senior Member; Fox Chase Cancer Center Philadelphia, Pa 19111 Timing: Fiscal Year 2001; Project Start 15-DEC-1988; Project End 31-JAN-2004 Summary: Worldwide, hepatocellular carcinoma (HCC) is the third most common cause of cancer deaths in men and the seventh most common in women. About 80% of the cases of HCC are associated with chronic infection with hepatitis B virus (HBV), but chronic carriers of HBV differ widely in their risk of HCC. Prospective studies of 60,984 men in Haimen City, China and 19,469 men in Senegal, west Africa, undertaken during the current funding period, revealed a 14-fold greater death rate from HCC among the Haimen than the Senegalese cohort. The age-adjusted prevalence of chronic HBV infection is about 20% in both cohorts. Exposure to aflatoxin, a postulated major risk factor for HCC, does not distinguish these two populations; Senegalese men were universally and heavily exposed. The prevalence of viremia (HBV DNA in serum) among HBV carriers throughout adult life is much higher among the Chinese than the Senegalese population and may be related to the mechanism by which chronic HV infection induces HCC. The mechanism, however, is still unknown. Therefore, the purpose of this program project is to understand the inter- relationships of HBV and other viral infections, environmental factors, genetic events and gene-environment interactions to the etiology and pathogenesis of (HCC). The Specific Aims are: 1) To compare variations in viral, genetic, and environmental factors associated with development of HCC to variations in risk of HCC observed in 3 cohort studies in China, Senegal, and Philadelphia. 2) To understand the cellular and molecular changes in the liver induced by chronic molecular genetic changes in tumor cells associated with HCC. 4) To identify genetic factors and gene- environment interactions associated with susceptibility to HCC. A multi- disciplinary team of scientists from China, Senegal, and the Fox Chase Cancer Center will address these Aims in three Projects (Molecular Epidemiology of HBV and HCC in Three Populations, Genetic Epidemiology of HCC, and Pathobiology of Acute and Chronic Hepadnavirus Infections) supported by three Core facilities (Population Resources, Laboratory Services, Administration). The ultimate goal of this research is to develop strategies for reducing the global burden of HCC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR DITHIOLETHIONES

MECHANISMS

OF

CHEMOPREVENTION--

Principal Investigator & Institution: Kensler, Thomas W.; Professor; Environmental Health Sciences; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-SEP-1985; Project End 31-JAN-2004 Summary: Cancer prevention involving reduction or elimination of human exposure to environmental carcinogens may not always be possible. Inhibition of the development of cancer by the administration of anticarcinogenic age may offer a practical alternative for reducing human cancer burden. However, the successful utilization of chemopreventive interventions will require solid mechanistic understanding of the action(s) of these agents. The proposed studies will continue to investigate the modes of protection afforded by oltipraz and other 1,2-dithiole-3-thiones on aflatoxin (AFB1) hepatocarcinogenesis in the rat. Oltipraz is an effective and potent inhibitor of experimental carcinogenesis induced by many agents in many tissues. Oltipraz is

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currently being evaluated in Phase I and II clinical chemoprevention trials. This project will continue the development and evaluation of dithiolethiones more active than oltipraz on a) inhibition of AFB1-induced tumorigenesis in rats; b) altered AFB- DNA adduct formation; and c) induction of carcinogen detoxication ("phase 2") enzymes. Using a large series of analogs synthesized previously, the structure-activity relationships for inhibition of cytochrome P450 activation of AFB1 metabolism will also be determined. Using molecular genetic approaches, the identification and characterization of genes induced by dithiolethiones in rat liver will be continued together with elucidation of the role(s) of these gene products in protection against aflatoxin toxicity and carcinogenicity. Several novel inducible genes recently identified may protect against inflammation and oxidative stress. Finally, the chemopreventive actions and efficacy of oltipraz will be evaluated in a unique experimental model, the tree shrew, in which infection with human hepatitis B virus and exposure to AFB1 synergistically enhance the incidence of liver cancer, as occurs in humans. Collectively, these multifaceted, integrated studies will more fully define the chemical, molecular, biochemical and biological mechanisms of action of this versatile class of chemoprotective agents. The long-term goal of this project is to facilitate the most efficient and effective use dithiolethiones as protective agents in human populations exposed to environmental toxicants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR GENOTYPING

STANDARDS

FOR

HEPATITIS

B

AND

C

Principal Investigator & Institution: Neuwald, Paul D.; Acrometrix Corporation 1440 4Th St Berkeley, Ca 94710 Timing: Fiscal Year 2001; Project Start 15-JUN-2001; Project End 30-NOV-2001 Summary: (Applicant's Abstract): Nucleic acid testing procedures for genotyping of viral pathogens provide results that are utilized in the diagnosis and treatment of diseases such as hepatitis and AIDS. Medical products that directly measure these genetic variants currently utilize internal standards developed by the test manufacturers. The need exists for third party genotyping standards that offer common units of measure and provide testing laboratories with independent methods for ensuring accuracy, reproducibility and consistency in their test procedures. During Phase I, clinical specimens representing the major genotypes of hepatitis B virus (HBV genotypes A - F) and hepatitis C virus (HCV genotypes 1 - 6) will be obtained for calibration against World Health Organization International Standards for these virus nucleic acids, and evaluated for use as potential genotype standards using a variety of commercially available genotyping systems. During Phase II of this project, these materials will be further developed into viral and molecular (cloned DNA or RNA transcripts) standards for HBV and HCV genotyping. The HBV product will be further expanded to include standards for antiviral drug resistance mutations in this virus. All viral and molecular standards will be made commercially available during Phase Ill. PROPOSED COMMERCIAL APPLICATION: This research will lead to the development and commercialization of viral and molecular standards for HBV and HCV genotyping, including HBV drug resistance mutations. Such standardization, currently being implemented for viral load testing, is sorely needed for genotype testing, will facilitate the acceptance of common units of measure for assessing viral genotypes, and will help ensure that genotyping results obtained from multiple laboratories using a variety of test systems throughout the world are accurate,

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Hepatitis B

reproducible, consistent and high quality. Commercial manufacturers of genotype assays have expressed a need for independent genotype standards. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MUTATIONS IN HUMAN P53 SEQUENCES OF A P53 KNOCK-IN MOUSE Principal Investigator & Institution: Hollstein, Monica C.; German Cancer Research Center Im Neuenheimer Feld 280 Heidelberg, Timing: Fiscal Year 2001; Project Start 15-JUL-1999; Project End 30-JUN-2002 Summary: The long-term objectives of this proposal are to test a humanized genetargeted p53 tumor suppressor gene knock-in mouse as an experimental tool for molecular epidemiology, chemoprevention, and cancer therapy studies. This new model is designed to reflect and predict more faithfully than the currently used mouse models, human in vivo mutagenesis, carcinogenesis and responses to therapeutic drugs that target p53 protein. The specific aims are 1) to induce tumor mutations in human p53 sequences of knock-in mice exposed to human carcinogens, and compare them to human tumor p53 mutation spectra; 2) to test whether a p53 hotspot mutation common in aflatoxin-associated human liver cancers occurs in liver tumors of aflatoxin B1exposed, hepatitis B virus-transgenic/human p53 knock-in mice; 3) to generate mouse strains that harbor a mutant human p53 sequence identical to one of the inherited p53 mutations of cancer-prone Li-Fraumeni families. These p53 mutant mouse strains provide a new animal model, with an allelic configuration that parallels the human situation, for testing chemotherapeutic agents and chemopreventive dietary factors; 4) to replace mouse regulatory sequences with human elements, and determine how this alters p53 expression; these data may be useful in developing next generation p53 knock-in mouse strains. The research plan involves: 1) Construction of gene-targeting plasmids; 2) Generation of gene-targeted mouse strains in which exons 5-9 of the endogenous mouse p53 gene have been replaced by the corresponding human segment; 3) Treatment of p53 knock-in strains with human carcinogens; 4) Analysis of tumors and normal tissues for p53 mutations, and alterations in p53 message and protein. The methods to be used are: (a) Standard cloning procedures for plasmid construction; (b) gene-targeted technology with ES cells, and knock-in/knock-out strategies; (c) mouse breeding and treatment with carcinogens; (d) DNA sequencing, PCR and RT-PCR amplification; (e) immunohistochemistry; (f) mutation analysis by DGGE and allelespecific PCR. New pharmaceuticals designed to regenerate tumor suppressor functions of a mutated p53 in humans can be tested in vivo in these humanized" mice because they have a core domain identical to the human p53 protein rather than the mouse p53 protein. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEW HEPATITIS B SMALL MOLECULE INHIBITORS Principal Investigator & Institution: Mehta, Anand S.; Associate Professor; 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

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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 3TC-lamivudine. 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 •

Project Title: NONINJECTED HEROIN USE, HIV AND TRANSITIONS TO INJECTION Principal Investigator & Institution: Ouellet, Lawrence J.; Epidemiology and Biostatistics; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2001; Project Start 20-SEP-2000; Project End 31-AUG-2005 Summary: (adapted from the applicant's abstract): Growing cohorts of young noninjecting heroin users (NIHU) are making choices regarding drug injection that promise to shape the AIDS epidemic in Chicago and other U.S. cites for years to come. Despite the potential impact of NIHU on future AIDS trends, published research on this group in the U.S. is scarce and little is known about their transitions into injection. To help fill this void, we propose a five-year, longitudinal study of NIHU in Chicago that has three major aims: (1) measure the incidence of transitions by NIHU into drug injection and identify factors predicting this event; (2) measure the incidence and prevalence of HIV, hepatitis C, and hepatitis B infections among NIHU and identify factors associated with infection, and (3) explore the link between heroin use and risky sexual practices. The proposed study is grounded conceptually in social epidemiology, which models disease patterns as the product of interactions between an agent, host, and environment. The study will use a multi-method research design that combines a prospective epidemiologic survey, biologic testing, and qualitative interviewing. This design will enable causal analyses of the impact of independent variables on the outcomes of interest. The sample will consist of 1000 NIHU 16-30 years old recruited through respondent-driven sampling from areas across Chicago and its suburbs. Variable categories thought likely to predict major outcomes of interest are changing conditions in the properties and availability of heroin (agent/drug), individual characteristics (host/set), and the social settings within which drug use occurs (environment/setting). The goal of this study is to better understand current drug use patterns and HIV risk practices, particularly transitions to injection, among NIHU. We anticipate our findings being used to develop intervention strategies aimed at preventing drug injection and

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other HIV related behaviors among NIHU. To increase the scope and generalizability of findings, elements of the proposed study, including the survey questionnaire, have been designed for comparison with an ongoing NIDA-funded, prospective study of NIHU in New York City. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NONINJECTING HEROIN USERS, NEW INJECTORS AND HIV RISK Principal Investigator & Institution: Neaigus, Alan; National Development & Res Institutes Research Institutes, Inc. New York, Ny 10010 Timing: Fiscal Year 2001; Project Start 01-JUL-1995; Project End 31-MAR-2003 Summary: Non-injecting heroin use is widespread in New York City and in many other cities. Non-injecting heroin users (NIUs) are at high risk of becoming injecting drug users (IDUs). Increases in the number of new IDUs can lead to many new infections with HIV, hepatitis B (HBV) and hepatitis C (HCV). This study will continue the "HIV Risk and Transitions from Non- Injecting Heroin Use" (NIU) cohort study of approximately 600 NIUs. It will follow the NIU cohort and a cohort of new IDUs, to determine: (1) the incidence and time-trends in transitions to injecting; (2) behavioral and network risks for transitions to injecting and other drug use outcomes; (3) separately, for new IDUs and for NIUs, the incidence and time-trends in HIV, HBV and HCV seroconversions; (4) among NIUs, sexual and other non- injecting risk behaviors and networks predicting HIV, HBV and HCV seroconversion; (5) among new IDUs, drug injecting and sexual risk behaviors and risk networks predicting HIV, HBV and HCV seroconversion; (6) time-trends in the prevalence of drug and sexual risk behaviors and risk networks, and factors predicting these trends; and (7) the impact of changes in the quality and availability of heroin, and in other community factors, on modes of drug administration and other drug and sexual risk behaviors and risk networks. The sample will include: NIUs from the parent study; new IDUs recruited from a supplemental study of network risks for HIV, HBV and HCV infection; and NIUs and new IDUs recruited during the study continuation. Participants will be interviewed and tested for HIV, HBV, and HCV. Ethnography will be used to study the impact of drug markets. Analyses of risk factors for transitions to injecting and seroconversions will explore the "network facilitation" hypothesis by examining the extent to which network characteristics, in interaction with risk behaviors, facilitate transitions to injecting or the cessation of heroin use and other drug use outcomes, and seroconversions. This approach will advance our knowledge of the interaction between network processes and risk behaviors, and can be used to develop interventions to change both risk behaviors and risk networks, and to prevent transitions to injecting and the risk of HIV, HBV and HCV infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OCCULT HEPATITIS B Principal Investigator & Institution: Torbenson, Michael S.; Pathology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): The goal of this proposal is to provide Michael Torbenson, MD with a period of mentorship in the proper scientific environment so that he can acquire the necessary skills to become an independent clinician-scientist. Dr. Torbenson has a strong background in diagnostic liver pathology and has a specific interest in viral hepatitis. This proposal focuses on occult hepatitis B, an emerging

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infectious entity of potentially large medical significance. Occult hepatitis B has been associated with advanced liver fibrosis, coinfection with hepatitis C, IFN alpha resistance in treatment of hepatitis C, and hepatocellular carcinoma. The overall aim of Dr. Torbenson's proposal is to assess the prevalence and clinical significance of occult hepatitis B in high risk patient population of injection drug users. This study utilizes the unique resources of a pre-existing longitudinal collection of sera and liver tissue from the mentor's ongoing research, allowing assessment of the prevalence of occult hepatitis B over time and estimation of the rate of fibrosis progression in these individuals. The first aim examines the overall prevalence of occult hepatitis B and investigates the impact of Human Immunodeficiency Virus status on the presence of occult hepatitis B. The second aim assess the clinical significance of occult hepatitis B by correlating the presence of occult hepatitis B with the amount of inflammation and fibrosis on liver biopsy. The rate of fibrosis progression will be investigated by comparing the amount of fibrosis on initial liver biopsy to that on follow-up biopsies. In addition, aim 2 will examine the role of occult hepatitis B in HIV progression. The third aim focuses on potential mechanisms of occult hepatitis B and seeks to identify relevant hepatitis B gene mutations. As a final element of this aim, carefully selected (based on known involvement in typical hepatitis B viral infection) signaling pathways will be investigated by analysis of mRNA and protein expression to investigate host-viral interactions. 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

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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 •

Project Title: PATHOGENESIS OF LIVER DISEASE IN HEPATITIS Principal Investigator & Institution: Chisari, Francis V.; Professor & Head; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2001; Project Start 01-JUL-1983; Project End 30-JUN-2003 Summary: (adapted from the investigator's abstract) During the current funding interval Dr. Chisari established the technology required to detect, quantitative and characterize the cytotoxic T lymphocyte (CTL) response to the hepatitis B and C viruses. Using this technology he defined the salient features of the host-virus relationship during the acute and chronic phases of these infections and, in the process, established the rationale and identified the immunological targets for antigen-specific immunotherapy of chronic hepatitis. Despite these advances, the very early aspects of the host-virus relationship during HBV and HCV infection are completely unexplored because, for practical and ethical reasons, it is extremely difficult to access the incubation period in infected patients. Nonetheless, these early host-virus interactions are likely to be key determinants of the outcome of these infections. In the next funding interval, he will examine the virological, immunological and pathological features of the host-virus relationship from the moment of HBV and HCV infection until their final outcome in experimentally infected chimpanzees. As in humans, almost all adult onset HBV infections in chimps are self limited, while only half of chimp HCV infections are self limited and the rest become persistent. Thus, he will compare and contrast the early intrahepatic T cell responses to HBV and HCV to test the hypothesis that the outcome of these infections is determined by the kinetics, vigor, diversity and cytokine profiles of the intrahepatic T cell response and the ability of the virus to spread and to evade immune recognition during the early incubation period of each infection. Thanks to the close relatedness of chimps and humans, most of the reagents and techniques required to define the intrahepatic antigen specific T cell response to these viruses are already available. The information forthcoming from these studies will, for the first time, define the virological and immunological features of early HBV and HCV infection and determine the extent to which they influence viral clearance and disease pathogenesis in these diseases. 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 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

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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: 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 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

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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 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

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Project Title: REGULATION OF HBV REPLICATION BY OTHER HUMAN PATHOGENS Principal Investigator & Institution: Guidotti, Luca G.; Associate Professor; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2001; Project Start 01-JAN-1997; Project End 31-DEC-2001 Summary: The hepatitis B virus (HBV) causes acute and chronic necroinflammatory liver disease and hepatocellular carcinoma. Over 300 million people worldwide are persistently infected by HBV, representing an enormous reservoir for horizontal and vertical spread of this virus to others. The long term objective of this application is to understand the host- virus interactions responsible for HBV persistence with the ultimate hope that this knowledge will lead to the development of new therapeutic strategies to terminate persistent infection and its attendant costs and complications. Using transgenic mice that replicate HBV at high levels in the liver as recipients of HBVspecific CTL and hepatotropic viruses such as lymphocytic choriomeningitis virus (LCMV), we have shown that HBV replication is abolished by these agents, noncytopathically, as a result of the intrahepatic induction of interferon alpha, interferon gamma and tumor necrosis factor alpha (type 1 cytokines). We now propose to examine the antiviral regulatory networks that are activated in the LCMV-infected liver in order to identify the ligand-receptor interactions that trigger the hepatocyte to suppress HBV gene expression and replication in vivo. Since the intrahepatic macrophage (Kupffer cell) is an important and well placed source of potentially active antiviral mediators in this system, we will determine whether physiological and pharmacological activation of the Kupffer cell is sufficient to clear HBV from the hepatocyte in vivo. if successful, these studies would establish the concept that inducible cellular crosstalk can control viral infection, perhaps leading to the development of an entirely new area of viral immunotherapeutics. Finally, in view of our findings it is possible that HBV persistence might be favored by inflammatory responses dominated by type 2 cytokines (eg interleukins 4, 5 and 10). To explore this hypothesis, we will determine whether intrahepatic type 2 inflammatory responses initiated by schistosomal and leishmanial infection are able to clear HBV from the liver of these animals. The results of these experiments will not only provide insight into the basic immunological processes that may determine HBV persistence, but additionally they may also shed light on the basis for the more aggressive liver disease that occurs in millions of patients with chronic HBV infection who are superinfected by these parasites in developing countries throughout the world. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF TBP BY HBV X ON TRANSFORMATION Principal Investigator & Institution: Johnson, Deborah L.; Associate Professor; Molecular Pharm & Toxicology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2001; Project Start 10-MAY-1997; Project End 31-JAN-2005 Summary: (Adapted from the investigator's abstract) The Hepatitis B virus (HBV) is a common infectious agent. The HBV protein product, X, has shown to be essential for viral replication, and it is strongly implicated in the development of hepatocellular carcinoma in chronically infected HBV patients, yet its role in these events is not wellunderstood. Our previous work has comprehensively defined the mechanism for how X transactivated RNA polymerase I and III promoters. We made the interesting discovery that X induces the promoters by activating the Ras signal transduction pathway which

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then increases the cellular levels of the central transcription factor, TATA-binding protein (TBP). Increases in cellular TBP augment RNA pol I and III transcription and differentially regulate RNA pol II promoters. Our research plan will clearly delineate how X, an oncogenic Ras, increase cellular TBP levels. The proposed aims will rigorously investigate each event in the TBP gene expression process that gives rise to the final TBP product. By examining the individual contribution of each process, and how it differs when either X or oncegenic Ras is expressed in cells, we will obtain a good quantitative picture of how this X- and oncogenic Ras-mediated increase in TBP occurs. We have promising new data indicating that a key step leading to the increase in TBP is due to an increase in TBP promoter activity. Therefore, a major focus of the proposed studies will be to examine how the TBP promoter is regulated by X and by oncogenic Ras. We will comprehensively define the X-mediated signaling events downstream of Ras to the promoter that modulate TBP promoter activity. Since X has been shown to transform cells, and Ras is strongly oncegenic, we will also determine how alterations in the cellular levels of TBP can affect the transformation potential of cells. Focus formation, growth in soft agar, and mouse tumorigenesis assays will be used to assess whether directly overexpressing TBP can enhance transforming activity or whether down-regulating its production in cells can prevent Ras-induced transformation. Using mutant TBP proteins that are specifically defective in RNA pol II or pol III transcription, we will define specific changes in cellular gene expression occurring in TBPoverexpressing cells that contribute to transformation. These studies promise to make unique and important new contributions to our understanding of the function of the HBV X protein and oncegenic Ras, the regulation of TBP, and their consequences on cellular gene activity that leads to cellular transformation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REPLICATION AND PATHOGENESIS OF HEPATITIS B VIRUS Principal Investigator & Institution: Ou, Jing-Hsiung J.; Professor; Molecular Microbiol and Immun; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2001; Project Start 10-APR-1998; Project End 31-JAN-2002 Summary: Dr. Ou proposes to study three aspects of the HBV pathogenesis and its replication cycle: core protein phosphorylation, C gene transcription controls, and the role of the X gene in replication. Aim 1 will evaluate the model that core protein phosphorylation blocks virus assembly. Virions will be analyzed for phosphorylation; virus infection will be reconstituted with core proteins mutated to block phosphorylation at specific residues. Viral regulation, packaging efficiency, and virion production will be analyzed. Aim 2 deals with transcriptional regulation of the core gene, which actually encodes both precore and core proteins by initiating from two different transcription start sites. The study will focus on a critical regulatory site that binds COUP, HNF4, PPAR-RXR, and when mutated, HNF1. Preliminary studies have also characterized an upstream negative regulatory element (NRE) that binds RFX1/MDBP1 and MIBP1. The NRE will be further analyzed in Aim 3. Finally, Aim 4 will evaluate whether the X protein activates cell cycle-dependent genes to support HBV regulation. For these studies, a transgenic mouse will be constructed to incorporate a functional HBV genome, but with a defective X gene. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF GLYCINE DECARBOXYLASE IN HEPADNAVIRAL INFECTION Principal Investigator & Institution: Li, Jisu; Assistant Professor; Rhode Island Hospital (Providence, Ri) Providence, Ri 02903 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: Hepatitis B virus is a major cause of liver cirrhosis and hepatocellular carcinoma (HCC). A better understanding of the viral life cycle may provide targets for the intervention of HBV infection, thus reducing the risk of HBV-related HCC. However, the early stages of the viral life cycle and viral-host interactions that contribute to viral infection and pathogenicity are poorly understood. This 421 exploratory proposal focuses on studies on a hepadna virus interacting protein, p120/glycine decarboxylase. We have previous found that p120 is a binding partner of an avian hepatitis B virus envelope protein. It is expressed only in the virus infectable tissues and its expression level is directly correlated with the cellular susceptibility to virus infection. It is expressed only in the virus infectable tissues and its expression level is directly correlated with the cellular susceptibility to virus infection. Moreover, viral mutants with an ablated p120-binding site showed reduced infectivity despite wild-type replication capacity. These findings suggest that p120 is associated with the early stage of the viral life cycle. Therefore, we plan to further establish its role in the viral life cycle by genetic approaches. Specific Aim #1 will determine if inhibition of p120 expression or function in well-differentiated duck hepatocytes will reduce susceptibility to viral infection. Specific Aim #2 will examine whether reconstitution of p120 in dedifferentiated duck hepatocytes will restore productive viral infection. In addition, we will determine if p120 is defective in Muscovy ducks, a duck species resistant to hepadnavirus. We will also explore the possibility to restore viral infection by p120 derived from a susceptible Pekin ducks. These studies will provide further information on virus-cell interactions and may lead to development of novel anti-viral strategies for prevention of HBV induced liver cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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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 •

Project Title: SELF CLEAVING RNA AND TRANS ACTING RIBOZYMES Principal Investigator & Institution: Been, Michael D.; Professor; Biochemistry; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 30-SEP-1992; Project End 31-AUG-2002 Summary: The objective of the proposed research is to understand the structure, mechanism, and biological role of self-processing RNA (ribozymes). The ribozymes being studied are self-cleaving sequence associated with the genomic and antigenomic RNA of hepatitis delta virus (HDV). HDV is a human pathogen but is always found in association with hepatitis B virus. The combination leads to serious liver damage with a higher fatality rate that in patients infected only with hepatitis B virus. Thus, in populations where hepatitis B is endemic, HDV can be a serious health threat. It can either be co-transmitted with hepatitis B causing the acute form of the disease or it can infect hepatitis B carriers; the later tends to be more serious. The ribozyme activity is thought to be essential to the replication of the RNA genome of this virus. A greater understanding of the ribozyme structure, cleavage mechanism, and role in replication could lead to a method to block viral replication. In addition because the self-cleaving RNA from HDV is the first clear example of a self-cleaving RNA that functions naturally in human cells; an understanding those features that are unique to this RNA may facilitate the design of ribozymes to be used in therapeutics. The specific aims of the proposal are: (1) To generate and refine a three dimensional model for the HDV ribozyme and utilize the models to evaluate biochemical and genetic data on the ribozyme structure and mechanism. Molecular modeling programs, some of which are designed Specifically for RNA, will be used to generate models that are consistent with constraints on the structure established experimentally. Data gathered from physical methods will also be used, and towards this end methods for making large quantities of circular RNA will be used to produce RNA for crystallography. (2) To test and refine the structure through biochemical and genetic approaches. Methods include chemical protection, substitution interference, in vitro mutagenesis and in vitro selection. (3) To define the mechanism and requirements of the reaction. A complete kinetic scheme for the trans-reaction will developed and the stereochemistry of the reaction will defined. (4) To characterize and define cis-acting sequences that interfere with cleavage activity and may limit ribozyme cleavage to the nascent transcript. As part of this study templates for making concatameric RNA sequences that mimic replication of the RNA from a circular template will be developed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SEXUAL HEALTH PRACTICES OF HOMELESS ADOLESCENTS Principal Investigator & Institution: Rew, Donna L.; Professor; None; University of Texas Austin 101 E. 27Th/Po Box 7726 Austin, Tx 78712

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Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-MAR-2002 Summary: This study is in response to the program announcement, Health Risk Reduction: Community-Based Strategies, and is an essential step in developing culturally relevant interventions to promote positive sexual health practices and outcomes among homeless adolescents. The specific aims are to 1) describe the sexual health practices, including prevalence and incidence of STD testing, diagnosis, and treatment as well as the prevalence and incidence of immunizations for hepatitis B, of homeless adolescents; 2) examine the relationships among variables in the conceptual model of sexual health practices: sociodemographics, sexual history, culture of homelessness, cognitive perceptual factors, behavioral factors, and individual sexual health practices of homeless adolescents; 3) determine the indirect effects of sociodemographics, sexual history, and culture of homelessness, and the direct effects of cognitive perceptual factors and behavioral factors on individual sexual health practices of homeless adolescents; and 4) explore with homeless adolescents the feasibility of developing culturally relevant interventions to promote positive sexual practices in this population through (a) focus groups that explore their perceptions of factors that are culturally relevant, and (b) comparing characteristics of those subjects who remain connected to the project site for periods of 3, 6, 9, and 12 months and characteristics of those who leave the area during these time intervals. A convenience sample of 460 homeless youth will be surveyed to describe their sexual health practices and to examine relationships among theoretical variables through structural equation modeling. A subsample of 40 homeless youth will participate in focus groups to provide their perspectives on community-based interventions to reduce the risk of sexually transmitted diseases (STDs) that would be culturally relevant and feasible for them. The expected outcomes of the study are the refinement of a theoretical model of sexual health practices that will provide a framework for interventions to reduce the prevalence and incidence of STDs in vulnerable homeless adolescents. 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

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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 •

Project Title: STRUCTURE/FUNCTION STUDIES OF S100 PROTEINS AND P53 Principal Investigator & Institution: Weber, David J.; Associate Professor; Biochem and Molecular Biology; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 01-FEB-1999; Project End 31-JAN-2007 Summary: (provided by applicant): During the last 3 years, (i) high yields (>30 mg purified protein/liter media) of S 100B, S 100A 1, S 100A3, CAN19, mtsl, p53, p53(324393), p53(303-393), p53(303-367), hepatitis B viral protein X (HBVX), SUMO-1, Cterminal fragment of myosin IIA(1900-1961), and the HMG A box of the high mobility group protein- 1 (HMG-1) were prepared in minimal media as necessary for isotopic labeling (2H, 13C, 15N, etc). (ii) We determined the solution structures of apo-S 100B, apo-S 100A 1, calcium-bound S 100B, and calcium-bound S 100B in a complex with the negative regulatory domain of p53 (residues 367-388). (iii) We showed that dimeric S 100B is the physiologically relevant oligomerization state of S 100B, and that S 100B inhibits protein kinase C (PKC) phosphorylation of p53. (iv) We developed cellularbased assays for p53 and showed that p53 function is inhibited in tumor cell lines as a result of the calcium-dependent p53-S 100B interaction. This interaction includes both the oligomerization and negative regulatory domains at the C-terminus of p53. We plan to continue characterizing the calcium-dependent interaction of S 100B with the tumor suppressor protein p53. The effects that p53 phosphorylation, acetylation, and sumoylation have on S 100B binding will be examined. The binding of zinc to S 100B and heterodimer formation (i.e. S 100A 1/S 100B, CaN 19/S 100B and mts 1/S 100B etc.) will also be characterized. These data are necessary to determine whether covalent modifications of p53 and/or other S100B binding events affect S100B-p53 complex formation and function We will also determine the 3D structure of calcium-bound S100B complexed with a larger construct of p53 that includes both the oligomerization and the C-terminal regulatory domains of p53 (residues 324-393; Kd=24nM). Heteronuclear relaxation measurements for backbone and sidechain resonances are planned for all of the structures that we solve (or have solved) in order to clarify how calcium and p53 binding affects the dynamics of S100B (and p53). These dynamic data will be used in a search for small molecule inhibitors of the S 100B-p53 interaction. Lastly, the 3D solution structures of other proteins that bind the C-terminus of p53 will be examined including the metastasis protein 1 (mts 1), S100A3, the CaN 19 tumor suppressor, the hepatitis B viral protein (HBVX), the p53 binding domain of BLM, and the A box ofHMG-1. It will be interesting to determine whether these or other p53-binding proteins enhance and/or compete with the S 100B-p53 interaction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TARGETED GENE DELIVERY AND EXPRESSION IN HEPATOCYTES Principal Investigator & Institution: Wu, George Y.; Chief, Div of Gastroenterology; Medicine; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, Ct 060302806 Timing: Fiscal Year 2001; Project Start 01-JAN-1990; Project End 31-JAN-2006 Summary: (Adapted from the Applicant's Abstract): In the previous grant period, we developed a multicomponent DNA carrier that, through the incorporation of endosomolytic peptides, is capable of releasing targeted nucleic acids directly to the cytoplasm of hepatocytes. Using multicomponent carriers, the efficiency of delivery of nucleic acids into cells was increased by 3 orders of magnitude, and the amount of DNA introduced into the nuclei in animals was increased 1 to 2 orders of magnitude compared to the originally described system. Recently, we have developed new approaches to enhance integration of targeted genes in cell culture resulting in persistent transgene expression. The objective of the current project is to take advantage of these advances to evaluate a novel therapeutic strategy against hepatitis B viral infection: transfection-mediated therapeutic selection. The hypothesis is: integrative transfection of antiviral genes will result in continuous inhibition of HBV gene expression, and block production of viral antigens. Under the pressure of host cellmediated immune response against cells bearing HBV antigens, there will be a selective survival advantage to transfected cells and their progeny. The antiviral agents are proposed to be generated from genes whose products are directed against unique features of the HBV life cycle, blocking translation, and replication. These areas distinguish viral processes from those of the mammalian host in order to achieve efficacy without toxicity. Candidates will be screened using stable HBV expression models in cell culture first to identify optimal constructs. Agents will be targeted to liver by complexation with multicomponent carriers, and also by genetic engineering into chimeric adeno-associated viral vectors all with integration enhancement capability. After optimization and comparison in an HBV cell culture model system, antiviral agents will be used to test the therapeutic approach in an animal model of HBV infection. Agents will be prepared against analogous sequences in the Woodchuck Hepatitis Virus (WHV), a homologous hepadna virus. Efficacy of long-term inhibition of HBV gene expression and replication, and evidence of selective survival advantage of cells bearing integrated antiviral genes will be determined over the time course, and optimal agents compared. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: TRANSCRIPTION ACTIVATION BY HIV, TAT, HTLV TAX & HBV PX Principal Investigator & Institution: Green, Michael R.; Professor; Molecular Medicine; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2001; Project Start 01-SEP-1990; Project End 31-AUG-2005 Summary: (from investigator's abstract): This is a competitive renewal application. The previous grant was for studying how the trancriptional regulatory proteins of three pathogenic viruses activate transcription, specifically, the Tat protein of human immunodeficiency virus type 1 (HIV-1), the Tax protein of human T-cell leukemia virus type 1 (HTLV-1), and the pX protein of hepatitis B virus (HBV). In this application, the applicant seeks to understand in greater detail the mechanism of action of these viral regulatory proteins and their role in viral replication and human disease. The rationale

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for the proposal relies heavily on two relatively new technologies. First, the chromatin immunoprecipitation (ChIP) assay, which allows for the detection of specific proteins that are physically associated with DNA in living cells. Second, the genome-wide expression analysis using high density DNA microarrays, which enables the analysis of transcription profiles of a large array of human genes. The specific aims are: (1) To understand in greater detail how HIV-1 Tat stimulates transcription in vitro and in vivo. The investigator has identified a Tat cofactor, Tat-SF1, and has shown that it is a general transcription elongation factor. A second elongation factor has been implicated, AIEF, and remains to be identified. Tat-SF1 and AIEF and the mechanisms of Tat activation in vivo will be investigated further. (2) To study how HTLV-1 Tax and HBV pX regulates DNA binding of cellular bZIP proteins. The investigator has shown that Tax and pX dramatically increase the DNA binding activity and alter the target selectivity of a wide variety of cellular proteins that possess a basic region-leucine zipper (bZIP) DNA binding domain, through promotion of dimerization. Experiments are proposed to undersstand the basis of altered DNA binding specificity, the cellular proteins involved, and details of the DNA-protein interactions. (3) To analyze how HTLV-1 Tax and HBV pX activate transcription in vivo and transform cells. To test the prediction of different models of how these proteins activate transcription, to identify cellular proteins involved in the activation, and to identify cellular genes activated that may contribute to disease. (4) To understand the mechanism of BEF action. The investigator has identified a nuclear protein BEF (for bZIP-enhancing factor) which is required for bZIP prtoein functions, work synergistically with Tax and pX. However, BEF works by a different mechanism, as a molecular chaperone. Experiments are proposed to further study the mechanism of BEF action. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRANSIENT GLUCOSYLATION OF GLYCOPROTEINS Principal Investigator & Institution: Parodi, Armando J.; Instituto De Investigaciones Bioquimicas Bioquimicas Fundacion Campomar Buenos Aires, Timing: Fiscal Year 2001; Project Start 15-AUG-1990; Project End 31-MAY-2003 Summary: Protein glycosylation is initiated in the endoplasmic reticulum (ER) by transfer of an oligosaccharide (Glc3Man9GlcNAc2) to nascent polypeptide chains. Processing of the oligosaccharide by glucosidases I and II yields unglucosylated oligosaccharides that are reglucosylated by the UDP-Glc:glycoprotein glucosyltransferase (GT) only if the protein moieties of glycoproteins are not properly folded, as GT behaves as a sensor of glycoprotein conformations. Interaction of monoglucosylated glycoproteins (created by partialdeglucosylation of the transferred compound or by GT-mediated reglucosylation) with ER lectins (calnexin and calreticulin) facilitates acquisition of the proper tertiary structures and prevents secretion of not yet properly folded species. Folding facilitation mediated by the interaction of monoglucosylated glycoproteins and ER lectins is necessary for production of infective viral particles (vesicular stomatitis virus, HIV, hepatitis B virus) and also for the viability of yeasts when under severe ER stress conditions. The long term objective of the proposal is to gain thorough information of the structural features leading to the monoglucosylated glycoprotein-lectin interaction as this knowledge will undoubtedly provide useful information for understanding and/or preventing production of the etiological agents of several diseases. Within this long term objective, the Specific Aims of the proposed research are: a) to define the structural elements exclusively exposed in misfolded glycoproteins whose recognition is required for GTmediated glucosylation; b) to define GT domains responsible for substrate donor (UDP-

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Glc), and substrate acceptor (N-oligosaccharide) recognition and for the exclusive glucosylation of misfolded species and c) to study the possibility that folding facilitation mediated by the interaction of cruzipain, a cysteine proteinase from the protozoan parasite Trypanosoma cruzi and ER lectins could be absolutely necessary for parasite infectivity. T. cruzi is the causative agent of a disease endemic in Latin America (Chagas's disease) that affects about 16 million people. Cruzipain has been identified as one of the T. cruzi virulence factors and has been found to be the only glycoprotein interacting with ER lectins in the protozoon. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VIRAL INDUCED HCC?

ANTIGEN

GLYCOSYLATION--MARKER

FOR

HBV

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 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): In this exploratory program we propose to test the hypothesis that oligosaccharides associated with serum proteins can accurately serve as biomarkers. Oligosaccharide profiles of hepatitis B surface antigens (HBsAg), purified from patient sera of different clinical populations, will be generated using novel HPLC sequencing technology that can reproducibly quantitate greater than 0.1 percent of an individual oligosaccharide in a glycan pool. Our sample population will consist of patients at risk for, or diagnosed with, hepatocellular carcinoma (HCC). The data generated will allow HBsAg oligosaccharides to be compared between different patient populations and the potential diagnostic value to be assessed. Alteration in the oligosaccharides associated with glycoproteins is one of the many molecular changes that accompany malignant transformations. In the case of HCC, an increase in fucosylation of secreted liver proteins is a common alteration. This increase in fucosylation has been postulated as a marker for HCC, however, the proteins of interest that show this alteration are typically found in low abundance (e.g. alpha fetoprotein). Our hypothesis is that, in cases where infection with hepatitis B virus (HBV) leads to the development of HCC, the viral glycoproteins (present up to mg/ml concentration) themselves may display aberrant oligosaccharides that could serve as early detection markers for HCC. Infection with HBV is the major etiology of HCC and, although HCC is a less common cancer in the USA, recent studies have shown that the incidence of HCC is rising both in the USA and worldwide. In addition, HCC is one of the most aggressive malignancies with prognosis being poor due to the late diagnosis. With the paucity of organ donors for liver transplantation and the small number of treatable patients (due to, in part, late diagnosis), early diagnosis will allow intervention at an earlier stage. We expect that this pilot study will firstly generate preliminary data to support the stated hypothesis; secondly, the study will allow the feasibility of a larger study to be determined, and thirdly, the parameters required to design a larger study to determine the value of oligosaccharide structures as potential markers of disease status will be obtained. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VIRUSES AND CANCER Principal Investigator & Institution: Courtney, Richard J.; Professor; Microbiology and Immunology; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033

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Timing: Fiscal Year 2001; Project Start 06-MAY-1994; Project End 31-MAR-2004 Summary: Defining the complex mechanisms of viral oncogenesis requires a broad understanding in at least three areas of research: molecular and cellular biology, immunology, and virology. It is the goal of the proposed training program to provide graduate students and postdoctoral fellows a challenging and enriched scientific environment in which both formal and informal training within these three broad, but interrelated areas can occur. The breadth of the scientific interests of the training faculty create a blend of research areas, many of which incorporate virus systems to dissect the molecular events that occur within the normal versus the cancer cell. The specific research programs include (a) molecular and cellular biology-regulation of cell growth and gene expression, oncogenes, signal transduction, and mechanisms of neoplastic transformation; (b) immunology-expression, oncogenes, signal transduction, and mechanisms of neoplastic transformation; (b) immunology; and (c) virology-molecular studies of virus replication, assembly, oncogenesis, pathogenesis, latency, and gene regulation using adeno, cytomegalo, hepatitis B, herpes simplex, papilloma, papova, and retroviruses. The trainers associated with the proposed training grant have their primary academic appointments within the Department of Microbiology and Immunology. However, each of the trainers is associated with multiple interdisciplinary graduate programs which cross departmental and college boundaries. Graduate students eligible for appointment on the training grant may be associated with one of several graduate programs including Chemical Biology, Cell and Molecular Biology, Genetics, Microbiology and Immunology, Molecular Medicine, and Neurosciences. The potential of the trainers to recruit students from such a variety of programs helps to insure that a significant pool of highly qualified students will be available for appointment to the training grant. The training program for graduate students and postdoctoral fellows includes a dynamic research environment that has excellent research and core support facilities and faculty research laboratories with productive and well funded research programs. The research and training environment is further enhanced by numerous interactions among the various laboratories as well as journal clubs, student seminars, and visiting scientist seminar programs. Finally, the research areas of emphasis within the training program provide a broad foundation on which a creative student and postdoctoral fellow can base a productive career in research in the area of citruses and cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

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 Suite 211 Ub Commons Amherst, Ny 14228 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 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

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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 •

Project Title: WOMEN DRUG USERS, THEIR MALE PARTNERS AND HIV RISK Principal Investigator & Institution: Tortu, Stephanie A.; Associate Professor; National Development & Res Institutes Research Institutes, Inc. New York, Ny 10010 Timing: Fiscal Year 2001; Project Start 15-DEC-1999; Project End 30-NOV-2003 Summary: In the US, the number of women drug users diagnosed with AIDS continues to increase, and levels of sexual risk behaviors remain high. Theoretical and empirical work has indicated that drug using women's relationships with male sex partners are focal points of risky sexual behavior and drug use. To inform HIV prevention efforts, there is a need to explore women's relationship with their main sexual partners, and determine how relationship factors affect HIV risk. Drug using women (primarily African-American and Puerto Rican) will be recruited from the streets of East Harlem. Those who report use of crack/cocaine, injected drugs, of 360 couples (n=720) will complete structured interviews. In addition to demographic and socioeconomic characteristics, drug use, and HIV risk behaviors, the interview will measure: 1) dyadic factors (e.g., characteristics of the relationship, drug use patterns, interpersonal processes); 2) individual attributes (e.g., history of physical/sexual abuse, psychological functioning, HIV serostatus); and 3) situation specific variables in most recent sex events. HIV, hepatitis B, and Hepatitis C testing and counseling will be offered. Multivariate statistical techniques will be used to determine the effects of dyadic factors, individual attributes, and their interaction on HIV risk behaviors. The prevalence of HIV, HBV, and HCV infections will be assessed, as will the couples will be compared in terms of drug use patterns, interpersonal processes, relationship satisfaction, and partner support. Results of this project will be used to develop interventions targeted at drug using couples to reduce HIV risk behaviors and assist those who are living with HIV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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 B” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for hepatitis B in the PubMed Central database: •

(-)-cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine (524W91) inhibits hepatitis B virus replication in primary human hepatocytes. by Condreay LD, Condreay JP, Jansen RW, Paff MT, Averett DR.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163151

•

2',3'-dideoxy-beta-L-5-fluorocytidine inhibits duck hepatitis B virus reverse transcription and suppresses viral DNA synthesis in hepatocytes, both in vitro and in vivo. by Zoulim F, Dannaoui E, Borel C, Hantz O, Lin TS, Liu SH, Trepo C, Cheng YC.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163132

•

A bulged region of the hepatitis B virus RNA encapsidation signal contains the replication origin for discontinuous first-strand DNA synthesis. by Nassal M, Rieger A.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190133

•

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&artid=109410

•

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&artid=89731

•

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

3 4

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 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&artid=112021

•

A Hepatitis B Virus Pre-S-Retinoic Acid Receptor [beta] Chimera Transforms Erythrocytic Progenitor Cells In vitro. by Garcia M, de The H, Tiollais P, Samarut J, Dejean A.; 1993 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45605

•

A host factor that binds near the termini of hepatitis B virus pregenomic RNA. by Perri S, Ganem D.; 1996 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190725

•

A Metastable Form of the Large Envelope Protein of Duck Hepatitis B Virus: Low-pH Release Results in a Transition to a Hydrophobic, Potentially Fusogenic Conformation. by Grgacic EV, Schaller H.; 2000 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110864

•

A Modified Hepatitis B Virus Core Particle Containing Multiple Epitopes of the Plasmodium falciparum Circumsporozoite Protein Provides a Highly Immunogenic Malaria Vaccine in Preclinical Analyses in Rodent and Primate Hosts. by Birkett A, Lyons K, Schmidt A, Boyd D, Oliveira GA, Siddique A, Nussenzweig R, Calvo-Calle JM, Nardin E.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=133050

•

A Multicenter Study Evaluation of the Digene Hybrid Capture II Signal Amplification Technique for Detection of Hepatitis B Virus DNA in Serum Samples and Testing of EUROHEP Standards. by Niesters HG, Krajden M, Cork L, de Medina M, Hill M, Fries E, Osterhaus AD.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86750

•

A novel method for efficient amplification of whole hepatitis B virus genomes permits rapid functional analysis and reveals deletion mutants in immunosuppressed patients. by Gunther S, Li BC, Miska S, Kruger DH, Meisel H, Will H.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189390

•

A plant signal peptide --hepatitis B surface antigen fusion protein with enhanced stability and immunogenicity expressed in plant cells. by Sojikul P, Buehner N, Mason HS.; 2003 Mar 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151319

•

A Recombinant Measles Virus Expressing Hepatitis B Virus Surface Antigen Induces Humoral Immune Responses in Genetically Modified Mice. by Singh M, Cattaneo R, Billeter MA.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112525

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A revised secondary structure model for the 3'-end of hepatitis B virus pregenomic RNA. by Kidd AH, Kidd-Ljunggren K.; 1996 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=146111

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A short linear sequence in the pre-S domain of the large hepatitis B virus envelope protein required for virion formation. by Bruss V.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230238

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A Short N-Proximal Region in the Large Envelope Protein Harbors a Determinant That Contributes to the Species Specificity of Human Hepatitis B Virus. by Chouteau P, Le Seyec J, Cannie I, Nassal M, Guguen-Guillouzo C, Gripon P.; 2001 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114743

•

A Short Sequence within Domain C of Duck Carboxypeptidase D Is Critical for Duck Hepatitis B Virus Binding and Determines Host Specificity. by Spangenberg HC, Lee HB, Li J, Tan F, Skidgel R, Wands JR, Tong S.; 2001 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114645

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A Single Amino Acid in the Reverse Transcriptase Domain of Hepatitis B Virus Affects Virus Replication Efficiency. by Lin X, Yuan ZH, Wu L, Ding JP, Wen YM.; 2001 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114769

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A Small Molecule Inhibits and Misdirects Assembly of Hepatitis B Virus Capsids. by Zlotnick A, Ceres P, Singh S, Johnson JM.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136179

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A t(3;8) chromosomal translocation associated with hepatitis B virus intergration involves the carboxypeptidase N locus. by Pineau P, Marchio A, Terris B, Mattei MG, Tu ZX, Tiollais P, Dejean A.; 1996 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190789

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A Trans-Activator Function is Generated by Integration of Hepatitis B Virus PreS/S Sequences in Human Hepatocellular Carcinoma DNA. by Caselmann WH, Meyer M, Kekule AS, Lauer U, Hofschneider PH, Koshy R.; 1990 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53815

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A Truncated Mutant (Residues 58-140) of the Hepatitis B Virus X Protein Retains Transactivation Function. by Kumar V, Jayasuryan N, Kumar R.; 1996 May 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39302

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Aberrant trafficking of hepatitis B virus glycoproteins in cells in which N-glycan processing is inhibited. by Lu X, Mehta A, Dadmarz M, Dwek R, Blumberg BS, Block TM.; 1997 Mar 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20096

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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

•

Activation of a heterogeneous hepatitis B (HB) core and e antigen-specific CD4+ Tcell population during seroconversion to anti-HBe and anti-HBs in hepatitis B virus infection. by Jung MC, Diepolder HM, Spengler U, Wierenga EA, Zachoval R, Hoffmann RM, Eichenlaub D, Frosner G, Will H, Pape GR.; 1995 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189048

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Activation of hepatitis B virus S promoter by the viral large surface protein via induction of stress in the endoplasmic reticulum. by Xu Z, Jensen G, Yen TS.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=192084

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Acute hepatitis B infection associated with blood transfusion in England and Wales, 1991-7: review of database. by Soldan K, Ramsay M, Collins M.; 1999 Jan 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27683

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Acute Hepatitis in Rats Expressing Human Hepatitis B Virus Transgenes. by Takahashi H, Fujimoto J, Hanada S, Isselbacher KJ.; 1995 Feb 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42541

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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&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&artid=104572

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An 80-Kilodalton Protein That Binds to the Pre-S1 Domain of Hepatitis B Virus. by Ryu CJ, Cho DY, Gripon P, Kim HS, Guguen-Guillouzo C, Hong HJ.; 2000 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111519

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Analysis of Duck Hepatitis B Virus Reverse Transcription Indicates a Common Mechanism for the Two Template Switches during Plus-Strand DNA Synthesis. by Havert MB, Ji L, Loeb DD.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135997

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Anergic TH1 clones specific for hepatitis B virus (HBV) core peptides are inhibitory to other HBV core-specific CD4+ T cells in vitro. by Diepolder HM, Jung MC, Wierenga E, Hoffmann RM, Zachoval R, Gerlach TJ, Scholz S, Heavner G, Riethmuller G, Pape GR.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190822

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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&artid=96143

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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, 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&artid=104602

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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&artid=114797

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Anti-Hepatitis B Virus Activity and Metabolism of 2[prime prime or minute],3[prime prime or minute]-Dideoxy-2[prime prime or minute],3[prime prime or minute]Didehydro-[beta]-l([minus sign])-5-Fluorocytidine. by Zhu YL, Dutschman GE, Liu SH, Bridges EG, Cheng YC.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105687

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Antiviral Activities of MCC-478, a Novel and Specific Inhibitor of Hepatitis B Virus. by Kamiya N, Kubota A, Iwase Y, Sekiya K, Ubasawa M, Yuasa S.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127398

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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&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&artid=104546

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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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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&artid=88264

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Automated Quantitative Analysis of Hepatitis B Virus DNA by Using the Cobas Amplicor HBV Monitor Test. by Noborg U, Gusdal A, Pisa EK, Hedrum A, Lindh M.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85382

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Avian Hepatitis B Virus Infection Is Initiated by the Interaction of a Distinct Pre-S Subdomain with the Cellular Receptor gp180. by Urban S, Breiner KM, Fehler F, Klingmuller U, Schaller H.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110146

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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&artid=84333

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Carboxypeptidase D (gp180), a Golgi-Resident Protein, Functions in the Attachment and Entry of Avian Hepatitis B Viruses. by Breiner KM, Urban S, Schaller H.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110147

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Carboxypeptidase D Is an Avian Hepatitis B Virus Receptor. by Tong S, Li J, Wands JR.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112890

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Carrier-Mediated Delivery of 9-(2-Phosphonylmethoxyethyl)Adenine to Parenchymal Liver Cells: a Novel Therapeutic Approach for Hepatitis B. by de Vrueh RL, Rump ET,

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van de Bilt E, van Veghel R, Balzarini J, Biessen EA, van Berkel TJ, Bijsterbosch MK.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89714 •

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&artid=140637

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Cell Cycle Regulation of Nuclear Localization of Hepatitis B Virus Core Protein. by Yeh C, Wong SW, Fung Y, Ou J.; 1993 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46951

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Cellular Receptor Traffic Is Essential for Productive Duck Hepatitis B Virus Infection. by Breiner KM, Schaller H.; 2000 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111701

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Changes in the Antigenicity of a Hepatitis B Virus Mutant Stemming from Lamivudine Therapy. by Chen WN, Oon CJ.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89956

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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&artid=136184

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Characterization of a Conformational Epitope on Hepatitis B Virus Core Antigen and Quasiequivalent Variations in Antibody Binding. by Conway JF, Watts NR, Belnap DM, Cheng N, Stahl SJ, Wingfield PT, Steven AC.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155010

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Characterization of CD8+ cytotoxic T-lymphocyte responses after genetic immunization with retrovirus vectors expressing different forms of the hepatitis B virus core and e antigens. by Townsend K, Sallberg M, O'Dea J, Banks T, Driver D, Sauter S, Chang SM, Jolly DJ, Mento SJ, Milich DR, Lee WT.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191480

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Characterization of humoral and CD4+ cellular responses after genetic immunization with retroviral vectors expressing different forms of the hepatitis B virus core and e antigens. by Sallberg M, Townsend K, Chen M, O'Dea J, Banks T, Jolly DJ, Chang SM, Lee WT, Milich DR.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191766

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Characterization of Novel Human Hepatoma Cell Lines with Stable Hepatitis B Virus Secretion for Evaluating New Compounds against Lamivudine- and PenciclovirResistant Virus. by Fu L, Cheng YC.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90212

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Characterization of Nuclear RNases That Cleave Hepatitis B Virus RNA near the La Protein Binding Site. by Heise T, Guidotti LG, Chisari FV.; 2001 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114415

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Characterization of the Antiviral Effect of 2[prime prime or minute],3[prime prime or minute]-Dideoxy-2[prime prime or minute], 3[prime prime or minute]-Didehydro[beta]-l-5-Fluorocytidine in the Duck Hepatitis B Virus Infection Model. by Le

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Guerhier F, Pichoud C, Guerret S, Chevallier M, Jamard C, Hantz O, Li XY, Chen SH, King I, Trepo C, Cheng YC, Zoulim F.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89636 •

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&artid=110046

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Chimeric hepatitis B virus core particles as probes for studying peptide-integrin interactions. by Chambers MA, Dougan G, Newman J, Brown F, Crowther J, Mould AP, Humphries MJ, Francis MJ, Clarke B, Brown AL, Rowlands D.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190284

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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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Cloning and Characterization of a Novel Hepatitis B Virus x Binding Protein That Inhibits Viral Replication. by Melegari M, Scaglioni PP, Wands JR.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109461

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Combinatorial Screening and Intracellular Antiviral Activity of Hairpin Ribozymes Directed against Hepatitis B Virus. by zu Putlitz J, Yu Q, Burke JM, Wands JR.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112594

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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&artid=87814

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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&artid=95975

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Comparison of Anti-Hepatitis B Virus Activities of Lamivudine and Clevudine by a Quantitative Assay. by Abdelhamed AM, Kelley CM, Miller TG, Furman PA, Cable EE, Isom HC.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=148955

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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 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 Sequence Analysis and the INNO-LiPA HBV DR Line Probe Assay for Detection of Lamivudine-Resistant Hepatitis B Virus Strains in Patients under

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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&artid=88061 •

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&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&artid=87356

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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&artid=130099

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Core Protein Phosphorylation Modulates Pregenomic RNA Encapsidation to Different Extents in Human and Duck Hepatitis B Viruses. by Gazina EV, Fielding JE, Lin B, Anderson DA.; 2000 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111994

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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&artid=114371

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Critical Roles of Nuclear Receptor Response Elements in Replication of Hepatitis B Virus. by Yu X, Mertz JE.; 2001 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114721

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Cross-Resistance Testing of Antihepadnaviral Compounds Using Novel Recombinant Baculoviruses Which Encode Drug-Resistant Strains of Hepatitis B Virus. by Delaney WE IV, Edwards R, Colledge D, Shaw T, Torresi J, Miller TG, Isom HC, Bock CT, Manns MP, Trautwein C, Locarnini S.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90535

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Cytokine-Sensitive Replication of Hepatitis B Virus in Immortalized Mouse Hepatocyte Cultures. by Pasquetto V, Wieland SF, Uprichard SL, Tripodi M, Chisari FV.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137053

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Cytotoxic T Lymphocytes Inhibit Hepatitis B Virus Gene Expression by a Noncytolytic Mechanism in Transgenic Mice. by Guidotti LG, Ando K, Hobbs MV, Ishikawa T, Runkel L, Schreiber RD, Chisari FV.; 1994 Apr 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43662

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DDB2 Induces Nuclear Accumulation of the Hepatitis B Virus X Protein Independently of Binding to DDB1. by Nag A, Datta A, Yoo K, Bhattacharyya D, Chakrabortty A, Wang X, Slagle BL, Costa RH, Raychaudhuri P.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114612

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Hepatitis B

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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&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 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&artid=103945

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Detection of Duck Hepatitis B Virus DNA on Filter Paper by PCR and SYBR Green Dye-Based Quantitative PCR. by Wang CY, Giambrone JJ, Smith BF.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120600

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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&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&artid=111941

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Development and comparison of procedures for the selection of delta ribozyme cleavage sites within the hepatitis B virus. by Bergeron LJ, Perreault JP.; 2002 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135815

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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&artid=87141

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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&artid=115022

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Different Regions of Hepatitis B Virus X Protein Are Required for Enhancement of bZip-Mediated Transactivation versus Transrepression. by Barnabas S, Andrisani OM.; 2000 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111516

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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 Regulation of Hepatitis B Virus Gene Expression by the Sp1 Transcription Factor. by Li J, Ou JH.; 2001 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115085

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97

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Differential regulation of the pre-C and pregenomic promoters of human hepatitis B virus by members of the nuclear receptor superfamily. by Yu X, Mertz JE.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230240

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Direct Association and Nuclear Import of the Hepatitis B Virus X Protein with the NF-[kappa]B Inhibitor I[kappa]B[alpha]. by Weil R, Sirma H, Giannini C, Kremsdorf D, Bessia C, Dargemont C, Brechot C, Israel A.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84605

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Direct interaction of the hepatitis B virus HBx protein with p53 leads to inhibition by HBx of p53 response element-directed transactivation. by Truant R, Antunovic J, Greenblatt J, Prives C, Cromlish JA.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=188796

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Discontinuous Epitopes of Hepatitis B Surface Antigen Derived from a Filamentous Phage Peptide Library. by Chen YJ, Delbrook K, Dealwis C, Mimms L, Mushahwar IK, Mandecki W.; 1996 Mar 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39898

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Distinct Modes of Regulation of Transcription of Hepatitis B Virus by the Nuclear Receptors HNF4[alpha] and COUP-TF1. by Yu X, Mertz JE.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=141100

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Distribution of Hepatitis B Virus Genotypes among American Blood Donors Determined with a PreS2 Epitope Enzyme-Linked Immunosorbent Assay Kit. by Moriya T, Kuramoto IK, Yoshizawa H, Holland PV.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120221

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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&artid=105331

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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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DNA-Mediated Immunization to the Hepatitis B Surface Antigen in Mice: Aspects of the Humoral Response Mimic Hepatitis B Viral Infection in Humans. by Michel M, Davis HL, Schleef M, Mancini M, Tiollais P, Whalen RG.; 1995 Jun 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41683

98

Hepatitis B

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dNTP versus NTP discrimination by phenylalanine 451 in duck hepatitis B virus P protein indicates a common structure of the dNTP-binding pocket with other reverse transcriptases. by Beck J, Vogel M, Nassal M.; 2002 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101827

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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&artid=127249

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Double-Stranded Linear Duck Hepatitis B Virus (DHBV) Stably Integrates at a Higher Frequency than Wild-Type DHBV in LMH Chicken Hepatoma Cells. by Gong SS, Jensen AD, Chang CJ, Rogler CE.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103974

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Duck Hepatitis B Virus Expresses a Regulatory HBx-Like Protein from a Hidden Open Reading Frame. by Chang SF, Netter HJ, Hildt E, Schuster R, Schaefer S, Hsu YC, Rang A, Will H.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113909

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Duck Hepatitis B Virus Nucleocapsids Formed by N-Terminally Extended or CTerminally Truncated Core Proteins Disintegrate during Viral DNA Maturation. by Kock J, Wieland S, Blum HE, von Weizsacker F.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110329

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Duck Hepatitis B Virus Replication in Primary Bile Duct Epithelial Cells. by Lee JY, Culvenor JG, Angus P, Smallwood R, Nicoll A, Locarnini S.; 2001 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115000

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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&artid=84922

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Effects of a naturally occurring mutation in the hepatitis B virus basal core promoter on precore gene expression and viral replication. by Buckwold VE, Xu Z, Chen M, Yen TS, Ou JH.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190601

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Effects of Genomic Length on Translocation of Hepatitis B Virus Polymerase-Linked Oligomer. by Ho TC, Jeng KS, Hu CP, Chang C.; 2000 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102097

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Effects of mutations within and adjacent to the terminal repeats of hepatitis B virus pregenomic RNA on viral DNA synthesis. by Perri S, Ganem D.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=192307

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Effects of Pyrimidine and Purine Analog Combinations in the Duck Hepatitis B Virus Infection Model. by Seigneres B, Martin P, Werle B, Schorr O, Jamard C, Rimsky L, Trepo C, Zoulim F.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155836

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Efficacies of Entecavir against Lamivudine-Resistant Hepatitis B Virus Replication and Recombinant Polymerases In Vitro. by Levine S, Hernandez D, Yamanaka G, Zhang S, Rose R, Weinheimer S, Colonno RJ.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127388

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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&artid=106024

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Efficient Extraction of Virus DNA by NucliSens Extractor Allows Sensitive Detection of Hepatitis B Virus by PCR. by Gobbers E, Oosterlaken TA, van Bussel MJ, Melsert R, Kroes AC, Claas EC.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88546

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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&artid=114913

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Elimination of Duck Hepatitis B Virus RNA-Containing Capsids in Duck InterferonAlpha-Treated Hepatocytes. by Schultz U, Summers J, Staeheli P, Chisari FV.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112602

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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&artid=124627

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Enhancement of Hepatitis B Virus Replication by Its X Protein in Transgenic Mice. by Xu Z, Yen TS, Wu L, Madden CR, Tan W, Slagle BL, Ou JH.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153824

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Enrichment of a Precore-Minus Mutant of Duck Hepatitis B Virus in Experimental Mixed Infections. by Zhang YY, Summers J.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104136

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Envelope Protein-Mediated Down-Regulation of Hepatitis B Virus Receptor in Infected Hepatocytes. by Breiner KM, Urban S, Glass B, Schaller H.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113907

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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&artid=85549

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Epidermal Powder Immunization Induces both Cytotoxic T-Lymphocyte and Antibody Responses to Protein Antigens of Influenza and Hepatitis B Viruses. by Chen D, Weis KF, Chu Q, Erickson C, Endres R, Lively CR, Osorio J, Payne LG.; 2001 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114750

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European Proficiency Testing Program for Molecular Detection and Quantitation of Hepatitis B Virus DNA. by Valentine-Thon E, van Loon AM, Schirm J, Reid J, Klapper PE, Cleator GM.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88557

100 Hepatitis B

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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&artid=154615

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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 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 Quantitative PCR and Branched-Chain DNA Assay for Detection of Hepatitis B Virus DNA in Sera from Hepatocellular Carcinoma and Liver Transplant Patients. by Chen T, Luk JM, Cheung ST, Yu WC, Fan ST.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86641

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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 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&artid=149549

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Evidence for Increased in vitro Recombination with Insertion of Human Hepatitis B Virus DNA. by Hino O, Tabata S, Hotta Y.; 1991 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52691

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Evidence that the 5[prime prime or minute]-End Cap Structure Is Essential for Encapsidation of Hepatitis B Virus Pregenomic RNA. by Jeong JK, Yoon GS, Ryu WS.; 2000 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112035

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Evidence that the RNAseH activity of the duck hepatitis B virus is unable to act on exogenous substrates. by Gong Y, Yao E, Tavis JE.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=37354

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Export of hepatitis B virus RNA on a Rev-like pathway: inhibition by the regenerating liver inhibitory factor IkappaB alpha. by Roth J, Dobbelstein M.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=192368

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Expression of Functional Hepatitis B Virus Polymerase in Yeast Reveals it to be the Sole Viral Protein Required for Correct Initiation of Reverse Transcription. by Tavis JE, Ganem D.; 1993 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46455

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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&artid=110881

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Expression of the Terminal Protein Region of Hepatitis B Virus Inhibits Cellular Responses to Interferons [alpha] and [gamma] and Double-Stranded RNA. by Foster GR, Ackrill AM, Goldin RD, Kerr IM, Thomas HC, Stark GR.; 1991 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51345

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Extensive Mutagenesis of the Hepatitis B Virus Core Gene and Mapping of Mutations That Allow Capsid Formation. by Koschel M, Thomssen R, Bruss V.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104460

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Fibronectin of human liver sinusoids binds hepatitis B virus: identification by an anti-idiotypic antibody bearing the internal image of the pre-S2 domain. by Budkowska A, Bedossa P, Groh F, Louise A, Pillot J.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=188650

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Formation of a Functional Hepatitis B Virus Replication Initiation Complex Involves a Major Structural Alteration in the RNA Template. by Beck J, Nassal M.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109213

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Functional Analysis of a Liver-Specific Enhancer of the Hepatitis B Virus. by Trujillo MA, Letovsky J, Maguire HF, Lopez-Cabrera M, Siddiqui A.; 1991 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51540

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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&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&artid=113846

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Functions of the internal pre-S domain of the large surface protein in hepatitis B virus particle morphogenesis. by Bruss V, Vieluf K.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189574

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Generation of duck hepatitis B virus polymerase mutants through site-directed mutagenesis which demonstrate resistance to lamivudine [(--)-beta-L-2', 3'-dideoxy-3'thiacytidine] in vitro. by Fischer KP, Tyrrell DL.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163451

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Generation of Replication-Competent Hepatitis B Virus Nucleocapsids in Insect Cells. by Seifer M, Hamatake R, Bifano M, Standring DN.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109721

102 Hepatitis B

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Generation of Stable Cell Lines Expressing Lamivudine-Resistant Hepatitis B Virus for Antiviral-Compound Screening. by Walters KA, Tipples GA, Allen MI, Condreay LD, Addison WR, Tyrrell L.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155849

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Genetic Immunization of BALB/c mice with a Plasmid Bearing the Gene Coding for a Hybrid Merozoite Surface Protein 1-Hepatitis B Virus Surface Protein Fusion Protects Mice against Lethal Plasmodium chabaudi chabaudi PC1 Infection. by Wunderlich G, Moura IC, del Portillo HA.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101545

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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&artid=140384

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Glucagon Treatment Interferes with an Early Step of Duck Hepatitis B Virus Infection. by Hild M, Weber O, Schaller H.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109694

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Half-Life of the Duck Hepatitis B Virus Covalently Closed Circular DNA Pool In Vivo following Inhibition of Viral Replication. by Addison WR, Walters KA, Wong WW, Wilson JS, Madej D, Jewell LD, Tyrrell DL.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136192

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Hepatitis B immunisation in renal units in the United Kingdom: questionnaire study. by Ray S, Samuel T, Hawker J, Smith S.; 2002 Apr 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101399

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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&artid=90223

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Hepatitis B virus (HBV) envelope glycoproteins vary drastically in their sensitivity to glycan processing: Evidence that alteration of a single N-linked glycosylation site can regulate HBV secretion. by Mehta A, Lu X, Block TM, Blumberg BS, Dwek RA.; 1997 Mar 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20001

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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&artid=85438

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Hepatitis B Virus (HBV) Virion and Covalently Closed Circular DNA Formation in Primary Tupaia Hepatocytes and Human Hepatoma Cell Lines upon HBV Genome Transduction with Replication-Defective Adenovirus Vectors. by Ren S, Nassal M.; 2001 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114016

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

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Hepatitis B Virus Capsid Particles are Assembled from Core-Protein Dimer Precursors. by Zhou S, Standring DN.; 1992 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50274

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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&artid=114358

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Hepatitis B Virus Core Gene Mutations Which Block Nucleocapsid Envelopment. by Koschel M, Oed D, Gerelsaikhan T, Thomssen R, Bruss V.; 2000 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111506

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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&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&artid=150268

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Hepatitis B Virus HBx Protein Activates Ras-GTP Complex Formation and Establishes a Ras, Raf, MAP Kinase Signaling Cascade. by Benn J, Schneider RJ.; 1994 Oct 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45017

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Hepatitis B virus HBx protein activates transcription factor NF-kappaB by acting on multiple cytoplasmic inhibitors of rel-related proteins. by Su F, Schneider RJ.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190392

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Hepatitis B Virus HBx Protein Activation of Cyclin A --Cyclin-Dependent Kinase 2 Complexes and G1 Transit via a Src Kinase Pathway. by Bouchard M, Giannakopoulos S, Wang EH, Tanese N, Schneider RJ.; 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114170

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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 infected physicians and disclosure of transmission risks to patients: A critical analysis. by Barrigar DL, Flagel DC, Upshur RE.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59900

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Hepatitis B Virus Large Envelope Protein Interacts with [gamma]2-Adaptin, a Clathrin Adaptor-Related Protein. by Hartmann-Stuhler C, Prange R.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114939

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Hepatitis B virus nucleocapsid envelopment does not occur without genomic DNA synthesis. by Gerelsaikhan T, Tavis JE, Bruss V.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190358

104 Hepatitis B

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Hepatitis B Virus of Genotype B with or without Recombination with Genotype C over the Precore Region plus the Core Gene. by Sugauchi F, Orito E, Ichida T, Kato H, Sakugawa H, Kakumu S, Ishida T, Chutaputti A, Lai CL, Ueda R, Miyakawa Y, Mizokami M.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136227

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Hepatitis B Virus pX Targets TFIIB in Transcription Coactivation. by Haviv I, Shamay M, Doitsh G, Shaul Y.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108871

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Hepatitis B virus replication is cell cycle independent during liver regeneration in transgenic mice. by Guidotti LG, Matzke B, Chisari FV.; 1997 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191703

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Hepatitis B Virus RNA-Binding Proteins Associated with Cytokine-Induced Clearance of Viral RNA from the Liver of Transgenic Mice. by Heise T, Guidotti LG, Cavanaugh VJ, Chisari FV.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103854

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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&artid=87037

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Hepatitis B Virus Transactivator Protein, HBx, Associates with the Components of TFIIH and Stimulates the DNA Helicase Activity of TFIIH. by Qadri I, Conaway JW, Conaway RC, Schaack J, Siddiqui A.; 1996 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38195

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Hepatitis B Virus X Protein Acts as a Tumor Promoter in Development of Diethylnitrosamine-Induced Preneoplastic Lesions. by Madden CR, Finegold MJ, Slagle BL.; 2001 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114876

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Hepatitis B Virus X Protein and Simian Virus 5 V Protein Exhibit Similar UV-DDB1 Binding Properties To Mediate Distinct Activities. by Leupin O, Bontron S, Strubin M.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154990

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Hepatitis B Virus X Protein Colocalizes to Mitochondria with a Human VoltageDependent Anion Channel, HVDAC3, and Alters Its Transmembrane Potential. by Rahmani Z, Huh KW, Lasher R, Siddiqui A.; 2000 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111774

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Hepatitis B virus X protein induces RNA polymerase III-dependent gene transcription and increases cellular TATA-binding protein by activating the Ras signaling pathway. by Wang HD, Trivedi A, Johnson DL.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=232540

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Hepatitis B Virus X Protein Interferes with Cellular DNA Repair. by Becker SA, Lee TH, Butel JS, Slagle BL.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109372

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Hepatitis B Virus X Protein Is both a Substrate and a Potential Inhibitor of the Proteasome Complex. by Hu Z, Zhang Z, Doo E, Coux O, Goldberg AL, Liang TJ.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104247

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Hepatitis B virus, the vaccine, and the control of primary cancer of the liver. by Blumberg BS.; 1997 Jul 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33676

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Hepatitis B Virus-Mediated Changes of Apolipoprotein mRNA Abundance in Cultured Hepatoma Cells. by Norton PA, Gong Q, Mehta AS, Lu X, Block TM.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153946

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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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Hepatocyte Nuclear Factor 3[beta] Inhibits Hepatitis B Virus Replication In Vivo. by Banks KE, Anderson AL, Tang H, Hughes DE, Costa RH, McLachlan A.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136732

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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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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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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&artid=86257

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Host Cell-Virus Cross Talk: Phosphorylation of a Hepatitis B Virus Envelope Protein Mediates Intracellular Signaling. by Rothmann K, Schnolzer M, Radziwill G, Hildt E, Moelling K, Schaller H.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110552

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Hsp90 is Required for the Activity of a Hepatitis B Virus Reverse Transcriptase. by Hu J, Seeger C.; 1996 Feb 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40030

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Human Hepatitis B Virus Polymerase Interacts with the Molecular Chaperonin Hsp60. by Park SG, Jung G.; 2001 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114424

106 Hepatitis B

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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&artid=127167

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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 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&artid=136620

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Identification of BMS-200475 as a potent and selective inhibitor of hepatitis B virus. by Innaimo SF, Seifer M, Bisacchi GS, Standring DN, Zahler R, Colonno RJ.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163937

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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&artid=95865

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Identification of hepatitis B virus indigenous to chimpanzees. by Hu X, Margolis HS, Purcell RH, Ebert J, Robertson BH.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26492

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Identification of Multiple Transcription Factors, HLF, FTF, and E4BP4, Controlling Hepatitis B Virus Enhancer II. by Ishida H, Ueda K, Ohkawa K, Kanazawa Y, Hosui A, Nakanishi F, Mita E, Kasahara A, Sasaki Y, Hori M, Hayashi N.; 2000 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111458

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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&artid=155132

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Immunisation of infants at risk of perinatal transmission of hepatitis B: retrospective audit of vaccine uptake. by Wallis DE, Boxall EH.; 1999 Apr 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27844

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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&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&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

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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&artid=85302

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Improvement of hepatitis B virus DNA vaccines by plasmids coexpressing hepatitis B surface antigen and interleukin-2. by Chow YH, Huang WL, Chi WK, Chu YD, Tao MH.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191037

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In Vitro Reconstitution of a Functional Duck Hepatitis B Virus Reverse Transcriptase: Posttranslational Activation by Hsp90. by Hu J, Anselmo D.; 2000 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112423

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In Vitro Susceptibilities of Wild-Type or Drug-Resistant Hepatitis B Virus to ([minus sign])-[beta]-d-2,6-Diaminopurine Dioxolane and 2[prime prime or minute]-Fluoro-5Methyl-[beta]-l-Arabinofuranosyluracil. by Chin R, Shaw T, Torresi J, Sozzi V, Trautwein C, Bock T, Manns M, Isom H, Furman P, Locarnini S.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90683

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In vivo activity of the hepatitis B virus core promoter: tissue specificity and temporal regulation. by Billet O, Grimber G, Levrero M, Seye KA, Briand P, Joulin V.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189474

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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&artid=114731

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In Vivo Regulation of Hepatitis B Virus Replication by Peroxisome Proliferators. by Guidotti LG, Eggers CM, Raney AK, Chi SY, Peters JM, Gonzalez FJ, McLachlan A.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113093

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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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Inducible expression of human hepatitis B virus (HBV) in stably transfected hepatoblastoma cells: a novel system for screening potential inhibitors of HBV replication. by Ladner SK, Otto MJ, Barker CS, Zaifert K, Wang GH, Guo JT, Seeger C, King RW.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163991

108 Hepatitis B

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Infection of a human hepatoma cell line by hepatitis B virus. by Gripon P, Rumin S, Urban S, Le Seyec J, Glaise D, Cannie I, Guyomard C, Lucas J, Trepo C, GuguenGuillouzo C.; 2002 Nov 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137772

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Infection of Ducklings with Virus Particles Containing Linear Double-Stranded Duck Hepatitis B Virus DNA: Illegitimate Replication and Reversion. by Yang W, Summers J.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110285

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Infection Process of the Hepatitis B Virus Depends on the Presence of a Defined Sequence in the Pre-S1 Domain. by Le Seyec J, Chouteau P, Cannie I, GuguenGuillouzo C, Gripon P.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104448

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Influence of a Putative Intermolecular Interaction between Core and the Pre-S1 Domain of the Large Envelope Protein on Hepatitis B Virus Secretion. by Le Pogam S, Shih C.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136289

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Inhibition of Duck Hepatitis B Virus Replication by 9-(2Phosphonylmethoxyethyl)adenine, an Acyclic Phosphonate Nucleoside Analogue. by Nicoll AJ, Colledge DL, Toole JJ, Angus PW, Smallwood RA, Locarnini SA.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106011

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Inhibition of episomal hepatitis B virus DNA in vitro by 2,4-diamino-7- (2-deoxy-2by Ojwang JO, fluoro-beta-D-arabinofuranosyl)-pyrrolo[2,3-d]pyrimidine. Bhattacharya BK, Marshall HB, Korba BE, Revankar GR, Rando RF.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162987

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Inhibition of hepatitis B virus by a novel L-nucleoside, 2'-fluoro-5-methyl-beta-Larabinofuranosyl uracil. by Balakrishna Pai S, Liu SH, Zhu YL, Chu CK, Cheng YC.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163120

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Inhibition of Hepatitis B Virus Replication by Interferon Requires Proteasome Activity[dagger]. by Robek MD, Wieland SF, Chisari FV.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136040

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Inhibition of Hepatitis B Virus Replication by the Interferon-Inducible MxA Protein. by Gordien E, Rosmorduc O, Peltekian C, Garreau F, Brechot C, Kremsdorf D.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115893

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Inhibition of Hepatitis B Virus Replication during Adenovirus and Cytomegalovirus Infections in Transgenic Mice. by Cavanaugh VJ, Guidotti LG, Chisari FV.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109701

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Inhibition of Human Hepatitis B Virus Replication by AT-61, a Phenylpropenamide Derivative, Alone and in Combination with ([minus sign])[beta]-l-2[prime prime or minute],3[prime prime or minute]-Dideoxy-3[prime prime or minute]-Thiacytidine. by King RW, Ladner SK, Miller TJ, Zaifert K, Perni RB, Conway SC, Otto MJ.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106020

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Inhibition of replication of hepatitis B virus by cytallene in vitro. by Zhu YL, Pai SB, Liu SH, Grove KL, Jones BC, Simons C, Zemlicka J, Cheng YC.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163999

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Inhibition of the Replication of Hepatitis B Virus in vitro by 2',3'-Dideoxy-3'Thiacytidine and Related Analogues. by Doong S, Tsai C, Schinazi RF, Liotta DC, Cheng Y.; 1991 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52535

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Inhibitory Effect of 2[prime prime or minute]-Fluoro-5-Methyl-[beta]-lArabinofuranosyl-Uracil on Duck Hepatitis B Virus Replication. by Aguesse-Germon S, Liu SH, Chevallier M, Pichoud C, Jamard C, Borel C, Chu CK, Trepo C, Cheng YC, Zoulim F.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105416

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Inhibitory Effect of Adefovir on Viral DNA Synthesis and Covalently Closed Circular DNA Formation in Duck Hepatitis B Virus-Infected Hepatocytes In Vivo and In Vitro. by Delmas J, Schorr O, Jamard C, Gibbs C, Trepo C, Hantz O, Zoulim F.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127044

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Insertions within the hepatitis B virus capsid protein influence capsid formation and RNA encapsidation. by Beames B, Lanford RE.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189596

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Integrated Hepatitis B Virus DNA Preserves the Binding Sequence of Transcription Factor Yin and Yang 1 at the Virus-Cell Junction. by Nakanishi-Matsui M, Hayashi Y, Kitamura Y, Koike K.; 2000 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112043

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Interaction between Hepatitis B Virus Core Protein and Reverse Transcriptase. by Lott L, Beames B, Notvall L, Lanford RE.; 2000 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112427

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Interaction between STAT-3 and HNF-3 Leads to the Activation of Liver-Specific Hepatitis B Virus Enhancer 1 Function. by Waris G, Siddiqui A.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135980

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Interactions of the transcription factors MIBP1 and RFX1 with the EP element of the hepatitis B virus enhancer. by Blake M, Niklinski J, Zajac-Kaye M.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190627

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Interferon gene transfer by a hepatitis B virus vector efficiently suppresses wild-type virus infection. by Protzer U, Nassal M, Chiang PW, Kirschfink M, Schaller H.; 1999 Sep 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17966

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Interferon-Regulated Pathways That Control Hepatitis B Virus Replication in Transgenic Mice. by Guidotti LG, Morris A, Mendez H, Koch R, Silverman RH, Williams BR, Chisari FV.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135990

110 Hepatitis B

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Interleukin-12 inhibits hepatitis B virus replication in transgenic mice. by Cavanaugh VJ, Guidotti LG, Chisari FV.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191456

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Interleukin-18 Inhibits Hepatitis B Virus Replication in the Livers of Transgenic Mice. by Kimura K, Kakimi K, Wieland S, Guidotti LG, Chisari FV.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136645

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Intracellular Hepatitis B Virus Nucleocapsids Survive Cytotoxic T-LymphocyteInduced Apoptosis. by Pasquetto V, Wieland S, Chisari FV.; 2000 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112416

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Intracellular Retention of Hepatitis B Virus Surface Proteins Reduces Interleukin-2 Augmentation after Genetic Immunizations. by Geissler M, Bruss V, Michalak S, Hockenjos B, Ortmann D, Offensperger WB, Wands JR, Blum HE.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104209

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Intracellular retention of surface protein by a hepatitis B virus mutant that releases virion particles. by Xu Z, Yen TS.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189797

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Intrahepatic Induction of Alpha/Beta Interferon Eliminates Viral RNA-Containing Capsids in Hepatitis B Virus Transgenic Mice. by Wieland SF, Guidotti LG, Chisari FV.; 2000 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111931

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Is a Function of the Secreted Hepatitis B e Antigen to Induce Immunologic Tolerance in utero? by Milich DR, Jones JE, Hughes JL, Price J, Raney AK, McLachlan A.; 1990 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54584

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Kinetic Analysis of Wild-Type and YMDD Mutant Hepatitis B Virus Polymerases and Effects of Deoxyribonucleotide Concentrations on Polymerase Activity. by Gaillard RK, Barnard J, Lopez V, Hodges P, Bourne E, Johnson L, Allen MI, Condreay P, Miller WH, Condreay LD.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127103

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La Autoantigen Specifically Recognizes a Predicted Stem-Loop in Hepatitis B Virus RNA. by Heise T, Guidotti LG, Chisari FV.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112637

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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&artid=141095

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Leptomycin B Inhibits Equine Infectious Anemia Virus Rev and Feline Immunodeficiency Virus Rev Function but Not the Function of the Hepatitis B Virus Posttranscriptional Regulatory Element. by Otero GC, Harris ME, Donello JE, Hope TJ.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110012

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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&artid=86181

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Localization of the C terminus of the assembly domain of hepatitis B virus capsid protein: Implications for morphogenesis and organization of encapsidated RNA. by Zlotnick A, Cheng N, Stahl SJ, Conway JF, Steven AC, Wingfield PT.; 1997 Sep 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23216

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Localization of the N terminus of hepatitis B virus capsid protein by peptide-based difference mapping from cryoelectron microscopy. by Conway JF, Cheng N, Zlotnick A, Stahl SJ, Wingfield PT, Steven AC.; 1998 Dec 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24499

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Long PCR and its application to hepatitis viruses: amplification of hepatitis A, hepatitis B, and hepatitis C virus genomes. by Tellier R, Bukh J, Emerson SU, Miller RH, Purcell RH.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229463

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Long-Term Therapy with the Guanine Nucleoside Analog Penciclovir Controls Chronic Duck Hepatitis B Virus Infection In Vivo. by Lin E, Luscombe C, Colledge D, Wang YY, Locarnini S.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105885

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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-Level Secretion of Human Hepatitis B Virus Virions Caused by Two Independent, Naturally Occurring Mutations (P5T and L60V) in the Capsid Protein. by Le Pogam S, Yuan TT, Sahu GK, Chatterjee S, Shih C.; 2000 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102108

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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&artid=104984

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Mapping of Amino Acid Side Chains on the Surface of Hepatitis B Virus Capsids Required for Envelopment and Virion Formation. by Ponsel D, Bruss V.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140605

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Mapping of Homologous Interaction Sites in the Hepatitis B Virus Core Protein. by Konig S, Beterams G, Nassal M.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110062

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Mapping of the Hepatitis B Virus Reverse Transcriptase TP and RT Domains by Transcomplementation for Nucleotide Priming and by Protein-Protein Interaction. by Lanford RE, Kim YH, Lee H, Notvall L, Beames B.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104429

112 Hepatitis B

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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&artid=103946

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Mechanisms of Inhibition of Nuclear Hormone Receptor-Dependent Hepatitis B Virus Replication by Hepatocyte Nuclear Factor 3[beta]. by Tang H, McLachlan A.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136416

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Members of the nuclear receptor superfamily regulate transcription from the hepatitis B virus nucleocapsid promoter. by Raney AK, Johnson JL, Palmer CN, McLachlan A.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191157

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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&artid=110361

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Metabolic Studies on BMS-200475, a New Antiviral Compound Active against Hepatitis B Virus. by Yamanaka G, Wilson T, Innaimo S, Bisacchi GS, Egli P, Rinehart JK, Zahler R, Colonno RJ.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89048

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Mimovirus: a Novel Form of Vaccine That Induces Hepatitis B Virus-Specific Cytotoxic T-Lymphocyte Responses In Vivo. by Wu YZ, Zhao JP, Wan Y, Jia ZC, Zhou W, Bian J, Ni B, Zou LY, Tang Y.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136564

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Mitochondrially Associated Hepatitis B Virus X Protein Constitutively Activates Transcription Factors STAT-3 and NF-[kappa]B via Oxidative Stress. by Waris G, Huh KW, Siddiqui A.; 2001 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99943

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Molecular Basis for the Interaction of the Hepatitis B Virus Core Antigen with the Surface Immunoglobulin Receptor on Naive B Cells. by Lazdina U, Cao T, Steinbergs J, Alheim M, Pumpens P, Peterson DL, Milich DR, Leroux-Roels G, Sallberg M.; 2001 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114359

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Molecular Chaperone GRP78/BiP Interacts with the Large Surface Protein of Hepatitis B Virus In Vitro and In Vivo. by Cho DY, Yang GH, Ryu CJ, Hong HJ.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=141094

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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&artid=87966

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Molecular Cloning of a Rat Chromosome Putative Recombinogenic Sequence Homologous to the Hepatitis B Virus Encapsidation Signal. by Aoki H, Kajino K, Arakawa Y, Hino O.; 1996 Jul 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38978

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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&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&artid=110896

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Molecular Modeling and Biochemical Characterization Reveal the Mechanism of Hepatitis B Virus Polymerase Resistance to Lamivudine (3TC) and Emtricitabine (FTC). by Das K, Xiong X, Yang H, Westland CE, Gibbs CS, Sarafianos SG, Arnold E.; 2001 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114232

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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&artid=87954

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Multiple Liver-Specific Factors Bind to the Hepatitis B Virus Core/ Pregenomic Promoter: Trans-Activation and Repression by CCAAT/Enhancer Binding Protein. by Lopez-Cabrera M, Letovsky J, Hu K, Siddiqui A.; 1990 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54263

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Murine Retroviral Pseudotype Virus Containing Hepatitis B Virus Large and Small Surface Antigens Confers Specific Tropism for Primary Human Hepatocytes: a Potential Liver-Specific Targeting System. by Sung VM, Lai MM.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136820

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Mutations in the Carboxyl-Terminal Domain of the Small Hepatitis B Virus Envelope Protein Impair the Assembly of Hepatitis Delta Virus Particles. by Jenna S, Sureau C.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104099

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Mutations in the epsilon sequences of human hepatitis B virus affect both RNA encapsidation and reverse transcription. by Fallows DA, Goff SP.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189007

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Mutations in the Pre-Core Region of Hepatitis B Virus Serve to Enhance the Stability of the Secondary Structure of the Pre-Genome Encapsidation Signal. by Lok AS, Akarca U, Greene S.; 1994 Apr 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43726

114 Hepatitis B

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Mutations That Increase In Situ Priming Also Decrease Circularization for Duck Hepatitis B Virus. by Loeb DD, Tian R.; 2001 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114372

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Naturally Occurring Mutations Define a Novel Function of the Hepatitis B Virus Core Promoter in Core Protein Expression. by Baumert TF, Marrone A, Vergalla J, Liang TJ.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109887

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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 Hepatitis B Virus of Cranes That Has an Unexpected Broad Host Range. by Prassolov A, Hohenberg H, Kalinina T, Schneider C, Cova L, Krone O, Frolich K, Will H, Sirma H.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140978

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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&artid=112280

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Novel and frequent mutations of hepatitis B virus coincide with a major histocompatibility complex class I-restricted T-cell epitope of the surface antigen. by Tai PC, Banik D, Lin GI, Pai S, Pai K, Lin MH, Yuoh G, Che S, Hsu SH, Chen TC, Kuo TT, Lee CS, Yang CS, Shih C.; 1997 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191713

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Novel Nucleoside Analogue MCC-478 (LY582563) Is Effective against Wild-Type or Lamivudine-Resistant Hepatitis B Virus. by Ono-Nita SK, Kato N, Shiratori Y, Carrilho FJ, Omata M.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127322

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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&artid=115916

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Nucleic acid vaccination primes hepatitis B virus surface antigen-specific cytotoxic T lymphocytes in nonresponder mice. by Schirmbeck R, Bohm W, Ando K, Chisari FV, Reimann J.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189487

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Nucleic Acid-Based Cross-Linking Assay for Detection and Quantification of Hepatitis B Virus DNA. by Lai VC, Guan R, Wood ML, Lo SK, Yuen MF, Lai CL.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84196

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Nucleotide priming and reverse transcriptase activity of hepatitis B virus polymerase expressed in insect cells. by Lanford RE, Notvall L, Beames B.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189185

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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&artid=139665

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Oral immunization with hepatitis B surface antigen expressed in transgenic plants. by Kong Q, Richter L, Yang YF, Arntzen CJ, Mason HS, Thanavala Y.; 2001 Sep 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=58765

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Overlapping initiator and TATA box functions in the basal core promoter of hepatitis B virus. by Chen IH, Huang CJ, Ting LP.; 1995 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189080

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p53-Mediated Cellular Response to DNA Damage in Cells with Replicative Hepatitis B Virus. by Puisieux A, Ji J, Guillot C, Legros Y, Soussi T, Isselbacher K, Ozturk M.; 1995 Feb 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42515

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Paracrine in vivo inhibitory effects of hepatitis B virus X protein (HBx) on liver cell proliferation: An alternative mechanism of HBx-related pathogenesis. by Tralhao JG, Roudier J, Morosan S, Giannini C, Tu H, Goulenok C, Carnot F, Zavala F, Joulin V, Kremsdorf D, Brechot C.; 2002 May 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124516

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Penciclovir is a selective inhibitor of hepatitis B virus replication in cultured human hepatoblastoma cells. by Korba BE, Boyd MR.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163310

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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, 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&artid=127241

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Phenotypic mixing of rodent but not avian hepadnavirus surface proteins into human hepatitis B virus particles. by Gerhardt E, Bruss V.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=188693

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Phenylpropenamide Derivatives AT-61 and AT-130 Inhibit Replication of Wild-Type and Lamivudine-Resistant Strains of Hepatitis B Virus In Vitro. by Delaney IV WE, Edwards R, Colledge D, Shaw T, Furman P, Painter G, Locarnini S.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127422

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Phosphorylation of the anti-hepatitis B nucleoside analog 1-(2'-deoxy-2'-fluoro-1-betaD-arabinofuranosyl)-5-iodouracil (FIAU) by human cytosolic and mitochondrial thymidine kinase and implications for cytotoxicity. by Wang J, Eriksson S.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163369

116 Hepatitis B

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Phosphorylation of the Core Protein of Hepatitis B Virus by a 46-Kilodalton Serine Kinase. by Kau JH, Ting LP.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109602

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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&artid=88319

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Posttranscriptional Clearance of Hepatitis B Virus RNA by Cytotoxic T LymphocyteActivated Hepatocytes. by Tsui LV, Guidotti LG, Ishikawa T, Chisari FV.; 1995 Dec 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40365

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Posttranscriptional regulation of hepatitis B virus replication by the precore protein. by Scaglioni PP, Melegari M, Wands JR.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191057

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Potent Efficacy of Entecavir (BMS-200475) in a Duck Model of Hepatitis B Virus Replication. by Marion PL, Salazar FH, Winters MA, Colonno RJ.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126982

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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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Preferential recognition of hepatitis B nucleocapsid antigens by Th1 or Th2 cells is epitope and major histocompatibility complex dependent. by Milich DR, Peterson DL, Schodel F, Jones JE, Hughes JL.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=188971

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Pretreatment of Whole Blood for Use in Immunochromatographic Assays for Hepatitis B Virus Surface Antigen. by Shin HS, Kim CK, Shin KS, Chung HK, Heo TR.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96004

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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 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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Promoters for synthesis of the pre-C and pregenomic mRNAs of human hepatitis B virus are genetically distinct and differentially regulated. by Yu X, Mertz JE.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190967

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Properties of Monoclonal Antibodies Directed against Hepatitis B Virus Polymerase Protein. by zu Putlitz J, Lanford RE, Carlson RI, Notvall L, de la Monte SM, Wands JR.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104198

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Protease-induced infectivity of hepatitis B virus for a human hepatoblastoma cell line. by Lu X, Block TM, Gerlich WH.; 1996 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190069

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Proteasome complex as a potential cellular target of hepatitis B virus X protein. by Huang J, Kwong J, Sun EC, Liang TJ.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190518

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Protective Efficacy of DNA Vaccines against Duck Hepatitis B Virus Infection. by Triyatni M, Jilbert AR, Qiao M, Miller DS, Burrell CJ.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109352

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Quantitation of Hepatitis B Virus Genomic DNA by Real-Time Detection PCR. by Abe A, Inoue K, Tanaka T, Kato J, Kajiyama N, Kawaguchi R, Tanaka S, Yoshiba M, Kohara M.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85408

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Quantitative assay of PCR-amplified hepatitis B virus DNA using a peroxidaselabelled DNA probe and enhanced chemiluminescence. by Erhardt A, Schaefer S, Athanassiou N, Kann M, Gerlich WH.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229147

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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&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&artid=88403

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Quantitative Detection of Hepatitis B Virus DNA in Two International Reference Plasma Preparations. by Heermann KH, Gerlich WH, Chudy M, Schaefer S, Thomssen R.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84170

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Rapid and Specific Genotyping System for Hepatitis B Virus Corresponding to Six Major Genotypes by PCR Using Type-Specific Primers. by Naito H, Hayashi S, Abe K.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87732

118 Hepatitis B

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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&artid=155168

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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&artid=87379

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Recombinant Duck Interferon Gamma Inhibits Duck Hepatitis B Virus Replication in Primary Hepatocytes. by Schultz U, Chisari FV.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104078

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Reconstitution of a Functional Duck Hepatitis B Virus Replication Initiation Complex from Separate Reverse Transcriptase Domains Expressed in Escherichia coli. by Beck J, Nassal M.; 2001 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114976

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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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Regulation of Hepatitis B Virus Gene Expression by Its Two Enhancers. by Su H, Yee J.; 1992 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48731

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Regulation of Hepatocyte Nuclear Factor 1 Activity by Wild-Type and Mutant Hepatitis B Virus X Proteins. by Li J, Xu Z, Zheng Y, Johnson DL, Ou JH.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136206

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Regulation of RNA Polymerase I-Dependent Promoters by the Hepatitis B Virus X Protein via Activated Ras and TATA-Binding Protein. by Wang HD, Trivedi A, Johnson DL.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109290

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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&artid=111707

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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

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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&artid=136898

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119

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Replication of the Wild Type and a Natural Hepatitis B Virus Nucleocapsid Promoter Variant Is Differentially Regulated by Nuclear Hormone Receptors in Cell Culture. by Tang H, Raney AK, McLachlan A.; 2001 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114462

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Residues Critical for Duck Hepatitis B Virus Neutralization Are Involved in Host Cell Interaction. by Sunyach C, Rollier C, Robaczewska M, Borel C, Barraud L, Kay A, Trepo C, Will H, Cova L.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104011

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Retinoid X receptor alpha transactivates the hepatitis B virus enhancer 1 element by forming a heterodimeric complex with the peroxisome proliferator-activated receptor. by Huan B, Kosovsky MJ, Siddiqui A.; 1995 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=188608

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Retinoid X Receptor RXR[alpha] Binds to and Trans-Activates the Hepatitis B Virus Enhancer. by Huan B, Siddiqui A.; 1992 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50064

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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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RMP, a Novel RNA Polymerase II Subunit 5-Interacting Protein, Counteracts Transactivation by Hepatitis B Virus X Protein. by Dorjsuren D, Lin Y, Wei W, Yamashita T, Nomura T, Hayashi N, Murakami S.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109335

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Role for Calnexin and N-Linked Glycosylation in the Assembly and Secretion of Hepatitis B Virus Middle Envelope Protein Particles. by Werr M, Prange R.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109435

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Role of B cells in antigen presentation of the hepatitis B core. by Milich DR, Chen M, Schodel F, Peterson DL, Jones JE, Hughes JL.; 1997 Dec 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25082

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Role of N Glycosylation of Hepatitis B Virus Envelope Proteins in Morphogenesis and Infectivity of Hepatitis Delta Virus. by Sureau C, Fournier-Wirth C, Maurel P.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153980

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Role of NF-[kappa]B and Myc Proteins in Apoptosis Induced by Hepatitis B Virus HBx Protein. by Su F, Theodosis CN, Schneider RJ.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113915

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Role of Polypyrimidine Tract Binding Protein in the Function of the Hepatitis B Virus Posttranscriptional Regulatory Element. by Zang WQ, Li B, Huang PY, Lai MM, Yen TS.; 2001 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114659

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Role of the hepatitis B virus posttranscriptional regulatory element in export of intronless transcripts. by Huang ZM, Yen TS.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230626

120 Hepatitis B

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Role of the Pre-S2 Domain of the Large Envelope Protein in Hepatitis B Virus Assembly and Infectivity. by Le Seyec J, Chouteau P, Cannie I, Guguen-Guillouzo C, Gripon P.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110210

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Safety and immunogenicity in humans of an attenuated Salmonella typhi vaccine vector strain expressing plasmid-encoded hepatitis B antigens stabilized by the Asdbalanced lethal vector system. by Tacket CO, Kelly SM, Schodel F, Losonsky G, Nataro JP, Edelman R, Levine MM, Curtiss R 3rd.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175478

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Searching for Interferon-Induced Genes That Inhibit Hepatitis B Virus Replication in Transgenic Mouse Hepatocytes. by Wieland SF, Vega RG, Muller R, Evans CF, Hilbush B, Guidotti LG, Sutcliffe JG, Schultz PG, Chisari FV.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140855

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Secretion of Human Hepatitis B Virus is Inhibited by the Imino Sugar NButyldeoxynojirimycin. by Block TM, Lu X, Platt FM, Foster GR, Gerlich WH, Blumberg BS, Dwek RA.; 1994 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43345

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Selection of Peptide Inhibitors of Interactions Involved in Complex Protein Assemblies: Association of the Core and Surface Antigens of Hepatitis B Virus. by Dyson MR, Murray K.; 1995 Mar 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42450

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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&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&artid=153363

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Signals for Bidirectional Nucleocytoplasmic Transport in the Duck Hepatitis B Virus Capsid Protein. by Mabit H, Breiner KM, Knaust A, Zachmann-Brand B, Schaller H.; 2001 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115143

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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&artid=86341

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Specific hepatitis B virus minus-strand DNA synthesis requires only the 5' encapsidation signal and the 3'-proximal direct repeat DR1. by Rieger A, Nassal M.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189849

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Structure-Activity Relationship of a New Class of Anti-Hepatitis B Virus Agents. by Mehta A, Conyers B, Tyrrell DL, Walters KA, Tipples GA, Dwek RA, Block TM.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=132742

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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&artid=113064

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Sustained Activation of Mitogen-Activated Protein Kinases and Activator Protein 1 by the Hepatitis B Virus X Protein in Mouse Hepatocytes In Vivo. by Nijhara R, Jana SS, Goswami SK, Rana A, Majumdar SS, Kumar V, Sarkar DP.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114609

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The apical stem --loop of the hepatitis B virus encapsidation signal folds into a stable tri --loop with two underlying pyrimidine bulges. by Flodell S, Schleucher J, Cromsigt J, Ippel H, Kidd-Ljunggren K, Wijmenga S.; 2002 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135823

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The Binding Site of Transcription Factor YY1 Is Required for Intramolecular Recombination between Terminally Repeated Sequences of Linear Replicative Hepatitis B Virus DNA. by Hayashi Y, Kitamura Y, Nakanishi M, Koike K.; 2000 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112376

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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 Duck Hepatitis B Virus Polymerase Is Activated by Its RNA Packaging Signal, [var epsilon]. by Tavis JE, Massey B, Gong Y.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110380

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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&artid=111700

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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&artid=81543

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The hepatitis B virus (HBV) precore protein inhibits HBV replication in transgenic mice. by Guidotti LG, Matzke B, Pasquinelli C, Shoenberger JM, Rogler CE, Chisari FV.; 1996 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190756

122 Hepatitis B

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The hepatitis B virus core and e antigens elicit different Th cell subsets: antigen structure can affect Th cell phenotype. by Milich DR, Schodel F, Hughes JL, Jones JE, Peterson DL.; 1997 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191326

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The Hepatitis B Virus Core Promoter Is Strongly Activated by the Liver Nuclear Receptor Fetoprotein Transcription Factor or by Ectopically Expressed Steroidogenic Factor 1. by Gilbert S, Galarneau L, Lamontagne A, Roy S, Belanger L.; 2000 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110855

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The hepatitis B virus post-transcriptional regulatory element contains two conserved RNA stem-loops which are required for function. by Smith GJ 3rd, Donello JE, Luck R, Steger G, Hope TJ.; 1998 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=147918

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The hepatitis B virus posttranscriptional regulatory element is composed of two subelements. by Donello JE, Beeche AA, Smith GJ 3rd, Lucero GR, Hope TJ.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190367

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The hepatitis B virus X protein promotes tumor cell invasion by inducing membranetype matrix metalloproteinase-1 and cyclooxygenase-2 expression. by Lara-Pezzi E, Gomez-Gaviro MV, Galvez BG, Mira E, Iniguez MA, Fresno M, Martinez-A. C, Arroyo AG, Lopez-Cabrera M.; 2002 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151651

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The Hepatitis B Virus X Protein Targets the Basic Region-Leucine Zipper Domain of CREB. by Williams JS, Andrisani OM.; 1995 Apr 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42053

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The Hepatitis B Virus X Protein Transactivates Viral Core Gene Expression In Vivo. by Reifenberg K, Wilts H, Lohler J, Nusser P, Hanano R, Guidotti LG, Chisari FV, Schlicht HJ.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113095

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The M539V Polymerase Variant of Human Hepatitis B Virus Demonstrates Resistance to 2[prime prime or minute]-Deoxy-3[prime prime or minute]-Thiacytidine and a Reduced Ability to Synthesize Viral DNA. by Ladner SK, Miller TJ, King RW.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105884

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The Majority of Duck Hepatitis B Virus Reverse Transcriptase in Cells Is Nonencapsidated and Is Bound to a Cytoplasmic Structure. by Yao E, Gong Y, Chen N, Tavis JE.; 2000 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116376

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The Mechanism of an Immature Secretion Phenotype of a Highly Frequent Naturally Occurring Missense Mutation at Codon 97 of Human Hepatitis B Virus Core Antigen. by Yuan TT, Sahu GK, Whitehead WE, Greenberg R, Shih C.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112633

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The myc intron-binding polypeptide associates with RFX1 in vivo and binds to the major histocompatibility complex class II promoter region, to the hepatitis B virus

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enhancer, and to regulatory regions of several distinct viral genes. by Reinhold W, Emens L, Itkes A, Blake M, Ichinose I, Zajac-Kaye M.; 1995 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230535 •

The Pre-S Domain of the Large Viral Envelope Protein Determines Host Range in Avian Hepatitis B Viruses. by Ishikawa T, Ganem D.; 1995 Jul 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41497

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The PreS2 activator MHBst of hepatitis B virus activates c-raf-1 /Erk2 signaling in transgenic mice. by Hildt E, Munz B, Saher G, Reifenberg K, Hofschneider PH.; 2002 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125852

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The Role of Envelope Proteins in Hepatitis B Virus Assembly. by Bruss V, Ganem D.; 1991 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50954

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The small envelope protein is required for secretion of a naturally occurring hepatitis B virus mutant with pre-S1 deleted. by Melegari M, Scaglioni PP, Wands JR.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191785

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The X protein of hepatitis B virus coactivates potent activation domains. by Haviv I, Vaizel D, Shaul Y.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=232011

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Transactivation by Hepatitis B Virus X Protein is Promiscuous and Dependent on Mitogen-Activated Cellular Serine/Threonine Kinases. by Cross JC, Wen P, Rutter WJ.; 1993 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47291

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Trans-Activation Function of a 3' Truncated X Gene-Cell Fusion Product from Integrated Hepatitis B Virus DNA in Chronic Hepatitis Tissues. by Takada S, Koike K.; 1990 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54380

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Trans-Activation of HLA-DR Gene by Hepatitis B Virus X Gene Product. by Hu K, Vierling JM, Siddiqui A.; 1990 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54699

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Transcomplementation of nucleotide priming and reverse transcription between independently expressed TP and RT domains of the hepatitis B virus reverse transcriptase. by Lanford RE, Notvall L, Lee H, Beames B.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191428

124 Hepatitis B

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Transcription of hepatitis B virus in peripheral blood mononuclear cells from persistently infected patients. by Stoll-Becker S, Repp R, Glebe D, Schaefer S, Kreuder J, Kann M, Lampert F, Gerlich WH.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191779

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Transcriptional regulation of hepatitis B virus by nuclear hormone receptors is a critical determinant of viral tropism. by Tang H, McLachlan A.; 2001 Feb 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=29344

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Transcriptional Repression of Human Hepatitis B Virus Genes by a bZIP Family Member, E4BP4. by Lai CK, Ting LP.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104083

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Transfer of Hepatitis B Virus Genome by Adenovirus Vectors into Cultured Cells and Mice: Crossing the Species Barrier. by Sprinzl MF, Oberwinkler H, Schaller H, Protzer U.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114916

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Tumor Necrosis Factor Alpha Inhibition of Hepatitis B Virus Replication Involves Disruption of Capsid Integrity through Activation of NF-[kappa]B. by Biermer M, Puro R, Schneider RJ.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150632

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Turnover of Hepatitis B Virus X Protein Is Regulated by Damaged DNA-Binding Complex. by Bergametti F, Sitterlin D, Transy C.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136256

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Two Sensitive PCR-Based Methods for Detection of Hepatitis B Virus Variants Associated with Reduced Susceptibility to Lamivudine. by Allen MI, Gauthier J, DesLauriers M, Bourne EJ, Carrick KM, Baldanti F, Ross LL, Lutz MW, Condreay LD.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85560

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

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Up-Regulation of Intercellular Adhesion Molecule 1 Transcription by Hepatitis B Virus X Protein. by Hu K, Yu C, Vierling JM.; 1992 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50567

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Use of 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil as a novel antiviral agent for hepatitis B virus and Epstein-Barr virus. by Chu CK, Ma T, Shanmuganathan K, Wang C, Xiang Y, Pai SB, Yao GQ, Sommadossi JP, Cheng YC.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162665

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Use of Real-Time PCR and Fluorimetry To Detect Lamivudine Resistance-Associated Mutations in Hepatitis B Virus. by Cane PA, Cook P, Ratcliffe D, Mutimer D, Pillay D.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89331

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Use of the Hepatitis B Virus Recombinant Baculovirus-HepG2 System to Study the Effects of ([minus sign])-[beta]-2[prime prime or minute],3[prime prime or minute]Dideoxy-3[prime prime or minute]-Thiacytidine on Replication of Hepatitis B Virus and Accumulation of Covalently Closed Circular DNA. by Delaney WE IV, Miller TG, Isom HC.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89407

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Viral Cross Talk: Intracellular Inactivation of the Hepatitis B Virus during an Unrelated Viral Infection of the Liver. by Guidotti LG, Borrow P, Hobbs MV, Matzke B, Gresser I, Oldstone MB, Chisari FV.; 1996 May 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39321

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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

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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&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&artid=136708

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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

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.

126 Hepatitis B

To generate your own bibliography of studies dealing with hepatitis B, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “hepatitis B” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for hepatitis B (hyperlinks lead to article summaries): •

A rapid immunochromatographic assay for hepatitis B virus screening. Author(s): Lau DT, Ma H, Lemon SM, Doo E, Ghany MG, Miskovsky E, Woods GL, Park Y, Hoofnagle JH. Source: Journal of Viral Hepatitis. 2003 July; 10(4): 331-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823602&dopt=Abstract

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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 review of the case for hepatitis B vaccination of high-risk adults. Author(s): Rich JD, Ching CG, Lally MA, Gaitanis MM, Schwartzapfel B, Charuvastra A, Beckwith CG, Flanigan TP. Source: The American Journal of Medicine. 2003 March; 114(4): 316-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681460&dopt=Abstract

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A statewide hepatitis B vaccination program for school children in Hawaii: vaccination series completion and participation rates over consecutive school years. Author(s): Dilraj A, Strait-Jones J, Nagao M, Cui K, Terrell-Perica S, Effler PV. Source: Public Health Reports (Washington, D.C. : 1974). 2003 March-April; 118(2): 12733. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12690066&dopt=Abstract

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A survey of community pharmacists on prevention of HIV and hepatitis B and C: current practice and attitudes in Grampian. Author(s): Watson L, Bond C, Gault C. Source: Journal of Public Health Medicine. 2003 March; 25(1): 13-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669912&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 hepatitis B and isolated thrombocytopenia. Author(s): Ozaras R, Celik AD, Kisacik B, Mert A, Aki H, Ozturk R, Tabak F. Source: Journal of Clinical Gastroenterology. 2003 July; 37(1): 87-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811220&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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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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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 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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Analysis of clinical, biochemical and viral factors associated with early relapse after lamivudine treatment for hepatitis B e antigen-negative chronic hepatitis B patients in Taiwan. Author(s): Huang YH, Wu JC, Chang TT, Sheen IJ, Lee PC, Huo TI, Su CW, Wang YJ, Chang FY, Lee SD. Source: Journal of Viral Hepatitis. 2003 July; 10(4): 277-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823594&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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Analysis of hepatitis B virus-immunoglobulin isotype complexes by a novel immunocapture polymerase chain reaction method. Author(s): Zhou YL, Wang SY, Zhang JY, Peng XX. Source: Scandinavian Journal of Immunology. 2003 April; 57(4): 391-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12662303&dopt=Abstract

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Anticardiolipin antibodies in chronic hepatitis B and chronic hepatitis D infection, and hepatitis B-related hepatocellular carcinoma. Relationship with portal vein thrombosis. Author(s): Elefsiniotis IS, Diamantis ID, Dourakis SP, Kafiri G, Pantazis K, Mavrogiannis C. Source: European Journal of Gastroenterology & Hepatology. 2003 July; 15(7): 721-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811301&dopt=Abstract

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Antisense RNAs transcribed from the upstream region of the precore/core promoter of hepatitis B virus. Author(s): Moriyama K, Hayashida K, Shimada M, Nakano S, Nakashima Y, Fukumaki Y. Source: The Journal of General Virology. 2003 July; 84(Pt 7): 1907-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810886&dopt=Abstract

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Are we ready for marginal hepatitis B core antibody-positive living liver donors? Author(s): Fontana RJ, Merion RM. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003 August; 9(8): 833-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12884196&dopt=Abstract

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Auditing delivery of first dose of hepatitis B immunization to at risk groups may be more important than subsequent doses. Author(s): Sathia UL, McOwan A. Source: International Journal of Std & Aids. 2003 February; 14(2): 140-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12662396&dopt=Abstract

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Bacterial expression, purification, and in vitro N-myristoylation of fusion hepatitis B virus preS1 with the native-type N-terminus. Author(s): Ma HH, Yang L, Yang XY, Xu ZP, Li BL. Source: Protein Expression and Purification. 2003 January; 27(1): 49-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509984&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--hepatitis B and beyond. Interviewed by Pam Das. Author(s): Blumberg BS. Source: The Lancet Infectious Diseases. 2002 December; 2(12): 767-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467696&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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Beneficial effect of lamivudine for hepatitis B transplant recipients. Author(s): Mutimer D. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2002 May; 8(5): 440-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12004343&dopt=Abstract

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Biological impact of natural COOH-terminal deletions of hepatitis B virus X protein in hepatocellular carcinoma tissues. Author(s): Tu H, Bonura C, Giannini C, Mouly H, Soussan P, Kew M, Paterlini-Brechot P, Brechot C, Kremsdorf D. Source: Cancer Research. 2001 November 1; 61(21): 7803-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11691796&dopt=Abstract

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Brain metastasis from hepatocellular carcinoma associated with hepatitis B virus. Author(s): Frati A, Salvati M, Giarnieri E, Santoro A, Rocchi G, Frati L. Source: J Exp Clin Cancer Res. 2002 September; 21(3): 321-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12385572&dopt=Abstract

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Can serum HBV-DNA be used as a primary end point to assess efficacy of new treatments for chronic hepatitis B? Author(s): Alberti A. Source: Hepatology (Baltimore, Md.). 2003 July; 38(1): 18-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829981&dopt=Abstract

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Caspase-dependent alterations of Ca2+ signaling in the induction of apoptosis by hepatitis B virus X protein. Author(s): Chami M, Ferrari D, Nicotera P, Paterlini-Brechot P, Rizzuto R. Source: The Journal of Biological Chemistry. 2003 August 22; 278(34): 31745-55. Epub 2003 June 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799372&dopt=Abstract

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Characterization of antiviral activity of entecavir in transgenic mice expressing hepatitis B virus. Author(s): Julander JG, Colonno RJ, Sidwell RW, Morrey JD. Source: Antiviral Research. 2003 August; 59(3): 155-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927305&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 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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Clinical evaluation of a new enzyme immunoassay for hepatitis B virus core-related antigen; a marker distinct from viral DNA for monitoring lamivudine treatment. Author(s): Rokuhara A, Tanaka E, Matsumoto A, Kimura T, Yamaura T, Orii K, Sun X, Yagi S, Maki N, Kiyosawa K. Source: Journal of Viral Hepatitis. 2003 July; 10(4): 324-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823601&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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Coexistence of two distinct secretion mutations (P5T and I97L) in hepatitis B virus core produces a wild-type pattern of secretion. Author(s): Chua PK, Wen YM, Shih C. Source: Journal of Virology. 2003 July; 77(13): 7673-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12805468&dopt=Abstract

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Combination hepatitis B immune globulin and lamivudine versus hepatitis B immune globulin monotherapy in preventing recurrent hepatitis B virus infection in liver transplant recipients. Author(s): Ben-Ari Z, Mor E, Bar-Nathan N, Shaharabani E, Shapira Z, Tur-Kaspa R. Source: Transplantation Proceedings. 2003 March; 35(2): 609-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12644066&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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Comparison between levels of anti-HBS with a fixed administration dose of HBIG and a combination of HBIG and lamivudine for the prophylaxis of hepatitis B after liver transplantation. Author(s): Sousa JM, Pareja F, Serrano J, Gomez MA, Garcia I, Tamayo MJ, Diaz C, Martin C, Pascasio JM, Hinojosa R, Perez-Bernal JB, Canas E, Sayago M, Bernardos A. Source: Transplantation Proceedings. 2003 March; 35(2): 723-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12644112&dopt=Abstract

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Comparison of 12-month courses of interferon-alpha-2b-lamivudine combination therapy and interferon-alpha-2b monotherapy among patients with untreated chronic hepatitis B. Author(s): Yalcin K, Degertekin H, Yildiz F, Celik Y. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 June 15; 36(12): 1516-22. Epub 2003 Jun 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802750&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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Consistently low hepatitis B virus DNA saves patients from hepatocellular carcinogenesis in HBV-related cirrhosis. A nested case-control study using 96 untreated patients. Author(s): Ikeda K, Arase Y, Kobayashi M, Someya T, Saitoh S, Suzuki Y, Suzuki F, Tsubota A, Akuta N, Kumada H. Source: Intervirology. 2003; 46(2): 96-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684548&dopt=Abstract

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Cost-effective and safe ambulatory long-term immunoprophylaxis with intramuscular instead of intravenous hepatitis B immunoglobulin to prevent reinfection after orthotopic liver transplantation. Author(s): Faust D, Rabenau HF, Allwinn R, Caspary WF, Zeuzem S. Source: Clinical Transplantation. 2003 June; 17(3): 254-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780677&dopt=Abstract

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Cost-effectiveness analysis of interferon-alpha therapy in the treatment of chronic hepatitis B in Taiwan. Author(s): Pwu RF, Chan KA. Source: J Formos Med Assoc. 2002 September; 101(9): 632-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645191&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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Current status and prospects of studies on human genetic alleles associated with hepatitis B virus infection. Author(s): Wang FS. Source: World Journal of Gastroenterology : Wjg. 2003 April; 9(4): 641-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679901&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

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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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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 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

134 Hepatitis B

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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 T lymphocyte subsets and mIL-2R on surface of PBMC in patients with hepatitis B. Author(s): Wang KX, Peng JL, Wang XF, Tian Y, Wang J, Li CP. Source: World Journal of Gastroenterology : Wjg. 2003 September; 9(9): 2017-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970897&dopt=Abstract

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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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Developing partnerships in Washington State to prevent hepatitis B virus infection in Asian Americans and Pacific Islanders. Author(s): Chen AL, Kuss TT, McKeirnan S, Gleason CJ. Source: Asian Am Pac Isl J Health. 2001 Summer-Fall; 9(2): 195-204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11846365&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 hepatitis B virus resistance for lamivudine in chronic hepatitis B patients co-infected with the human immunodeficiency virus in a Dutch cohort. Author(s): Wolters LM, Niesters HG, Hansen BE, van der Ende ME, Kroon FP, Richter C, Brinkman K, Meenhorst PL, de Man RA. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2002 April; 24(3): 173-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11856618&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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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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Distribution of hepatitis B virus genotypes in HIV-infected patients with chronic hepatitis B: therapeutic implications. Author(s): Perez-Olmeda M, Nunez M, Garcia-Samaniego J, Rios P, Gonzalez-Lahoz J, Soriano V. Source: Aids Research and Human Retroviruses. 2003 August; 19(8): 657-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678467&dopt=Abstract

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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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Do patients who fail to complete a hepatitis A or hepatitis B vaccination series have to restart it? Author(s): Alter MJ. Source: Cleve Clin J Med. 2003 March; 70(3): 234. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678213&dopt=Abstract

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Dominant mutations of hepatitis B virus variants in hepatoma accumulate in B-cell and T-cell epitopes of the HBx antigen. Author(s): Hwang GY, Huang CJ, Lin CY, Wu CC. Source: Virus Research. 2003 April; 92(2): 157-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686424&dopt=Abstract

136 Hepatitis B

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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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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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Durability of serologic response after lamivudine treatment of chronic hepatitis B. Author(s): Dienstag JL, Cianciara J, Karayalcin S, Kowdley KV, Willems B, Plisek S, Woessner M, Gardner S, Schiff E. Source: Hepatology (Baltimore, Md.). 2003 April; 37(4): 748-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668966&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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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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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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Effects of hepatitis B virus infection on human sperm chromosomes. Author(s): Huang JM, Huang TH, Qiu HY, Fang XW, Zhuang TG, Liu HX, Wang YH, Deng LZ, Qiu JW. Source: World Journal of Gastroenterology : Wjg. 2003 April; 9(4): 736-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679922&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 GM-CSF as an adjuvant to hepatitis B vaccination in patients with chronic renal failure--results of a prospective, randomized trial. Author(s): Singh NP, Mandal SK, Thakur A, Kapoor D, Anuradha S, Prakash A, Kohli R, Agarwal SK. Source: Renal Failure. 2003 March; 25(2): 255-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12739832&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: Chinese Medical Journal. 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

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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

138 Hepatitis B

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Emergency living related liver transplantation for fulminant reactivation of hepatitis B virus after unrelated marrow transplantation. Author(s): Au WY, Lau GK, Lie AK, Liang R, Lo CM, Fan ST, Liu CL, Hawkins BR, Ng IO, Kwong YL. Source: Clinical Transplantation. 2003 April; 17(2): 121-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709077&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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Entecavir: a potent new antiviral drug for hepatitis B. Author(s): Honkoop P, De Man RA. Source: Expert Opinion on Investigational Drugs. 2003 April; 12(4): 683-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665423&dopt=Abstract

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Epidemiologic and virologic characteristics of hepatitis B virus genotype B having the recombination with genotype C. Author(s): Sugauchi F, Orito E, Ichida T, Kato H, Sakugawa H, Kakumu S, Ishida T, Chutaputti A, Lai CL, Gish RG, Ueda R, Miyakawa Y, Mizokami M. Source: Gastroenterology. 2003 April; 124(4): 925-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671889&dopt=Abstract

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Epidermal cis-urocanic acid levels correlate with lower specific cellular immune responses after hepatitis B vaccination of ultraviolet B-exposed humans. Author(s): Sleijffers A, Kammeyer A, de Gruijl FR, Boland GJ, van Hattum J, van Vloten WA, van Loveren H, Teunissen MB, Garssen J. Source: Photochemistry and Photobiology. 2003 March; 77(3): 271-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12685654&dopt=Abstract

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Evidence for dual effects of DNA-reactive bile acid derivatives (Bamets) on hepatitis B virus life cycle in an in vitro replicative system. Author(s): Romero MR, Martinez-Diez MC, Larena MG, Macias RI, Dominguez M, Garcia-Monzon C, Serrano MA, Marin JJ. Source: Antivir Chem Chemother. 2002 November; 13(6): 371-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12718409&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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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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Experience with lamivudine therapy for hepatitis B virus infection before and after liver transplantation, and review of the literature. Author(s): Ben-Ari Z, Mor E, Tur-Kaspa R. Source: Journal of Internal Medicine. 2003 May; 253(5): 544-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702032&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 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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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

140 Hepatitis B

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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 viral breakthrough in lamivudine monoprophylaxis of hepatitis B virus recurrence after liver transplantation. Author(s): Chan HL, Chui AK, Lau WY, Chan FK, Wong ML, Tse CH, Rao AR, Wong J, Sung JJ. Source: Journal of Medical Virology. 2002 October; 68(2): 182-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12210406&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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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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False-reactive test for hepatitis B surface antigen following administration of granulocyte-colony-stimulating factor. Author(s): Warren K, Eastlund T. Source: Vox Sanguinis. 2002 October; 83(3): 247-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12366767&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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Fatal hepatic failure after emergence of the hepatitis B virus mutant during lamivudine therapy in a patient with liver cirrhosis. Author(s): Wang JH, Lu SN, Lee CM, Lee JF, Chou YP. Source: Scandinavian Journal of Gastroenterology. 2002 March; 37(3): 366-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11916202&dopt=Abstract

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Fatal hepatitis B reactivation following discontinuation of nucleoside analogues for chronic hepatitis B. Author(s): Lim SG, Wai CT, Rajnakova A, Kajiji T, Guan R. Source: Gut. 2002 October; 51(4): 597-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12235087&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

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Fatal reactivation of hepatitis B virus following cytotoxic chemotherapy for acute myelogenous leukemia: fibrosing cholestatic hepatitis. Author(s): Kojima H, Abei M, Takei N, Mukai Y, Hasegawa Y, Iijima T, Nagasawa T. Source: European Journal of Haematology. 2002 August; 69(2): 101-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12366713&dopt=Abstract

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Fetal meconium peritonitis in the infant of a woman with fulminant hepatitis B. A case report. Author(s): Su WH, Wang PH, Yuan CC, Chang SP. Source: J Reprod Med. 2002 November; 47(11): 952-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12497690&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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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

142 Hepatitis B

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First dose of hepatitis B vaccine in infants. Author(s): Mathew A. Source: Indian Pediatrics. 2002 October; 39(10): 981-2; Author Reply 982-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428054&dopt=Abstract

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Frequency and load of hepatitis B virus DNA in first-time blood donors with antibodies to hepatitis B core antigen. Author(s): Hennig H, Puchta I, Luhm J, Schlenke P, Goerg S, Kirchner H. Source: Blood. 2002 October 1; 100(7): 2637-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239179&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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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 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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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 variability in hepatitis B viruses. Author(s): Kidd-Ljunggren K, Miyakawa Y, Kidd AH. Source: The Journal of General Virology. 2002 June; 83(Pt 6): 1267-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12029141&dopt=Abstract

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Genetic variation of hepatitis B surface antigen coding region among infants with chronic hepatitis B virus infection. Author(s): Nainan OV, Khristova ML, Byun K, Xia G, Taylor PE, Stevens CE, Margolis HS. Source: Journal of Medical Virology. 2002 November; 68(3): 319-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12226817&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 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 B hepatitis B virus is associated with severe icteric flare-up of chronic hepatitis B virus infection in Hong Kong. Author(s): Chan HL, Tsang SW, Wong ML, Tse CH, Leung NW, Chan FK, Sung JJ. Source: The American Journal of Gastroenterology. 2002 October; 97(10): 2629-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12385451&dopt=Abstract

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Genotype H: a new Amerindian genotype of hepatitis B virus revealed in Central America. Author(s): Arauz-Ruiz P, Norder H, Robertson BH, Magnius LO. Source: The Journal of General Virology. 2002 August; 83(Pt 8): 2059-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12124470&dopt=Abstract

144 Hepatitis B

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Genotype mixtures of hepatitis B virus in patients treated with interferon. Author(s): Hannoun C, Krogsgaard K, Horal P, Lindh M; Interpred trial group. Source: The Journal of Infectious Diseases. 2002 September 15; 186(6): 752-9. Epub 2002 August 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12198608&dopt=Abstract

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Genotype, serotype, and phylogenetic characterization of the complete genome sequence of hepatitis B virus isolates from Malawian chronic carriers of the virus. Author(s): Sugauchi F, Orito E, Kato H, Suzuki S, Kawakita S, Sakamoto Y, Fukushima K, Akiba T, Yoshihara N, Ueda R, Mizokami M. Source: Journal of Medical Virology. 2003 January; 69(1): 33-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12436475&dopt=Abstract

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Genotypes and clinical phenotypes of hepatitis B virus in patients with chronic hepatitis B virus infection. Author(s): Kao JH, Chen PJ, Lai MY, Chen DS. Source: Journal of Clinical Microbiology. 2002 April; 40(4): 1207-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11923332&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 and S-gene variability of Mexican hepatitis B virus strains. Author(s): Sanchez LV, Maldonado M, Bastidas-Ramirez BE, Norder H, Panduro A. Source: Journal of Medical Virology. 2002 September; 68(1): 24-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12210427&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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Genotyping study of hepatitis B virus in its intrauterine transmission. Author(s): Guo PF, Zhong M, Hou JL. Source: Di Yi June Yi Da Xue Xue Bao. 2002 April; 22(4): 303-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390728&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 hepatitis B virus infection. Author(s): Kao JH, Chen DS. Source: The Lancet Infectious Diseases. 2002 July; 2(7): 395-403. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127351&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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Gulliane Barre syndrome following vaccination with hepatitis B vaccine. Author(s): Seti NK, Reddi R, Anand I, Sethi PK. Source: J Assoc Physicians India. 2002 July; 50: 989. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12126370&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

146 Hepatitis B

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Hepatitis B and you: a patient education resource for pregnant women and new mothers. Author(s): Wilson HR. Source: Journal of Women's Health (2002). 2003 June; 12(5): 437-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869290&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 knowledge and practices among Chinese Canadian women in Vancouver, British Columbia. Author(s): Thompson MJ, Taylor VM, Yasui Y, Hislop TG, Jackson JC, Kuniyuki A, Teh C. Source: Canadian Journal of Public Health. Revue Canadienne De Sante Publique. 2003 July-August; 94(4): 281-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873087&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 for sex workers: do outreach programmes perform better? Author(s): Mak R, Traen A, Claeyssens M, Van Renterghem L, Leroux-Roels G, Van Damme P. Source: Sexually Transmitted Infections. 2003 April; 79(2): 157-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12690142&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 (HBV) and hepatitis C virus (HCV) infections in health care workers (HCWs): guidelines for prevention of transmission of HBV and HCV from HCW to patients. Author(s): Gunson RN, Shouval D, Roggendorf M, Zaaijer H, Nicholas H, Holzmann H, de Schryver A, Reynders D, Connell J, Gerlich WH, Marinho RT, Tsantoulas D, Rigopoulou E, Rosenheim M, Valla D, Puro V, Struwe J, Tedder R, Aitken C, Alter M, Schalm SW, Carman WF; European Consensus Group. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2003 August; 27(3): 213-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878084&dopt=Abstract

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Hepatitis B virus downregulates the human interferon-inducible MxA promoter through direct interaction of precore/core proteins. Author(s): Fernandez M, Quiroga JA, Carreno V. Source: The Journal of General Virology. 2003 August; 84(Pt 8): 2073-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867637&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 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 X protein induces cell death by causing loss of mitochondrial membrane potential. Author(s): Shirakata Y, Koike K. Source: The Journal of Biological Chemistry. 2003 June 13; 278(24): 22071-8. Epub 2003 April 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12676947&dopt=Abstract

148 Hepatitis B

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Hepatitis B virus X protein induces TNF-alpha expression via down-regulation of selenoprotein P in human hepatoma cell line, HepG2. Author(s): Yi YS, Park SG, Byeon SM, Kwon YG, Jung G. Source: Biochimica Et Biophysica Acta. 2003 July 30; 1638(3): 249-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878326&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 virus-induced defect of monocyte-derived dendritic cells leads to impaired T helper type 1 response in vitro: mechanisms for viral immune escape. Author(s): Beckebaum S, Cicinnati VR, Zhang X, Ferencik S, Frilling A, Grosse-Wilde H, Broelsch CE, Gerken G. Source: Immunology. 2003 August; 109(4): 487-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12871214&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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Hepatocellular carcinoma in a patient with primary biliary cirrhosis and seronegativity for markers of hepatitis B virus and hepatitis C virus: report of a case. Author(s): Sunagawa H, Takayama H, Yamashiro T, Sasaki H, Sashida Y, Matsuura K, Kayou M. Source: Surgery Today. 2003; 33(3): 219-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12658391&dopt=Abstract

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Histological improvements after a three-year lamivudine therapy in patients with chronic hepatitis B in whom YMDD mutants did not or did develop. Author(s): Suzuki Y, Arase Y, Ikeda K, Saitoh S, Tsubota A, Suzuki F, Kobayashi M, Akuta N, Someya T, Miyakawa Y, Kumada H. Source: Intervirology. 2003; 46(3): 164-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867754&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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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 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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Impact of the thimerosal controversy on hepatitis B vaccine coverage of infants born to women of unknown hepatitis B surface antigen status in Michigan. Author(s): Biroscak BJ, Fiore AE, Fasano N, Fineis P, Collins MP, Stoltman G. Source: Pediatrics. 2003 June; 111(6 Pt 1): E645-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777580&dopt=Abstract

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Impact of universal preadolescent vaccination against hepatitis B on antenatal seroprevalence of hepatitis B markers in British Columbia women. Author(s): Dawar M, Patrick DM, Bigham M, Cook D, Krajden M, Ng H. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 March 18; 168(6): 703-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642425&dopt=Abstract

150 Hepatitis B

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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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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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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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Influence of hepatitis B virus genotypes on the development of preS deletions and advanced liver disease. Author(s): Sugauchi F, Ohno T, Orito E, Sakugawa H, Ichida T, Komatsu M, Kuramitsu T, Ueda R, Miyakawa Y, Mizokami M. Source: Journal of Medical Virology. 2003 August; 70(4): 537-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794715&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 hepatitis B virus expression and replication by RNA interference. Author(s): Shlomai A, Shaul Y. Source: Hepatology (Baltimore, Md.). 2003 April; 37(4): 764-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668968&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

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Integrations of the hepatitis B virus (HBV) and human papillomavirus (HPV) into the human telomerase reverse transcriptase (hTERT) gene in liver and cervical cancers. Author(s): Ferber MJ, Montoya DP, Yu C, Aderca I, McGee A, Thorland EC, Nagorney DM, Gostout BS, Burgart LJ, Boix L, Bruix J, McMahon BJ, Cheung TH, Chung TK, Wong YF, Smith DI, Roberts LR. Source: Oncogene. 2003 June 12; 22(24): 3813-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802289&dopt=Abstract

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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 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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Intrafamilial transmission of hepatitis B virus in the eastern Anatolian region of Turkey. Author(s): Erol S, Ozkurt Z, Ertek M, Tasyaran MA. Source: European Journal of Gastroenterology & Hepatology. 2003 April; 15(4): 345-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655252&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

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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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Kala azar in a case of chronic hepatitis B with cirrhosis of liver. Author(s): Dhar MC, Chaudhuri S, Pain S, Sau TJ, Bagchi SR. Source: J Assoc Physicians India. 2001 November; 49: 1127. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11868875&dopt=Abstract

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Kinetic analysis of wild-type and YMDD mutant hepatitis B virus polymerases and effects of deoxyribonucleotide concentrations on polymerase activity. Author(s): Gaillard RK, Barnard J, Lopez V, Hodges P, Bourne E, Johnson L, Allen MI, Condreay P, Miller WH, Condreay LD. Source: Antimicrobial Agents and Chemotherapy. 2002 April; 46(4): 1005-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11897582&dopt=Abstract

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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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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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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 for hepatitis B in renal transplantation. Author(s): Santos FR, Haiashi AR, Araujo MR, Abensur H, Romao Junior JE, Noronha IL. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 2002 February; 35(2): 199-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11847523&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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Lethal liver failure in an elderly patient with hepatitis B superinfected with EpsteinBarr virus. Author(s): Jimenez-Saenz M, Perez-Pozo JM, Leal-Luna A, Herrerias-Gutierrez JM. Source: European Journal of Gastroenterology & Hepatology. 2002 November; 14(11): 1283-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439128&dopt=Abstract

154 Hepatitis B

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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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Limited efficacy of lamivudine against hepatitis B virus infection in allogeneic hematopoietic stem cell transplant recipients. Author(s): Ohnishi M, Kanda Y, Takeuchi T, Won Kim S, Hori A, Niiya H, Chizuka A, Nakai K, Saito T, Makimoto A, Tanosaki R, Watanabe T, Kobayashi Y, Tobinai K, Takaue Y, Mineishi S. Source: Transplantation. 2002 March 15; 73(5): 812-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11907433&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-term clinical remission induced by corticosteroid withdrawal therapy (CSWT) in patients with chronic hepatitis B infection: a prospective randomized controlled trial--CSWT with and without follow-up interferon-alpha therapy. Author(s): Akuta N, Suzuki F, Tsubota A, Arase Y, Suzuki Y, Someya T, Kobayashi M, Saitoh S, Ikeda K, Kumada H. Source: Digestive Diseases and Sciences. 2002 February; 47(2): 405-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11855559&dopt=Abstract

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Long-term follow-up of chronic hepatitis B virus infection in children of different ethnic origins. Author(s): Marx G, Martin SR, Chicoine JF, Alvarez F. Source: The Journal of Infectious Diseases. 2002 August 1; 186(3): 295-301. Epub 2002 July 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12134225&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 immunogenicity and efficacy of universal hepatitis B virus vaccination in Taiwan. Author(s): Lin YC, Chang MH, Ni YH, Hsu HY, Chen DS. Source: The Journal of Infectious Diseases. 2003 January 1; 187(1): 134-8. Epub 2002 December 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508157&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 pertussis-specific immune responses to a combined diphtheria, tetanus, tricomponent acellular pertussis and hepatitis B vaccine in pre-term infants. Author(s): Esposito S, Faldella G, Giammanco A, Bosis S, Friscia O, Clerici M, Principi N. Source: Vaccine. 2002 July 26; 20(23-24): 2928-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12126904&dopt=Abstract

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Long-term prognosis by lamivudine monotherapy for severe acute exacerbation in chronic hepatitis B infection: emergence of YMDD motif mutant and risk of breakthrough hepatitis -- an open-cohort study. Author(s): Akuta N, Tsubota A, Suzuki F, Suzuki Y, Hosaka T, Someya T, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kumada H. Source: Journal of Hepatology. 2003 January; 38(1): 91-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480565&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

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Low prevalence of hepatitis B and C markers in non-amazonian indigenous population. Author(s): Aguiar JI, de Souza JA, Aguiar ES, Oliveira JM, de Lemos ER, Yoshida CF. Source: The Brazilian Journal of Infectious Diseases : an Official Publication of the Brazilian Society of Infectious Diseases. 2002 October; 6(5): 269-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495611&dopt=Abstract

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Management of chronic hepatitis B. Author(s): Conjeevaram HS, Lok AS. Source: Journal of Hepatology. 2003; 38 Suppl 1: S90-103. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591188&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 B virus infected health care workers based on HBV DNA levels. Author(s): Schalm SW, Buster EH. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2003 August; 27(3): 231-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878085&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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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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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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Molecular and serological aspects of HBsAg-negative hepatitis B virus infections in North America. Author(s): Hsia CC, Scudamore CH, Di Bisceglie AM, Tabor E. Source: Journal of Medical Virology. 2003 May; 70(1): 20-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629639&dopt=Abstract

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Molecular aspects of hepatitis B viral infection and the viral carcinogenesis. Author(s): Ryu WS. Source: J Biochem Mol Biol. 2003 January 31; 36(1): 138-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12542984&dopt=Abstract

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Molecular chaperone GRP78/BiP interacts with the large surface protein of hepatitis B virus in vitro and in vivo. Author(s): Cho DY, Yang GH, Ryu CJ, Hong HJ. Source: Journal of Virology. 2003 February; 77(4): 2784-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552023&dopt=Abstract

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Molecular characterization of hepatitis B virus surface antigen mutants in Singapore patients with hepatocellular carcinoma and hepatitis B virus carriers negative for HBsAg but positive for anti-HBs and anti-HBc. Author(s): Oon CJ, Chen WN, Goh KT, Mesenas S, Ng HS, Chiang G, Tan C, Koh S, Teng SW, Toh I, Moh MC, Goo KS, Tan K, Leong AL, Tan GS. Source: Journal of Gastroenterology and Hepatology. 2002 December; 17 Suppl: S491-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534784&dopt=Abstract

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Molecular epidemiology and immunology of hepatitis B virus infection - an update. Author(s): Pumpens P, Grens E, Nassal M. Source: Intervirology. 2002; 45(4-6): 218-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566704&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

158 Hepatitis B

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Molecular epidemiology of gibbon hepatitis B virus transmission. Author(s): Noppornpanth S, Haagmans BL, Bhattarakosol P, Ratanakorn P, Niesters HG, Osterhaus AD, Poovorawan Y. Source: The Journal of General Virology. 2003 January; 84(Pt 1): 147-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12533711&dopt=Abstract

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Molecular epidemiology of hepatitis B viral serotypes and genotypes in taiwan. Author(s): Liu CJ, Kao JH, Chen PJ, Lai MY, Chen DS. Source: Journal of Biomedical Science. 2002 March-April; 9(2): 166-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11914584&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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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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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 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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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 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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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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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

160 Hepatitis B

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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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Observational study of vaccine efficacy 14 years after trial of hepatitis B vaccination in Gambian children. Author(s): Whittle H, Jaffar S, Wansbrough M, Mendy M, Dumpis U, Collinson A, Hall A. Source: Bmj (Clinical Research Ed.). 2002 September 14; 325(7364): 569. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12228132&dopt=Abstract

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Occult hepatitis B virus infection and clinical outcomes of patients with chronic hepatitis C. Author(s): Kao JH, Chen PJ, Lai MY, Chen DS. Source: Journal of Clinical Microbiology. 2002 November; 40(11): 4068-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409376&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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Occult hepatitis B. Author(s): Torbenson M, Thomas DL. Source: The Lancet Infectious Diseases. 2002 August; 2(8): 479-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150847&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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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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One two tandem of lamivudine and inferferon might work for patients with chronic hepatitis B who failed inferferon monotherapy. Author(s): Kaplan DD, Reddy KR. Source: The American Journal of Gastroenterology. 2002 September; 97(9): 2465-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12358276&dopt=Abstract

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Oral ganciclovir for treatment of lamivudine-resistant hepatitis B virus infection: a pilot study. Author(s): Bozkaya H, Yurdaydin C, Bozdayi AM, Erkan O, Karayalcin S, Uzunalimoglu O. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 October 15; 35(8): 960-5. Epub 2002 September 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12355383&dopt=Abstract

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Overexpression and purification of the hepatitis B e antigen precursor. Author(s): Laine S, Salhi S, Rossignol JM. Source: Journal of Virological Methods. 2002 May; 103(1): 67-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11906734&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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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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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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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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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 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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Previous hepatitis B virus infection is associated with worse disease stage and occult hepatitis B virus infection has low prevalence and pathogenicity in hepatitis C viruspositive patients. Author(s): Giannini E, Ceppa P, Botta F, Fasoli A, Romagnoli P, Ansaldi F, Durando P, Risso D, Lantieri PB, Icardi GC, Testa R. Source: Liver International : Official Journal of the International Association for the Study of the Liver. 2003 February; 23(1): 12-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640722&dopt=Abstract

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Prognostic factors in severe exacerbation of chronic hepatitis B. Author(s): Yuen MF, Sablon E, Hui CK, Li TM, Yuan HJ, Wong DK, Doutreloigne J, Bogaerts V, Wong BC, Fan ST, Lai CL. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 April 15; 36(8): 979-84. Epub 2003 Apr 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684909&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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Quantification and genotyping in management of chronic hepatitis B and C. Author(s): Zoulim F. Source: Virus Research. 2002 January 30; 82(1-2): 45-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11885949&dopt=Abstract

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Quantitative analysis of hepatitis B virus DNA by real-lime amplification. Author(s): Zanella I, Rossini A, Domenighini D, Albertini A, Cariani E. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2002 January; 21(1): 22-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11913497&dopt=Abstract

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Quantitative detection of hepatitis B virus DNA in serum by a new rapid real-time fluorescence PCR assay. Author(s): Jardi R, Rodriguez F, Buti M, Costa X, Cotrina M, Valdes A, Galimany R, Esteban R, Guardia J. Source: Journal of Viral Hepatitis. 2001 November; 8(6): 465-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11703579&dopt=Abstract

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Quantitative serum HBV DNA levels during different stages of chronic hepatitis B infection. Author(s): Chu CJ, Hussain M, Lok AS. Source: Hepatology (Baltimore, Md.). 2002 December; 36(6): 1408-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447866&dopt=Abstract

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Rapid hepatitis B virus-DNA decay in co-infected HIV-hepatitis B virus 'e-minus' patients with YMDD mutations after 4 weeks of tenofovir therapy. Author(s): Bruno R, Sacchi P, Zocchetti C, Ciappina V, Puoti M, Filice G. Source: Aids (London, England). 2003 March 28; 17(5): 783-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12646813&dopt=Abstract

164 Hepatitis B

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Re: Hormonal markers and hepatitis B virus-related hepatocellular carcinoma risk: a nested case-control study among men. Author(s): Sung YM, Tang NL, Lai PB, Chan PK, Chan FK. Source: Journal of the National Cancer Institute. 2003 April 2; 95(7): 559-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671025&dopt=Abstract

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Recombinant hepatitis B vaccination in renal failure patients. Author(s): Vlassopoulos D. Source: Current Pharmaceutical Biotechnology. 2003 April; 4(2): 141-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678888&dopt=Abstract

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Recurrent hepatitis B flares in an HIV-positive patient. Author(s): Jenny-Avital ER. Source: Aids Clin Care. 2003 January; 15(1): 4-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12685421&dopt=Abstract

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Regulation of p21 and p27 expression by the hepatitis B virus X protein and the alternate initiation site X proteins, AUG2 and AUG3. Author(s): Leach JK, Qiao L, Fang Y, Han SL, Gilfor D, Fisher PB, Grant S, Hylemon PB, Peterson D, Dent P. Source: Journal of Gastroenterology and Hepatology. 2003 April; 18(4): 376-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653885&dopt=Abstract

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Response predictors and results of a long-term treatment with lamivudine in patients with chronic hepatitis B. Author(s): Mihm U, Sarrazin C, Herrmann E, Teuber G, von Wagner M, Kronenberger B, Zeuzem S. Source: Zeitschrift Fur Gastroenterologie. 2003 March; 41(3): 249-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664345&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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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 hepatitis B virus infection in pathogenesis of IgA nephropathy. Author(s): Wang NS, Wu ZL, Zhang YE, Guo MY, Liao LT. Source: World Journal of Gastroenterology : Wjg. 2003 September; 9(9): 2004-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970894&dopt=Abstract

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Routine hepatitis B immunization in India: cost effectiveness needs reassessment. Author(s): Puliyel JM, Mittal R, Tyagi V, Gupta S. Source: Indian J Pediatr. 2003 February; 70(2): 188. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661821&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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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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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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Serum cytokine profiles associated with clinical presentation in Vietnamese infected with hepatitis B virus. Author(s): Song le H, Binh VQ, Duy DN, Kun JF, Bock TC, Kremsner PG, Luty AJ. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2003 September; 28(1): 93-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927756&dopt=Abstract

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Serum zinc as a factor predicting response to interferon-alpha2b therapy in children with chronic hepatitis B. Author(s): Ozbal E, Helvaci M, Kasirga E, Akdenizoglu F, Kizilgunesler A. Source: Biological Trace Element Research. 2002 Winter; 90(1-3): 31-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12666823&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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Spontaneous viral clearance after 6-21 years of hepatitis B and C viruses coinfection in high HBV endemic area. Author(s): Fan CL, Wei L, Jiang D, Chen HS, Gao Y, Li RB, Wang Y. Source: World Journal of Gastroenterology : Wjg. 2003 September; 9(9): 2012-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970896&dopt=Abstract

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Structure-activity relationships of (S,Z)-2-aminopurine methylenecyclopropane analogues of nucleosides. Variation of purine-6 substituents and activity against herpesviruses and hepatitis B virus. Author(s): Chen X, Kern ER, Drach JC, Gullen E, Cheng YC, Zemlicka J. Source: Journal of Medicinal Chemistry. 2003 April 10; 46(8): 1531-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672254&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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The delivery of hepatitis B vaccine. Author(s): Chislett L. Source: Nurs Times. 2003 February 18-24; 99(7): 50-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655755&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 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

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Therapeutic vaccination in the immunotolerant phase of children with chronic hepatitis B infection. Author(s): Dikici B, Kalayci AG, Ozgenc F, Bosnak M, Davutoglu M, Ece A, Ozkan T, Ozeke T, Yagci RV, Haspolat K. Source: The Pediatric Infectious Disease Journal. 2003 April; 22(4): 345-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12690275&dopt=Abstract

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Transcriptional repression of the human p53 gene by hepatitis B viral core protein (HBc) in human liver cells. Author(s): Kwon JA, Rho HM. Source: Biological Chemistry. 2003 February; 384(2): 203-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12675512&dopt=Abstract

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Transfer of humoral and cellular hepatitis B immunity by allogeneic hematopoietic cell transplantation. Author(s): Lindemann M, Barsegian V, Runde V, Fiedler M, Heermann KH, Schaefer UW, Roggendorf M, Grosse-Wilde H. Source: Transplantation. 2003 March 27; 75(6): 833-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660511&dopt=Abstract

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Transient hepatitis B surface antigenemia in a blood donor after a combination hepatitis A and B vaccine. Author(s): Davis AR, Brotchie HL, Mundkur BA, Ismay SL. Source: Transfusion. 2003 April; 43(4): 545. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12662290&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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Ultrapure dialysis fluid and response to hepatitis B vaccine. Author(s): Schiffl H, Wendinger H, Lang SM. Source: Nephron. 2002 July; 91(3): 530-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12119493&dopt=Abstract

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Understanding correlates of hepatitis B virus vaccination in men who have sex with men: what have we learned? Author(s): Yee LJ, Rhodes SD. Source: Sexually Transmitted Infections. 2002 October; 78(5): 374-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12407244&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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Update on hepatitis B treatment. Author(s): Firpi RJ, Martin P. Source: Medgenmed [electronic Resource] : Medscape General Medicine. 2002 September 24; 4(3): 9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466752&dopt=Abstract

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Update on the management of chronic hepatitis B. Author(s): Davis GL. Source: Reviews in Gastroenterological Disorders. 2002 Summer; 2(3): 106-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12227214&dopt=Abstract

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Use of hepatitis B core antibody-positive donors for liver transplantation. Author(s): Munoz SJ. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2002 October; 8(10 Suppl 1): S82-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12362304&dopt=Abstract

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Use of hepatitis B core antibody-positive donors in recipients without evidence of hepatitis B infection: a survey of current practice in the United States. Author(s): Burton JR Jr, Shaw-Stiffel TA. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003 August; 9(8): 837-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12884197&dopt=Abstract

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Use of lidocaine-prilocaine patch to decrease intramuscular injection pain does not adversely affect the antibody response to diphtheria-tetanus-acellular pertussisinactivated poliovirus-Haemophilus influenzae type b conjugate and hepatitis B vaccines in infants from birth to six months of age. Author(s): Halperin BA, Halperin SA, McGrath P, Smith B, Houston T. Source: The Pediatric Infectious Disease Journal. 2002 May; 21(5): 399-405. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150176&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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Vaccinating Asian Pacific Islander children against hepatitis B: ethnic-specific influences and barriers. Author(s): Pulido MJ, Alvarado EA, Berger W, Nelson A, Todoroff C. Source: Asian Am Pac Isl J Health. 2001 Summer-Fall; 9(2): 211-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11846367&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 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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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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Viral genotypes and response to interferon in patients with acute prolonged hepatitis B virus infection of adulthood in Japan. Author(s): 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. Source: Journal of Medical Virology. 2002 December; 68(4): 522-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376960&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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Virus-specific CD8+ lymphocytes share the same effector-memory phenotype but exhibit functional differences in acute hepatitis B and C. Author(s): Urbani S, Boni C, Missale G, Elia G, Cavallo C, Massari M, Raimondo G, Ferrari C. Source: Journal of Virology. 2002 December; 76(24): 12423-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12438568&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 optimal therapy for chronic hepatitis B? Author(s): Lyra AC, Di Bisceglie AM. Source: Minerva Med. 2001 December; 92(6): 431-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11740431&dopt=Abstract

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Why can't Chinese Han drink alcohol? Hepatitis B virus infection and the evolution of acetaldehyde dehydrogenase deficiency. Author(s): Lin YP, Cheng TJ. Source: Medical Hypotheses. 2002 August; 59(2): 204-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208210&dopt=Abstract

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Why do gay men want to be vaccinated against hepatitis B? An assessment of psychosocial determinants of vaccination intention. Author(s): Schutten M, de Wit JB, van Steenbergen JE. Source: International Journal of Std & Aids. 2002 February; 13(2): 86-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11839162&dopt=Abstract

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Wild-type and 'a' epitope variants in chronic hepatitis B virus carriers positive for hepatitis B surface antigen and antibody. Author(s): Mesenas SJ, Chow WC, Zhao Y, Lim GK, Oon CJ, Ng HS. Source: Journal of Gastroenterology and Hepatology. 2002 February; 17(2): 148-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966944&dopt=Abstract

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World-wide epidemiology of HBeAg-negative chronic hepatitis B and associated precore and core promoter variants. Author(s): Funk ML, Rosenberg DM, Lok AS. Source: Journal of Viral Hepatitis. 2002 January; 9(1): 52-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11851903&dopt=Abstract

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CHAPTER 2. NUTRITION AND HEPATITIS B Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and hepatitis B.

Finding Nutrition Studies on Hepatitis B 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 B” (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 information is typical of that found when using the “Full IBIDS Database” to search for “hepatitis B” (or a synonym): •

A case history of plant-derived drug research: phyllanthus and hepatitis B virus. Source: Blumberg, B.S. Medicinal plants their role in health and biodiversity /. Philadelphia : University of Pennsylvania Press, c1998. page 3-10. ISBN: 0812234316 (cloth : alk paper)

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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 comparative study of Phyllanthus amarus compound and interferon in the treatment of chronic viral hepatitis B. Author(s): Tropical Medicine Institute, Guangzhou University of Traditional Chinese Medicine, Guangdong, People's Republic of China. Source: Xin Hua, W Chang Qing, L Xing Bo, G Lin Chun, F Southeast-Asian-J-TropMed-Public-Health. 2001 March; 32(1): 140-2 0125-1562

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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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Characterization of a 120-kilodalton pre-S-binding protein as a candidate duck hepatitis B virus receptor. Source: Li, J.S. Tong, S.P. Wands, J.R. J-virol. Washington, D.C. : American Society for Microbiology. Sept 1996. volume 70 (9) page 6029-6035. 0022-538X

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Chinese medicinal herbs for asymptomatic carriers of hepatitis B virus infection. Author(s): The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, Dept. 7701, H:S Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark, DK-2100. [email protected] Source: Liu, J P McIntosh, H Lin, H Cochrane-Database-Syst-Revolume 2001; (2): CD002231 1469-493X

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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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Determination of hepatic zinc content in chronic liver disease due to hepatitis B virus. Author(s): Hacettepe University, Faculty of Medicine, Department of Internal Medicine, Ankara-Turkey. Source: Gur, G Bayraktar, Y Ozer, D Ozdogan, M Kayhan, B Hepatogastroenterology. 1998 Mar-April; 45(20): 472-6 0172-6390

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Effects of acupuncture on the immunological functions in hepatitis B virus carriers. Author(s): First Municipal Hospital, Zhuzhou, Hunan Province. Source: Chen, J Chen, M Zhao, B Wang, Y J-Tradit-Chin-Med. 1999 December; 19(4): 26872 0254-6272

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Genus Phyllanthus for chronic hepatitis B virus infection: a systematic review. Author(s): The Cochrane Hepato-Biliary Group, The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, Copenhagen, Denmark. [email protected] Source: Liu, J Lin, H McIntosh, H J-Viral-Hepat. 2001 September; 8(5): 358-66 1352-0504

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Hepatitis B infection in China. Author(s): University Department of Medicine, Queen Mary Hospital, Hong Kong, SAR, China. [email protected] Source: Lau, G K Clin-Liver-Dis. 2001 May; 5(2): 361-79 1089-3261

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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

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Identification of two separable modules in the duck hepatitis B virus core protein. [Erratum: Apr 1997, v. 71 (4), p. 3363.]. Source: Weizsacker, F. von Wieland, S. Blum, H.E. J-virol. Washington, D.C. : American Society for Microbiology. April 1995. volume 69 (4) page 2704-2707. 0022-538X

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Immune-mediated pathology following hepatitis B vaccination. Two cases of polyarteritis nodosa and one case of pityriasis rosea-like drug eruption. Author(s): Department of Rheumatology, University Hospital Gent, Belgium. [email protected] Source: De Keyser, F Naeyaert, J M Hindryckx, P Elewaut, D Verplancke, P Peene, I Praet, M Veys, E Clin-Exp-Rheumatol. 2000 Jan-February; 18(1): 81-5 0392-856X

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In vitro anti-hepatitis B virus activities of 5”-O-myristoyl analogue derivatives of 3”fluoro-2”,3”-dideoxythymidine (FLT) and 3”-azido-2”,3”-dideoxythymidine (AZT). Author(s): Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada. Source: Knaus, E E Parang, K Wiebe, L I Huang, J S Tyrrell, D L J-Pharm-Pharm-Sci. 1998 Sep-December; 1(3): 108-14 1482-1826

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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

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Interaction of fucoidan from Pelvetia fastigiata with surface antigens of hepatitis B and woodchuck hepatitis viruses. Source: Venkateswaran, P.S. Millman, I. Blumberg, B.S. Plant-Med. Stuttgart, W. Ger. : Georg Thieme Verlag. June 1989. volume 55 (3) page 265-270. 0032-0943

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Leptomycin B inhibits equine infectious anemia virus Rev and feline immunodeficiency virus rev function but not the function of the hepatitis B virus posttranscriptional regulatory element. Author(s): Infectious Disease Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA. Source: Otero, G C Harris, M E Donello, J E Hope, T J J-Virol. 1998 September; 72(9): 7593-7 0022-538X

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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

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Management of chronic hepatitis B infection: an update. Author(s): Department of Gastroenterology, VIMS, RKM Seva Pratisthan, Calcutta. Source: Mazumdar, T N J-Indian-Med-Assoc. 2001 June; 99(6): 306-8, 310 0019-5847

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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

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Nutritional therapy of chronic hepatitis by whey protein (non-heated). Author(s): Third Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.

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Source: Watanabe, A Okada, K Shimizu, Y Wakabayashi, H Higuchi, K Niiya, K Kuwabara, Y Yasuyama, T Ito, H Tsukishiro, T Kondoh, Y Emi, N Kohri, H J-Med. 2000; 31(5-6): 283-302 0025-7850 •

One year follow-up of patients treated with misoprostol in acute phase of viral hepatitis B. Author(s): Department of Infectious Diseases, Medical Academy of Bialystok, Zurawia Str 14, 15-540, Bialystok, Poland. [email protected] Source: Flisiak, R Prokopowicz, D Prostaglandins-Other-Lipid-Mediat. 2000 March; 60(4-6): 161-5 1098-8823

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Oral prostaglandin (PGE2) therapy for chronic viral hepatitis B and C. Author(s): Department of Medicine, University of Toronto, Canada. Source: Hyman, A Yim, C Krajden, M Read, S Basinski, A S Wanless, I Levy, G Heathcote, J J-Viral-Hepat. 1999 July; 6(4): 329-36 1352-0504

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Packaging of up to 240 subunits of a 17 kDa nuclease into the interior of recombinant hepatitis B virus capsids. Author(s): University Hospital Freiburg, Department of Internal Medicine II, Molecular Biology, Hugstetter Str. 55, D-79107 Freiburg, Germany. Source: Beterams, G Bottcher, B Nassal, M FEBS-Lett. 2000 September 15; 481(2): 169-76 0014-5793

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Phenotypic mixing of rodent but not avian hepadnavirus surface proteins into human hepatitis B virus particles. Source: Gerhardt, E. Bruss, V. J-virol. Washington, D.C. : American Society for Microbiology. February 1995. volume 69 (2) page 1201-1208. 0022-538X

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Possible role of retinoids in hepatitis B virus-associated liver damage. Author(s): Public Health Program, Des Moines University Osteopathic Medical Center, 3200 Grand Avenue, Des Moines, Iowa 50312, USA. [email protected] Source: Mawson, A R Steele, T A Exp-Biol-Med-(Maywood). 2001 September; 226(8): 734-9 1535-3702

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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

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Production in yeast versus mammalian cells of the first recombinant DNA human vaccine and its proved safety, efficacy, and economy: hepatitis B vaccine. Source: Stephenne, J. Adv-Biotechnol-Processes. New York, N.Y. : Allan R. Liss. 1990. volume 14 page 279-299. ill. 0736-2293

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Reactivation of hepatitis B but not hepatitis C in patients with malignant lymphoma and immunosuppressive therapy. A prospective study in 305 patients. Author(s): Institute of Oncology, Ljubljana, Slovenia. [email protected] Source: Markovic, S Drozina, G Vovk, M Fidler Jenko, M Hepatogastroenterology. 1999 Sep-October; 46(29): 2925-30 0172-6390

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Replication of the wild type and a natural hepatitis B virus nucleocapsid promoter variant is differentially regulated by nuclear hormone receptors in cell culture. Author(s): Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA.

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Source: Tang, H Raney, A K McLachlan, A J-Virol. 2001 October; 75(19): 8937-48 0022538X •

Selected mutations of the duck hepatitis B virus P gene RNase H domain affect both RNA packaging and priming of minus-strand DNA synthesis. Source: Chen, Y. Robinson, W.S. Marion, P.L. J-virol. Washington, D.C. : American Society for Microbiology. August 1994. volume 68 (8) page 5232-5238. 0022-538X

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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

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Serum level of interferon alpha in patients with acute viral hepatitis B. Author(s): Department of Infectious Diseases, Epidemiology and Parasitology, Higher Medical Institute, Plovdiv, Bulgaria. Source: Geneva Popova, M Folia-Med-(Plovdiv). 1998; 40(1): 46-51 0204-8043

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Sustained activation of mitogen-activated protein kinases and activator protein 1 by the hepatitis B virus X protein in mouse hepatocytes in vivo. Author(s): Department of Biochemistry, University of Delhi South Campus, New Delhi110021, India. Source: Nijhara, R Jana, S S Goswami, S K Rana, A Majumdar, S S KuMarch, V Sarkar, D P J-Virol. 2001 November; 75(21): 10348-58 0022-538X

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The effect of interferon and desferrioxamine on serum ferritin and hepatic iron concentrations in chronic hepatitis B. Author(s): Department of Gastroenterology, School of Medicine, Hacettepe University, Ankara, Turkey. Source: Bayraktar, Y Saglam, F Temizer, A Uzunalimodlu, B van Thiel, D H Hepatogastroenterology. 1998 Nov-December; 45(24): 2322-7 0172-6390

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The proapoptotic effect of hepatitis B virus HBx protein correlates with its transactivation activity in stably transfected cell lines. Author(s): Unite de Recombinaison et Expression Genetique (INSERM U163), Institut Pasteur, Paris, France. Source: Bergametti, F Prigent, S Luber, B Benoit, A Tiollais, P Sarasin, A Transy, C Oncogene. 1999 May 6; 18(18): 2860-71 0950-9232

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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 treatment of chronic hepatitis B: results of a phase III multicentre, randomized, double-blind and placebo-controlled study. Author(s): Division of Gastroenterology, Department of Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA.

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Source: Mutchnick, M G Lindsay, K L Schiff, E R Cummings, G D Appelman, H D Peleman, R R Silva, M Roach, K C Simmons, F Milstein, S Gordon, S C Ehrinpreis, M N J-Viral-Hepat. 1999 September; 6(5): 397-403 1352-0504 •

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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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

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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WebMD®Health: 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 B; 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 E Source: Prima Communications, Inc.www.personalhealthzone.com

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Minerals Selenium Source: Prima Communications, Inc.www.personalhealthzone.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND HEPATITIS B Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to hepatitis B. At the conclusion of this chapter, we will provide additional sources.

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 B 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 B” (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 B: •

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 large outbreak of acupuncture-associated hepatitis B. Author(s): Kent GP, Brondum J, Keenlyside RA, LaFazia LM, Scott HD. Source: American Journal of Epidemiology. 1988 March; 127(3): 591-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3341362&dopt=Abstract

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A novel oral adjuvant for hepatitis B virus (HBV) vaccines. Author(s): Ishizaka S, Kuriyama S, Kikuchi E, Nishimura K, Tsujii T.

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Source: Journal of Hepatology. 1990 November; 11(3): 326-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2290023&dopt=Abstract •

A plant-derived edible vaccine against hepatitis B virus. Author(s): Kapusta J, Modelska A, Figlerowicz M, Pniewski T, Letellier M, Lisowa O, Yusibov V, Koprowski H, Plucienniczak A, Legocki AB. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 1999 October; 13(13): 1796-9. Erratum In: Faseb J 1999 December; 13(15): 2339. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10506582&dopt=Abstract

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A randomized controlled trial of kurorinone versus interferon-alpha2a treatment in patients with chronic hepatitis B. Author(s): Chen C, Guo SM, Liu B. Source: Journal of Viral Hepatitis. 2000 May; 7(3): 225-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10849265&dopt=Abstract

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A two-stage clinical trial of Phyllanthus amarus in hepatitis B carriers: failure to eradicate the surface antigen. Author(s): Doshi JC, Vaidya AB, Antarkar DS, Deolalikar R, Antani DH. Source: Indian J Gastroenterol. 1994 January; 13(1): 7-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8119752&dopt=Abstract

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Active compounds from Saussurea lappa Clarks that suppress hepatitis B virus surface antigen gene expression in human hepatoma cells. Author(s): Chen HC, Chou CK, Lee SD, Wang JC, Yeh SF. Source: Antiviral Research. 1995 May; 27(1-2): 99-109. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7486962&dopt=Abstract

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Acupuncture and possible hepatitis B infection. Author(s): Li FP, Shiang EL. Source: Jama : the Journal of the American Medical Association. 1980 April 11; 243(14): 1423. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7359710&dopt=Abstract

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Acute exacerbation of hepatitis due to reactivation of hepatitis B virus with mutations in the core region after chemotherapy for malignant lymphoma. Author(s): Sato T, Kato J, Kawanishi J, Kogawa K, Ohya M, Sakamaki S, Niitsu Y. Source: Journal of Gastroenterology. 1997 October; 32(5): 668-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9349995&dopt=Abstract

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Acute hepatic injury after discontinuation of chemotherapy in a patient with nonHodgkin's lymphoma and chronic hepatitis B virus infection. Author(s): Haanen JB, Bieger R, van't Wout JW. Source: The Netherlands Journal of Medicine. 1996 December; 49(6): 239-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8990863&dopt=Abstract

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Aflatoxin exposure, hepatitis B virus infection and liver cancer in Swaziland. Author(s): Peers F, Bosch X, Kaldor J, Linsell A, Pluijmen M. Source: International Journal of Cancer. Journal International Du Cancer. 1987 May 15; 39(5): 545-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3570547&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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AM3, an adjuvant to hepatitis B revaccination in non-responder healthy persons. Author(s): Sanchez L, Pena E, Civantos A, Sada G, Alvarez MM, Chirigos MA, Villarrubia VG. Source: Journal of Hepatology. 1995 January; 22(1): 119-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7751580&dopt=Abstract

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An acupuncture-associated outbreak of hepatitis B in Jerusalem. Author(s): Slater PE, Ben-Ishai P, Leventhal A, Zahger D, Bashary A, Moses A, Costin C, Shouval D. Source: European Journal of Epidemiology. 1988 September; 4(3): 322-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3181383&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. 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

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Beneficial effects of Phyllanthus amarus for chronic hepatitis B, not confirmed. Author(s): Berk L, de Man RA, Schalm SW, Labadie RP, Heijtink RA. Source: Journal of Hepatology. 1991 May; 12(3): 405-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1940272&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. 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

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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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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 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.

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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 •

Complement-mediated changes in morphology of hepatitis B antigen-antibody complexes. Author(s): Hirschman SZ, Kochwa S, Rosenfield R, Schwartz J. Source: Vox Sanguinis. 1974 March; 26(3): 222-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4209321&dopt=Abstract

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Detection of hepatitis B and woodchuck hepatitis viral DNA in plasma and mononuclear cells from heparinized blood by the polymerase chain reaction. Author(s): Pardoe IU, Michalak TI. Source: Journal of Virological Methods. 1995 February; 51(2-3): 277-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7738148&dopt=Abstract

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Development of an enzyme immunoassay for the detection of hepatitis B surface antigen employing monoclonal antibodies. Author(s): Toplikar E, Carlomagno A, Rojkin LF, Gariglio R, Lorenzo LE. Source: Journal of Clinical Laboratory Analysis. 1993; 7(6): 324-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8277356&dopt=Abstract

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Disclosure of trauma and immune response to a hepatitis B vaccination program. Author(s): Petrie KJ, Booth RJ, Pennebaker JW, Davison KP, Thomas MG. Source: Journal of Consulting and Clinical Psychology. 1995 October; 63(5): 787-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7593871&dopt=Abstract

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Do bedbugs transmit hepatitis B? Author(s): Mayans MV, Hall AJ, Inskip HM, Lindsay SW, Chotard J, Mendy M, Whittle HC. Source: Lancet. 1994 March 26; 343(8900): 761-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7907732&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.

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Duck hepatitis B virus model for screening of antiviral agents from medicinal herbs. Author(s): Mi Z, Chen H, Zhang X, Shao X, Li Z, Wu X. Source: Chinese Medical Journal. 1995 September; 108(9): 660-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8575230&dopt=Abstract

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Effect of an extract from Phyllanthus amarus on hepatitis B surface antigen gene expression in human hepatoma cells. Author(s): Yeh SF, Hong CY, Huang YL, Liu TY, Choo KB, Chou CK. Source: Antiviral Research. 1993 March; 20(3): 185-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8470882&dopt=Abstract

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Effect of lymphatic and splenic pump techniques on the antibody response to hepatitis B vaccine: a pilot study. Author(s): Jackson KM, Steele TF, Dugan EP, Kukulka G, Blue W, Roberts A. Source: J Am Osteopath Assoc. 1998 March; 98(3): 155-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9558831&dopt=Abstract

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Effect of misoprostol on serum beta2-microglobulin in the course of viral hepatitis B. Author(s): Flisiak R, Prokopowicz D. Source: European Journal of Gastroenterology & Hepatology. 1999 November; 11(11): 1227-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10563531&dopt=Abstract

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Effect of misoprostol on the course of viral hepatitis B. Author(s): Flisiak R, Prokopowicz D. Source: Hepatogastroenterology. 1997 September-October; 44(17): 1419-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9356866&dopt=Abstract

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Effect of Phyllanthus amarus on chronic carriers of hepatitis B virus. Author(s): Brook MG. Source: Lancet. 1988 October 29; 2(8618): 1017-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2902445&dopt=Abstract

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Effect of Phyllanthus amarus on chronic carriers of hepatitis B virus. Author(s): Thyagarajan SP, Subramanian S, Thirunalasundari T, Venkateswaran PS, Blumberg BS. Source: Lancet. 1988 October 1; 2(8614): 764-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2901611&dopt=Abstract

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Effect of Phyllanthus amarus on duck hepatitis B virus replication in vivo. Author(s): Niu JZ, Wang YY, Qiao M, Gowans E, Edwards P, Thyagarajan SP, Gust I, Locarnini S. Source: Journal of Medical Virology. 1990 December; 32(4): 212-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2081970&dopt=Abstract

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Effect of sho-saiko-to(xiao-chai-hu-tang) on HBeAg clearance in children with chronic hepatitis B virus infection and with sustained liver disease. Author(s): Tajiri H, Kozaiwa K, Ozaki Y, Miki K, Shimuzu K, Okada S. Source: The American Journal of Chinese Medicine. 1991; 19(2): 121-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1816724&dopt=Abstract

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Effect of sizofiran, a polysaccharide, on interferon gamma, antibody production and lymphocyte proliferation specific for hepatitis B virus antigen in patients with chronic hepatitis B. Author(s): Kakumu S, Ishikawa T, Wakita T, Yoshioka K, Ito Y, Shinagawa T. Source: International Journal of Immunopharmacology. 1991; 13(7): 969-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1761362&dopt=Abstract

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Effect of thymic extract on allogeneic MLR and mitogen-induced responses in patients with chronic active hepatitis B. Author(s): Zeman K, Dworniak D, Tchorzewski H, Pokoca L, Majewska E. Source: Immunological Investigations. 1991 December; 20(7): 545-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1836778&dopt=Abstract

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Effectiveness of thymostimulin treatment in hepatitis B surface antigen-positive chronic active liver disease. Results of a randomized clinical trial. Author(s): Romeo F, Arcoria D, Palmisano L, Polosa P. Source: Arzneimittel-Forschung. 1985; 35(8): 1317-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3907642&dopt=Abstract

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Effects of acupuncture on the immunological functions in hepatitis B virus carriers. Author(s): Chen J, Chen M, Zhao B, Wang Y. Source: J Tradit Chin Med. 1999 December; 19(4): 268-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10921130&dopt=Abstract

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Effects of an extract from Phyllanthus niruri on hepatitis B and woodchuck hepatitis viruses: in vitro and in vivo studies. Author(s): Venkateswaran PS, Millman I, Blumberg BS. Source: Proceedings of the National Academy of Sciences of the United States of America. 1987 January; 84(1): 274-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3467354&dopt=Abstract

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Effects of Phyllanthus plant extracts on duck hepatitis B virus in vitro and in vivo. Author(s): Shead A, Vickery K, Pajkos A, Medhurst R, Freiman J, Dixon R, Cossart Y. Source: Antiviral Research. 1992 June; 18(2): 127-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1416905&dopt=Abstract

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Effects of TJ-9 Sho-saiko-to (kampo medicine) on interferon gamma and antibody production specific for hepatitis B virus antigen in patients with type B chronic hepatitis. Author(s): Kakumu S, Yoshioka K, Wakita T, Ishikawa T. Source: International Journal of Immunopharmacology. 1991; 13(2-3): 141-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1906436&dopt=Abstract

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Efficacy of Phyllanthus amarus for eradication of hepatitis B virus in chronic carriers. Author(s): Thamlikitkul V, Wasuwat S, Kanchanapee P. Source: J Med Assoc Thai. 1991 September; 74(9): 381-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1791391&dopt=Abstract

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Enhancement of interferon-gamma production in glycyrrhizin-treated human peripheral lymphocytes in response to concanavalin A and to surface antigen of hepatitis B virus. Author(s): Shinada M, Azuma M, Kawai H, Sazaki K, Yoshida I, Yoshida T, Suzutani T, Sakuma T. Source: Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.). 1986 February; 181(2): 205-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3080754&dopt=Abstract

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Enzyme-antibody conjugation by a heterobifunctional reagent and its application in enzyme-linked immunosorbent assay (ELISA) for the detection of hepatitis B surface antigen. Author(s): Gadkari DA, Fields HA, Maynard JE. Source: Journal of Virological Methods. 1985 March; 10(3): 215-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3886682&dopt=Abstract

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Epidemiology of hepatitis B virus infection in the Asia-Pacific region. Author(s): Chen CJ, Wang LY, Yu MW. Source: Journal of Gastroenterology and Hepatology. 2000 May; 15 Suppl: E3-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10921373&dopt=Abstract

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Essential fatty acid supplementation in chronic hepatitis B. Author(s): Jenkins AP, Green AT, Thompson RP. Source: Alimentary Pharmacology & Therapeutics. 1996 August; 10(4): 665-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8853774&dopt=Abstract

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Evaluation of anti-hepadnavirus activity of Phyllanthus amarus and Phyllanthus maderaspatensis in duck hepatitis B virus carrier Pekin ducks. Author(s): Munshi A, Mehrotra R, Ramesh R, Panda SK. Source: Journal of Medical Virology. 1993 December; 41(4): 275-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8106861&dopt=Abstract

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Evaluation of Phyllanthus amarus and Phyllanthus maderaspatensis as agents for postexposure prophylaxis in neonatal duck hepatitis B virus infection. Author(s): Munshi A, Mehrotra R, Panda SK. Source: Journal of Medical Virology. 1993 May; 40(1): 53-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8515247&dopt=Abstract

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Exacerbation of hepatitis in hepatitis B carriers following chemotherapy for haematological malignancies. Author(s): Wong GC, Tan P, Goh YT, Ng HS, Chong R, Lee LH. Source: Ann Acad Med Singapore. 1996 July; 25(4): 500-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8893918&dopt=Abstract

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Experimental studies on the inhibition effects of 1000 Chinese medicinal herbs on the surface antigen of hepatitis B virus. Author(s): Zheng M, Zheng Y. Source: J Tradit Chin Med. 1992 September; 12(3): 193-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1453758&dopt=Abstract

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Failure of New Zealand hepatitis B carriers to respond to Phyllanthus amarus. Author(s): Milne A, Hopkirk N, Lucas CR, Waldon J, Foo Y. Source: N Z Med J. 1994 June 22; 107(980): 243. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8208497&dopt=Abstract

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Failure of Phyllanthus amarus to eradicate hepatitis B surface antigen from symptomless carriers. Author(s): Leelarasamee A, Trakulsomboon S, Maunwongyathi P, Somanabandhu A, Pidetcha P, Matrakool B, Lebnak T, Ridthimat W, Chandanayingyong D. Source: Lancet. 1990 June 30; 335(8705): 1600-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1972525&dopt=Abstract

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Familial clustering of hepatitis B and C viruses in Korea. Author(s): Kim YS, Ahn YO, Kim DW. Source: Journal of Korean Medical Science. 1994 December; 9(6): 444-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7786439&dopt=Abstract

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Functional and structural similarity between the X protein of hepatitis B virus and nucleoside diphosphate kinases. Author(s): De-Medina T, Shaul Y. Source: Febs Letters. 1994 September 12; 351(3): 423-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8082807&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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HBsAg-like structures in immunosuppressed mice inoculated with human hepatitis B virus. Author(s): Schaff Z, Pohl O, Bencsath M, Brojnas J, Lapis K, Kopper L, Hollos I. Source: Virchows Arch B Cell Pathol Incl Mol Pathol. 1982 August; 40(2): 249-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6127839&dopt=Abstract

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Hepatitis after withdrawal of chemotherapy in a patient with chronic hepatitis B. Author(s): Schofield K, Morris D, Klapper P. Source: The Journal of Infection. 1993 July; 27(1): 101-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7690376&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. 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

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Hepatitis B and C virus, Clonorchis sinensis for the risk of liver cancer: a case-control study in Pusan, Korea. Author(s): Shin HR, Lee CU, Park HJ, Seol SY, Chung JM, Choi HC, Ahn YO, Shigemastu T. Source: International Journal of Epidemiology. 1996 October; 25(5): 933-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8921477&dopt=Abstract

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Hepatitis B antigen, alpha-fetoglobulins and primary hepatocellular carcinoma in Ethiopia. Author(s): Tsega E, Gold P, Shuster J, Whittemore B, Lester FT. Source: J Trop Med Hyg. 1976 October; 79(10): 230-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=64619&dopt=Abstract

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Hepatitis B control in China: knowledge and practices among village doctors. Author(s): Clayton S, Yang H, Guan J, Lin Z, Wang R.

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Hepatitis B epidemiology and cultural practices in Amerindian populations of Amazonia: the Tupi-Monde and the Xavante from Brazil. Author(s): Coimbra Junior CE, Santos RV, Yoshida CF, Baptista ML, Flowers NM, do Valle AC. Source: Social Science & Medicine (1982). 1996 June; 42(12): 1735-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8783434&dopt=Abstract

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Hepatitis B in Nuremberg, Germany. Epidemiology of a drug-associated epidemic. Among US Army soldiers. Author(s): Cates W Jr, Warren JW. Source: Jama : the Journal of the American Medical Association. 1975 December 1; 234(9): 930-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1242490&dopt=Abstract

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Hepatitis B infection and renal transplantation: the absence of anti-delta antibodies and the possible beneficial effect of silymarin during acute episodes of hepatic dysfunction. Author(s): Chan MK, Chan PC, Wong KK, Cheng IK, Li MK, Chang WK. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1989; 4(4): 297-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2502738&dopt=Abstract

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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 B infection in patients with lymphomas. Author(s): Liang RH, Lok AS, Lai CL, Chan TK, Todd D, Chiu EK. Source: Hematological Oncology. 1990 September-October; 8(5): 261-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1701155&dopt=Abstract

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Hepatitis B vaccination in the skin penetration industry. Author(s): Bouwman R, Cannata S, Fett MJ. Source: The Medical Journal of Australia. 1994 February 7; 160(3): 165. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8295594&dopt=Abstract

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Hepatitis B virus and hepatocellular carcinoma--treatment of HBV carriers with Phyllanthus amarus. Author(s): Blumberg BS, Millman I, Venkateswaran PS, Thyagarajan SP.

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Hepatitis B virus and primary hepatocellular carcinoma: treatment of HBV carriers with Phyllanthus amarus. Author(s): Blumberg BS, Millman I, Venkateswaran PS, Thyagarajan SP. Source: Vaccine. 1990 March; 8 Suppl: S86-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2158192&dopt=Abstract

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Hepatitis B: therapeutic perspectives. Author(s): Rizzetto M, Lagget M. Source: Forum (Genova). 2001 April-June; 11(2): 137-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11948359&dopt=Abstract

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Hepatocellular carcinoma, hepatic cirrhosis, and hepatitis B virus infection in Nigeria. Author(s): Otu AA. Source: Cancer. 1987 November 15; 60(10): 2581-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2822223&dopt=Abstract

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Herbs of the genus Phyllanthus in the treatment of chronic hepatitis B: observations with three preparations from different geographic sites. Author(s): Wang M, Cheng H, Li Y, Meng L, Zhao G, Mai K. Source: The Journal of Laboratory and Clinical Medicine. 1995 October; 126(4): 350-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7561442&dopt=Abstract

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High cytoplasmic expression in E. coli, purification, and in vitro refolding of a single chain Fv antibody fragment against the hepatitis B surface antigen. Author(s): Sanchez L, Ayala M, Freyre F, Pedroso I, Bell H, Falcon V, Gavilondo JV. Source: Journal of Biotechnology. 1999 June 11; 72(1-2): 13-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10406095&dopt=Abstract

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History of blood transfusion, tattooing, acupuncture and risk of hepatitis B surface antigenaemia among Chinese men in Singapore. Author(s): Phoon WO, Fong NP, Lee J. Source: American Journal of Public Health. 1988 August; 78(8): 958-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3389434&dopt=Abstract

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Identification of a protein kinase C (PKC) activator, daphnoretin, that suppresses hepatitis B virus gene expression in human hepatoma cells. Author(s): Chen HC, Chou CK, Kuo YH, Yeh SF.

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Immunogenicity and safety of low doses of recombinant yeast-derived hepatitis B vaccine. Author(s): Tan KL, Oon CJ, Goh KT, Wong LY, Chan SH. Source: Acta Paediatr Scand. 1990 June-July; 79(6-7): 593-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2143619&dopt=Abstract

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In vitro studies on the effect of certain natural products against hepatitis B virus. Author(s): Mehrotra R, Rawat S, Kulshreshtha DK, Patnaik GK, Dhawan BN. Source: The Indian Journal of Medical Research. 1990 April; 92: 133-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2370093&dopt=Abstract

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Influence of perceived psychological stress and distress on antibody response to low dose rDNA hepatitis B vaccine. Author(s): Jabaaij L, Grosheide PM, Heijtink RA, Duivenvoorden HJ, Ballieux RE, Vingerhoets AJ. Source: Journal of Psychosomatic Research. 1993 May; 37(4): 361-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8510062&dopt=Abstract

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Inhibition of hepatitis B surface antigen secretion on human hepatoma cells. Components from Rubia cordifolia. Author(s): Ho LK, Don MJ, Chen HC, Yeh SF, Chen JM. Source: Journal of Natural Products. 1996 March; 59(3): 330-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8882438&dopt=Abstract

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Interaction of fucoidan from Pelvetia fastigiata with surface antigens of hepatitis B and woodchuck hepatitis viruses. Author(s): Venkateswaran PS, Millman I, Blumberg BS. Source: Planta Medica. 1989 June; 55(3): 265-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2544915&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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Leeches and hepatitis B. Author(s): Narendranathan M.

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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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Modulation of immune response to rDNA hepatitis B vaccination by psychological stress. Author(s): Jabaaij L, van Hattum J, Vingerhoets JJ, Oostveen FG, Duivenvoorden HJ, Ballieux RE. Source: Journal of Psychosomatic Research. 1996 August; 41(2): 129-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8887826&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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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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Obstacles to hepatitis B vaccine uptake by health care staff. Author(s): Briggs MJ, Thomas J. Source: Public Health. 1994 March; 108(2): 137-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8183969&dopt=Abstract

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Occurrence of hepatitis and hepatitis B surface antigen in adult patients with acute leukemia. Author(s): Cowan DH, Kouroupis GM, Leers WD. Source: Can Med Assoc J. 1975 March 22; 112(6): 693-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1054615&dopt=Abstract

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Osthole increases glycosylation of hepatitis B surface antigen and suppresses the secretion of hepatitis B virus in vitro. Author(s): Huang RL, Chen CC, Huang YL, Hsieh DJ, Hu CP, Chen CF, Chang C.

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Outbreak of hepatitis B associated with acupuncture. Author(s): Stryker WS, Gunn RA, Francis DP. Source: The Journal of Family Practice. 1986 February; 22(2): 155-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3944549&dopt=Abstract

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Outbreak of hepatitis B in an acupuncture clinic. Author(s): Walsh B, Maguire H, Carrington D. Source: Commun Dis Public Health. 1999 June; 2(2): 137-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10402750&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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Phyllanthus amarus and hepatitis B. Author(s): Thyagarajan SP, Jayaram S, Valliammai T, Madanagopalan N, Pal VG, Jayaraman K. Source: Lancet. 1990 October 13; 336(8720): 949-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1976968&dopt=Abstract

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Phyllanthus amarus down-regulates hepatitis B virus mRNA transcription and replication. Author(s): Lee CD, Ott M, Thyagarajan SP, Shafritz DA, Burk RD, Gupta S. Source: European Journal of Clinical Investigation. 1996 December; 26(12): 1069-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9013081&dopt=Abstract

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Phyllanthus amarus suppresses hepatitis B virus by interrupting interactions between HBV enhancer I and cellular transcription factors. Author(s): Ott M, Thyagarajan SP, Gupta S. Source: European Journal of Clinical Investigation. 1997 November; 27(11): 908-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9395786&dopt=Abstract

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Potent synergistic effect of sho-saiko-to, a herbal medicine, during vaccine therapy in a murine model of hepatitis B virus carrier. Author(s): Akbar SM, Yamamoto K, Abe M, Ninomiya T, Tanimoto K, Masumoto T, Michitaka K, Horiike N, Onji M.

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Source: European Journal of Clinical Investigation. 1999 September; 29(9): 786-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10469167&dopt=Abstract •

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. 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

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Prevalence of hepatitis B and C viruses in healthy Indonesian blood donors. Author(s): Sulaiman HA, Julitasari, Sie A, Rustam M, Melani W, Corwin A, Jennings GB. Source: Trans R Soc Trop Med Hyg. 1995 March-April; 89(2): 167-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7539951&dopt=Abstract

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Prevalence of syphilis and hepatitis B among homosexual men in two saunas in Amsterdam. Author(s): Bleeker A, Coutinho RA, Bakker-Kok J, Tio D, de Koning GA. Source: Br J Vener Dis. 1981 June; 57(3): 196-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7237084&dopt=Abstract

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Prevention and therapy of hepatitis B. Author(s): Tao Q, Feng B. Source: Chinese Medical Journal. 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.

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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 •

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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Reversal of the immunosenescent phenotype by dehydroepiandrosterone: hormone treatment provides an adjuvant effect on the immunization of aged mice with recombinant hepatitis B surface antigen. Author(s): Araneo BA, Woods ML 2nd, Daynes RA. Source: The Journal of Infectious Diseases. 1993 April; 167(4): 830-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8450248&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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Seroconversion rate, hepatitis B vaccination, hemodialysis, and zinc supplementation. Author(s): Rawer P, Willems WR, Breidenbach T, Guttmann W, Pabst W, Schutterle G. Source: Kidney International. Supplement. 1987 October; 22: 149-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3481000&dopt=Abstract

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Simultaneous extraction of hepatitis C virus (HCV), hepatitis B virus, and HIV-1 from plasma and detection of HCV RNA by a reverse transcriptase-polymerase chain reaction assay designed for screening pooled units of donated blood. Author(s): Sun R, Schilling W, Jayakar H, Ku J, Wang J, Rosenstraus M, Spadoro J. Source: Transfusion. 1999 October; 39(10): 1111-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10532606&dopt=Abstract

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Specific expression of hepatitis B surface antigen (HBsAg) in transgenic mice. Author(s): Babinet C, Farza H, Morello D, Hadchouel M, Pourcel C. Source: Science. 1985 December 6; 230(4730): 1160-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3865370&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

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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 •

Steroid-free chemotherapy decreases the risk of hepatitis flare-up in hepatitis B virus carriers with non-Hodgkin's lymphoma. Author(s): Cheng AL. Source: Blood. 1996 February 1; 87(3): 1202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8562950&dopt=Abstract

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Subtypes, genotypes and molecular epidemiology of the hepatitis B virus as reflected by sequence variability of the S-gene. Author(s): Magnius LO, Norder H. Source: Intervirology. 1995; 38(1-2): 24-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8666521&dopt=Abstract

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Successful treatment of decompensated chronic viral hepatitis by bursal disease virus vaccine. Author(s): Csatary LK, Schnabel R, Bakacs T. Source: Anticancer Res. 1999 January-February; 19(1B): 629-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10216467&dopt=Abstract

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Suppressive effects of metabolites from Alternaria brassicaea on the hepatitis B surface antigen. Author(s): Sun CM, Chen HC, Yeh SF. Source: Planta Medica. 1994 February; 60(1): 87-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8134423&dopt=Abstract

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The adjuvant effect of stearyl tyrosine on a recombinant subunit hepatitis B surface antigen. Author(s): Nixon-George A, Moran T, Dionne G, Penney CL, Lafleur D, Bona CA. Source: Journal of Immunology (Baltimore, Md. : 1950). 1990 June 15; 144(12): 4798-802. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2351829&dopt=Abstract

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The asialoglycoprotein receptor mediates hepatic binding and uptake of natural hepatitis B virus particles derived from viraemic carriers. Author(s): Treichel U, Meyer zum Buschenfelde KH, Stockert RJ, Poralla T, Gerken G. Source: The Journal of General Virology. 1994 November; 75 ( Pt 11): 3021-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7964611&dopt=Abstract

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The effect of long-term thymosine factor x/TFx/treatment on T lymphocyte subpopulations and peripheral blood mononuclear cell cytotoxicity in chronic active

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hepatitis B. Author(s): Baj Z, Pokoca L, Tchorzewski H, Dworniak D, Tkacz B. Source: J Investig Allergol Clin Immunol. 1991 August; 1(4): 239-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1669583&dopt=Abstract •

The hepatitis B virus-associated delta antigen: isolation from liver, development of solid-phase radioimmunoassays for delta antigen and anti-delta and partial characterization of delta antigen. Author(s): Rizzetto M, Shih JW, Gerin JL. Source: Journal of Immunology (Baltimore, Md. : 1950). 1980 July; 125(1): 318-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6769999&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 proapoptotic effect of hepatitis B virus HBx protein correlates with its transactivation activity in stably transfected cell lines. Author(s): Bergametti F, Prigent S, Luber B, Benoit A, Tiollais P, Sarasin A, Transy C. Source: Oncogene. 1999 May 6; 18(18): 2860-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10362257&dopt=Abstract

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The witch-doctor and tribal scarification of the skin and the hepatitis B antigen. Author(s): Kew MC, Reis P, Macnab GM, Seftel HC, Bersohn I. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1973 December 22; 47(50): 2419-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4795161&dopt=Abstract

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Therapeutic effects of biphenyl dimethyl dicarboxylate (DDB) on chronic viral hepatitis B. Author(s): Liu GT. Source: Proc Chin Acad Med Sci Peking Union Med Coll. 1987; 2(4): 228-33. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3451287&dopt=Abstract

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Thymic factor X treatment of chronic hepatitis B. Author(s): Cianciara J, Laskus T. Source: Hepatology (Baltimore, Md.). 1992 December; 16(6): 1507-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1446904&dopt=Abstract

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Thymostimulin in the treatment of hepatitis B surface antigen-positive chronic active hepatitis. Controlled clinical trial--two years follow-up. Author(s): Romeo F, Palmisano L, Arcoria D. Source: Arzneimittel-Forschung. 1987 April; 37(4): 450-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3300664&dopt=Abstract

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Treatment of chronic hepatitis B in australia and New Zealand. Author(s): Stace N. Source: Journal of Gastroenterology and Hepatology. 2000 May; 15 Suppl: E79-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10921387&dopt=Abstract

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Treatment of chronic hepatitis B in China. Author(s): Yao GB. Source: Journal of Gastroenterology and Hepatology. 2000 May; 15 Suppl: E61-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10921384&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 hepatitis B virus-associated membranous nephropathy with adenine arabinoside and thymic extract. Author(s): Lin CY, Lo SC. Source: Kidney International. 1991 February; 39(2): 301-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2002643&dopt=Abstract

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Treatment with thymic extract TFX for chronic active hepatitis B. Author(s): Dworniak D, Tchorzewski H, Pokoca L, Tkacz B, Drobnik S, Baj Z, Luciak M. Source: Arch Immunol Ther Exp (Warsz). 1991; 39(5-6): 537-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1841551&dopt=Abstract

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Use of glycyrrhizin for recurrence of hepatitis B after liver transplantation. Author(s): Matsunami H, Lynch SV, Balderson GA, Strong RW. Source: The American Journal of Gastroenterology. 1993 January; 88(1): 152-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8420262&dopt=Abstract

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Zinc supplementation and hepatitis B vaccination in chronic haemodialysis patients: a multicentre study. Author(s): Brodersen HP, Holtkamp W, Larbig D, Beckers B, Thiery J, Lautenschlager J, Probst HJ, Ropertz S, Yavari A.

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Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1995; 10(9): 1780. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8559509&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.com®: 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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WebMD®Health: 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 B; 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: •

General Overview Cancer Prevention and Diet Source: Healthnotes, Inc.; www.healthnotes.com Hemophilia Source: Integrative Medicine Communications; www.drkoop.com Hepatitis Source: Healthnotes, Inc.; www.healthnotes.com Hives Source: Healthnotes, Inc.; www.healthnotes.com

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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

•

Herbs and Supplements Alpha-Lipoic Acid Source: Integrative Medicine Communications; www.drkoop.com Astragalus Mem Alternative names: Huang-Qi; Astragalus membranaceus Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Bupleurum Alternative names: Bupleurum chinense, Bupleurum falcatum Source: Healthnotes, Inc.; www.healthnotes.com Glycyrrhiza1 Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Interferon Source: Healthnotes, Inc.; www.healthnotes.com 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 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 Shiitake Alternative names: Lentinus edodes Source: Healthnotes, Inc.; www.healthnotes.com

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Smilax Alternative names: Sarsaparilla; Smilax glabra Roxb. 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

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 B Overview In this chapter, we will give you a bibliography on recent dissertations relating to hepatitis B. 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 B” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on hepatitis B, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Hepatitis B 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 B. 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: •

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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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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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 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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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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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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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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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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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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Molecular Studies of Hepatitis B and C Viruses by Xu, Zhenming; PhD from University of Southern California, 2002, 222 pages http://wwwlib.umi.com/dissertations/fullcit/3093947

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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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Studies of Hepatitis B Virus and Hepatitis C Virus Infection by Sung, Ming-Hsiang; PhD from University of Southern California, 2002, 191 pages http://wwwlib.umi.com/dissertations/fullcit/3093922

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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 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

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 B Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning hepatitis B.

Recent Trials on Hepatitis B The following is a list of recent trials dedicated to hepatitis B.8 Further information on a trial is available at the Web site indicated. •

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

8

These are listed at www.ClinicalTrials.gov.

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033163 •

A Phase II Study of the Safety and Efficacy of Adding Entecavir to Current Lamivudine Therapy in HIV and HBV Co-Infected Patients Who Have Hepatitis B Viremia While Being Treated with Lamivudine Condition(s): Hepatitis B Study Status: This study is currently recruiting patients. Sponsor(s): Bristol-Myers Squibb Purpose - Excerpt: The purpose of this clinical research study is to assess the safety and effectiveness of entecavir, when being added to lamivudine, in the treatment of adults with chronic hepatitis B infection who are co-infected with HIV. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00051038

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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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Comparison of Entecavir to Adefovir in chronic HBV patients with hepatic decompensation Condition(s): Hepatitis B Study Status: This study is currently recruiting patients. Sponsor(s): Bristol-Myers Squibb Purpose - Excerpt: This is a phase IIIb comparitive study of entecavir 1.0 mg QD vs adefovir 10 mg QD in patients who have chronic hepatitis B infection and hepatic decompensation. The patients are treated for up to 96 weeks. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00065507

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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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Frequency of Parenteral and Non-Parenteral Exposures to Blood Among Healthcare Workers at the Clinical Center, NIH and at Seven Academic Hospitals in Japan Condition(s): Hepatitis B; Hepatitis C; HIV Infection Study Status: This study is currently recruiting patients. Sponsor(s): Warren G Magnuson Clinical Center (CC) Purpose - Excerpt: Following guidelines issued by the Centers for Disease Control, the Clinical Center implemented a Universal Precautions policy in November 1987 in an attempt to reduce healthcare workers' risks for occupational exposures to bloodborne pathogens. All hospital personnel whose jobs entailed potential exposure to patients' blood and body substances were required to attend a training session and complete a written examination. Based on data from surveys conducted before and twelve months after training in Universal Precautions, the frequency of cutaneous exposure to blood decreased by 50% in temporal association with implementation of Universal Precautions. Staff at the Clinical Center are required to take a refresher course in Universal Precautions annually. The prevalence of bloodborne infections is high in Japan; however, Universal Precautions are not widely practiced in Japan. This study is designed: 1) to evaluate and compare nurses' knowledge of the epidemiology, pathogenesis, occupational risks, and appropriate prevention strategies for managing patients infected with bloodborne pathogens in the healthcare setting in seven university hospitals in Japan and at the Clinical Center of the National Institutes of Health in the US; 2) to compare self-reported levels of compliance with existing infection control recommendations designed to limit risk for exposure to bloodborne pathogens in all four institutions; 3) to compare self-reported frequencies of cutaneous exposures to blood at the four hospitals in the study; and 4) to evaluate the effect of educational intervention on nurses perceived compliance with recommendations and on the frequency of self-reported exposures to blood. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001712

212 Hepatitis B

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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 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

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Prevention of Recurrent Hepatitis B after Liver Transplantation Condition(s): Hepatitis B; Cirrhosis; Acute Liver Failure; Hepatocellular Carcinoma Study Status: This study is currently recruiting patients.

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Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Hepatitis B accounts for approximately 5000 deaths per year in the United States. Liver transplantation offers the only hope for patients who develop endstage liver disease. Early results of liver transplantation for hepatitis B were poor with recurrence rate of 80% and 1-year survival of only 50%. Recent studies found that preventive therapy using hepatitis B immune globulin (HBIG) or antiviral medications such as lamivudine can reduce the recurrence rate to roughly 30% with accompanying improvement in survival. However, HBIG when given as intravenous infusion in high doses is very expensive, while long-term use of lamivudine is associated with drug resistance. Some studies found that preventive therapy using both HBIG and lamivudine may decrease recurrence rate to less than 10% but the dose and duration of HBIG needed when used in combination with lamivudine is not clear. Adefovir, a new antiviral medication, is effective against lamivudine resistant hepatitis B but its role in liver transplantation is uncertain because of the risk of kidney damage. Many studies showed that the risk of recurrent hepatitis B is related to the viral load before transplant. Thus, it may be possible to tailor the preventive therapy according to the risk. The aim of this study is to establish the most cost-effective preventive therapy for recurrent hepatitis B after liver transplantation. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00059267 •

Randomized, Double Blind Trial of LdT (Telbivudine) versus Lamivudine in Adults with Compensated Chronic Hepatitis B Condition(s): Chronic Hepatitis B Study Status: This study is currently recruiting patients. Sponsor(s): Idenix Pharmaceuticals Purpose - Excerpt: Idenix Pharmaceuticals, Inc is conducting this research study to see if the investigational medication, LdT (Telbivudine), is safe and effective (that is, how well it works by decreasing the level of hepatitis B virus in your blood and improving the condition of your liver) in the treatment of hepatitis B infection. The results for patients taking LdT will be compared to results for patients taking lamivudine, which is a drug currently approved by the Food and Drug Adminstration (FDA) for the treatment of hepatitis B infection. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00057265

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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)

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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 •

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. 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

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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 Phase III Study of Entecavir vs Lamivudine in Chronic Hepatitis B Subjects with Incomplete Response to Lamivudine Condition(s): Chronic Hepatitis B Study Status: This study is no longer recruiting patients. Sponsor(s): Bristol-Myers Squibb

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Purpose - Excerpt: The purpose of this clinical research study is to assess the safety and effectiveness of switching to entecavir compared to continued lamivudine in patients with chronic hepatitis B. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00036608 •

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 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

216 Hepatitis B

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 •

Efficacy and safety study of Pegasys in the treatment of chronic hepatitis B. Condition(s): Chronic Hepatitis B Study Status: This study is no longer recruiting patients. Sponsor(s): Hoffmann-La Roche Purpose - Excerpt: The purpose of this study is to determine the safety and efficacy of Pegasys + placebo + lamivudine versus lamivudine alone in patients with lamivudine versus lamivudine alone in patients with hepatitis B antigen CHB. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00048945

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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

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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 •

Lamivudine for Chronic Hepatitis B Condition(s): Chronic Polyarteritis Nodosa

Hepatitis

B;

Chronic

Hepatitis

D;

Glomerulonephritis;

Study Status: This study is no longer recruiting patients. 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

218 Hepatitis B

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 •

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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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. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00037622

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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. 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

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Hepatitis B Vaccine Clinical Trial Condition(s): Hepatitis B; Hepatitis, Viral, Human; Liver Diseases Study Status: This study is completed.

220 Hepatitis B

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 •

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 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

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The Tolerance of HIV-Infected Patients with Herpes Group Virus Infections to Oral Doses of FIAU Condition(s): Herpes Simplex; HIV Infections; Hepatitis B Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID); Oclassen Pharmaceuticals Purpose - Excerpt: To determine the tolerance of HIV-infected patients to TID oral doses of FIAU syrup at 4 different dose levels. To determine the peak and trough blood levels of FIAU and its metabolites during two weeks of oral dosing with FIAU. The pyrimidine nucleoside analog FIAC and its primary deaminated uracil metabolite FIAU are highly and specifically active compounds in vitro against several herpes group viruses, particularly herpes simplex virus (HSV) types 1 and 2, varicella zoster (VZV), and cytomegalovirus (CMV), as well as hepatitis B virus (HBV). Since FIAU is the primary metabolite of FIAC and the administration of FIAU simplifies the metabolism of FIAC, it is anticipated from clinical studies of FIAC that FIAU will be tolerated at least as well as FIAC. A single-dose, pharmacokinetic (blood level) study showed that FIAC, when taken orally, is readily absorbed into the bloodstream, and most of it is converted to FIAU. Daily oral doses are expected to provide concentrations of FIAU exceeding the in vitro minimum inhibitory concentration for nearly all the herpes group viruses. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below

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Web Site: http://clinicaltrials.gov/ct/show/NCT00000654

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 B” (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/

•

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

222 Hepatitis B

•

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 B 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 B” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on hepatitis B, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Hepatitis B By performing a patent search focusing on hepatitis B, 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 will tell you how to obtain this information later in the chapter. The following is an 9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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example of the type of information that you can expect to obtain from a patent search on hepatitis B: •

2-heterocyclically substituted dihydropyrimidines Inventor(s): Goldmann; Siegfried (Wuppertal, DE), Graef; Erwin (Velbert, DE), Lottmann; Stefan (Wuppertal, DE), Paessens; Arnold (Haan, DE), Stoltefuss; Jurgen (Haan, DE) Assignee(s): Bayer Aktiengesellschaft (Leverkusen, DE) Patent Number: 6,503,913 Date filed: October 18, 2000 Abstract: The invention relates to new 2-heterocyclically substituted dihydropyrimidines, medicaments which contain these 2-heterocyclically substituted dihydropyrimidines, and a process for preparation of medicaments. The invention furthermore relates to the use of the 2-heterocyclically substituted dihydropyrimidines for the production of a medicament, in particular for the treatment of acute or chronic viral diseases, in particular for the production of a medicament for the treatment of acute or chronic hepatitis B infections. Excerpt(s): The present invention relates to new 2-heterocyclically substituted dihydropyrimidines, processes for their preparation and their use as medicaments, in particular as medicaments for the treatment and prophylaxis of hepatitis B. The publication EP 103 796 A2 has already disclosed dihydropyrimidines having an action affecting the circulation. and their salts. Web site: http://www.delphion.com/details?pn=US06503913__

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Adenovirus vector with multiple expression cassettes Inventor(s): Wang; Danher (Mt. Pleasant, SC) Assignee(s): GenPhar, Inc. (Mt. Pleasant, SC) Patent Number: 6,544,780 Date filed: June 2, 2000 Abstract: Genetic vaccines and methods are provided for enhancing the immunity of a host such as a human to one or more pathogens. In one embodiment, a recombinant benign virus is provided as the genetic vaccine. The recombinant virus comprises: an antigen sequence heterologous to the recombinant virus that encodes a viral antigen from a pathogenic virus, expression of the viral antigen eliciting an immune response directed against the viral antigen and cells expressing the viral antigen in a host upon infection of the host by the recombinant virus; and an immuno-stimulator sequence heterologous to the recombinant virus that encodes an immuno-stimulator whose expression in the host enhances the immunogenicity of the viral antigen. The recombinant virus is replication-incompetent and does not causes a malignancy naturally associated with the pathogenic virus in the host. The genetic vaccines can be used for immunizing a host against a wide variety of pathogens, such as HIV, Ebola virus, hepatitis B virus, hepatitis C virus, influenza virus, pathogenic bacteria and parasites.

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Excerpt(s): This invention relates to vaccines for stimulating immune responses in human and other hosts, and, in particular, relates to recombinant viruses that express heterologous antigens of pathogenic viruses, such as Ebola, HIV, hepatitis, and influenza viruses. Current techniques for developing vaccines are largely based on the concept of using denatured virus or purified viral proteins made from bacteria. These types of vaccines may be effective for only a limited number of infectious agents, and the protection rates are limited. For viruses that contain membrane (envelope) glycoproteins (GPs), including the Ebola virus and the HIV virus, use of denatured virus or purified viral proteins often does not work satisfactorily. There may be several reasons for this. First, the GPs of these viruses are sensitive to the denaturing procedures so that the epitopes of the proteins are altered by the denaturing process. Second, the sugar moieties of the GPs are important antigenic determinants for neutralizing antibodies. In comparison, proteins made in bacteria are not properly glycosylated and can fold into somewhat different structures that can have antigenecities different from those of the natural viral proteins. Further, many vaccines that are based on attenuated or denatured virus provide a weak immune response to poorly immunogenic antigens. In addition, the vaccine preparations frequently offer only limited protection, not lifelong immunity as desired. Web site: http://www.delphion.com/details?pn=US06544780__ •

Antibodies and other binding molecules specific for hepatitis B viral antigens Inventor(s): Paulij; Wilhelmina Petronella (Schijndel, NL), Van Kessel-Koens; Marjolijn Jacqueline (St. Oederode, NL) Assignee(s): Akzo Nobel N.V. (NL) Patent Number: 6,541,198 Date filed: January 13, 2000 Abstract: The present invention relates to antibodies and other binding molecules specific for hepatitis B viral antigens (HBV), peptides comprising epitopes recognized by such molecules, and cell lines capable of producing antibodies. The invention is further concerned with the use of such molecules in diagnosis of HBV. The invention further relates to a method for the diagnosis of hepatitis B, the method comprising contacting the sample suspected to contain hepatitis B particles or antigens with a specific binding molecule according to the invention. The invention further relates to an assay kit for the detection of a hepatitis B particle or antigen, the kit comprising a specific binding molecule of the invention and means for detecting whether the specific binding molecule is bound to a hepatitis B particle or antigen. Excerpt(s): The present invention relates to antibodies land other binding molecules specific for hepatitis B viral antigens (HBV), peptides comprising epitopes recognised by such molecules, and cell lines capable of producing antibodies. The invention is further concerned with the use of such molecules in diagnosis of hepatitis B virus (HBV). The virus that causes hepatitis B or serum hepatitis appears to infect only man and chimpanzees. Hepatitis B virus (HBV) infection in humans is widespread. The hepatitis infection is transmitted by three general mechanisms: (1) by parenteral inoculation of infected blood or body fluids, either in large amounts as in blood transfusions or in minute amounts as through an accidental skin prick; (2) by close family or sexual contact; and (3) by some mothers, who infected during pregnancy, transmit the virus to their new-born children. Under natural conditions, HBV is not highly contagious. Transmission by inhalation occurs rarely, if ever.

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Web site: http://www.delphion.com/details?pn=US06541198__ •

Antisense ogligonucleotides against Hepatitis B viral replication Inventor(s): Gerin; John L. (Bethesda, MD), Korba; Brent E. (Laurel, MD) Assignee(s): Georgetown University (Washington, DC) Patent Number: 6,503,533 Date filed: November 25, 1998 Abstract: Antisense oligonucleotides that hybridize to segments of the pres1, S, C, and.epsilon. regions of the hepatitis B virus (HBV) RNA pregenome inhibit replication of the virus. Pharmaceutical compositions which contain these oligonucleotides as the active ingredients are effective against HBV infection. Excerpt(s): The present invention was made utilizing funds from contracts NO1-AI72623 and NO1-AI-45179 between the National Institute for Allergy and Infectious Diseases and Georgetown University. The present invention relates to compositions for the treatment of Hepatitis B virus (HBV) infection. In particular, the invention relates to antisense oligonucleotides and their use to inhibit HBV replication. Hepatitis B virus, a member of the Hepadnaviridae family, is a blood-borne, hepatotropic pathogen which infects large numbers of people annually. In 1987 there were approximately 25,000 newly reported cases of disease attributable to HBV infection in the US. It is estimated that 60-70% of HBV infections lead to subclinical (asymptomatic) disease, and it is therefore probable that the actual number of new HBV infections each year is much higher. Of those infected with HBV, 90% make a full recovery, but 2-10% of infected patients develop chronic, persistent HBV infection. It is estimated that 1 million people in the US and 300 million people worldwide are chronically infected with HBV. In parts of Asia and Africa it is thought that between 5 and 20% of the population are chronically infected with HBV. Web site: http://www.delphion.com/details?pn=US06503533__

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Antiviral combinations Inventor(s): Brown; Nathaniel A. (Chapel Hill, NC), Condreay; Lynn D. (Raleigh, NC), Gray; Douglas Fraser (Greenford, GB), Rubin; Marc (Chapel Hill, NC) Assignee(s): SmithKline Beecham Corporation (Philadelphia, PA) Patent Number: 6,432,966 Date filed: October 29, 1999 Abstract: The present invention relates to therapeutic combinations comprising (2R,cis)4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-pyrimidin-2-one (lamivudine) and BMS-200475 which have anti-hepatitis B virus (HBV) activity. The present invention is also concerned with pharmaceutical compositions containing said combinations and their use in the treatment of HBV infections including infections with HBV mutants bearing resistance to nucleoside and/or non-nucleoside inhibitors. Excerpt(s): The present invention relates to therapeutic combinations comprising (2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-pyrimidin-2-one (lamivudine) and BMS-200475, a cyclopentyl guanosine analogue. The present invention is also concerned with pharmaceutical compositions containing said combinations and their

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use in the treatment of HBV infections including infections with HBV mutants bearing resistance to nucleoside and/or non-nucleoside inhibitors of the replication of the hepatitis B virus. Hepatitis B is a viral disease transmitted orally or parentally by contaminated material such as blood or blood products, contaminated needles, sexually, and vertically from infected or carrier mothers to their off-spring. In those areas of the world where the disease is common, vertical transmission at an early age results in a high proportion of infected individuals becoming chronic carriers of hepatitis B. An estimated 350 million people world-wide are chronically infected with hepatitis B and as many as 150 million may die from liver disease in the absence of intervention. Currently, the only established approach to treatment of hepatitis B is repeated injections of interferon, which may be associated with unpleasant side effects, and produces a long lasting response in only one third or less of those treated. Interferon is an immune modulator designed to boost the disease fighting ability of the immune system. Web site: http://www.delphion.com/details?pn=US06432966__ •

Biflavanoids and derivatives thereof as antiviral agents Inventor(s): Flavin; Michael T. (Darien, IL), Lin; Yuh-Meei (Naperville, IL), Schure; Ralph (Darien, IL), Zembower; David E. (La Grange Park, IL), Zhao; Geng-Xian (Woodridge, IL) Assignee(s): Advanced Life Sciences, Inc. (Lemont, IL) Patent Number: 6,399,654 Date filed: April 15, 1998 Abstract: Substantially purified antiviral biflavanoids robustaflavone, hinokiflavone, amentoflavone, agathisflavone, volkensiflavone, morelloflavone, rhusflavanone, succedaneaflavanone, GB-1a, and GB-2a are provided. Antiviral biflavanoid derivatives and salt forms thereof, e.g., robustaflavone tetrasulfate potassium salt, and methods for preparing the same are also disclosed. Pharmaceutical compositions which include the antiviral biflavanoids, derivatives or salts thereof are also provided alone or in combination with at least one antiviral agent such as 3TC. Also disclosed is an improved method for obtaining substantially pure robustaflavone from plant material. The biflavanoid compounds, derivatives or salts thereof of the invention may be used in a method for treating and/or preventing viral infections caused by viral agents such as influenza, e.g., influenza A and B; hepatitis, e.g., hepatitis B; human immunodeficiency virus, e.g., HIV-1; Herpes viruses (HSV-1 and HSV-2); Varicella Zoster virus (VZV); and measles. For instance, semi-synthetic hexa-O-acetate and hexa-O-methyl ether derivatives of robustaflavone have been found to be effective in a method for treating or preventing hepatitis B viral infections. Compositions which include these robustaflavone derivatives along with methods for preparing and using the same are also provided. These compositions may be used alone or in combination with at least one antiviral agent such as 3TC. Excerpt(s): The present invention relates to substantially pure antiviral biflavanoids, e.g., robustaflavone, biflavanoid derivatives and salts thereof such as esters, ethers, amines, sulfates, ethylene oxide adducts, and acid salts, and pharmaceutical compositions containing the same. Representative examples include hexa-O-acetate and hexa-Omethyl ether derivatives of robustaflavone and robustaflavone tetrasodium salt. The present invention also relates to methods for extracting substantially pure robustaflavone from plant material. The present invention also relates to a method for

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preventing and/or treating viral infections such as hepatitis B, influenza A and B, and HIV which employ robustaflavone or derivatives thereof alone or in combination with at least one antiviral agent such as 3TC. Viruses, an important etiologic agent in infectious disease in humans and other mammals, are a diverse group of infectious agents that differ greatly in size, shape, chemical composition, host range, and effects on hosts. After several decades of study, only a limited number of antiviral agents are available for the treatment and/or prevention of diseases caused by viruses such as hepatitis B, influenza A and B and HIV. Because of their toxic effects on a host, many antiviral agents are limited to topical applications. Accordingly, there is a need for safe and effective antiviral agents with a wide-spectrum of anti-viral activity with reduced toxicity to the host. Since the identification of the human immunodeficiency virus (HIV) as the causative agent of AIDS,.sup.36,46 the search for safe and effective treatments for HIV infection has become a major focus for drug discovery groups around the world. Investigations into the molecular processes of HIV have identified a number of macromolecular targets for drug design, such as HIV-1 reverse transcriptase (HIV-RT), protease and integrase enzymes, and regulatory proteins (e.g., TAT and REV). Other targets are enzymes which aid in virus attachment and fusion. HIV-RT is an essential enzyme in the life cycle of HIV, which catalyzes the transcription of HIV-encoded single-stranded RNA into double-stranded DNA. Furthermore, the RNA-dependent DNA polymerase function of HIV-RT does not have an analogous process in mammalian metabolism, and thus is a suitable target for a chemotherapeutic agent. Web site: http://www.delphion.com/details?pn=US06399654__ •

Combination therapy method for treating chronic hepatitis B Inventor(s): Horwitz; David L. (Hillsborough, CA) Assignee(s): SciClone Pharmaceuticals, Inc. (San Mateo, CA) Patent Number: 6,495,521 Date filed: January 17, 2001 Abstract: The present invention is aimed at augmenting the success rate of using thymosin in treatment of chronic hepatitis B, by employing a combination therapy using thymosin with antiviral agents which are effective in inhibiting DNA synthesis or DNA polymerase during replication of the hepatitis B virus. Excerpt(s): The instant invention relates to a method for treating chronic hepatitis B infections. More specifically, the instant invention relates to a method for treating chronic hepatitis B infections using both thymosin and an antiviral drug. Hepatitis B is the most prevalent form of hepatitis and is the second most common infectious disease worldwide. Worldwide estimates of those chronically infected with hepatitis B virus (HBV) are in excess of 300,000,000. The disease is caused by the hepatitis B virus, a DNA virus. The virus is transmitted through blood transfusions, contaminated needles, sexual contact and vertical transmission from mother to child. Moreover, a significant number of people are infected by unknown means. Carriers of the virus can exhibit various forms of disease, one of which is chronic hepatitis B. Approximately 50% of the carriers show chronic inflammatory changes in the liver and, of these, about 50% have histopathologic changes, which are termed "chronic active hepatitis", that may lead to fibrosis and ultimately to cirrhosis and progressive liver failure. Carriers without chronic inflammatory changes may also develop chronic active hepatitis. Liver cancer develops in about 10 to 30% of hepatitis B carriers. It has been estimated that

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approximately 4 million carriers of hepatitis B virus die each year from liver cancer or cirrhosis. Web site: http://www.delphion.com/details?pn=US06495521__ •

Combined hepatitis and herpesvirus antigen compositions Inventor(s): Stephenne; Jean (Rixensart, BE), Wettendorff; Martine Anne Cecile (RhodeSaint-Genese, BE) Assignee(s): SmithKline Beecham Biologicals S.A. (Rixensart, BE) Patent Number: 6,451,320 Date filed: October 27, 2000 Abstract: Novel combined vaccine compositions preferentially for administration to adolescents are provided, comprising a hepatitis B viral antigen and a herpes simplex viral antigen and optionally in addition one or more of the following: an EBV antigen, a hepatitis A antigen or inactivated attenuated virus, an HPV antigen, a VZV antigen, an HCMV antigen, a Toxoplasma gondii antigen. The vaccine compositions are formulated with an adjuvant which is a preferential stimulator of TH1 cell response such as 3DMPL and QS21. Excerpt(s): This application is a 371 of International Application PCT/EP99/01406, filed Mar. 4, 1999, which claims priority from GB 9805105.5, filed Mar. 9, 1998 and GB 9813561.9, filed Jun. 23, 1998. This invention relates to novel vaccine formulations, methods for preparing them and their use in therapy. In particular the present invention relates to combination vaccines for administration to adolescents. Genital herpes is estimated to occur in about 5 million people in the U.S.A. alone with 500,000 clinical cases recorded every year (primary and recurrent infection). Primary infection typically occurs after puberty and is characterised by the localised appearance of painful skin lesions, which persist for a period of between 2 to 3 weeks. Within the following six months after primary infection 50% of patients will experience a recurrence of the disease. About 25% of patients may experience between 10-15 recurrent episodes of the disease each year. In immunocompromised patients the incidence of high frequency recurrence is statistically higher than in the normal patient population. Web site: http://www.delphion.com/details?pn=US06451320__

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Expression of immunogenic hepatitis B surface antigens in transgenic plants Inventor(s): Arntzen; Charles Joel (Ithaca, NY), Mason; Hugh S. (Ithaca, NY), Richter; Elizabeth (Ithaca, NY), Thanavala; Yasmin (Williamsville, NY) Assignee(s): Boyce Thompson Institute for Plant Research (Ithaca, NY) Patent Number: 6,551,820 Date filed: December 23, 1999 Abstract: Plant expression vectors comprising at least two expression cassettes are provided which function to reduce transcriptional silencing of polynucleotide expression. Further, novel plant expression vectors for expression of immunogenic polypeptides, including HBsAg, are provided. The plant expression vectors can be used to produce immunogenic polypeptides, including HBsAg, in edible plant tissues. The

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edible plant tissues can be used to elicit an immune response in humans and animals when the plant tissues are consumed. Excerpt(s): The present invention relates to oral vaccines, particularly those provided by edible plants. The invention employs genetic engineering techniques to produce transgenic plants capable of expressing immunogenic polypeptides, including hepatitis B antigen (HBsAg) in quantities sufficient to elicit an immune response in a human or animal that consumes all or a part of the plant. A vaccine for hepatitis B was the first "new generation" recombinant vaccine licensed by the FDA for human use. The immunogenic subunit in this formulation is produced by expressing the gene encoding HBsAg in recombinant yeast; the protein is purified from the genetically engineered yeast and is used for parenteral delivery. In the developed world, the recombinant vaccine has displaced the use of an earlier vaccine derived from the plasma of infected individuals. Both plasma-derived and rHBsAg vaccines are shown to be reasonably safe and effective in high-risk adult populations and newborn infants. However, the cost of the rHBsAg vaccine prevents its extensive availability in developing countries. The envelope of the hepatitis B virus (HBV) contains three size classes of proteins that share carboxy-terminal sequences. These proteins, called hepatitis B surface antigens (HBsAgs), include large (L, containing a pre-S.sub.2 domain), medium (M.sub.1 containing a pre-S.sub.1 domain), and small (S, containing only the S domain) size classes. All three proteins are found in infectious virions (often referred to as Dane particles) recovered as 42 nm spheres from the serum of infected patients. Serum samples also contain empty spherical particles averaging 22 nm, which contain primarily S class proteins. Mammalian cell lines transfected exclusively with DNA encoding the S protein release 20 nm empty spheres similar to those from infected cells. Moreover, yeast cells transformed with the same gene form analogous spheres, which are found to be equally immunogenic as the 22 nm spheres from infected cells. The yeast-derived material forms the active constituents of the currently available commercial vaccines ENGERIX (SKB) and RECOMBIVAX (Merck). Web site: http://www.delphion.com/details?pn=US06551820__ •

Glucamine compounds for treating hepatitis virus infections Inventor(s): Bryant; Martin L. (Carlisle, MA), Mueller; Richard A. (Glencoe, IL), Partis; Richard A. (Evanston, IL) Assignee(s): G.D. Searle & Co. (Chicago, IL) Patent Number: 6,515,028 Date filed: February 14, 2000 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 agents 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

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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 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://www.delphion.com/details?pn=US06515028__ •

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 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

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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 inhibitors Inventor(s): Dyson; Michael Richard (Edinburgh, GB), Murray; Kenneth (Edinburgh, GB) Assignee(s): Biogen, Inc. (Cambridge, MA) Patent Number: 6,544,520 Date filed: April 29, 1999 Excerpt(s): Peptides and other molecules which inhibit the assembly of the hepatitis B virus, methods of treatment, and pharmaceutical compositions comprising them. The present invention relates to peptide compositions specific for the diagnosis, treatment or prevention of hepatitis B virus infection. Hepatitis B virus ("HBV") infects human at a very high rate. It is estimated that at least about 300 million people are chronic carriers of HBV. Despite extensive research, additional safe and effective therapies remain to be identified. Web site: http://www.delphion.com/details?pn=US06544520__

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Hepatitis vaccines containing 3-0-deacylated monophoshoryl lipid A Inventor(s): Garcon-Johnson; Nathalie Marie-Josephe Claude (Wavre, BE), Hauser; Pierre (Chaumont-Gistoux, BE), Thiriart; Clothilde (Brussels, BE), Voet; Pierre (Izel, 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

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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__ •

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): Chen; Wei Ning (Singapore, SG), Leong; Ai Lin (Singapore, SG), Lim; Gek Keow (Singapore, SG), Oon; Chong Jin (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` 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__

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Low dose entecavir formulation and use Inventor(s): Colonno; Richard J. (Farmington, CT), Desai; Divyakant (West Windsor, NJ), Fakes; Michael G. (Belle Mead, NJ), Harianawala; Abizer (North Brunswick, NJ), Sprockel; Omar L. (Bridgewater, 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 for immunization against hepatitis B Inventor(s): Mancini; Maryline (Paris, FR), Michel; Marie-Louise (Paris, FR) Assignee(s): Institut de la Sante et de la Recherche Medicale (Paris, FR), Institut Pasteur (Paris, FR) Patent Number: 6,429,201 Date filed: May 12, 2000 Abstract: Nucleotide vector composition containing such vector and vaccine for immunization against hepatitis. Nucleotide vector comprising at least one gene or one complementary DNA coding for at least a portion of a virus, and a promoter providing for the expression of such gene in muscle cells. The gene may be the S gene of the hepatitis B virus. A nucleotide vector composition when administered to even chronic HBV carriers is capable of breaking T cell tolerance to the surface antigens of hepatitis B virus. A vaccine preparation containing said bare DNA is injected into the host previously treated with a substance capable of inducing a coagulating necrosis of the muscle fibers. Excerpt(s): The present invention relates to compositions for inducing protective antibodies against hepatitis. It also relates to a vector comprising a nucleotide sequence coding for at least a portion of a virus protein, which is capable of being expressed in muscle cells. In addition, the invention relates to compositions capable of inducing a T cell response in chronic HBV carriers. Hepatitis B is a widespread and serious international health problem. In addition to causing acute hepatitis and liver damage, the hepatitis B virus (HBV) can cause cirrhosis and hepatocellular carcinoma (Davis, Hum. Molec. Genet. 2:1847-1851 (1993)). The HBV is a 42-nm particle (Dane particle)

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consisting of a lipoprotein envelope enclosing a core protein (capsid) and the viral genome, which contains only four genes (S, C, P, X). The major (or small) envelope protein, which includes the surface antigen of HBV (HBsAG) is encoded by the S gene and is organized into dimers of one glycosylated and one unglycosylated polypeptide (Petersen, J. Biol. Chem. 256:6975-6983 (1981)). Present in smaller amounts are the middle and large envelope proteins, which are encoded by the pre-S2 and S or pre-S1, pre-S2 and S genes, respectively. The predominant form of HBsAg secreted by infected cells is not the Dane particle, however, but 22-nm particles or filaments, which are empty viral envelopes composed solely or predominantly of major (small) envelope protein and sometimes small amounts of middle and large proteins (Maupas, Lancet 1:1367-1370 (1976)). The 22-nm particles are seen to persist in the plasma of chronic carriers (Davis, 1993). Web site: http://www.delphion.com/details?pn=US06429201__ •

Methods and compositions to investigate infection by hepatitis B virus and agents to prevent and treat the infection Inventor(s): Delaney, IV; William E. (San Bruno, CA), Isom; Harriet C. (Hershey, PA) 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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Mutant human hepatitis B viral strain and uses thereof Inventor(s): Chen; Wei Ning (Singapore, SG), Lim; Gek Keow (Singapore, SG), Oon; Chong Jin (Singapore, SG), Zhao; Yi (Singapore, SG) Assignee(s): Government of Republic of Singapore (Singapore, SG) Patent Number: 6,558,675 Date filed: April 30, 2001 Abstract: An isolated strain of Hepatitis B virus designated Human Hepatitis B Virus Surface Antigen-`S`-133 Oon Strain (Methionine to Threonine) of Cell. Also, an isolated nucleic acid encoding a polypeptide which is a mutant major surface antigen of a strain of hepatitis B virus, such polypeptide having an amino acid sequence which differs

236 Hepatitis B

from the amino acid sequence of a major surface antigen of a wild type hepatitis B virus in that the amino acid at position number 133 of such polypeptide is a threonine rather than methionine. Excerpt(s): Throughout this application, various references are referred to within parentheses. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. The present invention concerns the human hepatitis B virus genome, isolated from hepatocellular carcinoma (HCC), and with a mutation at amino acid residue 133 (Methionine to Threonine) within the major surface antigen, its nucleotide sequence, the deduced amino acid sequence of the four major proteins, antigen, antibody, detection systems, development of effective vaccines, and antiviral agents. One of the major causes of chronic liver diseases is hepatitis B viral infection. First discovered in 1963 as a human virus that is transmitted parenterally, chronic hepatitis B viral infection has been most commonly implicated in serological undefined pathogenesis of HCC. Despite the fact that hepatitis B virus does not display features of a complete viral oncogene, its involvement in the development of HCC can be attributed to various aspects of its interaction with host hepatocyte cells. These include the promiscuous transcriptional activity of the smallest viral protein, X, which enhances the expression level of many cellular target genes including proto-oncogenes. On the other hand, integrated viral DNA in the host chromosomes is regularly found in HCC patients. There is also evidence for an active role in the development of HCC by the major surface antigen. This protein has served as the main detection marker for carriers of hepatitis B virus. The most antigenic epitope is a highly conserved region spanning 23 amino acid residues and located from amino acid position 124 to 147 of the major surface antigen. This small region designated as the group specific determinant "a" is found in all subtypes and isolates of hepatitis B viral genomes. Its antigenic properties seem due to its proposed double loop structure, to which the vaccine-induced neutralizing antibody binds. Web site: http://www.delphion.com/details?pn=US06558675__ •

Nucleosides with anti-hepatitis B virus activity Inventor(s): Gosselin; Gilles (Montpellier, FR), Imbach; Jean-Louis (Montpellier, FR), Schinazi; Raymond F. (Decatur, GA), Sommadossi; Jean-Pierre (Birmingham, AL) Assignee(s): Emory University (Atlanta, GA), University of Alabama Research Foundation, Inc. (Birmingham, AL) Patent Number: 6,525,033 Date filed: November 22, 1999 Abstract: A method for treating HBV infections via administration of 2', 3' dideoxynucleoside compounds. Excerpt(s): This invention is in the area of methods for the treatment of hepatitis B virus (also referred to as "HBV") that includes administering an effective amount of one or more of the active compounds disclosed herein, or a pharmaceutically acceptable derivative or prodrug of one of these compounds. Hepatitis B virus has reached epidemic levels worldwide. After a two to six month incubation period in which the host is unaware of the infection, HBV infection can lead to acute hepatitis and liver damage, that causes abdominal pain, jaundice, and elevated blood levels of certain enzymes. HBV can cause fulminant hepatitis, a rapidly progressive, often fatal form of

Patents 237

the disease in which massive sections of the liver are destroyed. Patients typically recover from acute viral hepatitis. In some patients, however, high levels of viral antigen persist in the blood for an extended, or indefinite, period, causing a chronic infection. Chronic infections can lead to chronic persistent hepatitis. Patients infected with chronic persistent HBV are most common in developing countries. By mid-1991, there were approximately 225 million chronic carriers of HBV in Asia alone, and worldwide, almost 300 million carriers. Chronic persistent hepatitis can cause fatigue, cirrhosis of the liver, and hepatocellular carcinoma, a primary liver cancer. In western industrialized countries, high risk groups for HBV infection include those in contact with HBV carriers or their blood samples. The epidemiology of HBV is in fact very similar to that of acquired immunodeficiency syndrome, which accounts for why HBV infection is common among patients with AIDS or HIV-associated infections. However, HBV is more contagious than HIV. Web site: http://www.delphion.com/details?pn=US06525033__ •

Nucleotide vector composition containing such vector and vaccine for immunization against hepatitis Inventor(s): Davis; Heather Lynn (Ottawa, CA), Michel; Marie-Louise (Paris, FR), Whalen; Robert Gerald (Paris, FR) Assignee(s): Institut National de la Sant et de la Recherche Medical (Paris, FR), Institut Pasteur (Paris, FR), Universite d'Ottawa (Ottawa, CA) 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__

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Peptides for inducing cytotoxic T lymphocyte responses to hepatitus B virus Inventor(s): Chisari; Francis V. (Del Mar, CA), Ferrari; Carlo (Parma, IT), Missael; Gabriele (Parma, IT), Penna; Amalia (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

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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__ •

Pharmaceutical composition for treating hepatitis B virus (HBV) infection Inventor(s): Blum; Hubert E. (Freiburg, DE), Galun; Eithan (Har Adar, IL), Nahor; Orit (Jerusalem, IL) Assignee(s): Hadasit Medical Research Services & Development Co., Ltd. (Jerusalem, IL) Patent Number: 6,410,009 Date filed: November 12, 1999 Abstract: The invention provides a pharmaceutical composition for the treatment of hepatitis B virus (HBV) infection, comprising an amount of a soluble active agent which interacts with at least one of the binding sites between hIL6 and pS1 and between hIL6 and hepatocytes and other HBV-permissive cells, the active agent being present in sufficient amount to competitively bind to at least one of the sites and thereby to prevent hIL6-mediated HBV infection of hepatocytes and other HBV-permissive cells. Excerpt(s): The present invention relates to pharmaceutical compositions for the treatment of hepatitis B virus (HBV) infection. In a study reported by Neurath, et al. [A. Neurath, et al., J. Exp. Med., Vol. 175, pp. 461-469 (1992)] hIL-6 was shown to bind the pS1 (aa 21-47) segment of the HBV envelope. Putative candidates for the HBV receptor were recently reported, including Annexin V (endohexin II) [K. Hertogs, et al., Virology, Vol. 197, pp. 549-557 (1993)]; apolipoprotein H [H. Mehdi, et al., Journal of Virology, Vol. 68, pp. 2415-2424 (1994)]; and asialoglycoprotein receptor [U. Treichel, et al., Journal of General Virology, Vol. 75, pp. 3021-3029 (1994)]. Binding experiments have demonstrated that the pre-SI (pS1)region of the viral envelope protein contains a recognition site for the host cell [A.R. Neurath, et al., Cell, Vol. 46, pp. 429-436 (1986); M.

Patents 239

Petit, et al., Virology, Vol. 180, pp. 483-491 (1990); M. Petit, et al., Virology, Vol. 197, pp. 211-222 (1992)]. Although previous studies had suggested that HepG2 cells [R. Bchini, et al., Journal of Virology, Vol. 64, pp. 3025-3032 (1991)] and human hepatocytes [P. Gripon, et al., Journal of Virology, Vol. 62, pp. 4136-4143 (1988); T. Ochiya, et al., Proc. Natl. Acad. Sci. U.S.A., Vol. 86, pp. 1875-1879 (1989); P. Gripon, et al., Virology, Vol. 192, pp. 534-540 (1993); P. Galle, et al., Gastroenterology, Vol. 106, pp. 664-673 (1994)] could support HBV infection in vitro, no cellular receptor has as yet been defined in either system, and these models were of low experimental reproducibility. Web site: http://www.delphion.com/details?pn=US06410009__ •

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

240 Hepatitis B

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 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__ •

Polynucleotide decoys that inhibit MHC-II expression and uses thereof Inventor(s): Garovoy; Marvin R. (San Anselmo, CA), Hunt; C. Anthony (San Francisco, CA), Lim; Carol (San Francisco, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 6,410,721 Date filed: January 5, 1999 Abstract: The invention is directed to a newly discovered class of polynucleotide decoys that is capable of competitively inhibiting the binding of transcription factors to the Xbox sequence. This binding is necessary for the expression of MHC-II genes. The invention is also directed to methods of preparing these polynucleotide decoys, and methods of use thereof. In particular, we have identified a class of polynucleotide decoys that mimic the X-Box of MHC-II and competitively bind the MHC-II transcription factor RF-X, resulting in the modulation of MHC-II antigen expression. Thus, the invention can be used to inhibit the expression of HLA molecules on the surface of donor cells or organs, in order to render them invisible to the host's immune system, or in methods of treating an individual with an autoimmune disease characterized by dysfunctional expression of an MHC class II antigen. Further, because of the role of RF-X in the expression of several viral proteins, the polynucleotide decoys of the invention can be used in methods of treating an individual infected with hepatitis B virus, or cytomegalovirus. Excerpt(s): This invention relates to nucleotide therapeutics, transplantation and immunology. More specifically, it relates to a newly discovered class of polynucleotide decoy molecules and methods for making cells and organs that are less likely to be rejected when transplanted into a recipient host using these polynucleotide decoys, which are capable of binding to a specific gene regulatory factor and reducing the expression of MHC class II transplantation antigens. Among gene products that relate to transplantation antigens are the products of the Human Leukocyte Antigen (HLA) complex, also known as the major histocompatibility complex (MHC), located on the short arm of chromosome 6. The HLA antigens are divided into two classes depending on their structure. The genetic loci denoted HLA-A -B, and -C code for the HLA Class I antigens, and HLA-DP, -DQ and -DR code for the HLA Class II antigens. Regulation of HLA class II antigen expression occurs in part through a series of promoter regions such

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as the J, W, X (including X.sub.1 and X.sub.2), and Y boxes, and the gamma interferon response element. The X (including X.sub.1 and X.sub.2) and Y boxes are known to be required in the transcriptional regulation of all class II promoters. Ono, S. J. et al., Proc. Natl. Acad. Sci. (USA) (1991) 88:4304-4308. Web site: http://www.delphion.com/details?pn=US06410721__ •

Product comprising at least a double stranded RNA combined with at least an antiviral agent Inventor(s): de Paillette; Evelyne (Paris, FR) Assignee(s): Societe de Conseils de Recherches et d'Applications Scientifiques (FR) Patent Number: 6,509,154 Date filed: February 10, 2000 Abstract: This invention relates to a method for treating human hepatitis B or C by the combination of a complex of polyadenylic acid and polyuridylic acid and interferon.alpha. Excerpt(s): This application is a 371 of PCT/FR98/01727 filed Aug. 3, 1998. The present invention relates to a product containing at least one double-stranded RNA (dsRNA) in combination with at least one antiviral agent, preferably an interferon, for therapeutic use, simultaneously, separately or over a period of time, in the treatment of a viral disease. Such a product can be used in particular for the treatment of viral hepatitis. The Applicant has found that the combination of dsRNA with an antiviral agent, and in particular with an interferon, results in an unexpected synergistic effect in the treatment of viral diseases, in particular the treatment of viral hepatitis. Web site: http://www.delphion.com/details?pn=US06509154__

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Recombinant VP2 parvoviral pseudo-particles encoding CTL or T-helper cell epitopes Inventor(s): Casal; Ignacio (Madrid, ES), Leclerc; Claude (Paris, FR), Lo-Man; Richard (Paris, FR), Rueda; Paloma (Madrid, ES), Sarraseca; Javier (Madrid, ES), Sedlik; Christine (Argenteuil, FR) Assignee(s): Immunologia Y Genetica Aplicada S.A. (Madrid, ES), Institut Pasteur (Paris, FR) Patent Number: 6,458,362 Date filed: August 30, 1996 Abstract: Attempts to generate modified viral pseudo-particles that are capable of stably incorporating heterologous antigenic determinants has encountered a number of difficulties including inhibition of pseudo-particle formation following epitope insertion and failure of the epitope to retain its native configuration. The present invention is directed toward recombinant viral pseudo-particles of the family Parvoviridae that stably encode heterologous epitopes. Hybrid virus-like particles (VLP) were prepared by self-assembly of a modified porcine parvovirus (PPV) VP2 capsid protein carrying a CD8.sup.+ or CD4.sup.+ T cell epitope in the amino terminus. Immunization of mice with hybrid pseudo-particles carrying a lymphocytic choriomeningitis virus (LCMV) nucleoprotein CTL epitope, without adjuvant, induced strong cytotoxic T lymphocyte (CTL) responses against both peptide-coated- or virus-infected-target cells.

242 Hepatitis B

Immunization of mice with hybrid pseudo-particles carrying a hepatitis B virus (HBV) T helper cell epitope, without adjuvant, induced strong T helper lymphocyte responses against the reporter epitope. These recombinant viral pseudo-particles are easily produced by the baculovirus expression system and, therefore, represent a promising and safe strategy to induce strong CTL and T-helper cell responses for the elimination of virus-infected cells. Excerpt(s): The present invention relates to recombinant viral pseudo-particles of a virus of the Parvoviridae family or of a related virus, useful in particular for inducing cytotoxic CD8.sup.+ T lymphocyte (CTL) and CD4.sup.+ helper T lymphocyte responses in vivo at a high level. Another object is the use of these pseudo-particles for the production of antitumoral vaccines or drugs. It also covers compositions comprising said pseudo-particles in a physiologically acceptable excipient and/or diluent. Web site: http://www.delphion.com/details?pn=US06458362__ •

Sequences and methods for detection of hepatitis B virus Inventor(s): Berger; Dolores M. (Baltimore, MD), Fort; Thomas L. (Finksburg, MD), Hellyer; Tobin J. (Owings Mills, MD), Nussbaumer; William A. (Timonium, 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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Single-stranded antibody against hepatitis B virus core protein, gene thereof, and therapeutic agent for hepatitis B containing these Inventor(s): Hayashi; Norio (Kawanishi, JP), Tohdoh; Naoki (Kobe, JP), Yamamoto; Hiroko (Higashiosaka, JP), Yamamoto; Masato (Hoover, AL) Assignee(s): Sumitomo Pharmaceuticals Company, Limited (Osaka-fu, JP) Patent Number: 6,562,599 Date filed: April 27, 2000 Abstract: A DNA characterized by coding for a single-stranded antibody capable of binding to a hepatitis B virus core protein: a single-stranded antibody coding for the DNA: a therapeutic agent for hepatitis B comprising the single-stranded antibody as the active ingredient; and a gene therapeutic agent containing the DNA as the active ingredient. Excerpt(s): The present invention relates to single-chain antibodies against hepatitis B virus core protein, genes thereof, and therapeutic agents for hepatitis B using the same. In particular, the present invention relates to single-chain antibodies characterized in that they inhibit DNA synthesis of hepatitis B virus by binding to the core protein of said virus, DNAs encoding said single-chain antibodies, vectors comprising said DNAs, transformants transformed with said vectors, a process for producing said single-chain antibodies, and therapeutic agents for hepatitis B using such single-chain antibodies or genes thereof. In Japan, hepatitis B virus (hereinafter sometimes abbreviated as HBV) accounts for a large part of the etiology of chronic hepatitis, as well as hepatitis C virus. Although the proportion of the virus carriers tends to decrease as a result of the recent preventive treatment by vaccination, there still exists a substantial number of patients with chronic hepatitis B, and medical treatments for this disease is quite important in terms of prophylaxis of primary hepatic cancer. As medical treatments for patients with chronic hepatitis B, those treatments that aim to exclude the virus by eliciting the host immunity, such as the interferon therapy, the steroid withdrawal therapy, and the propagermanium therapy, or the antiviral agent therapies (adenine arabinoside monophosphate, hereinafter sometimes abbreviated as ara-AMP), Lamivudine) are now being used. In the interferon therapy, however, a long-term clinical improvement cannot be observed, although a transient decrease in amount of serological markers of viral activities occurs. Likewise, although ara-AMP has been used with some effect, it is hard to say that the results are satisfactory at present. A treatment in which interferon and ara-AMP are combined and alternately administered exhibits neurotoxicity, and therefore has problems in its use. Furthermore, fulminant hepatitis B, which is one of the forms of acute hepatitis B, is a disease causing a high lethality, and there exist no effective therapeutic agents for this disease presently. Thus, although there is a strong need for developing an anti-hepatitis B virus therapy based on a different mechanism from those of conventional methods, no useful therapies have not yet been developed. Web site: http://www.delphion.com/details?pn=US06562599__

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Steroid/thyroid hormone receptor-related gene which is inappropriately expressed in human hepatocellular carcinoma and which is a retinoic acid receptor Inventor(s): de The; Hugues Blaudin (Paris, FR), Dejean; Anne (Paris, FR), Marchio; Agnes (Paris, FR), Tiollais; Pierre (Paris, FR) Assignee(s): Institut Pasteur (Paris, FR) Patent Number: 6,531,585 Date filed: February 1, 1991 Abstract: A previously isolated hepatitis B virus (HBV) integration in a 147 bp cellular DNA fragment linked to hepatocellular carcinoma (HCC) was used as a probe to clone the corresponding complementary DNA from a human liver cDNA library. Nucleotide sequence analysis revealed that the overall structure of the cellular gene, which has been named hap, is similar to that of the DNA-binding hormone receptors. Six out of seven hepatoma and hepatoma-derived cell-lines express a 2.5 kb hap mRNA species which is undetectable in normal adult and fetal livers, but present in all nonhepactic tissues analyzed. Low stringency hybridization experiments revealed the existence of hap related genes in the human genome. The cloned DNA sequence is useful in the preparation of pure hap protein and as a probe in the detection and isolation of complementary DNA and RNA sequences. The hap protein is a retinoic acid (RA) receptor identified as RAR-.beta. Excerpt(s): This invention relates to nucleotide sequences, polypeptides encoded by the nucleotide sequences, and to their use in diagnostic and pharmaceutical applications. Primary hepatocellular carcinoma (HCC) represents the most common cancer, especially in young men, in many parts of the world (as in China and in much of Asia and Africa) (reviewed in Tiollais, et al., 1985). Its etiology was investigated mostly by epidemiological studies, which revealed that, beyond some minor potential agents such as aflatoxin and sex steroids, hormones, Hepatitis B virus (HBV) chronic infection could account for a large fraction of liver cancers (Beasley and Hwang, 1984). Liganddependent transcriptional activators, such as steroid or thyroid hormone receptors, have recently been cloned allowing rapid progress in the understanding of their mechanism of action. Nevertheless, there exists a need in the art for the identification of transcripts that may encode for activational elements, such as nuclear surface receptors, that may play a role in hepatocellular carcinoma. Such findings would aid in identifying corresponding transcripts in susceptible individuals. In addition, identification of transcripts could aid in elucidating the mechanisms by which HCC occurs. Web site: http://www.delphion.com/details?pn=US06531585__

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Synthesis, anti-human immunodeficiency virus, and anti-hepatitis B virus activities of 1,3-oxaselenolane nucleosides Inventor(s): Chu; Chung K. (Athens, GA), Du; Jinfa (Irvine, CA), Schinazi; Raymond F. (Decatur, GA) Assignee(s): Emory University (Atlanta, GA), The University of Georgia Research Foundation, Inc. (Athens, GA) Patent Number: 6,590,107 Date filed: March 5, 2001

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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__ •

Synthetic peptides that bind to the hepatitis B virus core and e antigens Inventor(s): Sallberg; Matti (Alvsjo, SE) Assignee(s): Tripep AB (Huddinge, SE) Patent Number: 6,417,324 Date filed: April 21, 2000 Abstract: The present invention relates generally to the field of virology. More particularly, the invention relates to the discovery that peptides, which bind to the Hepatitis B virus (HBV) core and e antigens, can be used to inhibit HBV infection. Embodiments concern "binding partners", which include peptides, peptidomimetics, and chemicals that resemble these molecules that interact with HBV core and e antigens, biological complexes having HBV core and e antigens joined to said binding partners, methods of identifying such binding partners, pharmaceuticals having binding partners, and methods of treatments and prevention of HBV infection. Excerpt(s): The present invention relates generally to the field of virology. More particularly, the invention relates to the discovery that peptides that bind to the hepatitis B virus (HBV) core and e antigens can be used to inhibit HBV infection. Of the many viral causes of human hepatitis, few are of greater global importance than hepatitis B virus (HBV). Approximately 300 million people worldwide are chronically infected and some of these chronically infected individuals develop severe pathologic consequences including chronic hepatic insufficiency, cirrhosis, and hepatocellular carcinoma (HCC). (See Fields Virology, third ed., edited by Fields et al., LipponcottRaven Publishers, Philidelphia 1996 pp. 2703 and Lee et al., Cancer, 72:2564-7 (1993)). Primary infection may be asymptomatic (e.g, in chronically infected individuals) or may result in varying degrees of acute liver injury. (Milich et al., Springer Seminars in Immunopathology, 17:149-66 (1995)). The invention described herein concerns the

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identification and manufacture of molecules that interact with HBcAg and/or HBeAg and thereby inhibit HBV infection or modulate a host immune system response or both. Molecules that interact with HBcAg and/or HBeAg, also referred to as "binding partners", are designed from fragments of antibodies and other proteins that interact with HBcAg and/or HBeAg. Accordingly, an amino acid sequence corresponding to the binding domains of monoclonal or polyclonal antibodies or proteins that bind HBcAg and/or HBeAg is used as a template for the design of synthetic molecules, including but not limited to, peptides, derivative or modified peptides, peptidomimetics, and chemicals. A preferred binding partner, for example, is a molecule called a "specificity exchanger", which comprises a first domain that interacts with HBcAg and/or HBeAg and a second domain that has an epitope for a high titer antibody, preferably an epitope on a pathogen or a toxin. The binding partners described herein can be manufactured by conventional techniques in peptide chemistry and/or organic chemistry. Web site: http://www.delphion.com/details?pn=US06417324__ •

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 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__

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•

Topical immunomodulating compositions for treatment of aids, Hepatitis B & C, other infectious diseases, and cancer Inventor(s): Kaplan; Leonard L. (One Minuteman Ct., East Brunswick, NJ 08316), Levis; William R. (17 Weaver St., Staten Island, NY 10312) Assignee(s): none reported Patent Number: 6,455,586 Date filed: December 13, 1999 Abstract: Topical drug compositions, containing contact sensitizing agents as the active components of the subject patent compositions, can provide a pharmacological action that induces a delayed hypersensitization reaction resulting in stimulation of cell mediated immunity when applied to the skin. The preferred composition contains, but is not limited to, Diphenylcyclpropenone as a preferred embodiment of the class of contact sensitizing drugs applied to the skin in an optimally prepared pharmaceutical formulation with controlled absorption properties to reach the peripheral circulation resulting in increases in CD4+ helper T cells of benefit to immunocompromised patients. Excerpt(s): Contact sensitizers such as dinitrochlorobenzene (DNCB) have been reported to raise CD4+ helper T cell counts and reduce viral load in HIV positive patients (1,2). The DNCB was applied to the skin in 10% concentration dissolved in the volatile solvent acetone which resulted in unreliable and unpredictable contact sensitization reactions. Biologically, increases in CD+ helper T cell counts are accompanied by variable decreases in HIV retroviral replication as measured by human immunovirus ribonucleic acid (RNA) levels in dendritic cells that are the primary antigen presenting cells of the human immune system. It is the dendritic cells and microphages that are infected during the initial phases of human immunovirus growth in AIDS patients. Optimally formulated contact sensitizers when topically applied, can induce TH-1 type immunity by releasing cytokines including Interleukin 2,valuable in treating hepatitis B&C, and forms of cancer as well as AIDS. On the other hand, the medical use of the preferred contact sensitizer diphenylcyclopropenone has been limited primarily to the treatment of alopecia areata as disclosed in referenced U.S. Pat. No. 4,985,464 wherein the volatile solvent acetone with unreliable absorption properties was used as the formulation vehicle. Other contact sensitizers referenced in the literature (3) are, but not limited to, squaric acid dibutylester, urishiol, oxazolone, dinitrofluorobenzene, and paraphenylenediamine. In all referenced cases, the volatile solvent acetone with unreliable absorption characteristics was used as the drug delivery system for the contact sensitizers. Accordingly, there is a need for a more reliable stabilized composition in which the contact sensitizers are soluble and will be reliably and predictably absorbed through the skin to reach the aforementioned dendritic cells of the dermis. This invention provides compositions for the topical application of contact sensitizers in a unique topical pharmaceutical emulsion drug delivery system to reliably penetrate the epidermis of immunocompromised human patients in order to stimulate the release of CD4+ helper T cells and induce TH-1 type immunity by releasing cytokines including Interleukin 2, valuable in treating AIDS, Hepatitis B&C, other viral infectious diseases, and Cancer. The compositions contain controlled amounts of diphenyl-cyclopropenone, dinitrochlorobenzene, dinitrofluorobenzene, squaric acid dibutylester, urishiol, oxazolone, paraphenylene-diamine or other medically useful contact sensitizers emulfified in a non-toxic drug delivery system formula consisting of pharmaceutically acceptable non-volatile, non-ionic surfactants and pharmaceutically acceptable emollients at optimized levels wherein the contact sensitizer(s) are reliably absorbed through the epidermis to reach the dendritic cells in the dermis during the

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early stages of viral infections in immunocompromised patients. A preferred embodiment of the invention includes diphenylcyclopropenone as the contact sensitizer uniquely formulated in a microemulsified drug delivery sytem consisting of the nonionic surfactant polyoxyethylene 20 sorbitan momooleate and the emollients isopropyl myristate and/or isopropyl palmitate. The immunmodulating compositions of this invention treat viral infections embodied by AIDS, Hepatitis B&C, other viral infectious diseases and certain types of cancer wherein the the patient's immune system is attacked by the disease. The active ingredients in these compositions are those that are classified pharmacologically as contact sensitizers such as dinitrochlorobenzene, dinitrofluorobenzene, diphenylcyclopropenone, oxazolone, paraphenylenediamine, squaric acid dibutylester, urushiol and the like that are generally recognized as pharmacologically active contact sensitizers. Topically applied, contact sensitizers have been shown to raise the CD4+ helper T cell counts and variably reduce viral load in HIV positive patients when applied as a concentrated solutions in Acetone as the vehicle (1,2,3). Web site: http://www.delphion.com/details?pn=US06455586__ •

Use of an amphipathic compound for providing an adjuvant to a subunit vaccine Inventor(s): Brunel; Florence (Genay, FR), Darbouret; Anne (Saint Maurice sur Dargoire, FR), Ronco; Jorge (La Mulatiere, FR) Assignee(s): Aventis Pasteur S.A. (FR) Patent Number: 6,472,159 Date filed: April 16, 2001 Abstract: The present invention provides a method of inducing an immune response to a subunit antigen in a non-responding subject by administering to the subject a composition comprising the subunit antigen and an amphipathic compound. A preferred antigen is a hepatitis B antigen, and a preferred amphipathic compound is DC-chol. Excerpt(s): The invention relates to the field of vaccine adjuvants. In particular, the invention relates to the use of an amphipathic compound for the manufacture of a vaccine composition intended for nonresponding subjects. It is known that, when a population of individuals is vaccinated against a disease, a number of them do not "respond" to the vaccination, that is to say that their immune system does not appear to react to the antigen administered. This problem is substantial to a greater or lesser degree depending on the diseases and the populations involved, but vaccine manufacturers are still trying to reduce, for each of the vaccines which they make available to doctors, the number of subjects likely to be "nonresponders". This problem is considered particularly for vaccines comprising purified antigens such as subunit vaccines produced by genetic engineering and in particular the hepatitis vaccine; however, while a number of amphipathic compounds, and in particular 3-.beta.-[N(N',N'-dimethylaminoethane)carbamoyl]cholesterol, commonly called DC-chol, are known which make it possible to increase the immune response in subjects who are already "responders", and are therefore considered to be good vaccine adjuvants, it is more difficult to find means of overcoming the problem of nonresponders, all the more so since all the reasons why an individual is a nonresponder have not yet been clearly identified. The research studies carried out in this field have shown that it was not possible to extrapolate the results obtained with adjuvants capable of increasing the immune response in "responding" subjects to the "nonresponding" subjects, given that

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some good adjuvants in responding subjects are found to have no effect in nonresponding subjects. The aim of the invention is therefore to provide an improved vaccine as regards the level of seroconversion which it makes possible to obtain. For that, the invention proposes the use of an amphipathic compound for the preparation of a vaccine composition comprising at least one subunit antigen intended to be administered to target populations comprising individuals who are "nonresponders" to said antigen. Web site: http://www.delphion.com/details?pn=US06472159__

Patent Applications on Hepatitis B 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 B: •

6-Methylnicotinamide derivatives as antiviral agents Inventor(s): Kim, Jong-Woo; (Kyunggi-do, KR), Kim, Nam-Doo; (Inchon-si, KR), Lee, Geun-Hyung; (Kyunggi-do, KR), Lee, Hak-Dong; (Kyunggi-do, KR), Lee, Jin-Soo; (Kyunggi-do, KR), Lee, Sang-Wook; (Kyunggi-do, KR), Park, Hee-Jeong; (Kyunggi-do, KR), Park, Sang-Jin; (Seoul, KR), Yoon, Sung-June; (Seoul, KR) Correspondence: Muserlian, Lucas And Mercanti, Llp; 600 Third Avenue; New York; NY; 10016; US Patent Application Number: 20030092709 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 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): R.sub.3 is 5-indazole or 6-indazole. 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. HBV genome consists of genes for polymerase (P), surface protein (pre-S1, pre-S2 and S), core protein (pre-C and C), and X protein. Of these proteins expressed from HBV genes, polymerase, surface protein, and core protein are structural proteins and X protein has a regulatory function. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

10

This has been a common practice outside the United States prior to December 2000.

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•

Acid-modified arabinogalactan protein composition Inventor(s): An, Jinhua; (Palo Alto, CA), Lennox, Edwin S.; (Stanford, CA), Leu, Karen S.; (Saratoga, CA), Musser, John H.; (San Carlos, CA) Correspondence: Heller Ehrman White & Mcauliffe Llp; 275 Middlefield Road; Menlo Park; CA; 94025-3506; US Patent Application Number: 20030211077 Date filed: November 27, 2002 Abstract: An acid-modified arabinogalactan protein composition, having an arabinosegalactose ratio of less than 3.5:1 or less than 80% of the arabinose:galactose ratio of the arabinogalactan protein component of the composition prior to acid modification, prepared from Astragalus membranaceus, especially from the roots of Atragalus membranaceus, is capable of reconstitution into an aqueous intravenously injectable formulation; and is useful for stimulating hematopoiesis, inducing the proliferation or maturation of megakaryocytes, stimulating the production of IL-1.beta., Il-6, TNF.alpha., IFN-.gamma., GM-CSF, or G-CSF, stimulating the production or action of neutrophils, treating neutropenia, anemia, or thrombocytopenia, accelerating recovery from exposure (e.g. accidental or non-therapeutic exposure, as well as therapeutic exposure) to cytotoxic agents or radiation, treating cachexia, emesis, or drug withdrawal symptoms, or modifying biological responses or protecting hepatic cells in hepatitis B, in a mammal when intravenously administered to the mammal. Excerpt(s): This invention relates to arabinogalactans. In particular, this invention relates to an acid-modified arabinogalactan protein composition, having an arabinose:galactose ratio of less than 3.5:1 or less than 80% of the arabinose:galactose ratio of the arabinogalactan protein component of the composition prior to acid modification, prepared from Astragalus membranaceus, especially from the roots of Astragalus membranaceus. Huang-qi, Radix Astragali, is the dried root of Astragalus membranaceus Bge. var. mongholicus (Bge.) Hsiao or A. membranaceus (Fisch.) Bge. (Fabaceae). Huang-qi is a very old and well known drug in traditional Chinese medicine. It is officially listed in the Chinese Pharmacopoeia and used mainly as a tonic and for treatment of nephritis and diabetes. It is commonly used as a decoction or "tea" alone or with other plants in the traditional medicines Shi-ka-ron (a combination with herbs Lithosperium erythrorhizon and Ligusticum wallachii) and Ren-shen-yang-rongtang (a combination of twelve herbs including Radix Astragali) [The section entitled "Astragalus membranaceus (Fisch.) Bge.", Section 26, pages 191-197, of "Chinese Drugs of Plant Origin", W. Tang and G. Eisenbrand, eds., Springer Verlag, Berlin, 1992]. Huang-qi decoctions, and solutions prepared from the alcohol-precipitated decoction, have also been administered by injection, and are reported to give improvement in the symptoms of gastric and duodenal ulcers and increase the white blood cell count in chronic leukopenia [The section entitled "Huangqi", pages 1041-1046, of "Pharmacology and Applications of Chinese Materia Medica", H.-M. Chang and P. P.-H. But, eds., World Scientific Publishing Co., Singapore, 1987]. Huang-qi decoctions, purified low molecular weight fractions (e.g. 25,000-35,000 MW), and decoctions of herb mixtures containing huang-qi, have also shown activity in restoring the immune system in local xenogeneic graft-versus-host reaction [D.-T. Chu et al., "Immunotherapy with Chinese medicinal herbs. I. ", J. Clin. Lab. Immunol., 25, 119-123 (1988)], reversing cyclophosphamide-induced immune suppression [D.-T. Chu et al., "Immunotherapy with Chinese medicinal herbs. II. ", J. Clin. Lab. Immunol., 25, 125-129 (1988)], potentiating LAK cell cytotoxicity generated by rIL-2 [D.-T. Chu et al., "Fractionated extract of Astragalus membranaceus. ", J. Clin. Lab. Immunol., 25, 183-187 (1988)],

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enhancing the immune response in immunodepressed mice [K. S. Zhao et al., "Enhancement of the immune response in mice by Astragalus membranaceus extracts", Immunopharmacology, 20, 225-234 (1990)], stimulating responses in mononuclear cells [Y. Sun et al., "Preliminary observations on the effects of the Chinese medicinal herbs. ", J. Biol. Response Modifiers, 2, 227-237 (1983)], and stimulating bone marrow hematopoiesis in mice [M. Rou et al., "The effect of radix astragali on mouse marrow hemopoiesis", J. Trad. Chin. Med., 3(3), 199-204 (1983); S.-I. Miura et al., "Effect of a traditional Chinese herbal medicine. ", Int. J Immunopharmacol., 7(11), 771-780 (1989); and Y. Ohnishi et al., "Effects of Juzen-taiho-toh (TJ-48). ", Exp. Hematol., 18, 18-22 (1990)]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Anti-viral 7-deaza L-nucleosides Inventor(s): Deziel, Robert; (Montreal, CA), Iyer, Radhakrishnan P.; (Shrewsbury, MA), Mekouar, Khalid; (Laval, CA), Mounir, Samir; (Laval, CA) Correspondence: Seed Intellectual Property Law Group Pllc; 701 Fifth Ave; Suite 6300; Seattle; WA; 98104-7092; US Patent Application Number: 20030153744 Date filed: December 20, 2002 Abstract: The present invention comprises 7-deaza L-nucleosides having unexpectedly high inhibitory activity against the hepatitis B virus. The invention further comprises pharmaceutical compositions comprising such compounds as well as methods of treating mammals, particularly humans, infected with HBV and other viral infections. Excerpt(s): The present invention is in the field of anti-viral agents, particularly antiviral L-nucleosides, and more particularly anti-viral 7-deaza L-nucleosides. Nucleoside and nucleotide analogs have long been studied as potential antiviral compounds. A number of D-nuceloside analogs are presently used as antiviral agents, including HIV reverse transcriptase inhibitors (such as AZT, ddI, ddC, and d4T). Similarly, purine Dnucleoside analogs have also been explored in search of immunomodulators. Guanosine analogs having substituents at the 7- and/or 8-positions, for example, have been shown to stimulate the immune system (for a review, see Weigle, W. O., CRC Crit Rev. Immunol. 7:285,1987; Lin et al., J. Med. Chem. 28:1194, 1985; Reitz et al., J. Med. Chem. 37:3561, 1994; Michael et al., J. Med. Chem. 36:3431,1993). 7-Deazaguanosine and analogs have been shown to exhibit antiviral activity in mice against a variety of RNA viruses, even though the compound lacks antiviral properties in cell culture. 3Deazaguanine nucleosides and nucleotides have also demonstrated significant broad spectrum antiviral activity against certain DNA and RNA viruses (Revanker et al., J. Med. Chem. 27:1389,1984). Certain 7- and 9-deazaguanine L-nucleosides exhibit the ability to protect mice against lethal challenge of Semliki Forest virus (Girgis et al., J. Med. Chem. 33:2750, 1990) (see also WO 98/16184, which discloses purine L-nuceloside analogs as antiviral agents). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Antiviral agent for drug-resistant virus Inventor(s): Kamiya, Naohiro; (Kawasaki-shi, JP), Omata, Masao; (Funabashi-shi, JP), Yuasa, Satoshi; (Kawasaki-shi, JP) Correspondence: Greenblum & Bernstein, P.L.C.; 1941 Roland Clarke Place; Reston; VA; 20191; US Patent Application Number: 20030109498 Date filed: October 29, 2001 Abstract: 2-amino-6-arylthiopurinephosphonate used in the antiviral agent of the present invention has no toxicity such as bone marrow cell growth inhibition or mutagenicity, and has a high antiviral activity, oral absorbency and safety. Furthermore, the compound of the present invention is effective for a mutant virus which is known to exhibit resistance to the conventional antiviral agents. Therefore, the present invention can provide a useful antiviral agent which leads to the establishment of a method for treating hepatitis B, which is a medically important object. Excerpt(s): The present invention relates to a method for treating a YMDD mutant virus disease which shows a drug-resistance against lamivudine ((-)-.beta.-L-2',3'-dideoxy-3'thiacytidine, which is referred to as 3TC) which is a conventional antiviral agent. More specifically, the present invention relates to a method for treating a virus disease which comprises administering a phosphonate nucleotide compound having the abovementioned antiviral activity, or a salt thereof, or a hydrate thereof or a solvate thereof. Among virus diseases, especially human immunodeficiency virus (HIV) infection (i.e., acquired immune deficiency syndrome (AIDS)) and hepatitis B virus (HBV) infection (i.e., hepatitis B) are considered to be a medically crucial problem because of the high absolute number of patients presented in the world. For the purpose of treating these diseases, various agents having an antiviral activity has been actively developed. Among such agents, lamivudine was developed as the first antiviral agent which inhibits the replication of both HIV and HBV, and it has already been approved as an agent for HIV infection in large number of countries. Lamivudine has recently been approved also for HBV infection in some countries, and there are many reports that lamivudine has clinically been used. The greatest problem regarding the treatment of HBV infection with lamivudine discussed in these reports is that an emergence of drugresistant viruses increases after the long term administration of lamivudine. It is known that these drug-resistant viruses, as is in the case of HIV, have the mutation of methionine residue in an amino acid sequence, tyrosine-methionine-aspartic acidaspartic acid (YMDD) motif located in an active center of a viral DNA polymerase. In the case of HIV, there has been reported a result of the X-ray crystallographic analysis of a YMDD mutant polymerase (Sarafianos, S. G. et al., Proc. Natl. Acad. Sci., USA 96, 10027-10032 (1999)). This result suggests a possibility that the substitution of methionine by isoleucine or valine interferes the binding of lamivudine triphosphate to an active center and a possibility of cross-resistance to other nucleoside derivatives having.beta.L-ring occurs. On the other hand, in the case of HBV, the single substitution of leucine by methionine (L528M) on the B domain of HBV polymerase identified by the clinical trial of Famciclovir (2-[2-(2-amino-9H-purin-9-yl)ethyl]-1,3-pro- panediol diacetate) against HBV infection shows a resistance to Famciclovir (Seigneres, B., et al., J. Infect. Dis., 181, 1221-1233 (2000)). It is suggested, however, that since a YMDD mutant HBV also having a L528M mutation acquires a higher ability to replicate viral DNA than HBV having a single YMDD mutation, and emerges as a cross drug-resistant HBV (Ono, S. K., et al., J. Clin. Invest., 107, 449-455 (2001)). Summarizing several reports, the emergence rate of a YMDD mutant virus in hepatitis B patients is 17 to 46% after the continuous

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use of lamivudine for 1 year, and 65 to 75% after the use of lamivudine for 3 to 4 years (Ono, S. K., et al., J. Clin. Invest., 107, 449-455 (2001)). The emergence of a drug-resistant mutant virus reduces the efficacy of the agent. As a result, even if the administration of the agent is continued, proliferation of the virus occurs, resulting in the recurrence of hepatitis B. If the administration of the agent is stopped at this moment, a wild type of HBV having a higher replication ability than drug-resistant mutant virus proliferates again, resulting in the fear of the occurrence of fulminate hepatitis in some cases. However, since it is only lamivudine that has been approved as an antiviral agent against HBV, there is a therapeutic contradiction in that the patients is administered with lamivudine, even if lamivudine is ineffective, and this contradiction would cause some hesitation in administrating the agent to a new hepatitis B patient. The present inventors have already found that some of phosphonate nucloetide compounds show a high oral absorbency (EP632048), and have obtained an antiviral agent having anti-HBV activity without toxicity such as bone marrow cell growth inhibition or mutagenicity by changing the base portion of those compounds to a specific structure (EP785208). These compounds having a several ten-fold activity as compared with lamivudine, have been developed as novel agents for treating hepatitis B. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Assay Inventor(s): Bartholomeusz, Angeline; (Victoria, AU), Chen, Robert Yung Ming; (Victoria, AU), Delaney, William IV; (San Meteo, CA), Isom, Harriet; (Hummelstown, PA), Locarnini, Stephen Alister; (Victoria, AU) Correspondence: Scully, Scott, Murphy & Presser; 400 Garden City Plaza; Garden City; NY; 11530; US Patent Application Number: 20030096222 Date filed: February 2, 2001 Abstract: The present invention relates generally to an assay for detecting variant Hepatitis B viruses (HBVs) which exhibit altered sensitivity to agents. The variant HBVs are delivered to cells using a baculovirus vector. The same agents generally have a particular effect or absence of effect on a reference HBV. The altered sensitivity is in relation to the effects of the agent on one or more stages of infection, replication, assembly or release of virus or virus-like particles including any intermediary steps during the processes of viral infection, replication, assembly and/or release. The identification of variant HBVs with altered sensitivities to anti-HBV agents provides a means of monitoring cross resistance, or the development of new therapeutics effective against variant HBVs with altered sensitivities to other anti-HBV agents, as well as monitoring therapeutic protocols which may then need to be modified to ensure the appropriate anti-HBV agent is administered or that the appropriate therapeutic protocol is instituted. The present invention further provides variant HBVs detected by the assay of the present invention and to components thereof as well as recombinant, chemical analogue, homologue and derivative forms of such components. Excerpt(s): This application claims priority from U. S. Provisional Application No. 60/179,948, filed on Feb. 3, 2000. Reference to any prior art in this specification is not, and should not be taken as, an acknowledgment or any form of suggestion that this prior art forms part of the common general knowledge in Australia or any other country.

254 Hepatitis B

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

•

Combination therapy to treat hepatitis B virus Inventor(s): Barry, David W.; (Chapel Hill, NC), Furman, Phillip A.; (Durham, NC), Painter, George R. III; (Chapel Hill, NC), Rousseau, Franck; (Durham, NC) Correspondence: Clark G. Sullivan, ESQ.; King & Spalding Llp; 45th Floor; 191 Peachtree Street, N.E.; Atlanta; GA; 30303; US Patent Application Number: 20030158150 Date filed: February 25, 2003 Abstract: The present invention is directed to a method for treating hepatitis B virus infection in humans comprising administering a synergistically effective amount of agents having known anti-hepatitis B virus activity in combination or alternation. Specifically, the invention is directed to a method for treating hepatitis B virus infection

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comprising administering FTC in combination or alternation with penciclovir, famciclovir or Bis-POM-PMEA. Additionally, the invention is directed to a method for treating hepatitis B virus infection comprising administering L-FMAU in combination or alternation with DAPD, penciclovir or Bis-POM-PMEA. The invention is further directed to a method for treating hepatitis B virus infection comprising administering DAPD in combination or alternation with Bis-POM-PMEA. Excerpt(s): This invention is in the area of methods for the treatment of hepatitis B virus (also referred to as "HBV") that includes administering to a host in need thereof, an effective combination of nucleosides which have known anti-hepatitis B activity. This application claims priority to U.S. provisional patent application No. 60/106,664, filed on Nov. 2, 1998. HBV is second only to tobacco as a cause of human cancer. The mechanism by which HBV induces cancer is unknown, although it is postulated that it may directly trigger tumor development, or indirectly trigger tumor development through chronic inflammation, cirrhosis, and cell regeneration associated with the infection. Hepatitis B virus has reached epidemic levels worldwide. After a two to three month incubation period in which the host is unaware of the infection, HBV infection can lead to acute hepatitis and liver damage, that causes abdominal pain, jaundice, and elevated blood levels of certain enzymes. HBV can cause fulminant hepatitis, a rapidly progressive, often fatal form of the disease in which massive sections of the liver are destroyed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Combined vaccine compositions Inventor(s): Stephenne, Jean; (Rixensart, BE), Wettendorff, Martine Anne Cecile; (RhodeSaint-Genese, BE) Correspondence: Glaxosmithkline; Corporate Intellectual Property - Uw2220; P.O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20030129199 Date filed: August 23, 2002 Abstract: Novel combined vaccine composition preferentially for administration to adolescents are provided, comprising a hepatitis B viral antigen and a herpes simplex viral antigen and optionally in addition one or more of the following: an EBV antigen, a hepatitis A antigen or inactivated attenuated virus, an HPV antigen, a V2V antigen, a HCMV antigen, a Toxoplasma gondii antigen. The vaccine compositions are formulated with an adjuvant which is a preferential stimulator of TH1 cell response such as 3DMPL and QS21. Excerpt(s): This invention relates to novel vaccine formulations, methods for preparing them and their use in therapy. In particular the present invention relates to combination vaccines for administration to adolescents. HSV-2 is the primary etiological agent of herpes genitalis. HSV-2 and HSV-1 (the causative agent of herpes labialis) are characterised by their ability to induce both acute diseases and to establish a latent infection, primarily in neuronal ganglia cells. Genital herpes is estimated to occur in about 5 million people in the U.S.A. alone with 500,000 clinical cases recorded every year (primary and recurrent infection). Primary infection typically occurs after puberty and is characterised by the localised appearance of painful skin lesions, which persist for a period of between 2 to 3 weeks. Within the following six months after primary infection 50% of patients will experience a recurrence of the disease. About 25% of

256 Hepatitis B

patients may experience between 10-15 recurrent episodes of the disease each year. In immunocompromised patients the incidence of high frequency recurrence is statistically higher than in the normal patient population. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Compositions and methods for eliciting CTL immunity Inventor(s): Celis, Esteban; (San Diego, CA), Chesnut, Robert W.; (Cardiff-by-the-Sea, CA), Grey, Howard; (La Jolla, CA), Sette, Alessandro D.; (La Jolla, CA), Vitiello, Maria A.; (La Jolla, CA) Correspondence: Bruce D. Grant; Morrison & Foerster Llp; Suite 500; 3811 Valley Centre Drive; San Diego; CA; 92130; US Patent Application Number: 20030099634 Date filed: April 22, 2002 Abstract: Cytotoxic T lymphocyte responses are effectively induced to an antigen of interest, particularly viral, bacterial, parasitic and tumor antigens. Compositions, including pharmaceutical compositions, of CTL-inducing peptide and an adjuvant or a lipidated peptide which induces a helper T cell (HTL) response stimulate the antigen specific CTL response. Among the viral antigens to which the CTL responses are effectively induced in humans are those of hepatitis B. The CTL response may be optimized by a regimen of two or more booster administrations. Cocktails of two or more CTL inducing peptides are employed to optimize epitope and/or MHC class I restricted coverage. Excerpt(s): The present application is a continuation of U.S. application Ser. No. 08/197,484, filed Feb. 16, 1994 which is a continuation-in-part of U.S. application Ser. No. 07/935,811, filed Aug. 26, 1992, which is a continuation-in-part of U.S. application Ser. No. 07/874,491, filed Apr. 27, 1992 and now abandoned, which is a continuation-inpart of U.S. application Ser. No. 07/827,682, filed Jan. 29, 1992 and now abandoned, which is a continuation-in-part of U.S. application Ser. No. 07/749,568, filed Aug. 26, 1991 and now abandoned, each of which is incorporated herein by reference. Cytotoxic T lymphocytes ("CTL") represent an important component of an animal's immune response against a variety of pathogens and cancers. CTL which have been specifically activated against a particular antigen are capable of killing the cell that contains or expresses the antigen. CTL are particularly important in providing an effective immune response against intracellular pathogens, such as a wide variety of viruses, and some bacteria and parasites. CTL responses are also believed to be capable of contributing to anti-tumor responses in afflicted or susceptible individuals. The receptors on the surface of the CTL cannot recognize a foreign antigen directly, however. The CTL express an.alpha.-.beta.heterodimeric T cell receptor which is capable of recognizing foreign antigen fragments bound to major histocompatibility complex (MHC) class I molecules on the surface of the effected (e.g., infected) cells. CTL also express the non-polymorphic CD8 antigen. This cell surface protein interacts with the third domain of the class I molecule on the antigen presenting cells and plays a role in both stabilizing the interaction between the CTL and the antigen presenting cell and in CTL activation (Salter et al., Nature 345:41-46 (1990)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 257

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Compounds comprising disulfide-containing peptides and nitrogenous bases, and medical uses thereof Inventor(s): Kozhemyakin, Andrew L.; (St. Petersburg, RU), Kozhemyakin, Leonid A.; (St. Petersburg, RU) Correspondence: Wolf Greenfield & Sacks, PC; Federal Reserve Plaza; 600 Atlantic Avenue; Boston; MA; 02210-2211; US Patent Application Number: 20030105026 Date filed: February 7, 2002 Abstract: The invention relates to new compositions and medical uses, such as antiinfectious pharmacology. The compositions include salts and compounds of GSSG including at least one counterion comprising a nitrogenous base. Examples of such nitrogenous bases include DNA bases, nucleosides of DNA bases, nucleotides of DNA bases, RNA bases, nucleosides of RNA bases, nucleotides of RNA bases, inosine, nucleotides of inosine, and homologues, analogues and derivatives thereof. The invention is also directed to methods for treatment and prevention of infectious diseases such as viral hepatitis B and C, AIDS and herpes. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/903,443, filed Jul. 11, 2001, which is a continuation-in-part of U.S. patent application Ser. No. 09/887,537, filed Jun. 22, 2001. This application also claims priority to Russian application no. 2001103535/14, filed Feb. 8, 2001, the entire contents of which is incorporated herein by reference. The invention relates to new compositions and medical uses, such as anti-infectious pharmacology. The invention also relates to the development of new therapeutic agents based on active metabolites of peptides, nucleosides and nucleotides that are intended to be used for treatment and prevention of infectious diseases such as viral hepatitis B and C, AIDS and herpes. The function of pleiotropic cytokine, IL-12 can be a factor for host immune response regulation. By regulating the Th1/Th2 balance, IL-12 modulates macrophage functions, especially for liver resident macrophages (Kuppfer's cells). For chronic hepatitis C or B, IL-12 activates cytokine release in the Th1 cells, inhibiting corresponding Th2 function. Chronic forms and an unfavorable courses of viral hepatitis are accompanied with a decreased IL-12 content. (Schlaak, J. F. et al., J. Med. Virol. 1998, 56: 112-117.) Thus, T-cell immunity relating to the course and outcome of HBV and HCV infections and successful treatment is dependent on endogenous production of appropriate cytokines capable of responding to an antigen stimulus. The host immune response and production of these cytokines, which are in competition with the generation of new "quasi-species", both can determine the capability for modulating the targeting and intensity of the host immune response. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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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

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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 •

Glucamine salts for treating hepatitis virus infections Inventor(s): Bryant, Martin L.; (Carisle, MA), Mueller, Richard A.; (Glencoe, IL), Partis, Richard A.; (Evanston, 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 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,

Patents 259

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): 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

260 Hepatitis B

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 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.

Patents 261

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 vaccines containing 3-O-deacylated monophoshoryl lipid A Inventor(s): Garcon-Johnson, Nathalie Marie-Joseph Claude; (Wavre, BE), Hauser, Pierre; (Chaumont-Gistoux, BE), Thiriart, Clothilde; (Brussels, BE), Voet, Pierre; (Izel, BE) Correspondence: Smithkline Beecham Corporation; Corporate Intellectual Property-us, Uw2220; P. O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20030211120 Date filed: June 19, 2003 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. L., 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://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Humanized antibody to surface antigen s of hepatitis b virus and a preparing method thereof Inventor(s): Hong, Hyo-Jeong; (Taejeon-si, KR), Kim, Keun-Soo; (Kyunggi-do, KR) Correspondence: Gates & Cooper Llp; Howard Hughes Center; 6701 Center Drive West, Suite 1050; Los Angeles; CA; 90045; US Patent Application Number: 20030096403 Date filed: June 3, 2002 Abstract: The present invention relates to the humanized antibodies to surface antigen S of hepatitis B virus and a preparing method thereof. Particularly, it relates to the humanized antibodies which comprise heavy and light chains having amino acid sequences originated from human antibodies at the HCDR1, HCDR2, HCDR3 and LCDR1, LCDR2, LCDR3 of their variable regions, expression vectors containing each of the heavy and light chain genes of the humanized antibody and transformant which can produce humanized antibody by transfection with heavy and light chain expression vectors and a preparing method thereof. A humanized antibody of the present invention is more humanized than that of the previous arts. So, it minimizes the probability of immune response in humans and has good antigen binding capacity, making it a excellent candidate for prevention and treatment of the hepatitis B virus infection. Excerpt(s): Hepatitis B virus (HBV) invades into human body and causes chronic and acute hepatitis. If the condition grows worse, it can be a pathogen causing cirrhosis and cancer of the liver. It is estimated that up to three hundred millions patients in the world are infected with HBV (Tiollais & Buendia, Sci. Am., 264, 48, 1991). The envelope of HBV is composed of 3 types of proteins. Specifically, it is composed of major protein comprising S antigen, middle protein comprising S antigen and pre-S2 antigen, and large protein comprising S antigen, pre-S2 antigen and pre-S1 antigen (Neurath, A. R. and Kent, S. B. H., Adv. Vir. Res., 34: 65-142, 1988). All of the above-mentioned HBV surface antigen proteins can induce antibodies which neutralize HBV. Among them, S antigen takes part of about 80% of the total envelop protein and has neutralizing epitope called "Common a" which is commonly present in all of HBV subtypes. When infected with HBV, for example, in cases of new-born babies born from HBV positive mother or medical institution employees exposed to HBV or recipients undergoing liver transplantation from patient having HBV-related liver diseases, HB immune globulin (HBIG) has been used to prevent the HBV infection (Beasley et al., Lancet, 2, 1099, 1983; Todo et al., Hepatol., 13, 619, 1991). However, since the currently used HBIG is prepared from human plasma, it has the disadvantages that the specificity against antigen is low and the probability of contamination is relatively high. Moreover, human blood has to be continuously supplied. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Identification of oligonucleotides for the capture, detection and quantitation of hepatitis B viral DNA Inventor(s): Shyamala, Venkatakrishna; (Oakland, CA) Correspondence: Chiron Corporation; Intellectual Property - R440; P.O. Box 8097; Emeryville; CA; 94662-8097; US Patent Application Number: 20030143527 Date filed: October 9, 2002

Patents 263

Abstract: Hepatitis B virus capture oligonucleotides, primers and probes derived from conserved regions of the hepatitis B virus genome are disclosed. Also disclosed are nucleic acid-based assays using the capture oligonucleotides, primers and probes. Excerpt(s): This application is related to provisional patent applications serial No. 60/328,492 filed Oct. 9, 2001, serial No. 60/368,823 filed Mar. 29, 2002, and serial No. 60/393,561 filed Jul. 2, 2002, from which priority is claimed under 35 USC.sctn.119(e)(1) and which applications are incorporated herein by reference in their entireties. The present invention pertains generally to viral diagnostics. In particular, the invention relates to nucleic acid-based assays for accurately diagnosing hepatitis B infection. Hepatitis B virus (HBV) is a member of a group of small DNA-containing viruses that cause persistent noncytopathic infections of the liver. HBV infection in humans can cause severe jaundice, liver degeneration and death. HBV enters predominantly by the parenteral route, has a characteristic incubation period of 60 to 160 days, and may persist in the blood for years in chronic carriers. It is estimated that about 6 to 7% of the human population is infected, with the level of infection being as high as 20% of the population in certain regions of Southeast Asia and sub-Sahara Africa. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Immunogenic HBc chimer particles having enhanced stability Inventor(s): Birkett, Ashley J.; (Escondido, CA) Correspondence: Welsh & Katz, Ltd; 120 S Riverside Plaza; 22nd Floor; Chicago; IL; 60606; US Patent Application Number: 20030138769 Date filed: August 15, 2001 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 display of the immunogenic epitope is displayed in the immunogenic loop of HBc, whereas the enhanced stability of self-assembled particles is obtained by the presence of at least one heterologous cysteine residue near the carboxy-terminus of the chimer molecule. Methods of making and using the chimers are also disclosed. Excerpt(s): This a continuation-in-part of application Serial No. 60/225,843, filed Aug. 16, 2000, and application Serial No. 60/226,867, filed Aug. 22, 2000 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 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, unless the discussion is referring to a specific example. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method and device for the rapid clinical diagnosis of hepatitis B virus (HBV) infection in biological samples Inventor(s): Kondiboyina, Venkata Ramana; (Mumbai, IN), Sharma, Vijay; (Mumbai, IN) Correspondence: Lackenbach Siegel; One Chase Road; Scarsdale; NY; 10583; US Patent Application Number: 20030157478 Date filed: January 3, 2002 Abstract: There is provided a method and kit for rapid clinical diagnosis of HBV in which the amplimers are transcripts of a pre-core or envelop region gene of HBV. The amplicons are hybridized to a specific oligonucleotide probe, which allows the amplicons to be detected. Excerpt(s): The present invention relates to methods and devices for the diagnosis of infections. In particular, the present invention relates to methods and kits for detection of Hepatitis B Virus Viremia (HBV). Hepatitis B virus (HBV) is an enveloped hepatotropic DNA virus. Acute and chronic HBV infection causes significant liver diseases and it is estimated that more than 300 million individuals world wide are chronically infected with HBV. The HBV genome is unique in the world of viruses due to its compact nature, use of overlapping reading frames, and dependence on a reversetranscriptional step, though the virion contains primarily DNA. The human hepatitis B virus is a member of the Hepadna Viridae family which includes duck hepatitis virus (DHBV), Ground squirrel hepatitis virus (GSHV), snow goose hepatitis B virus (sgHBV), woodchuck hepatitis virus (WHV) and wooly monkey hepatitis virus. Furthermore, persistent viral infection leads to chronic active hepatitis, liver cirrhosis and the development of hepatocellular carcinoma. It has recently been appreciated that individuals who recover from HBV infection have a broad based cellular immune response to HBV structural proteins. Indeed, cytotoxic lymphocyte activity (CTL) may be critical for promoting viral clearance from the liver and CTL activity has been detected many years after resolution of acute infection. The presence of CTL activity may be due to persistence of low level HBV infection in the liver that can be identified only by molecular techniques such as PCR. Thus, the concept has arisen that even if individuals serologically recover from HBV infection, the virus, in most instances is never completely irradicated from the liver. Hepatitis B is of great medical importance because Hepatocellular carcinomas(HCC), one of the most common cancers afflicting humans, is primarily caused by chronic HBV infection. In the last few decades, the correlation between HBV and the development of HCC has been well established. However, the mechanism by which HBV transforms hepatocytes remains elusive. It is noticed that before HBV can transform a cell, the virus first infects it. However, the mechanism through which HBV enters hepatocyte has not been resolved despite further understanding of the viral protein involved. Much more research is needed before it is fully understood by the scientist and the spread of this infectious agent is controlled. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method and kit for detecting hepatitis B virus Inventor(s): Lee, Tzong Hae; (San Francisco, CA) Correspondence: Stevens, Davis, Miller & Mosher, L.L.P.; 1615 L Street, N.W., Suite 850; P.O. Box 34387; Washington; DC; 20036; US Patent Application Number: 20030215790 Date filed: May 20, 2002 Abstract: A method for detecting Hepatitis B virus (HBV) in a sample includes the steps of (a) adding to the sample a thermostable polymerase, appropriate nucleoside triphosphates, a nucleic-acid-binding fluorescent entity, and a pair of primers substantially complementary to a target nucleic acid having the sequence shown in SEQ ID NO:1 or the complement of the target nucleic acid; (b) thermally cycling the sample between at least a denaturation temperature and an elongation temperature; (c) illuminating the sample with a selected wavelength of light that is absorbed by the fluorescent entity during the thermally cycling step; (d) determining the amount of fluorescence generated by the fluorescent entity; and (e) detecting the presence of the target nucleic acid by analyzing the amount of luminescence determined after at least one amplification cycle. The invention further provides kits for detection of HBV in samples. Excerpt(s): This invention relates to a method for detecting or quantifying Hepatitis B virus (HBV) in a sample. The disease known as hepatitis B is caused by the infectious Hepatitis B virus (HBV). It has been estimated by the World Health Organization (WHO) that HBV have infected over two billion people worldwide. This makes HBV one of the most common human pathogens. Approximately 500 million are chronic carriers. Hepatocellular carcinomas (HCC), one of the most common cancers afflicting humans, is primarily caused by chronic HBV infection. Transmission of HBV is primarily through blood and/or sexual contact, though other methods of transmission have been suggested. Before HBV can transform a cell, the virus must first infect it. However, the mechanism through which HBV enters hepatocytes has not been resolved despite further understanding of the viral proteins involved. Vaccines are available against HBV, but they may not be 100% effective against all variants of HBV. Furthermore, there is no cure for individuals already infected. Much more research is needed before we fully understand and control the spread of HBV. Currently, a sensitive, specific and rapid assay to detect HBV DNA is not available. Traditional PCR methods have been utilized in humans to measure viral load for diagnosis of hepatitis B. However, traditional PCR methods do not allow accurate quantitation as the product is monitored beyond the exponential phase of PCR reaction and require laborious postPCR processing. Moreover, methods such as southern blot analysis are not sensitive or quantitative enough to reliably monitor decrease in viral reduction during antiviral therapy. Accordingly, there exists a need in the art for a rapid and sensitive method for detecting or quantifying HBV in a sample. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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METHOD OF DETECTING ANTIBODIES TO HCV Inventor(s): CHOO, QUI-LIM; (EL CERRITO, CA), HOUGHTON, MICHAEL; (DANVILLE, CA), KUO, GEORGE; (SAN FRANCISCO, CA) Correspondence: Chiron Corporation; Intellectual Property-r440; P.O. Box 8097; Emeryville; CA; 94662; US Patent Application Number: 20030162167 Date filed: July 25, 1996 Abstract: A family of cDNA sequences derived from hepatitis C virus (HCV) are provided. These sequences encode antigens which react immunologically with antibodies present in individuals with non-A non-B hepatitis (NANBH), but which are absent from individuals infected with hepatitis A virus, or hepatitis B virus, and also are absent in control individuals. The HCV cDNA sequences lack substantial homology to the sequences of hepatitis delta virus (HDV) and HBV. A comparison of the sequences of amino acids encoded in the HCV cDNA with the sequences of Flaviviruses indicates that HCV may be related to the Flaviviruses.The HCV cDNA sequences and the polypeptides encoded therein are useful as reagents for the detection and therapy of HCV. The reagents provided in the invention are also useful for the isolation of NANBH agent(s), for the propagation of these agents in tissue culture, and for the screening of antiviral agents for HCV. Excerpt(s): This application is a continuation-in-part of attorney docket 2300-0063.28 (U.S. Ser. No. 07/355,002) filed May 18, 1989; which is a continuation-in-part of attorney docket number 2300-0063.29 (U.S. Ser. No. 07/341,334)filed Apr. 20, 1989; which is a continuation-in-part of attorney docket number 2300-0063.59 (PCT/US88/04125) filed Nov. 18, 1988, converted to U.S. National phase on Apr. 21, 1989 and assigned attorney docket number 2300-0063.26 (U.S. Ser. No. 353,896) and a continuation-in-part of attorney docket number 2300-0063.25 (U.S. Ser. No. 07/325,338) filed Mar. 17, 1989 (now abandoned); which are continuations-in-part of attorney docket number 2300-0063.24 (U.S. Ser. No. 271,450) filed Nov. 14, 1988, now abandoned; which is a continuation-inpart of attorney docket number 2300-0063.23 (U.S. Ser. No. 263,584) filed Oct. 26, 1988, now abandoned; which is a continuation-in-part of attorney docket number 23000063.22 (formerly 2300-0237, U.S. Ser. No. 191,263) filed May 6, 1988, now abandoned; which is a continuation-in-part of attorney docket number 2300-0063.21 (formerly 23000228, U.S. Ser. No. 151,072) filed Feb. 26, 1988, now abandoned; which is a continuationin-part of attorney docket number 2300-0063.20 (formerly 2300-0219, U.S. Ser. No. 139,886)filed Dec. 30, 1987, now abandoned; which is a continuation-in-part of attorney docket number 2300-0063 (formerly 2300-0203, U.S. Ser. No. 122,714) ailed Nov. 18, 1987, now abandoned; the aforementioned applications are, in their entirety, incorporated herein by reference. The invention relates to materials and methodologies for managing the spread of non-A, non-B hepatitis virus (NANBV) infection. More specifically, it relates to diagnostic DNA fragments, diagnostic proteins, diagnostic antibodies and protective antigens and antibodies for an etiologic agent of NANB hepatitis, i.e., hepatitis C virus. Barr et al. (1986), Biotechniques 4:428. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of protein production using mitochondrial translation system Inventor(s): Paik, Kye-Hyung; (Ranch Santa Fe, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 92614; US Patent Application Number: 20030099669 Date filed: January 6, 2003 Abstract: A method of producing viral antigens in vitro by infecting animal organ tissue rich in mitochondria with a virus, including human hepatitis B virus (HBV), and culturing the infected tissue in vitro is disclosed. A method of producing proteins in vitro by transfecting mitochondria-rich animal tissue with a recombinant HBV-based vector and culturing the transfected tissue in a dynamic tissue culture system is disclosed. Excerpt(s): This-application is a continuation of copending application 09/124,638 filed on Jul. 29, 1998, which is a continuation of PCTUS97/00601 filed on Jan. 21, 1997, which claimed priority to 60/010,717 filed on Jan. 29, 1996. The present invention relates to protein expression of recombinant nucleic acid molecules, and specifically relates to producing proteins, including viral proteins, in animal tissue cultured in vitro by infecting the host tissue with a virus or transfecting the host tissue with a recombinant nucleic acid in a virus-based expression vector and utilizing translation in mitochondriarich tissue. Translation of proteins from transfected nucleic acids generally is accomplished using the universal translation systems present in prokaryotic or eucaryotic cells (Sambrook et al., Molecular Cloning, A Laboratory Manual, 2nd Ed., Vol. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., 1989). Mitochondria found in eucaryotic cells have transcription and translation systems for expression of the endogenous mitochondrial DNA (mtDNA) that use a non-universal genetic code. The mitochondrial translation system, however, has not been used to translate foreign nucleic acids. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of treating hepatitis delta virus infection Inventor(s): Casey, John L.; (Potomac, MD), Chu, Chung K.; (Athens, GA), Cote, Paul J.; (New Market, MD), Gerin, John L.; (Bethesda, MD), Korba, Brent E.; (Laurel, MD), Tennant, Bud C.; (Ithaca, NY) Correspondence: King & Spalding; 191 Peachtree Street; Atlanta; GA; 30303; US Patent Application Number: 20030158149 Date filed: November 22, 2002 Abstract: A method for the treatment for hepatitis delta infection in a host, that includes administering an effective amount of a nucleoside or a nucleoside analog that suppresses the expression of the hepatitis B surface or preS1 antigen in the host 100-fold or more relative to pretreatment values in vivo; or to not more than 1 microgram per milliliter in vivo. In a preferred embodiment, the nucleoside is L-FMAU, or a pharmaceutically acceptable salt or prodrug thereof. Excerpt(s): This application claims priority to U.S. Ser. No. 60/193,135, filed on Mar. 29, 2000. 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 compound, in particular a nucleoside or nucleoside analog, that substantially reduces the level of hepatitis B surface antigen. In one nonlimiting embodiment, the nucleoside analog is 2'-fluoro-5-methyl-.beta.-Larabinof- uranosyl-uridine (also referred to as "L-FMAU") 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 sub-viral satellite of hepatitis B virus (HBV) (Smedile, A., et al. (1994) Prog Liver Dis 12, 157-75). 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. (1994) Prog Liver Dis 12, 157-75; Rizzetto, M., et al. (1983) Ann Intern Med 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. & Rizzetto, M. (1992) Int J Clin Lab Res 22, 211-215; Wright, T. L. & Pereira, B. (1995) Liver Transplant Surgery 1, 30-42). Chronic disease affects 15 million persons worldwide, about 70,000 of whom are in the U.S. The Centers for Disease Control estimates 1,000 deaths annually in the U.S. due to HDV infection (Alter, M. J. & Hadler, S. C. (1993) Prog Clin Biol Res 382, 243-50; Alter, M. J. & Mast, E. E. (1994) Gastroenterol Clin North Am 23, 437-55). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods and reagents for the inhibition of hepatitis B virus replication Inventor(s): McSwiggen, James; (Boulder, CO), Morrissey, David; (Boulder, CO) Correspondence: Mcdonnell Boehnen Hulbert & Berghoff; 300 South Wacker Drive; Suite 3200; Chicago; IL; 60606; US Patent Application Number: 20030148985 Date filed: December 5, 2002 Abstract: The present invention relates to nucleic acid molecules that modulate Hepatitis B virus (HBV) gene expression and HBV replication, and methods thereof. Specifically, the present invention relates to nucleic acid decoy molecules and aptamers that bind to HBV reverse transcriptase and/or HBV reverse transcriptase primer sequences and methods for their use alone or in combination with other therapies. The present invention also relates to nucleic acid molecules that specifically bind the Enhancer I region of HBV DNA and methods for their use. Excerpt(s): The present invention concerns compounds, compositions, and methods for the study, diagnosis, and treatment of degenerative and disease states related to hepatitis B virus (HBV) infection, replication and gene expression. Specifically, the invention relates to nucleic acid molecules used to modulate expression of HBV. The following is a discussion of studies relating to hepatitis B virus (HBV). The discussion is not meant to be complete and 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. Chronic hepatitis B is caused by an enveloped virus, commonly known as the hepatitis B virus or HBV. HBV is transmitted via infected blood or other body fluids, especially saliva and semen, during delivery, sexual activity, or sharing of needles contaminated by infected blood. Individuals may be "carriers" and

Patents 269

transmit the infection to others without ever having experienced symptoms of the disease. Persons at highest risk are those with multiple sex partners, those with a history of sexually transmitted diseases, parenteral drug users, infants born to infected mothers, "close" contacts or sexual partners of infected persons, and healthcare personnel or other service employees who have contact with blood. Transmission is also possible via tattooing, ear or body piercing, and acupuncture; the virus is also stable on razors, toothbrushes, baby bottles, eating utensils, and some hospital equipment such as respirators, scopes and instruments. There is no evidence that HBsAg positive food handlers pose a health risk in an occupational setting, nor should they be excluded from work. Hepatitis B has never been documented as being a food-borne disease. The average incubation period is 60 to 90 days, with a range of 45 to 180; the number of days appears to be related to the amount of virus to which the person was exposed. However, determining the length of incubation is difficult, since onset of symptoms is insidious. Approximately 50% of patients develop symptoms of acute hepatitis that last from 1 to 4 weeks. Two percent or less of these individuals develop fulminant hepatitis resulting in liver failure and death. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods of suppressing hepatitis virus infection using immunomodulatory polynucleotide sequences Inventor(s): Eiden, Joseph J. JR.; (Danville, CA), Van Nest, Gary; (Martinez, CA) Correspondence: Karen R. Zachow; Morrison & Foerster Llp; Suite 500; 3811 Valley Centre Drive; San Diego; CA; 92130-2332; US Patent Application Number: 20030216340 Date filed: February 3, 2003 Abstract: Methods are provided for the treatment of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. A polynucleotide comprising an immunostimulatory sequence is administered to a individual who has been exposed to or infected by HBV and/or HCV. The polynucleotide is not administered with a HCV or HBV antigen. Administration of the polynucleotide results in amelioration of symptoms of HBV and/or HCV infection. Excerpt(s): This application claims the priority benefit of U.S. Provisional application 60/188,301, filed Mar. 10, 2000, which is hereby incorporated herein by reference in its entirety. This invention is in the field of immunomodulatory polynucleotides, more particularly their use in ameliorating or preventing hepatitis viral infection and/or symptoms of hepatitis virus infection. Hepatitis is a generic term for disease involving inflammation of the liver. A variety of agents can cause hepatitis, including viruses, drugs, toxins, and autoimmune disorders. Additionally, hepatitis can arise secondary to non liver-related disorders. Viral infection is the most common cause of hepatitis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Multivalent vaccine composition Inventor(s): Boutriau, Dominique; (Rixensart, BE), Capiau, Carine; (Rixensart, BE), Desmons, Pierre Michel; (Rixensart, BE), Lemoine, Dominique; (Rixensart, BE), Poolman, Jan; (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 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

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Mutated hepatitis b virus, its nucleic and protein constituents and uses thereof Inventor(s): Chemin, Isabelle; (Caluire, FR), Kay, Alan; (Lyon, FR), Komurian-Pradel, Florence; (Poleymieux au Mont D'Or, FR), Mandrand, Bernard; (Villeurbanne, FR), Trepo, Christian; (Bron, FR) Correspondence: Young & Thompson; 745 South 23rd Street 2nd Floor; Arlington; VA; 22202 Patent Application Number: 20030129202 Date filed: December 16, 2002

Patents 271

Abstract: The invention concerns an isolated mHBV having the following characteristics: (i) a genome with partly double-strand circular DNA, (ii) the genome including the PreS, S, C, P and X genes, (iii) the Pre-S genes coding for surface antigens, the S gene coding for a HBsAg envelope protein, the C gene coding for a HBeAg protein and aHBcAg protein, the P gene coding for a DNA reverse polymerase/transcriptase enzyme and the X gene coding for a HBxAg protein. The invention is characterised in that the gene S comprises a DNA nucleotide sequence referenced SEQ ID NO 1 and the Pre-S gene comprises a nucleotide sequence referenced SED ID NO 3. The invention also concerns DNA molecule, RNA molecule, modified surface proteins and their uses in particular for diagnostic, therapeutic and vaccine purposes. Excerpt(s): Five types of viral hepatitis--hepatitis A, B, C, D, E--are now quite well known. In each case the virus invades the liver and provokes an inflammatory state with destruction of the hepatic cells. Hepatitis B is caused by a virus, the human hepatitis B virus (HBV). The HBV virus was discovered by Blumberg et al.: A "new" antigen in leukemia sera, JAMA 191: 541, (1965). The virus is transmitted in the blood, by sexual contact or by perinatal transmission. In most cases infection by HBV does not lead to any symptoms and is responsible for asymptomatic acute hepatitis. Acute hepatitis is characterized by digestive disorders, abdominal pains, coloration of the urine and abnormal, discoloured faeces, asthenia and jaundice. Acute hepatitis can develop into a fulminant form with rapid liver necrosis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Non-viral vesicle vector for cardiac specific gene delivery Inventor(s): Chien, Kenneth; (La Jolla, CA), Hoshijima, Masahiko; (La Jolla, CA) Correspondence: Brown, Martin, Haller & Mcclain Llp; 1660 Union Street; San Diego; CA; 92101-2926; US Patent Application Number: 20030166593 Date filed: April 30, 2002 Abstract: The invention is a non-viral vesicle vector for the delivery of nucleic acid to various cardiac cell types. The vesicle vector contains the hepatitis B envelope protein wherein at least part of the liver targeting sequence is deleted and replaced with a specific cardiac cell targeting sequence. The targeting sequence may be derived from viruses that have the natural tropism desired (e.g. adenovirus type 5 knob protein for cardiomyocyte delivery) or mammalian sequences (e.g. endothelin-1 for vascular endothelial cell delivery). The vesicle vector contains an expression construct for the expression of therapeutic genes in cardiac tissues. Excerpt(s): This application claims the benefit of priority of U.S. provisional application Serial No. 60/287,423 filed Apr. 30, 2001 which is incorporated herein by reference in its entirety. A sequence listing is submitted herewith under 35 C.F.R.sctn.1.821 and is incorporated herein by reference. The utility of gene delivery vectors for gene therapy is limited by the nonselective nature in which the vectors, either non-viral or viral, interact with the cell surface, resulting in transduction of numerous cell types in addition to the target cells. Much effort has been devoted to understand the mechanisms of viral targeting to different cell types. The information derived from these studies is now being exploited to select viruses that have the desired natural tropism or to modify viral targeting signals to redirect viruses to the cell type of choice. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Novel hepatitis B virus Inventor(s): Zheng, Jian; (Raritan, NJ) Correspondence: Audley A. Ciamporcero JR.; Johnson & Johnson; One Johnson & Johnson Plaza; New Brunswick; NJ; 08933-7003; US Patent Application Number: 20030165816 Date filed: March 30, 2001 Abstract: We isolated and characterized a new surface mutant of the hepatitis B virus surface antigen (HBsAg). The mutant was isolated from a symptomatic patient with Down's syndrome who was found to be persistently positive for both for HBsAg and anti-HBs Antibody (Ab) with an equally long-lasting anti-HB core (c) IgM Ab Excerpt(s): Hepatitis B virus (HBV), a small double stranded DNA virus, can cause a wide spectrum of clinical presentations: asymptomatic carrier state, acute self-limited hepatitis, fulminant hepatitis, and chronic liver diseases including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. It has a circular genome of 3182 to 3221 base pairs (bp). Four major subtypes have been identified and can be differentiated by antibodies that recognize the different epitopes on the HBV surface. The HBsAg particles carry the common determinant, "a", as well as d or y and w or r subtype determinants, and are classified into the four major subtypes, i.e., adw, adr, ayw and ayr. Rare sera contain HBsAg particles with all four-subtype determinants (adywr). The antigenic determinants for the main HBV subtypes: adw, adr, ayw and ayr lie in the surface or "S" polypeptide. Two amino acid residues in particular, encoded by the S gene at codon positions 122 and 160, have been postulated to determine the different antigenic subtypes. While, the preC regions have frequently been reported to have mutations rendering HBe Ag negative. The virus has a high rate of mutation relative to other DNA viruses due to its mode of replication by reverse transcriptase of its pregenomic RNA. The importance of a novel mutant can be reflected in vaccine escape and HBsAg detection failure, implicating a public health problem. We have identified and characterized a new surface mutant of HBV. The mutant was isolated from a symptomatic patient with Down's syndrome who was found to be persistently positive for both for HBsAg and anti-HBs Antibody (Ab) with an equally long-lasting anti-HB core (c) IgM Ab. With a panel of six monoclonal antibodies (mAb(s)) to HBsAg, we evaluated the mutation influence on the major epitope of the "a" determinant antigenicity. A sample was taken from a 43-year-old white male patient with Down's syndrome who presented with jaundice to the American University of Beirut Medical Center in March 1999. The patient had no history of immunization to HBV, no transmissible risk factor including blood transfusion, IV drugs, homosexuality, family HBV infection or hemodialysis. During investigation, he was found to have elevated liver function tests (LFT): ALT 450 IU/L (range 10-35 IU/L), AST 250 IU/L (range 10-40 IU/L), gamma-GT 383 IU/L (range 10-50 IU/L), Bilirubin was 3.8/2.6 mg/dL (total/direct) (range, total: 0.1-1.2 IU/L and direct: 0.0-0.2 IU/L). More significantly, we noted incongruity in the HBV blood tests. The HBV markers test results using enzyme immunoassay (EIA) methodology were as follows: HBs Ag positive (>2/0.051), anti-HBs Ab positive (0.417/0.206), anti-HBc IgM Ab low positive (0.371/0.208), anti-HBc IgG Ab strong positive (>2/0.412), HBe Ag negative and anti-HBe Ab positive (0.197/0.830, a competitive assay). Both the anti-hepatitis A Ab and the anti-hepatitis C Ab were negative. Due to the discrepancy in the HBV markers, molecular methods were used to confirm the HBV antigen. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 273

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Novel steroid/thyroid hormone receptor-related gene, which is inappropriately expressed in human heptocellular carcinoma, and which is a retinoic acid receptor Inventor(s): Blaudin de The, Hugues; (Paris, FR), DeJean, Anne; (Paris, FR), Marchio, Agnes; (Paris, FR), Tiollais, Pierre; (Paris, FR) Correspondence: Finnegan, Henderson, Farabow, Garrett & Dunner; Llp; 1300 I Street, NW; Washington; DC; 20005; US Patent Application Number: 20030153740 Date filed: December 2, 2002 Abstract: A previously isolated hepatitis B virus (HBV) integration in a 147 bp cellular DNA fragment linked to hepatocellular carcinoma (HCC) was used as a probe to clone the corresponding complementary DNA from a human liver cDNA library. Nucleotide sequence analysis revealed that the overall structure of the cellular gene, which has been named hap, is similar to that of the DNA-binding hormone receptors. Six out of seven hepatoma and hepatoma-derived cell-lines express a 2.5 kb hap mRNA species which is undetectable in normal adult and fetal livers, but present in all non-hepatic tissues analyzed. Low stringency hybridization experiments revealed the existence of hap related genes in the human genome. The cloned DNA sequence is useful in the preparation of pure hap protein and as a probe in the detection and isolation of complementary DNA and RNA sequences. The hap protein is a retinoic acid (RA) receptor identified as RAR-.beta. Excerpt(s): This application is a continuation-in-part of application Ser. No. 209,009, filed Jun. 20, 1988, (Attorney Docket Past-059-B), which is a continuation-in-part of application Ser. No. 134,130, filed Dec. 17, 1987, (Attorney Docket PAST-059-A), which is a continuation-in-part of application Ser. No. 133,687, filed Dec. 16, 1987, (Attorney Docket PAST-059). The entire disclosure of each of these copending applications is relied upon and incorporated herein by reference. This invention relates to nucleotide sequences, polypeptides encoded by the nucleotide sequences, and to their use in diagnostic and pharmaceutical applications. Primary hepatocellular carcinoma (HCC) represents the most common cancer, especially in young men, in many parts of the world (as in China and in much of Asia and Africa) (reviewed in Tiollais et al., 1985). Its etiology was investigated mostly by epidemiological studies, which revealed that, beyond some minor potential agents such as aflatoxin and sex steroids, hormones, Hepatitis B virus (HBV) chronic infection could account for a large fraction of liver cancers (Beasley and Hwang, 1984). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Nucleic acid-based compounds and methods of use thereof Inventor(s): Iyer, Radhakrishnan P.; (Shrewsbury, MA), Jin, Yi; (Carlsbad, CA), Roland, Arlene; (Montreal, CA), Zhou, Wenqiang; (Bedford Hills, NY) Correspondence: Michael S. Greenfield; Mcdonnell Boehnen Hulbert & Berghoff; 32nd Floor; 300 S. Wacker Drive; Chicago; IL; 60606; US Patent Application Number: 20030109471 Date filed: May 15, 2002

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Abstract: The invention provides compounds capable of treating against hepatitis infections, particularly hepatitis B viral infections. Compounds of the invention are nucleic acid-based and preferably comprise 2, 3, 4, 5 or 6 nucleoside units. Excerpt(s): This application claims the benefit of U.S. provisional application no. 601291,471, filed May 16, 2001. The present invention relates to nucleic-acid based compounds. Compounds of the invention are useful for a variety of therapeutic applications, including treatment against hepatitis B virus. Hepatitis B virus (HBV) is a compact, enveloped DNA virus belonging to the Hepadnavirus family. The virus is a major cause of chronic liver disease and hepatocellular carcinoma worldwide (Hoofnagle (1990) N. Eng. J Med., 323:337-339). HBV is associated with acute and chronic hepatitis and hepatocellular carcinoma and may be a cofactor in the development of acquired immune deficiency syndrome (Dinestag et al. in Harrison's Principles of Internal Medicine, 13th Ed. (Isselbacher et al. eds.) McGrw-Hill, NY, N.Y. (1993) pp. 1458-1483). At least 400 million people are currently infected with HBV. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Oligonucleotides and methods for detecting hepatitis B viral nucleic acids Inventor(s): Hamdan, Hasnah; (Riverside, CA), Lewinski, Michael; (San Clemente, CA), Pasupuleti, Vijaya; (Irvine, CA) Correspondence: Foley & Lardner; P.O. Box 80278; San Diego; CA; 92138-0278; US Patent Application Number: 20030124651 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. 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://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 275

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Oral DNA composition for hepatitis B virus chronic infection Inventor(s): Ng, Mun-Hon; (Bagulo Villa, HK), Yuen, Kwok-Yung; (Baguio Villa, HK), Zheng, Bo-Jian; (Pokfulam Garden, HK) Correspondence: Sughrue Mion, Pllc; Suite 800; 2100 Pennsylvania AVE., N.W.; Washington; DC; 20037-3213; US Patent Application Number: 20030162741 Date filed: February 28, 2003 Abstract: The present invention provides an oral DNA composition for improving an impaired immunity associated with chronic infection of hepatitis B virus (HBV) and for suppressing transgene expression for a protrated period of time comprising an attenuated strain of bacterial cells which preferentially target phagocytic cells of the intestinal mucosa, and which serve as a vehicle for a plasmid vector carrying one or more genes or complementary DNA coding for at least a portion of a hepatitis B viral protein or peptide. Given orally, the DNA composition causes a transient and selflimiting infection of the intestinal tract through autolysis of the bacterial cells and release of the plasmid after gaining entry into infected host cells. A promotor contained within the plasmid allows for expression of the HBV gene(s) in the eurokaryotic environment, the viral products of which help to booster a cell-mediated immunity to clear the infection and reverse a state of immune tolerance characteristic of HBV chronic infection. Excerpt(s): The present invention relates to an oral DNA composition (ODV) for ameliorating an impaired immunity in individuals who are chronically infected with hepatitis B virus (HBV). The oral DNA composition serves to booster immunity against HBV, improve the immune deficits associated with the disease and clear the infection. The World Health Organization (WHO) estimated that there are 350 million people world wide, who are chronically infected with the hepatitis B virus (HBV) [1]. These individuals have a high risk of developing liver cirrhosis and liver cancer. In addition, being the only significant reservoir for HBV, these individuals also pose as a significant public health hazard. None of the treatments presently available for chronic HBV infection can clear the virus from these individuals and are only moderately effective in reducing virus replication [2-5]. The idea that HBV infection may be cleared through immune intervention is based on findings that acute self-limited HBV infection evokes vigorous, polyclonal T helper cell (Th) and cytotoxic T lymphocyte (CTL) responses against viral capsid and envelope antigens, leading to the clearance of the virus from the body. On the other hand, chronic HBV infection is associated with weak Th responses of a restricted spectrum of antiviral specificity and usually undetectable virus-specific CTL activity [6]. These findings suggested that an intact cell mediated immunity is the chief determinant of virus clearance and provided the rational basis for immune intervention of chronic HBV infection with the view to booster cell mediated immunity (CMI) against the virus in order to clear the infection [7]. The contention was further supported by findings from bone marrow transplantation showing that adoptive transfer of bone marrow cells from donors, who had acquired intact immunity against the virus from natural infection, can improve the immune deficits of the chronically infected recipients and thereby clear the infection [8]. 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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Process for the preparation of 2'-fluoro-5-methyl-beta-L-arabino-furanosyl- uridine Inventor(s): Choi, Yongseok; (Athens, GA), Chu, Chung K.; (Athens, GA), Du, Jinfa; (Irvine, CA) Correspondence: King & Spalding; 191 Peachtree Street, N.E.; Atlanta; GA; 30303-1763; US Patent Application Number: 20030139593 Date filed: January 24, 2003 Abstract: The present invention relates to a novel and improved process for preparing 2'-fluoro-5-methyl-.beta.-L-arabinofuranosyluridine represented by formula (1) which shows anti-viral activity, especially potent anti-viral activity against hepatitis B-virus and Epstein-Barr virus: 1 Excerpt(s): This application claims priority to U.S. provisional application serial No. 60/053,488, filed on Jul. 23, 1997, and also to U.S. application Ser. No. 09/121,294 filed on Jul. 23, 1998. R" represents hydrogen, acyl, alkyl, monophosphate, diphosphate or

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triphosphate. Nucleoside compounds of formula (2) exhibit anti-viral activity against HBV and EBV. Among these nucleoside compounds, L-FMAU shows particularly potent anti-viral activity against HBV and EBV with very low cytotoxicity and is, therefore, preferred as an anti-viral agent. Nucleoside compounds of formula (2), including L-FMAU, are useful in the prevention and treatment of HBV infections and related conditions, such as anti-HBV antibody positive and HBV-positive conditions, chronic liver inflammation caused by HBV, cirrhosis, acute hepatitis, fulminant hepatitis, chronic persistent hepatitis, and fatigue. In addition, they can also be used for the treatment of EBV-associated disorders. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

RECOMBINANT HEPATITIS B SURFACE ANTIGEN Inventor(s): ABRAHAM, DICKY G.; (NORTH WALES, PA), GERVAIS, DAVID P.; (HARLEYSVILLE, PA), GIMENEZ, JUAN; (LANSDALE, PA), SITRIN, ROBERT; (LAFEYETTE HILLS, PA), ZHAO, QINJIAN; (AMBLER, PA) Correspondence: Merck And CO Inc; P O Box 2000; Rahway; NJ; 070650907 Patent Application Number: 20030113342 Date filed: December 22, 1999 Abstract: The present invention provides an improved rHBsAg that exhibits a higher antigenicity and immunogenicity than that previously known in the art. A method of making the improved rHBsAg is also provided. The improved HBsAg is used to provide vaccines with lower amounts of active ingredient, vaccines with higher immunogenicity and combination vaccines which produce and protective immunization against infection by hepatitis B virus and other infectious agents. Excerpt(s): The invention relates to recombinant hepatitis B surface antigen (rHBsAg), prophylactic and therapeutic vaccines containing HBsAg and methods of preparing HBsAg and vaccines. Over the past two decades, recombinant hepatitis B surface antigen expressed as the S form in yeast cells (rHBsAg) has superseded plasma-derived antigen as a vaccine against hepatitis B infection (Valenzuela et al., 1982; McAleer et al., 1984). In the plasma of infected animals, the surface antigen protein assembles into 22 nm particles comprising lipids and HBsAg. However, the assembly of the yeast produced rHBsAg into these virus-like particles has remained poorly understood. It has been established that reduction of the disulfide bonds in HBsAg abolishes or greatly decreases both its antigenic and immunogenic properties (Reviewed by Tiollais et al., 1981, Guesser et al., 1988; Mishiro et al., 1980; Chen et al, 1996; Hauser, et al 1988). For example, eleven out of the total 14 cysteine residues are conserved among three different type of S protein of Hepatitis B viruses, namely, HBsAg of human, woodchuck, and ground squirrel viruses. However, these three types of S protein share only medium to low overall sequence homology among (Stirk et al, 1992). Interestingly, all 8 cysteine residues in the"a" determinant loop (62 aa between predicted Helix B and Helix C) are fully conserved. This indicates that disulfide bonds may have an important role in maintaining the structural integrity of the antigenic determinants or epitopes (Stirk et al., 1992). 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): Beigelman, Leonid; (Longmont, CO), McSwiggen, James A.; (Boulder, CO), Morrissey, David; (Boulder, 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 •

Use of recombinant hepatitis B core particles to develop vaccines against infectious pathogens and malignancies Inventor(s): Birkett, Ashley J.; (Escondido, CA), Zavala, Fidel; (New York, NY) 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

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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 •

Use of substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds for treating hepatitis virus infections Inventor(s): Bryant, Martin L.; (Carlisle, MA), Mueller, Richard A.; (Glencoe, IL), Partis, Richard A.; (Evanston, IL) Correspondence: Senniger Powers Leavitt And Roedel; One Metropolitan Square; 16th Floor; ST Louis; MO; 63102; US Patent Application Number: 20030220299 Date filed: January 14, 2003 Abstract: N-Substituted-1,5-dideoxy-1,5-imino-D-glucitol 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 virus infections, particularly hepatitis B and hepatitis C, in mammals, especially humans. The methods comprise administering substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds alone or in combination with nucleoside antiviral agents, nucleotide antiviral agents, mixtures thereof, or, alternatively, in combination with immunomodulating/-immunostimulating agents. Administration of substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds in combination with both a nucleoside and/or nucleotide type antiviral agent and an immunomodulating/immunostimulating agent or agents is also contemplated. 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 glycosylation patterns, glycoforms, changes or rates of change will have 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 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). Other hepatitis viruses significant as agents of human disease include Hepatitis A, Hepatitis B, Hepatitis C, Hepatitis Delta, Hepatitis E, Hepatitis F, and Hepatitis G (Coates, J. A. V., et.al., Exp. Opin. Ther. Patents (1995) 5(8):747-756). Hepatitis C infection is also on the increase and effective treatments are needed. In addition, there are animal hepatitis viruses that are species-specific, but

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serves as excellent models for the human disease. These include, for example, those infecting ducks, woodchucks, cattle and mice. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Vaccines against diseases caused by enteropathogenic organisms using antigens encapsulated within biodegradable-biocompatible microspheres Inventor(s): Boedeker, Edgar; (Crownsville, MD), Cassels, Frederick; (Ellicott City, MD), McQueen, Charles; (Olney, MD), Reid, Robert H.; (Kensington, MD), Setterstrom, Jean A.; (Alpharetta, GA), VanHamont, John; (Fort Meade, MD) Correspondence: Nash & Titus, Llc; 3415 Brookeville Road; Brookeville; MD; 20833; US Patent Application Number: 20030161889 Date filed: August 20, 2002 Abstract: This invention relates to an immunostimulating composition comprising encapsulating microspheres, which may contain a pharmaceutically-acceptab- le adjuvant, wherein said microspheres having a diameter between 1 nanometer (nm) to 10 microns (um) are comprised of (a) a biodegradable-biocompatible poly(DL-lactide-coglycolide) as the bulk matrix, wherein the relative ratio between the amount of lactide and glycolide components are within the range of 40:60 to 0:100 and wherein said poly (DL-lactide-co-glycolide) is present in an uncapped form and an end-capped form wherin a ratio of uncapped to end-capped forms is 99/1 to 1/99, and (b) an immunogenic substance comprising Colony Factor Antigen (CFA/II), hepatitis B surface antigen (HbsAg), or a physiologically similar antigen that serves to elicit the producton of antibodies in animal subjects. The preparation of its composition and its use as a vaccine is also disclosed. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/009,986 filed Jan. 21, 1998, which is a continuation-in-part of U.S. patent application Ser. No. 08/789,734 filed Jan. 27, 1997 which in turn is a continuation in part of U.S. patent application Ser. No. 08/362,944 filed Dec. 9, 1994 which in turn is a continuation of U.S. patent Ser. No. 08/034,949 filed Mar. 22, 1993 which in turn is a continuation-inpart of U.S. patent application Ser. No. 07/867,301 filed Apr. 10, 1992 which in turn is a continuation in part of U.S. patent application Ser. No. 07/805,721 which in turn is a continuation-in-part of U.S. patent application Ser. No. 07/690,485 filed Apr. 27, 1991, which in turn is a continuation-in-part of U.S. patent application Ser. No. 07/521,945 filed May 11, 1990, which in turn is a continuation-in-part of U.S. patent application Ser. No. 07/493,597 filed Mar. 15, 1990, which in turn is a continuation-in-part of U.S. patent application Ser. No. 06/590,308, filed Mar. 16, 1984. This invention relates to parenteral and oral-intestinal vaccines against diseases caused by enteropathogenic organisms using antigens encapsulated within biodegradable-biocompatible microspheres (matrix). Most infectious agents have their first contact with the host at a mucosal surface; therefore, mucosal protective immune mechanisms are of primary importance in preventing these agents from colonizing or penetrating the mucosal surface. Numerous studies have demonstrated that a protective mucosal immune response can best be initiated by introduction of the antigen at the mucosal surface, and parenteral immunization is not an effective method to induce mucosal immunity. Antigen taken up by the gut-associated lymphoid tissue (GALT), primarily by the Peyer's patches in mice, stimulates T helper cell (TH) to assist in IgA B cell responses or stimulates T suppressor cells (Ts) to mediate the unresponsiveness of oral tolerance. Particulate antigen appears to shift the response towards the (TH) whereas soluble antigens favor a response by the

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(Ts). Although studies have demonstrated that oral immunization does induce an intestinal mucosal immune response, large doses of antigen are usually required to achieve sufficient local concentrations in the Peyer's patches. Unprotected protein antigens may be degraded or may complex with secretory IgA in the intestinal luman. 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 B, 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 B” (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 B. You can also use this procedure to view pending patent applications concerning hepatitis B. 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 B Overview This chapter provides bibliographic book references relating to hepatitis B. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on hepatitis B 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 B” (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 B: •

Be in Charge: A Guide to Living with Chronic Hepatitis B and C Source: Kenilworth, NJ: Schering Corporation. 1998. 100 p. 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

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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. •

Hepatitis B Immunization in a STD Clinic: Lessons Learned in San Diego County: A Practical Guide Contact: Us Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Infectious Diseases, Division of AIDS STD and TB Laboratory Research, 1600 Clifton Rd A12, Atlanta, GA, 30333, (404) 639-4581, http://www.cdc.gov/ncidod/dastlr/default.htm. Summary: This monograph provides guidelines for the provision of hepatitis B immunizations in sexually transmitted disease (STD) clinics. The monograph discusses the facts about hepatitis B and its vaccine and outlines the components of an effective program to provide hepatitis B immunizations in STD clinics. It explains how a trial program fared in San Diego and evaluates the benefits of having hepatitis B vaccines in STD clinics.

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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 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

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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. •

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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First Year Hepatitis B: An Essential Guide for the Newly Diagnosed Source: New York, NY: Marlowe and Company. 2002. 264 p. 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.

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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 Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “hepatitis B” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “hepatitis B” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “hepatitis B” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

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 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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A. Hepatitis B and HIV/AIDS - Guidance to the Fire Service; B. The Construction (Design and Management) Regulations 1995 and Approved Code of Practice "Managing Construction for Health and Safety" (Fire Services (Firemaster) Letter: 8/1995) (1995); ISBN: 0748047514; http://www.amazon.com/exec/obidos/ASIN/0748047514/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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B3 LEAFLET (50)HEPATITIS B CAMPAIGN by DS; ISBN: 1903346541; http://www.amazon.com/exec/obidos/ASIN/1903346541/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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Compliance assistance guideline for the February 27, 1990 OSHA Instruction CPL 22.44B Enforcement Procedures for Occupational Exposure to Hepatitis B Virus and Human Immunodeficiency Virus (SuDoc L 35.8:C 73/3) by U.S. Dept of Labor; ISBN: B000106F2Q; http://www.amazon.com/exec/obidos/ASIN/B000106F2Q/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

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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

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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 Thierry Poynard; ISBN: 1841840777; http://www.amazon.com/exec/obidos/ASIN/1841840777/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 CAMP A3 POSTER by DS; ISBN: 1903346517; http://www.amazon.com/exec/obidos/ASIN/1903346517/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

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Hepatitis B vaccine : helping or hurting public health? : hearing before the Subcommittee on Criminal Justice, Drug Policy, and Human Resources of the Committee on Government Reform, House of Representatives, One Hundred Sixth Congress, first session, May 18, 1999 (SuDoc Y 4.G 74/7:H 41/2); ISBN: 0160606039; http://www.amazon.com/exec/obidos/ASIN/0160606039/icongroupinterna

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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 (Editor); ISBN: 0444803254; http://www.amazon.com/exec/obidos/ASIN/0444803254/icongroupinterna

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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, hepatitis C, and HIV in Irish prisoners, part II : prevalence and risk in committal prisoners 1999 : report prepared for the Minister for Justice, Equality, and Law Reform; ISBN: 0707664373; http://www.amazon.com/exec/obidos/ASIN/0707664373/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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Immunisation Against Hepatitis B; ISBN: 0727901990; http://www.amazon.com/exec/obidos/ASIN/0727901990/icongroupinterna

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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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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

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Lo que necesito saber sobre la Hepatitis B (SuDoc HE 20.3302:H 41/4/SPAN.) by U.S. Dept of Health and Human Services; ISBN: B0001113CC; http://www.amazon.com/exec/obidos/ASIN/B0001113CC/icongroupinterna

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Manual for hepatitis B antigen testing by Mary Ashcavai; ISBN: 0721614272; http://www.amazon.com/exec/obidos/ASIN/0721614272/icongroupinterna

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Molecular Biology of the Hepatitis B Virus by Alan McLachlan (Editor); ISBN: 0849355168; http://www.amazon.com/exec/obidos/ASIN/0849355168/icongroupinterna

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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

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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

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Oversight hearings on OSHA's proposed standard to protect health care workers against blood-borne pathogens including the AIDS and hepatitis B viruses : hearings before the Subcommittee on Health and Safety of the Committee on Education and

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Labor, House of Representatives, One Hundred First Congress, first session (SuDoc Y 4.Ed 8/1:101-83); ISBN: B000103AYW; http://www.amazon.com/exec/obidos/ASIN/B000103AYW/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

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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

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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

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Progress in Hepatitis B Immunization by P. Coursaget, M.J. Tong; ISBN: 0861962494; http://www.amazon.com/exec/obidos/ASIN/0861962494/icongroupinterna

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Protect yourself from the storm hepatitis B, herpes, gonorrhea, genital warts, chlamydia, syphilis, AIDS (SuDoc D 2.9:D 36/2/NO.111) by U.S. Dept of Defense; ISBN: B00010UV0I; http://www.amazon.com/exec/obidos/ASIN/B00010UV0I/icongroupinterna

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Safety in Health Service Laboratories: Hepatitis B; ISBN: 0118837818; http://www.amazon.com/exec/obidos/ASIN/0118837818/icongroupinterna

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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

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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

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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

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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

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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

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Treatment Algorithm 2002: Hepatitis B and C [DOWNLOAD: PDF] by Datamonitor (Author); ISBN: B00008R3Q1; http://www.amazon.com/exec/obidos/ASIN/B00008R3Q1/icongroupinterna

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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

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What I need to know about Hepatitis B (SuDoc HE 20.3302:H 41/4/2000) by U.S. Dept of Health and Human Services; ISBN: B000113546; http://www.amazon.com/exec/obidos/ASIN/B000113546/icongroupinterna

290 Hepatitis B

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When Your Doctor is Wrong, Hepatitis B Vaccine and Autism by Judy Converse; ISBN: 1401029736; http://www.amazon.com/exec/obidos/ASIN/1401029736/icongroupinterna

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Worker exposure to AIDS & hepatitis B (SuDoc L 35.2:W 89/4/990) by U.S. Dept of Labor; ISBN: B000103GXW; http://www.amazon.com/exec/obidos/ASIN/B000103GXW/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 B” (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 •

Carriers of hepatitis B antigen and transfusion hepatitis in Finland. Author: Helske, Timo.; Year: 1966; Copenhagen, Munksgaard, 1974

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Epidemiology of hepatitis B surface antigen, antibody and acute hepatitis in Finnish institutions for the mentally retarded Author: Tevaluoto-Aarnio, Marja.; Year: 1975; Helsinki: [s.n.], 1975; ISBN: 9519905332

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Hepatitis B Author: Alter, Harvey J.; Year: 1978; New York: Thieme-Stratton, 1981

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Hepatitis B antigen: isolation and application in lymphocyte stimulation tests Author: Houwen, Berend.; Year: 1976; Netherlands: [s.n., 1975]

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Hepatitis B surface antigen (HBs-Ag) and related studies in India--bibliography Author: Shanmugam, J.; Year: 1980; Trivandrum, India: Sree Chitra Tirunal Institute for Medical Sciences and Technology, [1983]

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Hepatitis B surface antigen subtypes and e antigen: methodological and epidemiological studies Author: Ukkonen, Pentti.; Year: 1976; Helsinki: [s.n.], 1978; ISBN: 9519918442

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Hepatitis B virus antigens in tissues Author: Ray, M. B.; Year: 1974; Lancaster, Eng.: MTP Press, c1979; ISBN: 085200284X http://www.amazon.com/exec/obidos/ASIN/085200284X/icongroupinterna

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Hepatitis B, a prospective, longitudinal study Author: Niermeijer, Peter.; Year: 1999; Zaltbommel [Netherlands]: Koninklijke Drukkerij van de Garde, 1979

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Hepatitis B, significance of antigenic specificities Author: Magnius, Lars.; Year: 1974; Stockholm: [s.n.], 1974

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Immunopathology of hepatitis B virus infection Author: Thomas, H. C. (Howard C.); Year: 1978; [New York]: Springer International, 1981

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 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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Primary hepatocellular carcinoma and hepatitis B virus Author: Blumberg, Baruch S.,; Year: 1979; Chicago: Year Book Medical Publishers, c1982; ISBN: 081519918X http://www.amazon.com/exec/obidos/ASIN/081519918X/icongroupinterna

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Programmed learning course on hepatitis B surface antigen (HBsAg) and antibody to hepatitis B surface antigen (anti-HBs). Author: Abbott Laboratories. Diagnostics Division.; Year: 1981; North Chicago, IL: Abbott Laboratories, Diagnostics Division, c1976

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Studies on transmission and prevention of hepatitis B Author: Reesink, H. W.; Year: 1975; Amsterdam: Rodopi, 1980

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Third report of the Advisory Group on Testing for the Presence of Hepatitis B Surface Antigen and its Antibody. Author: Great Britain. Advisory Group on Testing for the Presence of Hepatitis B Surface Antigen and its Antibody.; Year: 1971; [London?]: The Group, 1981

Chapters on Hepatitis B In order to find chapters that specifically relate to hepatitis B, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and hepatitis B 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 B” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on hepatitis B: •

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 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.

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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.

292 Hepatitis B

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. •

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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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 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.

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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.

294 Hepatitis B

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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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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 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).

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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

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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. •

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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CHAPTER 8. MULTIMEDIA ON HEPATITIS B Overview In this chapter, we show you how to keep current on multimedia sources of information on hepatitis B. 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 B is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “hepatitis B” 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 B” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on hepatitis B: •

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

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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 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 B: A Discovery Channel Program Source: Cedar Grove, NJ: Hepatitis Foundation International. 199x. (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: Free with membership; contact directly for current price for nonmembers. Summary: This video presents a health update on hepatitis B. After an introduction that reviews the anatomy and physiology of the liver, various health care providers (including two epidemiologists from the CDC) describe how all types of hepatitis affect the liver. The program continues with a discussion of hepatitis A, B, and C, and how each is transmitted and treated. The program then focuses on hepatitis B, covering details of transmission, symptoms, risk factors and behaviors, complications of hepatitis B virus (HBV) infection, including an increased risk of liver cancer, epidemiology, fulminant hepatitis, and the progression of HBV to chronic, carrier state. Additional sections describe the use of liver transplantation for people with hepatitis B and the psychosocial impact of chronic HBV infection. The program concludes with an interview with Thelma King Thiel, the founder and CEO of the Hepatitis Foundation International, an educational and support organization.

•

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 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

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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. •

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. 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.

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

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“Sound Recordings.” Type “hepatitis B” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on hepatitis B: •

OSHA/CDC Guidelines to Protect Health Care Workers Against AIDS and Hepatitis B Source: 3rd National Forum on AIDS and Hepatitis B. Washington, DC, November 2122, 1988. 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 Occupational Health and Safety Administration (OSHA) and Centers for Disease Control and Prevention (CDC) guidelines that are established to protect health care workers against Acquired immunodeficiency syndrome (AIDS) and Hepatitis B. The history of the development of the guidelines and regulations for the proper procedures surrounding blood and body fluids are outlined. The need to extend these regulations to ancillary staff in the hospital and to home health care workers who may not have access to institutional training is emphasized. The problems that may be encountered are discussed. The need to educate the classes of employees that encounter the greatest exposure to blood and body fluids is emphasized.

Bibliography: Multimedia on Hepatitis B 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 B (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 B: •

AIDS and hepatitis B precautions [videorecording] Source: by Elizabeth A. Criss; produced by Medfilms, Inc; Year: 1986; Format: Videorecording; Tucson, AZ: Medfilms, c1986

•

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

•

Developing an immunization program for hepatitis B virus [videorecording] Source: [presented by] the American Hospital Association; produced through the facilities of the Media Center; Year: 1982; Format: Videorecording; [Chicago, Ill.]: The Association, c1982

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Hepatitis B & I.V. drug abuse [slide] Source: P.D. Welsby; Year: 1984; Format: Slide; Chelmsford, Essex, UK: Graves Medical Audiovisual Library, [1984]

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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

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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

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Universal precautions [videorecording]: AIDS & hepatitis B prevention for healthcare workers Source: produced by Medcom/Trainex Inc., in association with the Presbyterian Hospital in the City of New York at Columbia-Presbyterian Medical Center; Year: 1992; Format: Videorecording; Garden Grove, CA: Medcom, c1992

•

Universal precautions [videorecording]: AIDS and hepatitis B prevention for health care workers Source: produced by Medcom/Trainex Inc., in association with the Presbyterian Hospital in the City of New York at Columbia-Presbyterian Medical Center; Year: 1989; Format: Videorecording; Garden Grove, CA: Medcom/Trainex, c1989

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CHAPTER 9. PERIODICALS AND NEWS ON HEPATITIS B Overview In this chapter, we suggest a number of news sources and present various periodicals that cover hepatitis B.

News Services and Press Releases One of the simplest ways of tracking press releases on hepatitis B 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 B” (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 B. 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 B” (or synonyms). The following was recently listed in this archive for hepatitis B: •

Roche scores again with Pegasys data in hepatitis B Source: Reuters Industry Breifing Date: October 28, 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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Gilead returns rights to hepatitis B drug Source: Reuters Industry Breifing Date: June 24, 2003

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Gene therapy may hold key to treating hepatitis B Source: Reuters Health eLine Date: May 12, 2003

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Roche says Pegasys tests well against hepatitis B Source: Reuters Industry Breifing Date: April 09, 2003

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Bio-Rad gets FDA nod for new Hepatitis B assays Source: Reuters Industry Breifing Date: April 07, 2003

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Gilead earns EU okay for hepatitis B drug Source: Reuters Industry Breifing Date: March 11, 2003

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Tenofovir potent anti-hepatitis B treatment for HIV-coinfected patients Source: Reuters Industry Breifing Date: December 16, 2002

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IL-18 active against hepatitis B in mice Source: Reuters Industry Breifing Date: November 22, 2002

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CPMP backs Gilead's Hepsera to treat chronic hepatitis B Source: Reuters Industry Breifing Date: November 21, 2002

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Report criticizes French hepatitis B vaccination campaign Source: Reuters Industry Breifing Date: November 14, 2002

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Hepatitis B vaccination rates among US adolescents have increased Source: Reuters Industry Breifing Date: November 08, 2002

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Chinese herbals studied as hepatitis B treatment Source: Reuters Health eLine Date: October 17, 2002

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FDA approves Gilead hepatitis B drug Source: Reuters Industry Breifing Date: September 23, 2002

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Hepatitis B vaccine safe and effective when combined with DTPa Source: Reuters Industry Breifing Date: September 16, 2002

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Virax, New York Blood Center to work on hepatitis B therapy Source: Reuters Industry Breifing Date: August 19, 2002

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Gilead earns FDA panel's unanimous endorsement for hepatitis B drug Source: Reuters Industry Breifing Date: August 06, 2002

Periodicals and News

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Diagnostic Products gets FDA clearance for additional hepatitis B assays Source: Reuters Industry Breifing Date: July 31, 2002

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Diagnostic Products shares rise on FDA approval for hepatitis B assays Source: Reuters Industry Breifing Date: July 23, 2002

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Hepatitis B proteins may indicate cancer risk Source: Reuters Health eLine Date: July 17, 2002

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Cases of hepatitis B linked to infected surgeon Source: Reuters Health eLine Date: July 12, 2002

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Hepatitis B vaccine safe and effective in rheumatoid arthritis patients Source: Reuters Industry Breifing Date: July 11, 2002

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Korean firm licenses Crucell technology for hepatitis B vaccine Source: Reuters Industry Breifing Date: July 03, 2002

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Oxxon starts phase II trials of therapeutic hepatitis B vaccine Source: Reuters Industry Breifing Date: July 01, 2002

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Lamivudine superior to famciclovir against chronic hepatitis B Source: Reuters Industry Breifing Date: June 24, 2002

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China launches hepatitis B vaccine project Source: Reuters Health eLine Date: June 03, 2002

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US Institute of Medicine finds hepatitis B vaccine safe Source: Reuters Industry Breifing Date: May 31, 2002

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Lamivudine moderately effective in children with chronic hepatitis B Source: Reuters Industry Breifing Date: May 30, 2002

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Hepatitis B, nerve diseases not linked: US report Source: Reuters Health eLine Date: May 30, 2002

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Scientists grow carrots containing hepatitis B vaccine Source: Reuters Industry Breifing Date: May 10, 2002

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Carrots modified to contain hepatitis B vaccine Source: Reuters Health eLine Date: May 10, 2002

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Gilead licenses hepatitis B drug to Glaxo in Asia, other markets Source: Reuters Industry Breifing Date: April 29, 2002

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Roche's Pegasys effective in hepatitis B study Source: Reuters Industry Breifing Date: April 19, 2002

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Nabi to begin shipment of hepatitis B vaccine from newly finished plant Source: Reuters Industry Breifing Date: March 27, 2002

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Gilead files for approval of hepatitis B drug in Europe Source: Reuters Industry Breifing Date: March 26, 2002

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Gilead Sciences files for US approval of hepatitis B therapy Source: Reuters Industry Breifing Date: March 22, 2002

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Hepatitis B on decline but many still at risk Source: Reuters Health eLine Date: March 18, 2002

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SciClone's Zadaxin combined with interferon successful in phase II hepatitis B study Source: Reuters Industry Breifing Date: March 13, 2002

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Gilead starts early-access program for hepatitis B drug Source: Reuters Industry Breifing Date: March 12, 2002

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SciClone drug performs well in phase III hepatitis B study Source: Reuters Industry Breifing Date: March 05, 2002

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Achillion moves hepatitis B drug into phase II studies Source: Reuters Industry Breifing Date: February 28, 2002 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. 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.

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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 B” (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 B” (or synonyms). If you know the name of a company that is relevant to hepatitis B, 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 B” (or synonyms).

Newsletters on Hepatitis B Find newsletters on hepatitis B 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 B.” 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 B” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: •

Drug-Induced Rheumatic Syndromes Source: Bulletin on the Rheumatic Diseases. 51(4): 1-4. 2002. Contact: Available from Arthritis Foundation. 1330 West Peachtree Street, Atlanta, GA 30309. (800) 268-6942 or (404) 872-7100. Fax (404) 872-9559. Website: www.arthritis.org. Summary: This newsletter provides health professionals with information on drug induced rheumatic syndromes. Categories of drug induced rheumatic diseases are drug induced lupus (DIL), drug induced myopathy/myositis (DIM), and drug induced vasculitis (DIV). Although more than 100 drugs have been implicated in DIL, the drugs most studied have been procainamide and hydralazine. However, these drugs are not commonly prescribed today, and the illness they produce is often different from those

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recently implicated in DIL. Minocycline is a treatment used for acne and rheumatoid arthritis that has caused immune and autoimmune phenomena. Several of the new recombinant biologics have been implicated in DIL, including interferon alpha, interferon gamma, and antitumor necrosis factor therapies. It is not possible to predict who will develop DIL, so patients with idiopathic lupus should be allowed to take potentially lupus inducing drugs but with careful monitoring. Drugs associated with the development of DIV include hematopoietic growth factors such as G-CSF and GM-CSF; vaccines for hepatitis B, influenza, and others; and leukotriene inhibitors. The article concludes that the number of drugs that are capable of inducing rheumatic syndromes is growing. Elements in the assessment of a possible association between exposure and the development of a rheumatic disorder include temporal association, lack of likely alternative explanations, rechallenge, and biological plausibility. 1 table and 23 references.

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 B” (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 B: •

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.

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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 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.

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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. 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

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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.

Academic Periodicals covering Hepatitis B Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to hepatitis B. In addition to these sources, you can search for articles covering hepatitis B 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 B. 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 DI® Advice for the Patient® 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 B. 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 B: 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

Factor IX •

Systemic - U.S. Brands: BeneFix; Mononine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202674.html

Famciclovir •

Systemic - U.S. Brands: Famvir http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202723.html

Hepatitis B Vaccine Recombinant •

Systemic - U.S. Brands: Engerix-B http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202281.html

Lamivudine •

Systemic - U.S. Brands: Epivir; Epivir-HBV http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202292.html

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Systemic - U.S. Brands: Epivir; Epivir-HBV http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202791.html

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Systemic - U.S. Brands: Epivir; Epivir-HBV http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203689.html

Neomycin •

Oral - U.S. Brands: Mycifradin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202396.html

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Topical - U.S. Brands: Myciguent http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202397.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.

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Mosby’s Drug Consult™ Mosby’s Drug Consult™ 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 B 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 B” (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 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 B: •

FIAU http://www.rarediseases.org/nord/search/nodd_full?code=491

314 Hepatitis B

•

Monoclonal antibody to hepatitis B virus (human) http://www.rarediseases.org/nord/search/nodd_full?code=151

•

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

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 Institute12: •

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

•

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/

12

These publications are typically written by one or more of the various NIH Institutes.

318 Hepatitis B

•

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

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

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

•

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.13 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:14 •

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

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

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/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

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

•

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

13

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). 14 See http://www.nlm.nih.gov/databases/databases.html.

320 Hepatitis B

•

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 B” 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 B” (or synonyms) into the “For these words:” box. The following is a sample result: •

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.

•

Health Care Workers and AIDS and Hepatitis B Contact: United Food and Commercial Workers International Union, 1775 "K" St NW, Washington, DC, 20006-1598. 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

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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. •

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. 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.

322 Hepatitis B

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. •

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.

•

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.

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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. •

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 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.

324 Hepatitis B

•

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. 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.

•

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

Physician Resources

reporting and retrospective recommendations. •

patient

notification,

and

dissemination

of

325

the

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 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 Gateway15 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.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “hepatitis B” (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 45844 496 514 1227 13 48094

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quick15

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

16

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). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18

The HSTAT URL is http://hstat.nlm.nih.gov/.

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reference 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.19 Simply search by “hepatitis B” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists20 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.21 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.22 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/.

•

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 B In the following section, we will discuss databases and references which relate to the Genome Project and hepatitis B.

19 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. 20 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 21 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. 22 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.

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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).23 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. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “hepatitis B” (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 B: •

Hepatitis B Vaccine, Response to Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?142395 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

•

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

•

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier

23 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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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

•

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

•

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

•

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

Physician Resources

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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

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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 B” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 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 Database25 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. 24

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 25 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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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 B” (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 B 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 B. 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 B. 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 B”:

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•

Guides on hepatitis B Hepatitis http://www.nlm.nih.gov/medlineplus/hepatitis.html Hepatitis B http://www.nlm.nih.gov/medlineplus/hepatitisb.html

•

Other guides Alpha-1 Antitrypsin Deficiency http://www.nlm.nih.gov/medlineplus/alpha1antitrypsindeficiency.html Hepatitis A http://www.nlm.nih.gov/medlineplus/hepatitisa.html Hepatitis C http://www.nlm.nih.gov/medlineplus/hepatitisc.html Hodgkin's Disease http://www.nlm.nih.gov/medlineplus/hodgkinsdisease.html Liver Diseases http://www.nlm.nih.gov/medlineplus/liverdiseases.html Lung Cancer http://www.nlm.nih.gov/medlineplus/lungcancer.html Lymphoma http://www.nlm.nih.gov/medlineplus/lymphoma.html Respiratory Diseases http://www.nlm.nih.gov/medlineplus/respiratorydiseases.html

Within the health topic page dedicated to hepatitis B, the following was listed: •

General/Overviews Hepatitis B and C Source: American Academy of Family Physicians http://familydoctor.org/handouts/032.html Hepatitis B Virus Source: Dept. of Veterans Affairs http://www.va.gov/hepatitisc/pted/hepb.htm Viral Hepatitis B: Frequently Asked Questions Source: National Center for Infectious Diseases http://www.cdc.gov/ncidod/diseases/hepatitis/b/faqb.htm

•

Diagnosis/Symptoms Hepatitis B Virus: The Test Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html

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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 •

Treatment FDA Approves New Treatment For Chronic Hepatitis B Source: Food and Drug Administration http://www.fda.gov/bbs/topics/ANSWERS/2002/ANS01163.html Hepatitis B Treatment Source: Hepatitis B Foundation http://www.hepb.org/02-0070.hepb

•

Specific Conditions/Aspects Getting a Letter from the Blood Bank: What Does It Mean? http://www.hepb.org/pdf/blood_bank.pdf Hepatitis, Viral, Type B: Health Information for International Travel, 2003-2004 Source: Centers for Disease Control and Prevention http://www.cdc.gov/travel/diseases/hbv.htm Vaccines and Hair Loss Source: Centers for Disease Control and Prevention http://www.cdc.gov/nip/vacsafe/concerns/Hairloss.htm What Is Your Risk of Getting AIDS or Hepatitis B on the Job? Source: American Liver Foundation http://www.liverfoundation.org/cgibin/dbs/articles.cgi?db=articles&uid=default&ID=1038&view_records=1

•

Children Advice for Parents Source: Hepatitis B Foundation http://www.hepb.org/02-0131.hepb Hepatitis B Source: American Academy of Pediatrics http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZ9VB53R7C& sub_cat=107 Hepatitis B Vaccine Is Imperative for Families Adopting from Abroad Source: Immunization Action Coalition http://www.immunize.org/catg.d/4153adop.htm

•

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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•

Journals/Newsletter Hepatitis B Foundation Newsletter Source: Hepatitis B Foundation http://www.hepb.org/02-0107.hepb

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Law and Policy Hepatitis B Prevention Mandates Source: Immunization Action Coalition http://www.immunize.org/laws/hepb.htm

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Men Hepatitis B: 100 Times Easier to Catch than HIV! Get Vaccinated Against This Disease! Source: Immunization Action Coalition http://www.immunize.org/catg.d/p4115.htm Hepatitis Information You Need to Know: Men Who Have Sex with Men Source: American Liver Foundation http://www.liverfoundation.org/cgibin/dbs/articles.cgi?db=articles&uid=default&ID=1034&view_records=1

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Organizations Hepatitis B Foundation http://www.hepb.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/

•

Prevention/Screening Add Hepatitis B Vaccination to Your Back to School List Source: National Center for Infectious Diseases http://www.cdc.gov/ncidod/diseases/hepatitis/spotlights/back_to_school.htm New Combination Vaccine Approved for Protection Against Two Hepatitis Viruses Source: Food and Drug Administration http://www.fda.gov/bbs/topics/ANSWERS/2001/ANS01084.html

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Other Prevention Measures Source: Hepatitis B Foundation http://www.hepb.org/02-0176.hepb Right Way to Use a Condom Source: American Social Health Association http://www.ashastd.org/stdfaqs/condom_a.html Vaccination for Hepatitis A & B Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/vaccinationshepab/index.htm Vaccines to Prevent Hepatitis A and Hepatitis B Source: National Center for HIV, STD, and TB Prevention http://www.cdc.gov/idu/hepatitis/vaccines.htm •

Statistics FASTATS: Viral Hepatitis Source: National Center for Health Statistics http://www.cdc.gov/nchs/fastats/hepatits.htm

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Teenagers Hepatitis B (HBV) Source: Nemours Foundation http://kidshealth.org/teen/sexual_health/stds/std_hepatitis.html How Hepatitis Can Hurt You Source: Nemours Foundation http://kidshealth.org/teen/infections/stds/hepatitis.html

•

Women Hepatitis B: Breaking the Cycle of Infection from Mother to Newborn Source: American Liver Foundation http://www.liverfoundation.org/cgibin/dbs/articles.cgi?db=articles&uid=default&ID=1036&view_records=1 Pregnant Women and Hepatitis B Source: Hepatitis B Foundation http://www.hepb.org/02-0068.hepb

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.

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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 B. 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: •

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.

•

Someone You Know Has Hepatitis B 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 brochure reviews the basics of hepatitis B and its prevention. The brochure discusses who is most at risk for contracting the virus, HBV infection in children and infants, the role of vaccination against HBV, and the work of the Hepatitis B Foundation (WWW.hepb.org). The brochure concludes with a tear-off form with which readers can contribute to the Hepatitis B Foundation and request additional information; a brief description of the goals and activities of the Foundation is also provided. 3 figures.

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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.].

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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 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). •

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 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).

•

Universal Prenatal Screening for Hepatitis B Source: Hepatitis B Coalition News. 3(1): 4-6. February-March-April 1993.

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Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Summary: In this article, the author addresses the issues of perinatal prevention of hepatitis B as well as universal hepatitis B vaccination. Topics include the incidence and prevalence of hepatitis B virus (HBV) infection in the United States; the prevention of neonatal HBV infection; the identification of risk groups; the rationale for universal screening, both medical and financial; and the need for universal screening, even in light of current recommendations for universal infant vaccination. The author also presents a case report on an infant with fulminant hepatitis B. 9 references. •

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, 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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Preventing Transmission of HIV and Hepatitis B in Day Care Source: Oklahoma HIV/STD Update. 93(2): 3-4. Spring 1993. Contact: Available from Oklahoma State Department of Health. 1000 North East 10th Street, Oklahoma City, OK 73117-1299. (405) 271-4636. PRICE: Single copy free. Summary: This article reviews how to prevent transmission of HIV and hepatitis B in day care settings. Designed to inform day care workers about the risk of transmission, the article focuses on how to protect both day care workers and children from exposure. The article reviews how HIV and hepatitis B are transmitted, the risks of transmission in the day care setting (very low for both diseases), and the recommendations of the Oklahoma State Department of Health. The article emphasizes that, despite the fact that the risk of transmission of HIV or hepatitis B in day care settings is very low, precautions must be taken to ensure that situations that could potentially result in transmission are avoided. The recommendations include staff training, hand washing, universal precautions, housekeeping considerations, disposal of blood contaminated materials, and what to do in case of a potentially infectious event.

•

Information About Hepatitis B Vaccine Source: Trenton, NJ: New Jersey Department of Health. 199x. 1 p. Contact: Available from Refugee Service Center, Center for Applied Linguistics. Attention: Health Education Materials. 1118 22nd Street, NW, Washington, DC 20037. (202) 429-9292. Fax (202) 659-5641. PRICE: Free. Item numbers: C2.8 (Cambodian), V2.17 (Vietnamese). Also available from New Jersey Department of Health, Refugee Health Program, Communicable Diseases, Cn 360, Trenton, NJ 08625. (609) 588-7500. Summary: This brief fact sheet provides information about hepatitis B vaccine. The brochure covers a definition of hepatitis B, symptoms, potential complications, the hepatitis B vaccine and indications for its use, and possible side effects from vaccination. The fact sheet includes a form for the patient to fill out indicating that he or she has read the fact sheet and gives consent for receiving the vaccination. The fact sheet is available in English, Vietnamese, and Cambodian.

•

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.

•

HIV/AIDS, Hepatitis B and Sport Contact: Victoria Health Department, Health & Community Services, AIDS/STD Unit, GPO Box 4057, Melbourne, (011) 616-7777. Summary: This brochure assures readers that there is little danger of contracting HIV or Hepatitis B during athletic competition. It explains ways in which HIV and Hepatitis are

340 Hepatitis B

and are not transmitted, and outlines universal precautions and infection-control procedures. •

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.

•

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.

•

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.

•

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 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.

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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 and bisexual reader population. The brochure reiterates the importance of vaccinations and includes the contact information for the Hepatitis B Coalition.

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What Is Your Risk of Getting AIDS or Hepatitis B on the Job Contact: American Liver Foundation, 75 Maiden Ln Ste 603, New York, NY, 10038-4826, (973) 256-2550, http://www.liverfoundation.org. Summary: This brochure instructs health care workers on the basic facts about Hepatitis B and Acquired immunodeficiency syndrome (AIDS). It compares statistics on new cases per year of Hepatitis B and AIDS in the field. It also examines the number of health-care workers infected, health workers' deaths, and chances of infection from a single contaminated needle stick. It also includes case histories that show the risk of being infected in health-care settings. It discusses Hepatitis B in the workplace, occupations who are at increased risk of exposure, and its transmission and prevention in the health-care setting. It emphasizes that there's no cure for Hepatitis B. Readers are urged to become vaccinated.

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If You, Your Parents, or Your Children Were Born in Any of These Places, Give this Brochure to Your Doctor and Ask to Find Out Your Hepatitis B Status Source: St. Paul, MN: Hepatitis B Coalition. 1995. 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 is designed to familiarize readers from specific countries with the hepatitis B virus (HBV) and the need for hepatitis testing and vaccination. Written in

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a question and answer format, the brochure covers topics including a description of hepatitis B; a definition of hepatitis B status, including susceptible, immune, or carrier; transmission; how the vaccine works; and how to obtain the vaccination. Countries and regions listed are Afghanistan, Africa, Albania, Bangladesh, Bosnia and Herzegovina, Bulgaria, Burma, Cambodia, China, Eastern Europe, Haiti, Hawaii, India, Indonesia, Iran, Iraq, Korea, Laos, Malaysia, the Middle East, Pakistan, the Pacific Islands, Philippines, Romania, former Soviet Union, South America's Amazon basin, Sri Lanka, Syria, Taiwan, Thailand, and Vietnam. The brochure includes a letter for readers to give to their physicians regarding testing and vaccination. The brochure is available in English, Hmong, Cambodian, Laotian, Vietnamese, Russian, Chinese, or Korean. •

Worker Exposure to AIDS and Hepatitis B Contact: US Department of Labor, Occupational Safety and Health Administration, 200 Constitution Ave NW, Rm N3101, Washington, DC, 20210, (202) 219-4667. Summary: This brochure is directed toward workers associated with tasks that may bring them in contact with individuals infected with Human immunodeficiency virus (HIV), Acquired immunodeficiency syndrome (AIDS), or Hepatitis B. This includes, but is not limited to, health-care workers, morticians, housekeepers, and laundry workers. An explanation of AIDS and AIDS-related complex (ARC) is included, as well as a separate discussion about Hepatitis B. A list of recommended practices for protection against occupational exposure to these diseases is set forth. The brochure also includes an Occupational Safety and Health Administration (OSHA) regional offices directory, and the phone numbers for the National AIDS Hotline.

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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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The AIDS Answer Book: Facts on AIDS, Hepatitis B and Infection Control Techniques Contact: Jems Communications, PO Box 2789, Carlsbad, CA, 92018, (619) 431-9797.

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Summary: This brochure provides emergency-care information on the prevention of infection with Acquired immunodeficiency syndrome (AIDS) and Hepatitis B. The causes, symptoms, and transmission of these two diseases and degree of risk to emergency personnel are discussed. The availability of a vaccine for Hepatitis B is noted. Infection-control procedures, such as sterilization of equipment and clothing, the use of protective clothing, disinfection of equipment and contaminated surfaces, and disposal of infectious wastes are discussed. A summary of universal precautions for health-care providers is included. •

Help Stop 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 brochure provides general and prevention information for the hepatitis B virus (HBV). The brochure describes HBV, its symptoms, and methods of transmission. It explains the long-term effects of HBV if left untreated and the risks it poses to infants. The brochure discusses how injection drugs users can clean their needle works and how the readers can practice safer sex with condoms as means of HBV prevention. It also recommends the HBV vaccine for individuals and their children as a means of protection against HBV.

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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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Hepatitis B: The Sexually Transmitted Disease With No Cure Contact: American Social Health Association, PO Box 13827, Research Triangle Park, NC, 27709, (919) 361-8400. Summary: This brochure warns that both Hepatitis B and Human immunodeficiency virus (HIV) can be spread through unsafe sexual practices. It notes that Hepatitis B is 100 times more infectious than HIV, but that there is a vaccine. The symptoms, treatment, and long-term risks of Hepatitis B are discussed. Safer sexual practices are also listed.

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Hepatitis B 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, provides information on the hepatitis B virus (HBV). It discusses the HBV vaccine, risk factors for contracting HBV including living with an infected individual and having sex with an HBV carrier, prevention, transmission, diagnosis, symptoms, and medical considerations. It recommends that all pregnant women be tested for HBV and that babies are vaccinated at birth.

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What Every Podiatric Physician Should Know About. AIDS (and Hepatitis B) Contact: American Podiatric Medical Association, 9312 Old Georgetown Rd, Bethesda, MD, 20814, (301) 571-9200, http://www.apma.org. Summary: This brochure, targeted toward podiatrists, briefly describes the transmission methods, symptoms, and treatment programs for Hepatitis B and Human immunodeficiency virus (HIV), which causes Acquired immunodeficiency syndrome (AIDS). One of the indications of AIDS is Kaposis sarcoma, which often develops first on the feet. Infection-control measures for podiatrists are outlined.

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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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How To Use The West Side Community Clinic Hepatitis B Flow Sheet Source: St. Paul, MN: Hepatitis B Coalition. June 4, 1991. 3 p. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. PRICE: $1 per copy. Summary: This document provides a hepatitis B flow sheet with instructions for the health care provider to use in gaining an overall picture of a particular household. The form includes space to record names of household members, identifying information including arrival date, results of laboratory investigations, and comments. The form is designed to help health care providers keep updated and accurate records.

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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

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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 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). •

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 bloodborne illnesses. The fact sheet outlines the policy of the center, and the responsibilities of the medical center director and medical center employees.

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Hepatitis B Information for Soviet Refugees Source: St. Paul, MN: Hepatitis B Coalition. 1995. 4 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. Summary: This fact sheet is designed to provide information about hepatitis B to Soviet refugees. Written in a question and answer format, the fact sheet covers topics including a definition of hepatitis B; transmission; symptoms; prevention with vaccination; who should get hepatitis B shots; and how to obtain vaccination and hepatitis B testing. The fact sheet also provides information for hepatitis B carriers, covering medical care for

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carriers; preventing transmission to others; and guidelines for recommended behaviors. The publication is available in English and Russian, and in a slightly different form in Cambodian, Hmong, Laotian, and Vietnamese. •

Management of Chronic Hepatitis B in Adults Source: St. Paul, MN: Hepatitis B Coalition. 1996. 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 lists suggestions for the management of chronic hepatitis B in adults. Topics include tests indicated for people with acute hepatitis B, the Hepatitis Carrier Registry, monitoring for hepatocellular carcinoma (HCC, a type of liver cancer), indications for alpha-interferon therapy, ongoing health monitoring (annual examinations), indications for liver biopsy, and recommendations for post-surgical follow up of persons with HCC. The author stresses that all persons who are HBsAg positive for more than six months must be placed on the Hepatitis Carrier Registry and monitored semi-annually for AFP to attempt to detect HCC at a potentially resectable stage. Hepatitis B carriers are encouraged to make a yearly appointment in the hepatitis clinic for a physical exam and for education regarding health promotion and prevention options. The reverse side of the fact sheet presents a patient care algorithm based on the results of liver function tests (AFP).

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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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Prevention Protocols for HBsAg Screening on Labor and Delivery Units and Nursery Clinical Guidelines to Prevent Perinatal Hepatitis B Infection Source: St. Paul, MN: Hepatitis B Coalition. 1996. 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 notes prevention protocols for HBsAg screening (for hepatitis B) on labor and delivery units in hospitals. In addition, the fact sheet provides nursery clinical guidelines to prevent perinatal hepatitis B infection. The labor and delivery guidelines focus primarily on recordkeeping and on obtaining consent, prior to the baby's delivery, to administer hepatitis B vaccine and hepatitis B immune globulin to the newborn of a mother who is HBsAg positive. The nursery clinical guidelines address topics including obtaining consent, administering vaccines to newborns, timing of vaccination, breastfeeding, reporting to the health department, and indications for

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follow up care. The guidelines are designed to be used by hospitals in the development of their own written perinatal hepatitis B prevention policies. •

Important Facts on Hepatitis B for Asian Pacific Americans Source: St. Paul, MN: Hepatitis B Coalition. 1993. 1 p. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104-6328. (612) 647-9009. Fax (612) 647-9131. PRICE: $1. Summary: This fact sheet provides a list of important facts on hepatitis B for Asian Pacific Americans. Topics include the complications of hepatitis B infection; statistics applicable to this specific patient population; transmission of hepatitis B; the role of newborn immunization; who should receive hepatitis B immunization; how the vaccine is administered; and the importance of education among Asian Americans about hepatitis B status and risk factors.

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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/. 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.

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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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Confused About the Hepatitis B Panel? Source: St. Paul, MN: Hepatitis B Coalition. 1997. 1 p.

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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 information for adoptive parents about hepatitis B and interpretation of the hepatitis B panel (diagnostic tests). The fact sheet includes a letter from an adoptive mother whose son was misdiagnosed as being a hepatitis B carrier. The woman encourages readers to educate themselves (and their health care providers, when necessary) about the hepatitis B panel and what the results mean. The fact sheet also provides some information on laboratory evaluation beyond the basic hepatitis B panel (which consists of HBsAg, anti-HBc, and anti-Hbs). The fact sheet lists the telephone number for five organizations that can provide readers with additional information. The fact sheet is illustrated with line drawings of a variety of adults and children. 1 table. •

Interferon Treatment for Hepatitis B and C Source: Cedar Grove, NJ: American Liver Foundation. 1993. 2 p. Contact: Available from American Liver Foundation. 1425 Pompton Avenue, Cedar Grove, NJ 07009. (800) 223-0179 or (201) 256-2550. PRICE: Single copy free. Summary: This fact sheet reviews the use of interferon to treat hepatitis B and C. Written in a question-and-answer format, the fact sheet includes a description of interferon and provides information about indications and contraindications for interferon treatment, for hepatitis B or hepatitis C; dosage and administration considerations; side effects; what can be expected from interferon treatment; the long term prognosis of hepatitis C without interferon treatment; and new drugs under study.

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Hepatitis B Information For Asian-Pacific Islander Americans Source: St. Paul, MN: Hepatitis B Coalition. 1995. 3 p. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. PRICE: $1.00 per copy. Summary: This fact sheet, designed for Asian-Pacific Americans, discusses hepatitis B. Topics include a definition of hepatitis B and why it is dangerous, transmission, symptoms, statistics of hepatitis occurrence in Asian-Americans, prevention, the hepatitis B vaccine, the problems of being a hepatitis B carrier, and how to receive hepatitis B shots in Minnesota. Contact information for the Hepatitis B Coalition is also included. This fact sheet is available in English, Vietnamese, Laotian, Cambodian, Tagalog, or Hmong.

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What the Physician Can Do to Help the Child Who is a Hepatitis B Carrier Source: St. Paul, MN: Hepatitis B Coalition. 1994. 1 p. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. PRICE: $1.00. Summary: This fact sheet, designed for physicians, reviews the recommended management of children who are hepatitis B carriers. Recommended actions include a yearly physical; hepatitis B testing every 3 years; liver enzymes, liver function tests, and a complete blood count; referral to a pediatric gastroenterologist; alpha-fetoprotein and ultrasound tests in patients with cirrhosis; testing and vaccination of household members; and hepatitis B education. Contact information for the author, a pediatric hepatitis B specialist at the University of Minnesota, is included.

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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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Facts About Adult 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 information about adult hepatitis B. Specifically it identifies 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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Questions Frequently Asked 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 the general public, discusses the hepatitis B virus (HBV) and hepatitis B. The fact sheet identifies groups at risk for this infection/disease and describes HBV transmission, common symptoms of HBV, testing and diagnosis, and the meaning of a positive test result. Information is provided on how people who are not in a high-risk group can contract the virus and the curability rates for hepatitis B in adults. For HBV carriers, individuals who are chronically infected with the virus, the fact sheet explains what it means to be a carrier and what these individuals can do to take care of themselves, especially if their liver disease has progressed. The fact sheet provides general information on the long-term effects of hepatitis B, its effects on

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pregnancy, how to prevent it, HBV vaccination issues, and the differences between HBV and the hepatitis A virus (HAV) and the hepatitis C virus (HCV). The fact sheet provides contact information for services from which individuals can learn more about HBV and describes the mission of the Hepatitis B Coalition. •

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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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 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.

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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 B: What You Need to 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 discusses the facts about the sexually transmitted disease (STD), hepatitis B. The pamphlet explains hepatitis B, how it is transmitted, how it

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affects the body, what individuals can do to help prevent its transmission, the symptoms, and what individuals should do if they contract this STD. •

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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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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Keep Safe 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 provides general information about hepatitis B. This viral infection of the liver is mainly spread from person to person through blood, semen, and

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vaginal fluids. It can be spread by having sex, sharing needles, or sharing personal items with an infected person. The pamphlet lists the signs of hepatitis B, discusses testing for the virus, and identifies people who should receive the hepatitis B vaccine. In addition, the pamphlet identifies ways people can protect themselves from the virus, including abstaining from sex, practicing safer sex, stopping injection drug use, avoiding sharing or reusing needles if continuing injection drug use, and avoiding sharing personal items. •

Chronic Hepatitis B and Chronic Hepatitis C Source: American Family Physician. 54(5): 1603-1605. October 1996. Summary: This patient education fact sheet describes chronic hepatitis B and chronic hepatitis C, similar kinds of liver infection that are caused by viruses. Written in a question and answer format, the fact sheet describes how a person can contract hepatitis B or hepatitis C, the symptoms of each disease in both the acute and chronic phases, the difference between acute hepatitis and chronic hepatitis, diagnostic tests used to confirm chronic hepatitis, treatment options (notably interferon alpha-2b), the side effects of interferon alpha-2b, and the prevention of hepatitis B or hepatitis C. The best way to prevent hepatitis B or hepatitis C is to avoid practices that increase the risk of getting infected. The risk of getting infected is increased by sharing needles and having sex with multiple partners. A vaccine is available for hepatitis B. This vaccine is recommended for people at high risk of contracting hepatitis B, including health care workers, all children, drug users, people who get tattoos or body piercing, prostitutes, and homosexuals with multiple sex partners. No vaccine is available for hepatitis C.

•

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. 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:

Patient Resources

•

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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

•

All Kids Need Hepatitis B Shots Source: Immunization Action Coalition http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7271

•

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

•

Do You Have Chronic Hepatitis B? Source: Immunization Action Coalition http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3382

•

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

•

FAQ - About Hepatitis B Source: Immunization Action Coalition http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3386

•

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

354 Hepatitis B

•

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

•

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

•

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

•

Hepatitis B in Asian Americans Source: Asian Liver Center at Stanford University http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6602

•

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

•

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

•

Hepatitis B Shots Are Recommended for All New Babies Source: Immunization Action Coalition http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7289

Patient Resources

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Hepatitis B Vaccine Source: Immunization Action Coalition http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7361

•

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

•

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

•

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

•

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

•

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

356 Hepatitis B

•

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

•

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 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 B. 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. PEDBASE Similar to NORD, PEDBASE covers relatively rare disorders, limited mainly to pediatric conditions. PEDBASE was designed by Dr. Alan Gandy. To access the database, which is more oriented to researchers than patients, you can view the current list of health topics covered at the following Web site: http://www.icondata.com/health/pedbase/pedlynx.htm. 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

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMD®Health: http://my.webmd.com/health_topics

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Associations and Hepatitis B The following is a list of associations that provide information on and resources relating to hepatitis B: •

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 English, Chinese, Korean, and Vietnamese; brochures; and comprehensive informational packets. Interactive email and a telephone HelpLine are also available. Relevant area(s) of interest: Hepatitis B

•

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 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. Relevant area(s) of interest: Hepatitis B

358 Hepatitis B

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to hepatitis B. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with hepatitis B. 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 B. 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 B” (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 your search to “Organizations” and “hepatitis B”. 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 B” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

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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 B” (or a synonym) into the search box, and click “Submit Query.”

361

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.26

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

26

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

362 Hepatitis B

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)27: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

27

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

•

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

•

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/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

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/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

364 Hepatitis B

•

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

•

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

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

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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•

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

•

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/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

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

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

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/

366 Hepatitis B

•

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/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

367

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 B: •

Basic Guidelines for Hepatitis B Chronic persistent hepatitis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000219.htm Cirrhosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000255.htm Hepatitis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001154.htm Hepatitis B Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000279.htm Hepatocellular carcinoma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000280.htm

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Signs & Symptoms for Hepatitis B Abdominal pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003120.htm Arthralgia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003261.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Hepatomegaly Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003275.htm Jaundice Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003243.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 Pruritus Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003217.htm Splenomegaly Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003276.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm

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Diagnostics and Tests for Hepatitis B Albumin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003480.htm Alkaline phosphatase Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003470.htm ALT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003473.htm AST Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003472.htm Bilirubin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003479.htm Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm

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CBC Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003642.htm ESR Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003638.htm Hb Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003645.htm HBsAg Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003558.htm Hepatitis B surface antigen Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003558.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 Prothrombin time Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003652.htm Serology Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003511.htm Sonogram Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003336.htm •

Surgery and Procedures for Hepatitis B Liver transplant Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003006.htm

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Background Topics for Hepatitis B Acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002215.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Condoms Web site: http://www.nlm.nih.gov/medlineplus/ency/article/004001.htm Hepatic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002378.htm Hepatitis B vaccine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002022.htm

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Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Liver disease - support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002182.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

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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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HEPATITIS B DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 2-Aminopurine: A purine that is an isomer of adenine (6-aminopurine). [NIH] 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] 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] Acculturation: Process of cultural change in which one group or members of a group assimilates various cultural patterns from another. [NIH] Acetaldehyde: A colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors. It is also an intermediate in the metabolism of alcohol. It has a general narcotic action and also causes irritation of mucous membranes. Large doses may cause death from respiratory paralysis. [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] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] 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] Actin: Essential component of the cell skeleton. [NIH] Acute Disease: Disease having a short and relatively severe course. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]

Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature

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blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous 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] Acyclovir: Functional analog of the nucleoside guanosine. It acts as an antimetabolite, especially in viruses. It is used as an antiviral agent, especially in herpes infections. [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] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [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] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [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] Adolescent Medicine: A branch of medicine pertaining to the diagnosis and treatment of diseases occurring during the period beginning with puberty until the cessation of somatic growth. [NIH] Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (immunotherapy, adoptive). [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [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] 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

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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] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [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] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is 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] 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] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [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]

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Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allogeneic: Taken from different individuals of the same species. [NIH] Allograft: An organ or tissue transplant between two humans. [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] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] 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 Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [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]

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Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] 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] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] 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] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anergy: Absence of immune response to particular substances. [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] 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] Anthropology: The science devoted to the comparative study of man. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [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]

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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] 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] Anticarcinogenic: Pertaining to something that prevents or delays the development of cancer. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [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] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] 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] 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] Antiproliferative: Counteracting a process of proliferation. [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] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [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

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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] Aqueous: Having to do with water. [NIH] Arabinofuranosyluracil: 1-beta-D-Arabinofuranosyluracil. A pyrimidine nucleoside formed in the body by the deamination of cytarabine. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arenavirus: The only genus in the family Arenaviridae. It contains two groups LCM-Lassa complex viruses and Tacaribe complex viruses, which are distinguished by antigenic relationships and geographic distribution. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [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] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asthenia: Clinical sign or symptom manifested as debility, or lack or loss of strength and energy. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a

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variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [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] 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] Autolysis: The spontaneous disintegration of tissues or cells by the action of their own autogenous enzymes. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autopsy: Postmortem examination of the body. [NIH] Avian: A plasmodial infection in birds. [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] 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] Bacteriophage lambda: A temperate inducible phage and type species of the genus lambdalike Phages, in the family Siphoviridae. Its natural host is E. coli K12. Its virion contains linear double-stranded DNA, except for 12 complementary bases at the 5'-termini of the polynucleotide chains. The DNA circularizes on infection. [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] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [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] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH]

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Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Beta-Galactosidase: A group of enzymes that catalyzes the hydrolysis of terminal, nonreducing beta-D-galactose residues in beta-galactosides. Deficiency of beta-Galactosidase A1 may cause gangliodisosis GM1. EC 3.2.1.23. [NIH] Bewilderment: Impairment or loss of will power. [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 Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [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] 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 preparation. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] 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] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Bioluminescence: The emission of light by living organisms such as the firefly, certain mollusks, beetles, fish, bacteria, fungi and protozoa. [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]

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Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] 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] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] Bladder: The organ that stores urine. [NIH] Blast phase: The phase of chronic myelogenous leukemia in which the number of immature, abnormal white blood cells in the bone marrow and blood is extremely high. Also called blast crisis. [NIH] 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] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [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 Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH]

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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] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breast Feeding: The nursing of an infant at the mother's breast. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [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] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]

Bupivacaine: A widely used local anesthetic agent. [NIH] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [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] 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] 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]

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Cardiac: Having to do with the heart. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [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] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [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] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Castor Oil: Oil obtained from seeds of Ricinus communis that is used as a cathartic and as a plasticizer. [NIH] Catalyse: To speed up a chemical reaction. [EU] 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] 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 Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter 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,

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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 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] Centriole: A small body which plays a part in the cell division. It is found near the nucleus of a cell. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] 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] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [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]

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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] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemoprotective: A quality of some drugs used in cancer treatment. Chemoprotective agents protect healthy tissue from the toxic effects of anticancer drugs. [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] Chenodeoxycholic Acid: A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones. [NIH] Chlamydia: A genus of the family Chlamydiaceae whose species cause a variety of diseases in vertebrates including humans, mice, and swine. Chlamydia species are gram-negative and produce glycogen. The type species is Chlamydia trachomatis. [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] Cholera Toxin: The enterotoxin from Vibrio cholerae. It is a protein that consists of two major components, the heavy (H) or A peptide and the light (L) or B peptide or choleragenoid. The B peptide anchors the protein to intestinal epithelial cells, while the A peptide, enters the cytoplasm, and activates adenylate cyclase, and production of cAMP. Increased levels of cAMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells. [NIH] Choleretic: A choleretic agent. [EU] 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] 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] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone

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proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [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 lymphocytic leukemia: A slowly progressing disease in which too many white blood cells (called lymphocytes) are found in the body. [NIH] Chronic myelogenous leukemia: CML. A slowly progressing disease in which too many white blood cells are made in the bone marrow. Also called chronic myeloid leukemia or chronic granulocytic leukemia. [NIH] Chronic phase: Refers to the early stages of chronic myelogenous leukemia or chronic lymphocytic leukemia. The number of mature and immature abnormal white blood cells in the bone marrow and blood is higher than normal, but lower than in the accelerated or blast phase. [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] 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] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH] 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

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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] Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of vitamins A and D. [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] 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] 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] Colloidal: Of the nature of a colloid. [EU] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [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] Communis: Common tendon of the rectus group of muscles that surrounds the optic foramen and a portion of the superior orbital fissure, to the anterior margin of which it is attached at the spina recti lateralis. [NIH] Compassionate: A process for providing experimental drugs to very sick patients who have no treatment options. [NIH] Compassionate use: Refers to providing a drug to a patient on humanitarian grounds before the drug has received official approval. [NIH]

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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 that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] 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] 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] Computer-Assisted Instruction: A self-learning technique, usually online, involving interaction of the student with programmed instructional materials. [NIH] Condoms: A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a

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form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [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] 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] 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]

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] Corneum: The superficial layer of the epidermis containing keratinized cells. [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 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

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results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] 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] Cost-benefit: A quantitative technique of economic analysis which, when applied to radiation practice, compares the health detriment from the radiation doses concerned with the cost of radiation dose reduction in that practice. [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] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cryoelectron Microscopy: Electron microscopy involving rapid freezing of the samples. The imaging of frozen-hydrated molecules and organelles permits the best possible resolution closest to the living state, free of chemical fixatives or stains. [NIH] Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH]

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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] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [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]

Cytarabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [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] Cytomegalovirus Infections: Infection with Cytomegalovirus, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults. [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] Cytotoxic: Cell-killing. [NIH] Cytotoxic chemotherapy: Anticancer drugs that kill cells, especially cancer cells. [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] Databases, Bibliographic: Extensive collections, reputedly complete, of references and

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citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Day Care: Institutional health care of patients during the day. The patients return home at night. [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] 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] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Delavirdine: A potent, non-nucleoside reverse transcriptase inhibitor with activity specific for HIV-1. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [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 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]

Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH]

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Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] 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] Dermatitis: Any inflammation of the skin. [NIH] Dermatologic Agents: Drugs used to treat or prevent skin disorders or for the routine care of skin. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] 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] Diagnostic procedure: A method used to identify a disease. [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] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] 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] 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] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Dinitrochlorobenzene: A skin irritant that may cause dermatitis of both primary and allergic types. Contact sensitization with DNCB has been used as a measure of cellular immunity. DNCB is also used as a reagent for the detection and determination of pyridine

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compounds. [NIH] Dinitrofluorobenzene: Irritants and reagents for labeling terminal amino acid groups. [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] 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] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [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] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] 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] 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

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dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [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] Duct: A tube through which body fluids pass. [NIH] Duodenal Ulcer: An ulcer in the lining of the first part of the small intestine (duodenum). [NIH]

Duodenum: The first part of the small intestine. [NIH] 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] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] 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] 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] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus

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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] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] 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] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]

Emollients: Oleagenous substances used topically to soothe, soften or protect skin or mucous membranes. They are used also as vehicles for other dermatologic agents. [NIH] Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [EU] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] 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] 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] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] 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]

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Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [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] Enhancer: Transcriptional element in the virus genome. [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] 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] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 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] 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]

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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]

Equine Infectious Anemia: Viral disease of horses caused by the equine infectious anemia virus (EIAV). It is characterized by intermittent fever, weakness, and anemia. Chronic infection consists of acute episodes with remissions. [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] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [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] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] 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] Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exons: Coding regions of messenger RNA included in the genetic transcript which survive the processing of RNA in cell nuclei to become part of a spliced messenger of structural RNA in the cytoplasm. They include joining and diversity exons of immunoglobulin genes. [NIH]

Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH] 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] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [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

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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] Extraction: The process or act of pulling or drawing out. [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] Factor X: Storage-stable glycoprotein blood coagulation factor that can be activated to factor Xa by both the intrinsic and extrinsic pathways. A deficiency of factor X, sometimes called Stuart-Prower factor deficiency, may lead to a systemic coagulation disorder. [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] 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] 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] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Fixatives: Agents employed in the preparation of histologic or pathologic specimens for the

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purpose of maintaining the existing form and structure of all of the constituent elements. Great numbers of different agents are used; some are also decalcifying and hardening agents. They must quickly kill and coagulate living tissue. [NIH] Flagellum: A whiplike appendage of a cell. It can function either as an organ of locomotion or as a device for moving the fluid surrounding the cell. [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 with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [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] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of

400 Hepatitis B

chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Galactosides: Glycosides formed by the reaction of the hydroxyl group on the anomeric carbon atom of galactose with an alcohol to form an acetal. They include both alpha- and beta-galactosides. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [NIH] Ganciclovir: Acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections. [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] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

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] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [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 Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genes, pol: DNA sequences that form the coding region for retroviral enzymes including reverse transcriptase, protease, and endonuclease/integrase. "pol" is short for polymerase,

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the enzyme class of reverse transcriptase. [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, 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] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geographic Locations: All of the continents and every country situated within, the United States and each of the constituent states arranged by region, Canada and each of its provinces, Australia and each of its states, the major bodies of water and major islands on both hemispheres, and selected major cities. Although the geographic locations are not printed in index medicus as main headings, in indexing they are significant in epidemiologic studies and historical articles and for locating administrative units in education and the delivery of health care. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] 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]

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] 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]

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] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] 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] Gonadal: Pertaining to a gonad. [EU] Gonorrhea: Acute infectious disease characterized by primary invasion of the urogenital tract. The etiologic agent, Neisseria gonorrhoeae, was isolated by Neisser in 1879. [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]

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] 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] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [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] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [NIH]

Haematemesis: The vomiting of blood. [EU] Haematological: Relating to haematology, that is that branch of medical science which treats of the morphology of the blood and blood-forming tissues. [EU] Haematology: The science of the blood, its nature, functions, and diseases. [NIH] Haemodialysis: The removal of certain elements from the blood by virtue of the difference

Dictionary 403

in the rates of their diffusion through a semipermeable membrane, e.g., by means of a haemodialyzer. [EU] 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] 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 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] Hematopoiesis: The development and formation of various types of blood cells. [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] 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 and two beta chains. [NIH]

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Hemoglobinuria: The presence of free hemoglobin in the urine. [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] Hemorrhage: Bleeding or escape of blood from a vessel. [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 B Virus: The type species of the genus orthohepadnavirus which causes human hepatitis B and is also apparently a causal agent in human hepatocellular carcinoma. The Dane particle is an intact hepatitis virion, named after its discoverer. Non-infectious spherical and tubular particles are also seen in the serum. [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 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 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] Hepatoblastoma: A type of liver tumor that occurs in infants and children. [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]

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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] 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 Genitalis: Herpes simplex of the genitals. [NIH] Herpes virus: A member of the herpes family of viruses. [NIH] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterodimer: 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]

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] Homeless Persons: Persons who have no permanent residence. The concept excludes nomadic peoples. [NIH] Homeless Youth: Runaway and homeless children and adolescents living on the streets of cities and having no fixed place of residence. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]

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] Homosexuality: Sexual attraction or relationship between members of the same sex. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormonal therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called hormone therapy or endocrine therapy. [NIH]

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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] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Horny layer: The superficial layer of the epidermis containing keratinized cells. [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] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [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] Hydralazine: A direct-acting vasodilator that is used as an antihypertensive agent. [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] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] 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

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are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [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] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune adjuvant: A drug that stimulates the immune system to respond to disease. [NIH] Immune Complex Diseases: Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides serum sickness and the arthus reaction, evidence supports a pathogenic role for immune complexes in many other systemic immunologic diseases including glomerulonephritis, systemic lupus erythematosus and polyarteritis nodosa. [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] 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] Immunization Schedule: Schedule giving optimum times usually for primary and/or secondary immunization. [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] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [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]

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Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction. [NIH]

Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera. [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] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [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 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] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] 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] 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]

Dictionary 409

Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [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 microorganisms. [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] 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] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Insertional: A technique in which foreign DNA is cloned into a restriction site which occupies a position within the coding sequence of a gene in the cloning vector molecule. Insertion interrupts the gene's sequence such that its original function is no longer expressed. [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] Integrase: An enzyme that inserts DNA into the host genome. It is encoded by the pol gene of retroviruses and also by temperate bacteriophages, the best known being bacteriophage

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lambda. EC 2.7.7.-. [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] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [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] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [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] Intrahepatic: Within the liver. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intramuscular injection: IM. Injection into a muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] 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]

Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH]

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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] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoleucine: An essential branched-chain amino acid found in many proteins. It is an isomer of LEUCINE. It is important in hemoglobin synthesis and regulation of blood sugar and energy levels. [NIH] Isoniazid: Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. [NIH] Isopropyl: A gene mutation inducer. [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] 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] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [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 Transplantation: The transference of a kidney from one human or animal to another. [NIH] Kinetic: Pertaining to or producing motion. [EU] 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] 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

412 Hepatitis B

colon. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

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] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] 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] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [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] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [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

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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] Lipopolysaccharides: 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 Regeneration: Repair or renewal of hepatic tissue. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [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] Long Interspersed Nucleotide Elements: Highly repeated sequences, 6K-8K base pairs in length, which contain RNA polymerase II promoters. They also have an open reading frame that is related to the reverse transcriptase of retroviruses but they do not contain LTRs (long terminal repeats). Copies of the LINE 1 (L1) family form about 15% of the human genome. The jockey elements of Drosophila are LINEs. [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

414 Hepatitis B

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] Luminescence: The property of giving off light without emitting a corresponding degree of heat. It includes the luminescence of inorganic matter or the bioluminescence of human matter, invertebrates and other living organisms. For the luminescence of bacteria, bacterial luminescence is available. [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 lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [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] 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] Lymphocyte Subsets: A classification of lymphocytes based on structurally or functionally different populations of cells. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphocytic Choriomeningitis Virus: The type species of arenavirus, part of the LCMLassa complex viruses, producing an inapparent infection in house and laboratory mice. In humans, infection with LCMV can be inapparent, or can present with an influenza-like illness, a benign aseptic meningitis, or a severe meningoencephalomyelitis. The virus can also infect monkeys, dogs, field mice, guinea pigs, and hamsters, the latter an epidemiologically important host. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [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] Maculopapular: Both macular and papular, as an eruption consisting of both macules and papules; sometimes erroneously used to designate a papule that is only slightly elevated. [EU]

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 responseassociated (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]

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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] 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] Measles Virus: The type species of morbillivirus and the cause of the highly infectious human disease measles, which affects mostly children. [NIH] Meconium: The thick green-to-black mucilaginous material found in the intestines of a fullterm fetus. It consists of secretions of the intestinal glands, bile pigments, fatty acids, amniotic fluid, and intrauterine debris. It constitutes the first stools passed by a newborn. [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 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] 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]

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Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [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] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [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] Menopause: Permanent cessation of menstruation. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] 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] 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 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] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] 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] 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]

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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] Mice Minute Virus: The type species of parvovirus prevalent in mouse colonies and found as a contaminant of many transplanted tumors or leukemias. [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] Microgram: A unit of mass (weight) of the metric system, being one-millionth of a gram (106 gm.) or one one-thousandth of a milligram (10-3 mg.). [EU] 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] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]

labeled

with

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] Milligram: A measure of weight. A milligram is approximately 450,000-times smaller than a pound and 28,000-times smaller than an ounce. [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] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family

418 Hepatitis B

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] 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] 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] 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] 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] Morbillivirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the virions have hemagglutinin but not neuraminidase activity. All members produce both cytoplasmic and intranuclear inclusion bodies. MEASLES VIRUS is the type species.

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[NIH]

Morphogenesis: The development of the form of an organ, part of the body, or organism. [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] Mucilaginous: Pertaining to or secreting mucus. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [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 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] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mutagenicity: Ability to damage DNA, the genetic material; the power to cause mutations. [NIH]

Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myalgia: Pain in a muscle or muscles. [EU] 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

420 Hepatitis B

other signs of autonomic dysfunction. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopathy: Any disease of a muscle. [EU] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myositis: Inflammation of a voluntary muscle. [EU] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Myristate: Pharmacological activator of protein kinase C. [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] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] 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] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [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 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] Neonatal: Pertaining to the first four weeks after birth. [EU] 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

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which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephropathy: Disease of the kidneys. [EU] 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] 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] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] 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] Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood cell. [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

422 Hepatitis B

with nucleoside analogues for treatment of HIV infection and AIDS. [NIH] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. 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] 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] 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] 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] 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] Odour: A volatile emanation that is perceived by the sense of smell. [EU]

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Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Oltipraz: A drug used in cancer prevention. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [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] 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] 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 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] Ori region: The point or region (origin) at which DNA replication begins in a bacterium or virus. Plasmids used in rec DNA research always contain an ori region, which gives very efficient initiation of replication. [NIH] Orthohepadnavirus: A genus of Hepadnaviridae causing hepatitis in humans, woodchucks, and ground squirrels. It is also associated with human hepatocellular carcinoma. Hepatitis B virus is the type species. [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] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [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

424 Hepatitis B

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] Oxazolone: Immunologic adjuvant and sensitizing agent. [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]

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] 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] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [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] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [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] 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] Particle: A tiny mass of material. [EU]

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Parvovirus: A genus of the family Parvoviridae, subfamily Parvovirinae, infecting a variety of vertebrates including humans. Parvoviruses are responsible for a number of important diseases but also can be non-pathogenic in certain hosts. The type species is mice minute virus. [NIH] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [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 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] 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 Gastroenterologist: A doctor who treats children with digestive diseases. [NIH] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pelvic: Pertaining to the pelvis. [EU] 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] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perceived risk: Estimate or evaluation of risk as observed through personal experience or personal study, and personal evaluation of consequences. [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] 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 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 Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory

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polyneuropathy." [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [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] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [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] Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [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] 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]

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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] 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] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [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] Phytotoxin: A substance which is toxic for plants. [NIH] Picornavirus: Any of a group of tiny RNA-containing viruses including the enteroviruses and rhinoviruses. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Pityriasis: A name originally applied to a group of skin diseases characterized by the formation of fine, branny scales, but now used only with a modifier. [EU] Pityriasis Rosea: A mild exanthematous inflammation of unknown etiology. It is characterized by the presence of salmon-colored maculopapular lesions. The most striking feature is the arrangement of the lesions such that the long axis is parallel to the lines of cleavage. The eruptions are usually generalized, affecting chiefly the trunk, and the course is often self-limiting. [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 proteins. [EU] 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]

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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] 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] Polyarteritis Nodosa: A form of necrotizing vasculitis involving small- and medium-sized arteries. The signs and symptoms result from infarction and scarring of the affected organ system. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] 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]

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] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [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] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the

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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] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: 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] 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] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [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] 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] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prenatal Care: Care provided the pregnant woman in order to prevent complications, and decrease the incidence of maternal and prenatal mortality. [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 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] 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]

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Procainamide: A derivative of procaine with less CNS action. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progeny: The offspring produced in any generation. [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] 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] 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 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] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids

Dictionary 431

having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [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] Prostitution: The practice of indulging in promiscuous sexual relations for money. [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 Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [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

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and phospholipids. The sensitivity of the enzyme can also be increased by phorbol esters and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. EC 2.7.1.-. [NIH] Protein p53: Nuclear phosphoprotein encoded by the p53 gene whose normal function is to control cell proliferation. A mutant or absent p53 protein has been found in leukemia, osteosarcoma, lung cancer, and colorectal cancer. [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] 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] 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] Proto-Oncogenes: Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Protooncogenes have names of the form c-onc. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] 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] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] 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] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] 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

Dictionary 433

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] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [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] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] 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] 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] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [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]

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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] 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] Reading Frames: The sequence of codons by which translation may occur. A segment of mRNA 5'AUCCGA3' could be translated in three reading frames, 5'AUC. or 5'UCC. or 5'CCG., depending on the location of the start codon. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] 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] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] 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

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treatment. [NIH] 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] 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] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Replication Origin: The point or region (origin) at which DNA replication begins in a bacterium or virus. Plasmids used in rec DNA research always contain an ori region, which gives very efficient initiation of replication. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [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] Respirators: These enable the wearer to breathe in atmospheres polluted by dust, poisonous vapors, smoke, etc., and are therefore used in certain industries or in warfare; they consist essentially of a mask, a metal frame with outlet and inlet valves, and a socket. [NIH] Respiratory Paralysis: Complete or severe weakness of the muscles of respiration. This condition may be associated with motor neuron diseases; peripheral nerve disorders; neuromuscular junction diseases; spinal cord diseases; injury to the phrenic nerve; and other disorders. [NIH] Response Elements: Nucleotide sequences, usually upstream, which are recognized by 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

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(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] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [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] 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] Retroelements: Elements that are transcribed into RNA, reverse-transcribed into DNA and then inserted into a new site in the genome. Long terminal repeats (LTRs) similar to those from retroviruses are contained in retrotransposons and retrovirus-like elements. Retroposons, such as long interspersed nucleotide elements and short interspersed nucleotide elements do not contain LTRs. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrotransposons: DNA sequence which is a copy of a RNA virus into a host's DNA and which can reinsert itself elsewhere in the genome. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Reverse Transcriptase Inhibitors: Inhibitors of reverse transcriptase (RNA-directed DNA polymerase), an enzyme that synthesizes DNA on an RNA template. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [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 infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [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] Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to

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proteins produced by the cell. [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] Ricin: A protein phytotoxin from the seeds of Ricinus communis, the castor oil plant. It agglutinates cells, is proteolytic, and causes lethal inflammation and hemorrhage if taken internally. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] 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] Rural Population: The inhabitants of rural areas or of small towns classified as rural. [NIH] Saline: A solution of salt and water. [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] Salvage Therapy: A therapeutic approach, involving chemotherapy, radiation therapy, or surgery, after initial regimens have failed to lead to improvement in a patient's condition. Salvage therapy is most often used for neoplastic diseases. [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] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [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

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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] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [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] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [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] 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] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [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] 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]

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Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [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] Serology: The study of serum, especially of antigen-antibody reactions in vitro. [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] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Sexual Partners: Married or single individuals who share sexual relations. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [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]

Short Interspersed Nucleotide Elements: Highly repeated sequences, 100-300 bases long, which contain RNA polymerase III promoters. The primate Alu (Alu elements) and the rodent B1 SINEs are derived from 7SL RNA, the RNA component of the signal recognition particle. Most other SINEs are derived from tRNAs including the MIRs (mammalian-wide interspersed repeats). [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] 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

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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] Sizofiran: A beta-D-glucan obtained from the Aphyllophoral fungus Schizophyllum commune. It is used as an immunoadjuvant in the treatment of neoplasms, especially tumors found in the stomach. [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] Skin Tests: Epicutaneous or intradermal application of a sensitizer for demonstration of either delayed or immediate hypersensitivity. Used in diagnosis of hypersensitivity or as a test for cellular immunity. [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] 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 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] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [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 displacement, or density, that propagates through the medium, or a superposition of such alterations. [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]

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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] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [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] Spinous: Like a spine or thorn in shape; having spines. [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] Splenic Vein: Vein formed by the union (at the hilus of the spleen) of several small veins from the stomach, pancreas, spleen and mesentery. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] State Government: The level of governmental organization and function below that of the national or country-wide government. [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] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other

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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]

Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [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] Stringency: Experimental conditions (e. g. temperature, salt concentration) used during the hybridization of nucleic acids. [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] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] 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] Sulfates: Inorganic salts of sulfuric acid. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S,

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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] 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] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppurative: Consisting of, containing, associated with, or identified by the formation of pus. [NIH] 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] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or 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] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [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

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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 condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [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] 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] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [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]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]

Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21. [NIH] Thymosin: A family of heat-stable, polypeptide hormones secreted by the thymus gland. 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] Thymus Gland: A single, unpaired primary lymphoid organ situated in the mediastinum, extending superiorly into the neck to the lower edge of the thyroid gland and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH]

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Time Management: Planning and control of time to improve efficiency and effectiveness. [NIH]

Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [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] 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] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [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] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] 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] 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

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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] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [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] Translocation: The movement of material in solution inside the body of the plant. [NIH] 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] Trichomonas: A genus of parasitic flagellate protozoans distinguished by the presence of four anterior flagella, an undulating membrane, and a trailing flagellum. [NIH] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberculostatic: Inhibiting the growth of Mycobacterium tuberculosis. [EU] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [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]

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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] 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] Ultrasound test: A test that bounces sound waves off tissues and internal organs and changes the echoes into pictures (sonograms). [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] Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [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]

Urinate: To release urine from the bladder to the outside. [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] Urocanic Acid: 4-Imidazoleacrylic acid. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Ursodeoxycholic Acid: An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic. [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] 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]

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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] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [NIH]

Valves: Flap-like structures that control the direction of blood flow through the heart. [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] 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] Venous: Of or pertaining to the veins. [EU] 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] 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] Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Vibrio cholerae: The etiologic agent of cholera. [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 Regulatory Proteins: Proteins which regulate the rate of transcription of viral structural genes. [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

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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] 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] Void: To urinate, empty the bladder. [NIH] Voluntary Health Agencies: Non-profit organizations concerned with various aspects of health, e.g., education, promotion, treatment, services, etc. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [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] 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]

450 Hepatitis B

X-ray therapy: The use of high-energy radiation from x-rays 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. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [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] 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] 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] Zygote: The fertilized ovum. [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]

451

INDEX 2 2-Aminopurine, 166, 371 A Abdomen, 371, 381, 410, 413, 424, 441, 442 Abdominal, 212, 215, 236, 246, 255, 271, 368, 371, 424, 426 Abdominal Pain, 236, 246, 255, 271, 371, 426 Aberrant, 85, 90, 151, 371 Acceptor, 85, 371, 413, 424, 444, 446 Acculturation, 55, 371 Acetaldehyde, 171, 371 Acetaminophen, 371, 399 Acetone, 247, 371, 411 Acidosis, 9, 371 Acne, 308, 371, 436 Acquired Immunodeficiency Syndrome, 237, 371, 405 Actin, 371, 420 Acute Disease, 238, 255, 299, 371 Acute leukemia, 194, 371 Acute myelogenous leukemia, 141, 371, 372 Acute myeloid leukemia, 371, 372 Acute nonlymphocytic leukemia, 371, 372 Acute renal, 372, 404 Acyclovir, 63, 372, 400 Acyl, 276, 372 Adaptability, 372, 382, 383 Adduct, 69, 372 Adenine, 92, 108, 200, 243, 371, 372 Adenocarcinoma, 372, 404 Adenovirus, 102, 108, 124, 224, 271, 372 Adenylate Cyclase, 372, 384 Adolescence, 372, 425 Adolescent Medicine, 54, 372 Adoptive Transfer, 275, 372 Adrenal Cortex, 372, 389, 430 Adverse Effect, 22, 30, 53, 372, 439 Aerobic, 372, 417 Affinity, 35, 260, 372 Aflatoxin B1, 91, 174, 373 Aflatoxins, 67, 373 Agar, 78, 373, 389, 408 Age-Adjusted, 68, 373 Alanine, 5, 11, 15, 21, 373 Alanine Transaminase, 15, 373 Albumin, 67, 368, 373, 427

Algorithms, 373, 380 Alimentary, 5, 136, 185, 188, 373, 424 Alkaline, 368, 371, 373, 381, 426 Alkaloid, 373, 386 Alkylating Agents, 373, 447 Alleles, 133, 373 Allergen, 374, 438 Allogeneic, 136, 154, 166, 167, 187, 374, 402 Allograft, 16, 19, 76, 153, 374 Alopecia, 247, 374, 390 Alpha Particles, 374, 433 Alpha-1, 314, 332, 374 Alpha-fetoprotein, 136, 348, 374, 398 Alternative medicine, 307, 374 Alum, 58, 232, 261, 374, 386 Aluminum, 374 Ameliorating, 269, 275, 374 Amino Acid Sequence, 235, 236, 246, 252, 254, 262, 374, 376, 401 Amino Acid Substitution, 143, 233, 374 Amino Acids, 266, 374, 377, 386, 401, 425, 428, 432, 437, 443, 446 Amino-terminal, 57, 374 Amniotic Fluid, 374, 415 Amphetamines, 374, 386 Amplification, 15, 52, 70, 89, 91, 94, 111, 117, 163, 233, 242, 265, 274, 375 Anaesthesia, 375, 408 Anal, 18, 34, 38, 344, 375, 396, 398, 413, 419 Analog, 30, 76, 98, 111, 115, 220, 267, 268, 372, 375, 400, 411 Analogous, 83, 228, 230, 375, 394, 445 Analytes, 332, 333, 375 Anaphylatoxins, 375, 387 Anatomical, 375, 408, 438 Androgens, 372, 375, 389 Anemia, 250, 328, 375, 397, 415 Anergy, 35, 375 Angiogenesis, 375, 415 Animal model, 11, 34, 36, 47, 50, 56, 59, 63, 67, 70, 83, 375 Anions, 373, 375, 411 Annealing, 375, 428 Anorexia, 246, 374, 375 Anthropology, 82, 375 Antiallergic, 375, 389 Antibacterial, 375, 393, 411, 441

452 Hepatitis B

Antibiotic, 375, 399, 425, 441 Anticarcinogenic, 68, 376 Anticoagulant, 376, 392, 431 Antigen-Antibody Complex, 185, 376, 387 Antigen-presenting cell, 376, 391 Antihypertensive, 376, 406 Anti-inflammatory, 371, 376, 389, 401, 429 Anti-Inflammatory Agents, 376, 389 Antimetabolite, 372, 376, 436 Antineoplastic, 373, 376, 389, 390, 410 Antioxidant, 51, 154, 376, 424, 440 Antiproliferative, 37, 376 Antiseptic, 371, 376, 444 Anus, 375, 376, 381 Anxiety, 133, 376 Apolipoproteins, 376, 413 Apoptosis, 34, 35, 37, 43, 73, 110, 119, 130, 377, 382 Aqueous, 239, 250, 377, 378, 390, 395, 406, 412 Arabinofuranosyluracil, 107, 124, 377 Arachidonic Acid, 377, 430 Arenavirus, 377, 414 Arginine, 375, 377, 410 Aromatic, 50, 377, 426 Arterial, 178, 377, 384, 406, 432 Arteries, 377, 380, 388, 413, 417, 428 Aseptic, 300, 377, 414, 423, 441 Aspartate, 15, 377 Aspartate Transaminase, 15, 377 Aspartic, 252, 377, 395 Aspartic Acid, 252, 377 Aspiration, 377, 398 Asthenia, 271, 377 Asymptomatic, 8, 174, 184, 226, 240, 245, 271, 272, 308, 377, 404 Ataxia, 328, 377, 444 Atrophy, 327, 328, 377 Attenuated, 63, 75, 120, 225, 229, 233, 255, 261, 275, 279, 378 Atypical, 25, 378 Audiovisual Aids, 357, 378 Autoimmune disease, 240, 378, 419 Autoimmune Hepatitis, 378, 404 Autolysis, 275, 378 Autonomic, 378, 420, 425 Autopsy, 141, 378 Avian, 79, 92, 115, 123, 177, 246, 263, 378 B Bacteremia, 378, 380 Bactericidal, 378, 397 Bacteriophage, 378, 409, 445

Bacteriophage lambda, 378, 410 Bacterium, 378, 388, 404, 423, 435, 447 Basal Ganglia, 377, 378, 400 Basal Ganglia Diseases, 377, 378 Base, 34, 86, 253, 257, 272, 372, 378, 390, 391, 399, 401, 411, 413, 426, 428, 443 Base Sequence, 378, 399, 401 Benign, 224, 379, 400, 403, 414, 420, 424, 433, 449 Beta-Galactosidase, 254, 379 Bewilderment, 379, 387 Bilateral, 379, 436 Bile, 98, 138, 139, 379, 384, 400, 406, 411, 413, 415, 429, 441, 447 Bile Acids, 379, 441 Bile Acids and Salts, 379 Bile Ducts, 379, 400, 429 Bile Pigments, 379, 411, 415 Biliary, 174, 175, 294, 379 Bilirubin, 15, 272, 368, 373, 379, 400, 406 Binding Sites, 238, 379 Bioassays, 67, 379 Bioavailability, 34, 379 Biological response modifier, 379, 410 Biological therapy, 379, 402 Biological Transport, 379, 392 Bioluminescence, 379, 414 Biomarkers, 40, 67, 85, 145, 379 Biopsy, 16, 37, 73, 212, 216, 217, 294, 308, 333, 346, 347, 351, 368, 369, 380, 425 Biosynthesis, 377, 380, 431 Biotechnology, 88, 125, 164, 176, 192, 290, 307, 319, 327, 328, 329, 380 Biotin, 41, 380 Bladder, 380, 408, 419, 421, 431, 447, 449 Blast phase, 380, 385 Blood Coagulation, 380, 381, 398, 444 Blood Glucose, 29, 380, 403 Blood Platelets, 380, 416, 444 Blood pressure, 376, 380, 382, 406, 418 Blood transfusion, 91, 192, 225, 228, 272, 380 Blood vessel, 375, 380, 382, 383, 396, 401, 404, 411, 440, 442, 443, 444, 448 Blood-Borne Pathogens, 5, 54, 59, 288, 322, 380 Blot, 265, 380 Body Fluids, 225, 268, 298, 300, 320, 323, 337, 349, 379, 380, 394, 446 Bone Marrow, 251, 252, 253, 275, 371, 372, 380, 381, 385, 407, 414, 416, 420, 441, 442 Bone Marrow Cells, 275, 380, 416

Index 453

Bone Marrow Transplantation, 275, 381 Bowel, 375, 381, 392, 410, 412, 421, 426 Bowel Movement, 381, 392 Brachytherapy, 381, 410, 411, 433, 450 Branch, 285, 324, 365, 372, 381, 390, 402, 425, 432, 440, 444 Breast Feeding, 46, 351, 381 Breeding, 70, 381 Bronchiseptica, 381, 426 Buccal, 381, 414, 442 Buffers, 49, 381 Bupivacaine, 381, 412 C Cachexia, 250, 381 Calcium, 82, 127, 381, 387, 415, 431, 439 Capsid, 101, 103, 109, 111, 118, 120, 124, 235, 241, 259, 275, 381, 422, 448 Capsular, 75, 270, 381 Carbohydrate, 381, 389, 402, 428, 438 Carboxy, 230, 254, 263, 278, 381 Carboxy-terminal, 230, 263, 278, 381 Carcinogen, 67, 69, 372, 381 Carcinogenesis, 34, 68, 70, 132, 157, 381, 384 Carcinogenic, 373, 381, 409, 423, 430, 441 Carcinoma, 6, 7, 8, 10, 13, 16, 17, 21, 24, 26, 28, 31, 32, 34, 36, 37, 40, 44, 50, 51, 55, 57, 59, 60, 65, 66, 68, 73, 77, 79, 85, 90, 100, 128, 129, 130, 132, 133, 137, 139, 143, 145, 148, 151, 157, 158, 162, 164, 166, 178, 185, 190, 191, 192, 212, 234, 235, 236, 237, 238, 239, 242, 244, 245, 246, 260, 264, 272, 273, 274, 279, 291, 292, 293, 294, 295, 321, 345, 346, 350, 367, 381, 404, 423 Cardiac, 271, 382, 391, 396, 412, 420, 441 Cardiomyopathy, 382 Cardiovascular, 354, 382 Cardiovascular disease, 354, 382 Carnitine, 217, 382 Carotenoids, 40, 382 Carrier State, 26, 97, 272, 298, 382 Case report, 29, 136, 141, 142, 338, 382, 385 Case series, 12, 29, 382, 385 Caspase, 43, 130, 382 Castor Oil, 382, 437 Catalyse, 258, 382 Causal, 71, 309, 382, 396, 404, 438, 443 Cause of Death, 40, 209, 382, 391 Cell Count, 247, 382 Cell Cycle, 34, 78, 80, 93, 104, 382, 432 Cell Death, 73, 147, 377, 382, 420

Cell Differentiation, 382, 439 Cell Division, 327, 378, 382, 383, 390, 402, 416, 418, 427, 430, 438 Cell membrane, 379, 382, 392, 426 Cell proliferation, 115, 383, 410, 432, 439 Cell Respiration, 383, 417, 435 Cell Size, 383, 399 Cell Survival, 206, 383, 402 Cell Transplantation, 167, 383 Cellulose, 383, 400, 427 Central Nervous System, 44, 56, 373, 374, 383, 386, 400, 403, 419, 423 Central Nervous System Infections, 383, 403 Centriole, 151, 383 Cerebellar, 377, 383, 434 Cerebral, 377, 378, 383, 396, 397, 415 Cerebrovascular, 378, 382, 383, 444 Cerebrum, 383, 446 Cervical, 151, 355, 383 Cervix, 383 Character, 383, 391 Check-up, 217, 383 Chemical Warfare, 383, 391 Chemical Warfare Agents, 383, 391 Chemoembolization, 178, 384 Chemoprevention, 69, 70, 384 Chemopreventive, 68, 70, 384 Chemoprotective, 69, 384 Chemotactic Factors, 384, 387 Chemotherapy, 5, 131, 136, 142, 152, 159, 182, 183, 184, 189, 190, 196, 197, 198, 384, 437 Chenodeoxycholic Acid, 384, 447 Chlamydia, 54, 289, 384 Chloroform, 94, 384 Cholangitis, 127, 384 Cholera, 33, 384, 439, 448 Cholera Toxin, 33, 384 Choleretic, 384, 447 Cholesterol, 130, 248, 379, 384, 385, 388, 400, 413, 441 Cholesterol Esters, 384, 413 Chorioretinitis, 384, 435 Choroid, 384, 435 Chromatin, 84, 377, 384, 421, 441 Chromosomal, 35, 90, 375, 385, 427, 436, 437 Chromosome, 113, 240, 385, 388, 403, 412, 437, 438 Chronic Disease, 53, 238, 284, 381, 385 Chronic lymphocytic leukemia, 385

454 Hepatitis B

Chronic myelogenous leukemia, 380, 385 Chronic phase, 74, 352, 385 Chronic renal, 32, 137, 139, 385, 428 Chylomicrons, 385, 413 CIS, 80, 88, 138, 226, 385 Cleave, 50, 93, 385 Clinical Medicine, 192, 385, 429 Clinical resistance, 36, 385 Clinical study, 184, 385, 388 Clone, 73, 127, 244, 273, 385 Cloning, 17, 70, 94, 113, 267, 380, 385, 409 Coagulation, 380, 385, 398, 427 Coca, 386 Cocaine, 39, 87, 386 Cod Liver Oil, 386, 395 Codon, 34, 49, 56, 122, 272, 386, 401, 434 Cofactor, 84, 274, 386, 432, 444 Cognitive restructuring, 386, 442 Cohort Studies, 33, 55, 68, 386, 396 Collagen, 386, 398, 400, 415 Colloidal, 373, 386, 426 Colorectal, 40, 386, 432 Colorectal Cancer, 40, 386, 432 Combination Therapy, 6, 8, 12, 26, 76, 132, 179, 228, 293, 386 Communicable disease, 386, 447 Communis, 382, 386, 437 Compassionate, 4, 386 Compassionate use, 4, 386 Complement, 52, 57, 128, 185, 265, 375, 387, 401, 414, 427, 438 Complementary and alternative medicine, 181, 203, 387 Complementary medicine, 181, 387 Complete remission, 387, 435 Computational Biology, 319, 327, 387 Computer-Assisted Instruction, 350, 387 Condoms, 343, 369, 387 Confusion, 59, 387, 393, 447 Conjugated, 379, 384, 387, 390 Conjugation, 188, 387 Conjunctiva, 388, 409 Connective Tissue, 380, 386, 388, 398, 400, 414, 436, 437, 442 Consciousness, 388, 391, 393 Constipation, 388, 426 Constitutional, 388, 436 Constriction, 388, 411, 437 Consultation, 21, 293, 388 Consumption, 47, 388, 392, 435 Contamination, 206, 262, 380, 388, 404, 405 Contraindications, ii, 22, 348, 388

Control group, 14, 51, 388, 433 Controlled clinical trial, 174, 200, 388 Controlled study, 136, 178, 185, 388 Coordination, 388, 419 Cornea, 388, 450 Corneum, 388, 396 Coronary, 382, 388, 389, 417 Coronary heart disease, 382, 388 Coronary Thrombosis, 389, 417 Cortex, 377, 389, 397, 434 Corticosteroid, 154, 389, 429 Cortisol, 75, 373, 389 Cortisone, 389, 429 Cost-benefit, 20, 389 Cowpox, 389, 447 Cowpox Virus, 389, 447 Cranial, 389, 403, 423, 425 Craniocerebral Trauma, 378, 389, 403, 444 Crossing-over, 389, 434 Cryoelectron Microscopy, 111, 389 Culture Media, 373, 389 Curative, 389, 444 Cutaneous, 211, 389, 414, 447 Cyclic, 258, 372, 390, 431 Cyclophosphamide, 250, 390 Cysteine, 85, 263, 277, 278, 279, 390, 395, 443 Cystine, 390 Cytarabine, 377, 390 Cytochrome, 35, 43, 69, 390 Cytogenetics, 390, 437 Cytokine, 43, 47, 74, 87, 95, 104, 165, 257, 293, 390 Cytomegalovirus, 46, 108, 220, 240, 325, 390, 400 Cytomegalovirus Infections, 108, 390, 400 Cytoplasm, 83, 274, 377, 383, 384, 390, 397, 402, 421, 437 Cytosine, 88, 390 Cytotoxic chemotherapy, 141, 390 Cytotoxicity, 37, 115, 198, 238, 250, 276, 277, 390 D Data Collection, 42, 390, 399 Databases, Bibliographic, 319, 390 Day Care, 339, 391 Deamination, 377, 391 Death Certificates, 40, 391 Decompensation, 13, 21, 210, 347, 391 Decontamination, 285, 323, 391 Degenerative, 268, 391, 404 Dehydration, 384, 391

Index 455

Dehydroepiandrosterone, 197, 391 Delavirdine, 391, 422 Deletion, 89, 101, 377, 391 Delivery of Health Care, 391, 401 Dementia, 34, 66, 371, 391 Denaturation, 265, 391, 428 Dendrites, 391, 421 Dendritic, 33, 66, 148, 247, 391, 416 Dendritic cell, 33, 66, 148, 247, 391 Density, 84, 391, 399, 413, 423, 428, 440 Dental Assistants, 16, 391 Dental Waste, 380, 391 Dentists, 15, 288, 391 Deoxyguanosine, 51, 67, 99, 391 Deoxyribonucleic, 391, 392, 436 Deoxyribonucleic acid, 392, 436 Depolarization, 43, 392, 439 Dermatitis, 392 Dermatologic Agents, 392, 395 Deuterium, 392, 406 Developed Countries, 44, 392 Developing Countries, 44, 77, 230, 237, 392 Dextran Sulfate, 260, 392 Diabetes Mellitus, 392, 403 Diagnostic procedure, 223, 307, 392 Dialyzer, 392, 403 Diarrhea, 351, 392 Diffusion, 53, 379, 392, 403, 408, 409 Digestion, 373, 379, 381, 392, 410, 413, 442 Digestive system, 221, 392, 400, 419 Dilatation, 392, 429 Dilated cardiomyopathy, 174, 392 Dimerization, 84, 392 Dimethyl, 199, 392 Dinitrochlorobenzene, 247, 392 Dinitrofluorobenzene, 247, 393 Diphtheria, 14, 139, 155, 169, 270, 393 Diploid, 393, 427 Discrimination, 98, 393 Disease Progression, 46, 52, 393, 448 Disease Susceptibility, 74, 393 Disease Transmission, 320, 393 Disease Transmission, Horizontal, 393 Disease Transmission, Vertical, 393 Disinfectant, 206, 393, 397 Disinfection, 299, 323, 343, 393 Disorientation, 387, 393 Dissociation, 372, 393 Distal, 393, 425, 432 Dopamine, 386, 393, 426

Drive, ii, vi, 6, 12, 15, 16, 26, 27, 28, 31, 34, 60, 173, 235, 394 Drug Design, 228, 313, 394 Drug Interactions, 34, 313, 394 Drug Resistance, 30, 63, 69, 111, 113, 213, 394 Drug Tolerance, 394, 445 Duct, 98, 139, 384, 394, 437 Duodenal Ulcer, 250, 394 Duodenum, 379, 394, 442 Dyes, 394, 399, 421, 443 Dysplasia, 34, 328, 394 Dyspnea, 391, 394 Dystrophy, 328, 394 E Edema, 391, 394 Effector, 56, 75, 125, 171, 279, 387, 394, 421 Ejaculation, 394, 438 Elective, 165, 394 Electrocardiogram, 212, 215, 216, 394 Electrolyte, 389, 394, 417, 429 Electron microscope, 254, 395 Electrons, 376, 378, 395, 410, 411, 424, 433 Emaciation, 371, 395 Embryo, 382, 395, 408 Emergency Medical Services, 320, 321, 395 Emesis, 250, 395 Emollients, 247, 395 Empiric, 10, 395 Empirical, 74, 87, 395 Emulsion, 247, 395, 398 Encapsulated, 281, 395 Encephalitis, 395 Encephalomyelitis, 56, 395 Endemic, 13, 55, 80, 85, 116, 166, 178, 354, 384, 395, 404, 415, 441 Endopeptidases, 395, 431 Endothelial cell, 271, 396, 444 Endotoxin, 396, 446 End-stage renal, 385, 396, 428 Enhancer, 48, 101, 106, 109, 113, 119, 121, 123, 124, 195, 268, 396, 435 Environmental Exposure, 396, 423 Environmental Health, 68, 318, 320, 396 Enzymatic, 100, 381, 387, 396, 428 Enzyme Inhibitors, 258, 396, 427 Enzyme-Linked Immunosorbent Assay, 97, 188, 396 Epidemic, 10, 53, 71, 191, 236, 255, 396, 441 Epidemiologic Studies, 396, 401

456 Hepatitis B

Epidemiological, 17, 28, 36, 52, 55, 76, 152, 244, 273, 290, 324, 340, 396 Epidermal, 99, 138, 396, 416, 449 Epidermis, 247, 388, 396, 406 Epinephrine, 393, 396, 447 Epithelial, 98, 372, 379, 384, 396, 424 Epithelial Cells, 98, 384, 396 Epithelium, 396, 424, 450 Epitope, 47, 93, 96, 97, 114, 116, 134, 171, 233, 236, 241, 246, 254, 256, 262, 263, 272, 397 Equine Infectious Anemia, 110, 176, 397 ERV, 58, 397 Erythrocytes, 375, 380, 397, 434, 438 Esophagus, 392, 397, 400, 426, 442 Essential Tremor, 328, 397 Ethanol, 47, 51, 397 Ether, 227, 397 Evoke, 397, 441 Excipient, 58, 242, 397 Excitation, 374, 397, 399 Exhaustion, 57, 397, 415 Exogenous, 100, 238, 276, 397, 449 Exons, 70, 397 Expiratory, 397 Expiratory Reserve Volume, 397 External-beam radiation, 397, 411, 433, 450 Extracellular, 103, 388, 397, 415, 418 Extracellular Matrix, 388, 397, 415 Extracellular Matrix Proteins, 397, 415 Extraction, 94, 99, 197, 206, 398 Eye Infections, 372, 398 F Factor X, 198, 398 Family Planning, 319, 398 Fat, 377, 379, 380, 388, 389, 398, 411, 412, 419, 436, 440, 443, 444 Fatigue, 237, 277, 284, 344, 351, 398 Fatty acids, 373, 398, 413, 415, 430 Ferritin, 178, 398 Fetoprotein, 85, 122, 398 Fetus, 374, 398, 407, 415, 429, 447 Fibrin, 380, 398, 426, 444 Fibrosis, 7, 13, 20, 37, 73, 137, 174, 184, 228, 328, 398, 438 Fixation, 398, 438 Fixatives, 389, 398 Flagellum, 399, 446 Flow Cytometry, 35, 66, 87, 399 Fluorescence, 163, 265, 399 Fluorescent Dyes, 399

Focus Groups, 62, 81, 399 Fold, 68, 225, 253, 267, 399, 416 Fractionation, 65, 399 Frameshift, 49, 399 Frameshift Mutation, 49, 399 Fulminant Hepatic Failure, 30, 399 Fungemia, 380, 399 Fungi, 373, 379, 387, 398, 399, 400, 417, 419, 450 Fungus, 399, 440 G Galactosides, 379, 400 Gallbladder, 371, 379, 392, 400 Gallstones, 379, 384, 400, 447 Ganciclovir, 161, 400 Ganglia, 255, 378, 400, 421, 425 Ganglion, 400, 423, 450 Gangrenous, 400, 439 Gas, 392, 397, 400, 406, 422 Gastric, 40, 250, 382, 400 Gastrin, 400, 406 Gastroenterologist, 345, 400 Gastrointestinal, 43, 51, 292, 396, 397, 400, 415, 442, 446, 448 Gastrointestinal tract, 292, 397, 400, 446 Gelatin, 389, 400, 402, 444 Gene, 33, 37, 43, 45, 47, 68, 69, 70, 73, 77, 78, 79, 83, 86, 95, 96, 98, 101, 102, 103, 104, 109, 113, 118, 122, 123, 129, 134, 144, 151, 178, 182, 186, 192, 198, 230, 234, 235, 237, 240, 242, 243, 244, 260, 264, 268, 271, 272, 273, 275, 278, 290, 293, 304, 329, 372, 373, 380, 400, 401, 409, 411, 423, 424, 435, 438, 446 Gene Expression, 43, 45, 77, 78, 83, 86, 95, 96, 98, 118, 122, 182, 186, 192, 268, 278, 329, 400 Genes, pol, 249, 400 Genetic Code, 267, 401, 422 Genetic Engineering, 19, 83, 230, 248, 380, 385, 401 Genetic Markers, 215, 401 Genetic testing, 401, 428 Genetic transcription, 401, 430, 445 Genetics, 86, 387, 390, 401 Genital, 229, 255, 289, 401, 447 Geographic Locations, 56, 401 Gestation, 87, 401, 425 Gland, 372, 389, 401, 414, 415, 424, 427, 431, 438, 441, 444 Glomerular, 401, 435 Glomerulus, 401, 421

Index 457

Glottis, 401, 426 Glucocorticoid, 401, 429, 449 Glucose, 327, 380, 383, 392, 401, 402, 403, 437 Glucosidases, 71, 84, 401 Glutamate, 373, 377, 402 Glutathione Peroxidase, 51, 402, 438 Glycine, 79, 379, 384, 402 Glycogen, 384, 402 Glycoprotein, 84, 231, 258, 280, 398, 402, 444, 446 Glycosidic, 402, 423 Glycosylation, 84, 102, 119, 194, 231, 258, 280, 402 Gonadal, 402, 441 Gonorrhea, 54, 289, 402 Governing Board, 402, 429 Gp120, 41, 402 Graft, 11, 16, 250, 295, 402, 406, 408 Graft Rejection, 402, 408 Gram-negative, 381, 384, 402, 448 Granulocytes, 402, 412, 439, 449 Growth factors, 34, 402 Guinea Pigs, 402, 414 H Haematemesis, 395, 402 Haematological, 189, 402 Haematology, 141, 166, 196, 402 Haemodialysis, 170, 200, 240, 402 Haploid, 403, 427 Haptens, 372, 403 Headache, 246, 403, 409 Headache Disorders, 403 Health Behavior, 61, 151, 403 Health Promotion, 342, 346, 355, 403 Health Services, 48, 391, 403 Health Status, 403 Heart attack, 382, 403 Hematopoiesis, 250, 251, 403 Hematopoietic growth factors, 308, 403 Heme, 379, 390, 403 Hemodialysis, 4, 118, 145, 183, 197, 272, 392, 403 Hemoglobin, 29, 375, 397, 403, 404, 411, 412 Hemoglobin A, 29, 403 Hemoglobinuria, 327, 404 Hemolytic, 94, 404 Hemorrhage, 389, 403, 404, 437, 442 Hepadnaviridae, 226, 263, 404, 423 Hepatitis A, 13, 14, 29, 45, 52, 54, 56, 69, 82, 142, 194, 225, 228, 229, 232, 234, 236,

238, 239, 242, 255, 257, 261, 270, 274, 280, 298, 332, 333, 335, 337, 345, 352, 404, 418 Hepatitis Antigens, 233, 261, 404 Hepatitis D, 10, 50, 59, 60, 80, 105, 113, 119, 130, 143, 182, 217, 239, 266, 267, 280, 294, 404 Hepatitis Delta Virus, 10, 50, 59, 60, 80, 113, 119, 130, 143, 266, 267, 294, 404 Hepatitis Viruses, 111, 152, 158, 176, 187, 193, 231, 232, 258, 261, 274, 280, 292, 334, 404 Hepatitis, Chronic, 277, 404 Hepatoblastoma, 107, 115, 117, 404 Hepatocyte, 34, 42, 77, 95, 105, 112, 114, 118, 121, 162, 236, 264, 404 Hepatologist, 345, 405 Hepatoma, 7, 56, 93, 98, 102, 105, 108, 135, 148, 182, 186, 192, 193, 240, 244, 273, 405 Hepatotoxic, 373, 405 Hepatotoxicity, 9, 51, 405 Hepatovirus, 404, 405 Hereditary, 405, 426, 436 Heredity, 400, 401, 405 Herpes, 46, 56, 86, 150, 220, 227, 229, 255, 257, 289, 372, 405 Herpes Genitalis, 255, 405 Herpes virus, 56, 227, 405 Herpes Zoster, 405 Heterodimer, 82, 405 Heterogeneity, 18, 47, 372, 405 Histidine, 405, 410 Histology, 12, 175, 405 Homeless Persons, 45, 405 Homeless Youth, 54, 81, 405 Homeostasis, 45, 405 Homodimer, 405, 446 Homologous, 83, 111, 113, 254, 260, 373, 389, 405, 419, 432, 438, 443 Homosexuality, 272, 405 Hormonal, 44, 164, 378, 389, 405 Hormonal therapy, 44, 405 Hormone therapy, 405, 406 Horny layer, 396, 406 Horseradish Peroxidase, 396, 406 Hospitals, Public, 406, 407 Housekeeping, 5, 321, 339, 406 Human papillomavirus, 151, 406 Humoral, 41, 47, 56, 63, 87, 89, 93, 97, 167, 402, 406 Humour, 406 Hybrid, 89, 95, 102, 241, 259, 385, 406

458 Hepatitis B

Hybridization, 117, 120, 242, 244, 273, 406, 442 Hydralazine, 307, 406 Hydration, 58, 406 Hydrogen, 276, 371, 378, 381, 391, 392, 397, 402, 406, 412, 418, 421, 422, 424, 432, 450 Hydrogen Peroxide, 402, 406, 412 Hydrolysis, 377, 379, 406, 426, 428, 432 Hydrophobic, 89, 406, 413 Hyperbilirubinemia, 406, 411 Hypersensitivity, 374, 406, 436, 438, 440 Hypertension, 382, 403, 406 I Id, 180, 201, 356, 364, 366, 407 Idiopathic, 308, 407 Imidazole, 380, 407 Immune adjuvant, 374, 407 Immune Complex Diseases, 376, 407 Immune function, 74, 407, 446 Immune Sera, 407 Immune Tolerance, 49, 64, 275, 407 Immunization Programs, 18, 26, 298, 407 Immunization Schedule, 32, 407 Immunoassay, 41, 91, 92, 94, 100, 114, 118, 120, 131, 159, 185, 272, 396, 407 Immunocompromised, 27, 31, 229, 240, 247, 256, 407 Immunodiffusion, 373, 408 Immunoelectrophoresis, 373, 408 Immunogen, 259, 279, 408 Immunogenic, 33, 89, 225, 229, 230, 237, 254, 259, 263, 277, 278, 281, 408 Immunoglobulin, 10, 11, 107, 112, 128, 132, 169, 376, 397, 408, 418 Immunohistochemistry, 70, 408 Immunologic, 52, 66, 75, 110, 161, 274, 372, 384, 405, 407, 408, 424, 433, 444 Immunomodulator, 27, 408 Immunosuppressive, 177, 295, 390, 401, 408 Immunosuppressive therapy, 177, 295, 408 Immunotherapy, 74, 106, 250, 372, 379, 408 Impairment, 211, 377, 379, 398, 408, 416 Implant radiation, 408, 410, 411, 433, 450 In situ, 145, 408 Incision, 408, 410 Incontinence, 408, 419 Incubation, 74, 112, 236, 255, 263, 269, 336, 349, 408, 412, 426

Incubation period, 74, 236, 255, 263, 269, 336, 349, 408, 412, 426 Indicative, 286, 408, 425, 448 Induction, 33, 35, 37, 45, 63, 64, 69, 77, 80, 91, 110, 130, 240, 375, 408 Infancy, 87, 409 Infarction, 389, 409, 417, 428 Infection Control, 14, 211, 288, 320, 322, 324, 342, 409 Infiltration, 409, 430, 450 Influenza, 99, 224, 225, 227, 228, 258, 308, 349, 409, 414 Informed Consent, 338, 409 Infusion, 213, 409, 446 Ingestion, 40, 409, 417, 428 Inhalation, 225, 409, 428 Initiation, 10, 14, 47, 49, 65, 100, 101, 102, 118, 164, 409, 423, 430, 435, 445 Initiator, 115, 409 Inorganic, 409, 414, 442 Insertional, 44, 409 Insight, 22, 57, 58, 77, 409 Insulator, 409, 419 Integrase, 228, 400, 409 Interferon Alfa-2b, 9, 20, 25, 30, 349, 410 Interferon-alpha, 37, 131, 132, 133, 154, 166, 174, 175, 177, 182, 184, 196, 410 Interleukin-2, 95, 107, 110, 410 Interleukins, 77, 410 Intermittent, 13, 397, 410, 413 Internal Medicine, 27, 46, 61, 76, 139, 175, 176, 177, 178, 274, 400, 410 Internal radiation, 410, 411, 433, 450 Interstitial, 381, 410, 411, 421, 435, 450 Intestinal, 34, 275, 281, 384, 410, 414, 415 Intestine, 379, 381, 386, 410, 411 Intoxication, 410, 449 Intracellular, 87, 94, 105, 110, 111, 125, 238, 256, 276, 409, 410, 429, 431, 438, 439, 449 Intrahepatic, 74, 77, 110, 410 Intramuscular, 87, 132, 169, 410, 424 Intramuscular injection, 87, 169, 410 Intravenous, 4, 18, 105, 132, 213, 240, 298, 314, 399, 409, 410, 424 Intrinsic, 373, 398, 410 Invasive, 321, 323, 338, 407, 410 Invertebrates, 410, 414 Involuntary, 378, 397, 410, 420, 434, 440 Ionizing, 374, 396, 410, 433, 449 Ions, 378, 381, 393, 394, 406, 411 Irradiation, 43, 411, 450 Ischemia, 378, 411, 419

Index 459

Isoleucine, 252, 411 Isoniazid, 38, 411 Isopropyl, 248, 411 J Jaundice, 9, 15, 236, 255, 263, 271, 272, 297, 344, 368, 406, 411 Joint, 55, 59, 324, 344, 411, 443 K Kb, 244, 273, 318, 411 Ketone Bodies, 371, 411 Kidney Disease, 212, 213, 217, 221, 318, 328, 334, 351, 356, 411 Kidney Transplantation, 16, 17, 155, 411 Kinetic, 47, 80, 110, 152, 410, 411 L Labile, 33, 387, 411 Laceration, 411, 444 Large Intestine, 386, 392, 410, 411, 434, 440 Latency, 86, 412 Latent, 38, 62, 255, 412, 449 Laxative, 373, 384, 412 Lectin, 84, 412 Lens, 381, 412 Lentivirus, 405, 412 Lethal, 102, 120, 153, 251, 378, 412, 437 Leucine, 84, 122, 252, 412 Leucocyte, 374, 412 Leukemia, 83, 271, 327, 385, 412, 432 Leukocytes, 380, 384, 402, 410, 412, 421, 426, 446 Leukopenia, 250, 412 Library Services, 364, 412 Lidocaine, 169, 412 Life cycle, 50, 55, 79, 83, 138, 228, 399, 412 Life Expectancy, 20, 292, 412 Ligament, 412, 431 Ligands, 35, 259, 412 Ligation, 50, 412 Linkage, 59, 401, 412 Lipid, 51, 177, 232, 261, 376, 412, 413, 419, 424 Lipid Peroxidation, 51, 412, 424 Lipid Peroxides, 51, 413 Lipopolysaccharides, 413, 449 Lipoprotein, 235, 402, 413, 448 Liver Cirrhosis, 7, 50, 51, 79, 127, 140, 215, 217, 242, 249, 260, 264, 272, 275, 345, 350, 413 Liver Regeneration, 104, 413 Localization, 93, 111, 408, 413 Localized, 393, 395, 398, 409, 413, 419, 427, 444, 447

Locomotion, 399, 413, 427 Long Interspersed Nucleotide Elements, 413, 436 Longitudinal study, 52, 71, 290, 413 Long-Term Care, 38, 413 Loop, 57, 110, 121, 236, 263, 277, 278, 413 Low-density lipoprotein, 413 Luminescence, 265, 414 Lupus, 307, 407, 414 Lymph, 383, 396, 405, 406, 414 Lymph node, 383, 414 Lymphadenopathy, 405, 414 Lymphatic, 186, 409, 414, 441, 444 Lymphocyte Count, 371, 414 Lymphocyte Subsets, 134, 414 Lymphocytic, 77, 241, 414 Lymphocytic Choriomeningitis Virus, 77, 241, 414 Lymphoid, 66, 75, 196, 281, 376, 412, 414, 444 Lymphoma, 177, 182, 183, 197, 198, 327, 332, 414 Lytic, 238, 414, 439 M Macrophage, 11, 12, 77, 257, 414 Maculopapular, 414, 427 Major Histocompatibility Complex, 114, 116, 122, 240, 256, 414 Malabsorption, 327, 414 Malaise, 246, 368, 415 Malaria, 75, 89, 415 Malaria, Falciparum, 415 Malaria, Vivax, 415 Malignancy, 5, 224, 415, 424 Malignant, 85, 177, 182, 327, 371, 372, 376, 413, 415, 420, 433, 437, 443 Malnutrition, 51, 373, 378, 381, 415, 419 Malondialdehyde, 154, 415 Mastitis, 415, 439 Matrix metalloproteinase, 122, 415 Measles Virus, 63, 89, 415 Meconium, 141, 415 Mediate, 40, 93, 104, 185, 281, 394, 415 Mediator, 410, 415 Medical Assistance, 127, 415 Medical Records, 5, 415 Medicament, 224, 415 MEDLINE, 26, 319, 327, 328, 415 Megakaryocytes, 250, 380, 416 Meiosis, 416, 419, 443 Melanin, 416, 426, 447 Melanocytes, 416

460 Hepatitis B

Melanoma, 327, 416 Memory, 87, 125, 171, 375, 391, 416 Meninges, 383, 389, 416 Meningitis, 414, 416 Menopause, 44, 416 Menstruation, 416 Mental Disorders, 48, 222, 416 Mental Health, iv, 32, 58, 222, 318, 326, 416, 433 Mental Processes, 393, 416, 432 Mentors, 38, 43, 416 Mercury, 399, 416 Mesenteric, 416, 428 Meta-Analysis, 184, 416 Metabolite, 220, 392, 416, 430 Metastasis, 82, 130, 415, 416 Methanol, 246, 417 Methionine, 176, 235, 236, 252, 392, 417, 443 MI, 102, 110, 124, 142, 152, 178, 370, 417 Mice Minute Virus, 417, 425 Microbe, 417, 445 Microcirculation, 413, 417 Microgram, 267, 417 Microorganism, 386, 417, 425, 449 Micro-organism, 417, 438 Microscopy, 389, 406, 417 Microspheres, 281, 417 Milk Thistle, 417, 439 Milligram, 417 Milliliter, 267, 417 Mineralocorticoids, 372, 389, 417 Mitochondria, 43, 44, 104, 267, 417, 423 Mitochondrial Swelling, 417, 420 Mitogen-Activated Protein Kinase Kinases, 417, 418 Mitogen-Activated Protein Kinases, 103, 121, 178, 418 Mitosis, 377, 418 Mitotic, 151, 418 Mobility, 82, 418 Mode of Transmission, 27, 320, 418 Modeling, 61, 66, 80, 81, 113, 394, 418, 431 Modification, 30, 231, 250, 259, 280, 285, 401, 418, 433, 450 Modulator, 25, 227, 418 Molecule, 35, 82, 90, 124, 225, 246, 254, 256, 263, 271, 278, 376, 378, 379, 387, 393, 394, 397, 402, 406, 409, 412, 418, 422, 424, 427, 428, 433, 434, 439, 445, 448 Monitor, 32, 35, 41, 92, 242, 265, 294, 418, 422

Monoclonal, 112, 117, 118, 134, 185, 246, 272, 314, 411, 418, 433, 437, 450 Monoclonal antibodies, 185, 272, 418, 437 Monocyte, 148, 175, 418 Mononuclear, 96, 124, 185, 198, 251, 418, 446 Monophosphate, 63, 243, 276, 418 Monotherapy, 8, 12, 26, 36, 71, 131, 132, 155, 161, 293, 295, 418 Morbillivirus, 415, 418 Morphogenesis, 56, 60, 101, 111, 119, 419 Morphology, 185, 402, 419 Motion Sickness, 419, 420 Mucilaginous, 415, 419 Mucins, 419, 437 Mucosa, 275, 414, 419, 442 Mucositis, 419, 444 Multiple sclerosis, 147, 309, 419 Multivalent, 259, 270, 419 Multivariate Analysis, 14, 419 Muscle Fibers, 234, 419, 420 Muscular Atrophy, 328, 419 Muscular Dystrophies, 394, 419 Mutagenesis, 44, 65, 67, 70, 73, 80, 101, 419, 431 Mutagenic, 373, 419 Mutagenicity, 252, 253, 419 Mutagens, 399, 419 Myalgia, 409, 419 Mycotoxins, 373, 419 Myelin, 419, 438 Myelitis, 136, 419 Myelogenous, 420 Myeloma, 37, 420 Myocarditis, 393, 420 Myocardium, 417, 420 Myopathy, 307, 420 Myosin, 82, 420 Myositis, 307, 420 Myotonic Dystrophy, 328, 420 Myristate, 248, 420 N Naive, 87, 103, 112, 218, 420 Narcotic, 371, 420 Nasal Mucosa, 409, 420 Nausea, 15, 246, 344, 351, 420, 447 NCI, 1, 47, 221, 317, 385, 420 Necrosis, 35, 58, 234, 271, 308, 377, 404, 409, 417, 420 Need, 3, 6, 16, 18, 20, 23, 27, 28, 29, 36, 41, 58, 69, 71, 76, 87, 209, 228, 239, 243, 244, 247, 253, 255, 265, 283, 284, 285, 289,

Index 461

291, 292, 293, 297, 300, 307, 308, 313, 320, 322, 323, 324, 334, 338, 341, 343, 345, 349, 350, 351, 353, 356, 358, 372, 385, 402, 415, 420, 445 Needle Sharing, 52, 339, 351, 420 Neonatal, 10, 64, 86, 189, 338, 420 Neonatal period, 86, 420 Neoplasia, 327, 420 Neoplasm, 420, 424, 437 Neoplastic, 34, 86, 279, 414, 420, 437 Nephritis, 250, 420 Nephropathy, 165, 200, 411, 421 Nerve, 305, 377, 391, 400, 415, 419, 421, 423, 425, 429, 430, 435, 438, 441, 450 Nervous System, 328, 383, 415, 421, 425 Networks, 55, 72, 77, 82, 421 Neural, 398, 406, 421 Neural tube defects, 398, 421 Neurologic, 66, 405, 421 Neurology, 56, 61, 421 Neuronal, 255, 421 Neurons, 386, 391, 400, 421, 443 Neuropathy, 421, 425 Neurophysiology, 392, 421 Neuroretinitis, 421, 436 Neurotoxicity, 243, 421 Neurotransmitters, 418, 421 Neutrons, 374, 411, 421, 433 Neutropenia, 250, 399, 421 Neutrophils, 96, 250, 402, 412, 421 Nevirapine, 421, 422 Nitrogen, 373, 375, 390, 397, 398, 422 Non-nucleoside, 226, 227, 391, 421, 422 Nosocomial, 10, 422 Nuclei, 83, 274, 374, 388, 395, 397, 401, 418, 421, 422, 423, 432 Nucleic Acid Hybridization, 406, 422 Nucleocapsid, 64, 96, 103, 105, 112, 116, 119, 177, 259, 263, 278, 279, 422 Nucleoprotein, 64, 241, 404, 422 Nucleus, 79, 377, 378, 383, 385, 390, 392, 416, 418, 421, 422, 430, 432, 442, 444 O Observational study, 115, 116, 160, 422 Occult, 8, 12, 72, 115, 135, 142, 160, 162, 422 Occupational Exposure, 156, 211, 285, 286, 299, 322, 324, 342, 422 Odds Ratio, 15, 422, 435 Odour, 377, 422 Oligosaccharides, 84, 85, 423 Oltipraz, 68, 423

Oncogene, 151, 178, 199, 236, 327, 423 Oncogenic, 78, 412, 423 Opacity, 391, 423 Operon, 423, 430 Opportunistic Infections, 371, 423 Optic Nerve, 421, 423, 435 Oral Health, 148, 423 Organ Culture, 423, 445 Organ Transplantation, 32, 423 Organelles, 389, 390, 416, 423 Ori region, 423, 435 Orthohepadnavirus, 404, 423 Osmotic, 373, 417, 423 Osteosarcoma, 423, 432 Outpatient, 23, 41, 167, 423 Overdose, 399, 423 Ovum, 401, 412, 424, 430, 450 Oxaloacetate, 377, 424 Oxazolone, 247, 424 Oxidation, 371, 376, 390, 402, 412, 413, 424 Oxidative Stress, 51, 67, 69, 112, 424 P P53 gene, 70, 167, 424, 432 Palate, 424, 442 Palliative, 424, 444 Pancreas, 371, 379, 380, 392, 400, 424, 441, 446 Pancreatic, 327, 382, 424 Pancreatic cancer, 327, 424 Papilloma, 86, 424 Papillomavirus, 424 Paramedic, 285, 424 Parapoxvirus, 150, 424 Parasite, 85, 424 Parasitic, 256, 424, 446 Parenteral, 195, 211, 225, 230, 234, 263, 269, 281, 320, 424 Paroxysmal, 327, 403, 424, 426, 449 Partial remission, 424, 435 Particle, 89, 101, 225, 231, 234, 241, 254, 259, 274, 279, 404, 424, 439, 440, 445, 449 Parvovirus, 241, 417, 425 Patch, 169, 425 Pathogen, 50, 63, 80, 226, 235, 246, 262, 408, 425 Pathologic, 15, 245, 371, 377, 380, 388, 398, 406, 425, 432 Pathologic Processes, 377, 425 Patient Education, 146, 336, 352, 362, 364, 370, 425 Patient Selection, 20, 425 Pediatric Gastroenterologist, 348, 425

462 Hepatitis B

Pediatrics, 38, 54, 60, 86, 136, 142, 149, 309, 310, 333, 354, 425 Pelvic, 425, 431 Penicillin, 425, 448 Penis, 387, 394, 425 Perceived risk, 61, 425 Percutaneous, 42, 425 Perinatal, 31, 46, 49, 64, 106, 153, 271, 299, 309, 338, 346, 425 Peripheral blood, 124, 198, 410, 425 Peripheral Nervous System, 425, 442 Peripheral Neuropathy, 66, 425, 450 Peritoneum, 426 Peritonitis, 141, 426 Peroxidase, 117, 412, 426 Peroxide, 426 Pertussis, 14, 139, 155, 169, 206, 218, 270, 426, 449 Petrolatum, 395, 426 Pharmacists, 126, 426 Pharmacokinetic, 220, 426 Pharmacologic, 426, 445 Pharynx, 409, 426 Phenolphthalein, 395, 426 Phenotype, 36, 47, 56, 75, 89, 122, 125, 171, 197, 426 Phenylalanine, 98, 426, 447 Phospholipases, 426, 439 Phospholipids, 398, 413, 426, 431 Phosphorus, 381, 427 Phosphorylation, 63, 78, 80, 82, 95, 105, 115, 116, 245, 418, 427, 432 Physical Examination, 9, 212, 215, 216, 383, 427 Physiologic, 32, 380, 416, 427, 430, 434 Physiology, 298, 400, 421, 427 Phytotoxin, 427, 437 Picornavirus, 63, 427 Pigment, 379, 416, 427 Pilot study, 85, 161, 186, 427 Pituitary Gland, 389, 427 Pityriasis, 176, 427 Pityriasis Rosea, 176, 427 Plants, 49, 115, 174, 229, 230, 250, 373, 377, 381, 386, 401, 412, 419, 427, 437, 445, 446, 449 Plasma cells, 376, 420, 427 Plasma protein, 373, 427 Plasmid, 70, 102, 120, 237, 275, 427, 448 Platelet Activation, 427, 439 Platinum, 413, 428 Pneumococcal Infections, 218, 428

Pneumococcal Vaccines, 218, 428 Point Mutation, 49, 159, 428 Poisoning, 410, 416, 420, 428 Polyarteritis Nodosa, 176, 217, 407, 428 Polycystic, 328, 428 Polyethylene, 26, 428 Polymerase Chain Reaction, 12, 17, 56, 126, 128, 135, 159, 185, 197, 428 Polymorphic, 256, 428 Polypeptide, 84, 122, 231, 233, 235, 254, 260, 261, 272, 374, 381, 386, 406, 428, 431, 444, 450 Polyposis, 386, 428 Polysaccharide, 187, 218, 270, 376, 383, 428 Polyvalent, 134, 259, 428 Population Dynamics, 66, 428 Portal Vein, 128, 428 Posterior, 375, 377, 384, 424, 429 Postnatal, 87, 429, 441 Postsynaptic, 429, 439 Potassium, 227, 417, 429 Potentiate, 49, 429 Potentiating, 250, 429 Potentiation, 429, 439 Practice Guidelines, 325, 429 Precancerous, 384, 429 Preclinical, 36, 89, 429 Precursor, 47, 161, 377, 390, 393, 394, 396, 426, 429, 430, 446, 447, 448 Prednisolone, 429 Prednisone, 30, 429 Prenatal, 10, 24, 294, 337, 395, 429 Prenatal Care, 24, 429 Preventive Health Services, 324, 429 Primary Biliary Cirrhosis, 148, 429 Probe, 94, 111, 117, 242, 244, 260, 264, 273, 429 Procainamide, 307, 430 Procaine, 412, 430 Prodrug, 63, 236, 267, 268, 430 Progeny, 83, 388, 430 Progesterone, 430, 441 Prognostic factor, 16, 163, 297, 430 Programmed Instruction, 387, 430 Progression, 7, 8, 21, 25, 38, 46, 52, 65, 73, 79, 298, 375, 430 Progressive, 9, 36, 56, 228, 236, 255, 268, 382, 385, 391, 394, 402, 419, 420, 427, 430, 435 Progressive disease, 36, 430 Promoter, 12, 21, 49, 55, 78, 91, 98, 104, 107, 111, 112, 113, 114, 115, 119, 122,

Index 463

124, 128, 129, 143, 147, 172, 177, 233, 234, 237, 240, 430 Promotor, 21, 275, 430, 435 Prone, 70, 321, 323, 430 Prophase, 419, 430, 443 Proportional, 396, 430 Prospective study, 32, 72, 135, 177, 413, 430 Prostaglandin, 177, 430 Prostaglandins A, 430, 431 Prostate, 327, 379, 431, 446 Prostitution, 45, 431 Protease, 34, 66, 102, 117, 214, 228, 386, 400, 431 Protease Inhibitors, 34, 214, 431 Protective Agents, 69, 431 Protective Clothing, 298, 343, 431 Protein Conformation, 374, 431 Protein Engineering, 263, 279, 431 Protein Folding, 231, 259, 280, 431 Protein Kinase C, 418, 431 Protein p53, 82, 432 Protein S, 254, 277, 290, 328, 329, 376, 380, 401, 431, 432, 437 Protein-Serine-Threonine Kinases, 418, 432 Proteolytic, 50, 374, 387, 432, 437 Protocol, 34, 38, 65, 75, 157, 210, 253, 432 Protons, 374, 406, 410, 432, 433 Proto-Oncogenes, 236, 432 Protozoa, 379, 387, 417, 432 Proximal, 90, 120, 393, 432 Psoriasis, 432, 436 Psychology, 82, 185, 393, 432 Psyllium, 202, 432 Puberty, 229, 255, 372, 432, 444 Public Assistance, 415, 432 Public Policy, 319, 433 Publishing, 4, 30, 88, 250, 291, 292, 294, 298, 433 Pulmonary, 23, 380, 388, 433, 443, 448 Pulse, 58, 418, 433 Purifying, 260, 433 Pyogenic, 433, 438 Q Quality of Life, 62, 75, 357, 433 Quaternary, 431, 433 R Radiation, 250, 389, 396, 397, 399, 407, 410, 411, 433, 437, 449, 450 Radiation therapy, 397, 399, 410, 411, 433, 437, 450

Radioactive, 391, 406, 408, 410, 411, 418, 422, 423, 433, 450 Radiolabeled, 411, 433, 450 Radiological, 425, 433 Radiotherapy, 381, 411, 433, 450 Random Allocation, 433 Randomization, 176, 194, 433 Randomized clinical trial, 187, 434 Reactivation, 5, 13, 56, 131, 138, 141, 177, 182, 184, 196, 197, 294, 434 Reactive Oxygen Species, 43, 45, 51, 67, 434 Reading Frames, 264, 412, 434 Reagent, 188, 392, 434 Recombinant Proteins, 41, 434 Recombination, 100, 104, 121, 138, 388, 401, 434 Reconstitution, 65, 79, 107, 118, 250, 292, 434 Rectum, 376, 381, 386, 392, 400, 408, 411, 431, 434 Recurrence, 11, 19, 76, 137, 140, 200, 213, 229, 253, 255, 384, 434 Red blood cells, 397, 404, 434, 437 Red Nucleus, 377, 434 Refer, 1, 233, 261, 381, 387, 398, 399, 405, 413, 420, 421, 422, 434 Reflex, 44, 434 Refraction, 434, 441 Regeneration, 193, 255, 434 Regimen, 38, 102, 214, 256, 292, 394, 434, 436 Relapse, 12, 22, 26, 128, 294, 435 Relative risk, 24, 57, 435 Remission, 22, 28, 31, 154, 347, 434, 435 Renal failure, 156, 164, 435 Replication Origin, 88, 435 Research Design, 39, 71, 435 Resection, 137, 178, 435 Respiration, 418, 435 Respirators, 269, 435 Respiratory Paralysis, 371, 435 Response Elements, 95, 175, 435 Response rate, 4, 5, 6, 19, 20, 25, 47, 435 Restoration, 434, 435, 444, 449 Retina, 384, 412, 421, 423, 435 Retinitis, 62, 435 Retinoblastoma, 327, 436 Retinoids, 177, 436 Retinol, 86, 436 Retinyl palmitate, 87, 436 Retreatment, 116, 196, 436

464 Hepatitis B

Retroelements, 59, 436 Retrospective, 46, 47, 106, 325, 436 Retrotransposons, 436 Retroviral vector, 93, 436 Retrovirus, 93, 436 Reverse Transcriptase Inhibitors, 214, 251, 436 Rheumatic Diseases, 174, 307, 436 Rheumatism, 436 Rheumatoid, 305, 308, 436 Rheumatoid arthritis, 305, 308, 436 Rhinitis, 381, 436, 439 Ribavirin, 6, 9, 22, 26, 28, 47, 219, 436 Ribonucleic acid, 247, 436 Ribosome, 437, 446 Ricin, 35, 437 Rigidity, 427, 437 Risk factor, 4, 14, 27, 28, 34, 39, 40, 45, 46, 48, 51, 52, 68, 72, 82, 116, 119, 272, 298, 321, 341, 342, 343, 347, 349, 350, 396, 430, 435, 437 Risk patient, 73, 437 Risk-Taking, 52, 437 Rituximab, 141, 437 Rural Population, 150, 437 S Saline, 87, 437 Saliva, 75, 268, 391, 437 Salivary, 390, 392, 424, 437 Salivary glands, 390, 392, 437 Salvage Therapy, 34, 437 Saponins, 437, 441 Sarcoma, 66, 344, 423, 437 Satellite, 268, 404, 437 Schizoid, 437, 449 Schizophrenia, 437, 438, 449 Schizotypal Personality Disorder, 437, 449 Sclerosis, 328, 419, 438 Secondary tumor, 416, 438 Secretory, 50, 282, 438 Sedative, 216, 438 Segregation, 434, 438 Seizures, 424, 438 Selenium, 51, 180, 438 Semen, 18, 66, 268, 351, 394, 431, 438 Sensitization, 247, 392, 438 Sensor, 41, 84, 438 Sensory loss, 419, 438, 444 Septicaemia, 127, 438, 439 Sequence Analysis, 94, 96, 238, 244, 260, 273, 276, 438 Sequence Homology, 277, 438

Sequencing, 47, 65, 70, 85, 135, 428, 439 Seroconversion, 8, 11, 13, 16, 21, 25, 32, 42, 49, 52, 72, 90, 116, 197, 249, 293, 439 Serologic, 23, 27, 136, 338, 349, 407, 439 Serology, 15, 25, 40, 48, 369, 439 Serotypes, 75, 158, 439 Sex Characteristics, 372, 375, 432, 439 Sex Determination, 328, 439 Sexual Partners, 87, 269, 298, 342, 439 Sexually Transmitted Diseases, 18, 25, 81, 163, 269, 439 Shock, 439, 446 Short Interspersed Nucleotide Elements, 436, 439 Signal Transduction, 43, 77, 79, 86, 439 Signs and Symptoms, 5, 20, 428, 435, 439 Silymarin, 191, 417, 439 Sizofiran, 187, 440 Skeleton, 371, 411, 430, 440 Skin Tests, 39, 440 Skull, 389, 421, 440, 443 Small intestine, 379, 384, 385, 394, 406, 410, 440 Smallpox, 440, 447 Smooth muscle, 374, 375, 440, 442 Sneezing, 351, 426, 440 Social Environment, 433, 440 Social Support, 440, 442 Soft tissue, 380, 440 Solvent, 239, 247, 371, 384, 397, 417, 423, 440 Somatic, 372, 406, 416, 418, 425, 440, 443 Sound wave, 215, 440, 447 Spasmodic, 426, 440 Specialist, 54, 348, 358, 440 Specificity, 84, 90, 107, 134, 135, 231, 246, 259, 262, 275, 280, 372, 395, 440 Spectrum, 10, 37, 91, 174, 228, 251, 272, 275, 441 Sperm, 137, 260, 375, 385, 441 Spermatozoa, 438, 441 Spinal cord, 383, 384, 395, 400, 416, 419, 421, 425, 434, 435, 441 Spinal Cord Vascular Diseases, 419, 441 Spinous, 396, 441 Spirochete, 441, 443 Spleen, 390, 414, 441 Splenic Vein, 429, 441 Sporadic, 436, 441 Standard therapy, 4, 38, 441 State Government, 43, 441 Stem cell transplantation, 136, 166, 441

Index 465

Stem Cells, 441 Sterile, 52, 323, 337, 377, 441 Sterility, 390, 441 Sterilization, 343, 441 Steroid, 4, 197, 198, 243, 244, 273, 379, 389, 437, 441 Stimulant, 48, 441, 448 Stimulus, 257, 394, 397, 412, 434, 441 Stomach, 40, 49, 351, 371, 392, 397, 400, 406, 420, 426, 440, 441, 442 Stomatitis, 84, 442 Strand, 57, 88, 91, 120, 178, 245, 271, 428, 442 Stress, 5, 19, 51, 73, 74, 84, 91, 193, 194, 239, 284, 285, 309, 389, 418, 420, 424, 436, 442 Stress management, 285, 442 Stringency, 244, 273, 442 Stroke, 40, 222, 318, 382, 442 Stromal, 380, 442 Stromal Cells, 380, 442 Structure-Activity Relationship, 69, 121, 442 Subacute, 409, 442 Subarachnoid, 403, 442 Subclinical, 10, 226, 409, 438, 442 Subcutaneous, 394, 400, 424, 442 Subspecies, 440, 442, 447 Substance P, 6, 416, 434, 438, 442 Substrate, 84, 105, 396, 442 Sulfates, 227, 442 Sulfur, 392, 397, 411, 417, 442 Sulfuric acid, 442, 443 Supplementation, 86, 188, 197, 200, 443 Support group, 285, 336, 346, 370, 443 Suppression, 11, 30, 35, 63, 76, 112, 155, 212, 250, 389, 443 Suppurative, 127, 400, 443 Surfactant, 248, 443 Survival Rate, 13, 17, 443 Symphysis, 431, 443 Symptomatic, 46, 240, 272, 443 Synaptic, 439, 443 Synergistic, 51, 195, 241, 443 Syphilis, 25, 196, 289, 443 Systemic, 33, 47, 49, 312, 380, 393, 396, 398, 407, 409, 411, 429, 433, 442, 443, 445, 447, 450 T Telangiectasia, 328, 443 Telomerase, 151, 443 Temporal, 63, 107, 211, 308, 403, 443

Teratogenic, 373, 443 Terminator, 386, 443, 450 Tetani, 270, 443, 444 Tetanic, 443, 444 Tetanus, 14, 87, 139, 155, 169, 270, 443 Thalamic, 377, 444 Thalamic Diseases, 377, 444 Therapeutics, 5, 63, 80, 136, 185, 188, 240, 253, 279, 313, 444 Thermal, 393, 421, 428, 444 Thimerosal, 149, 309, 444 Threonine, 123, 235, 236, 417, 431, 432, 444 Thrombin, 398, 431, 444 Thrombocytopenia, 127, 250, 444 Thrombomodulin, 431, 444 Thrombosis, 128, 432, 442, 444 Thymidine, 115, 444 Thymidine Kinase, 115, 444 Thymosin, 5, 9, 32, 174, 175, 177, 178, 179, 228, 314, 444 Thymus, 407, 414, 444 Thymus Gland, 444 Thyroid, 244, 273, 444, 447 Thyroxine, 373, 426, 444 Time Management, 442, 445 Tin, 425, 428, 445 Tissue Culture, 56, 70, 266, 267, 445 Titre, 13, 445 Tolerance, 37, 64, 110, 220, 234, 240, 281, 295, 372, 445 Tonic, 250, 445 Topical, 228, 247, 312, 397, 406, 426, 444, 445 Toxicity, 9, 33, 36, 38, 52, 69, 71, 83, 87, 228, 252, 253, 394, 416, 445 Toxicology, 36, 77, 320, 445 Toxins, 28, 269, 376, 395, 409, 418, 419, 445 Toxoid, 87, 270, 445 Trachea, 426, 444, 445 Transcription Factors, 45, 106, 109, 112, 195, 240, 435, 445 Transduction, 79, 86, 102, 271, 439, 445 Transfection, 83, 262, 380, 445 Transfer Factor, 407, 445 Transferases, 402, 445 Transforming Growth Factor beta, 43, 446 Transfusion, 13, 18, 36, 44, 167, 197, 290, 404, 446 Translating, 233, 446 Translation, 50, 83, 260, 267, 434, 446 Translational, 49, 446 Translocation, 57, 90, 98, 446

466 Hepatitis B

Trauma, 185, 420, 446 Trichomonas, 54, 446 Tropism, 56, 113, 124, 271, 446 Tuberculosis, 38, 39, 62, 75, 354, 388, 411, 414, 446 Tuberculostatic, 411, 446 Tuberous Sclerosis, 328, 446 Tumor marker, 379, 446 Tumor Necrosis Factor, 43, 55, 77, 110, 124, 446 Tumor suppressor gene, 34, 70, 424, 446 TYPHI, 75, 120, 447 Typhoid fever, 447 Tyrosine, 79, 127, 198, 252, 393, 447 U Ulcer, 394, 447 Ultrasound test, 348, 447 Unconscious, 407, 447 Uracil, 108, 109, 220, 447 Uremia, 435, 447 Urethra, 425, 431, 447 Urinate, 447, 449 Urine, 10, 40, 67, 113, 212, 215, 216, 260, 271, 297, 344, 351, 380, 404, 408, 411, 447 Urocanic Acid, 138, 447 Urogenital, 402, 447 Ursodeoxycholic Acid, 9, 447 Uterus, 383, 416, 430, 447, 448 V Vaccine adjuvant, 248, 293, 447 Vaccinia, 279, 447 Vaccinia Virus, 279, 447 Vagina, 383, 416, 448 Vaginal, 337, 344, 352, 448 Valine, 252, 448 Valves, 435, 448 Varicella, 206, 220, 227, 448 Variola, 447, 448 Vascular, 271, 384, 403, 409, 413, 417, 441, 448 Vasculitis, 307, 428, 448 Vasodilator, 394, 406, 448 Vector, 33, 75, 109, 120, 224, 234, 235, 237, 253, 267, 271, 275, 409, 445, 447, 448 Vein, 410, 422, 428, 437, 441, 448 Venereal, 443, 448 Venous, 391, 432, 448 Ventricle, 433, 448 Vesicular, 49, 84, 405, 440, 448 Veterinary Medicine, 319, 448

Vibrio, 384, 448 Vibrio cholerae, 384, 448 Viraemia, 32, 448 Viral Load, 12, 36, 51, 69, 213, 217, 247, 265, 295, 448 Viral Regulatory Proteins, 83, 448 Viral vector, 83, 279, 448 Viremia, 55, 68, 91, 111, 210, 264, 380, 448 Virion, 56, 78, 90, 102, 110, 111, 143, 264, 378, 404, 422, 448 Virulence, 85, 378, 445, 449 Virus Activation, 142, 449 Virus Diseases, 252, 376, 449 Virus Replication, 7, 28, 56, 86, 88, 90, 98, 99, 101, 104, 105, 107, 108, 109, 110, 112, 115, 116, 118, 120, 124, 127, 165, 187, 268, 275, 449 Vitro, 34, 35, 36, 37, 41, 44, 56, 57, 67, 80, 84, 88, 89, 91, 99, 100, 101, 107, 108, 109, 112, 115, 121, 129, 138, 148, 157, 170, 176, 187, 188, 192, 193, 194, 197, 220, 233, 239, 267, 408, 428, 439, 445, 449 Vivo, 35, 36, 41, 47, 58, 59, 63, 66, 67, 70, 71, 74, 77, 84, 88, 102, 103, 105, 107, 109, 111, 112, 115, 121, 122, 157, 176, 178, 187, 188, 231, 242, 267, 408, 413, 449 Void, 71, 449 Voluntary Health Agencies, 407, 449 W Warts, 289, 406, 449 Waste Management, 323, 449 White blood cell, 215, 250, 376, 380, 385, 412, 414, 418, 420, 421, 427, 449 Whooping Cough, 426, 449 Windpipe, 426, 444, 449 Withdrawal, 154, 190, 243, 250, 449 Wound Healing, 415, 449 X Xenograft, 375, 449 X-ray, 212, 215, 216, 252, 399, 411, 422, 433, 449, 450 X-ray therapy, 411, 450 Y Yeasts, 84, 399, 426, 450 Z Zalcitabine, 411, 450 Zoster, 206, 220, 227, 450 Zygote, 388, 450 Zymogen, 431, 450

Index 467

468 Hepatitis B

Hepatitis B - 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

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

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

B-Cell Lymphoma - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Butternut Squash: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

Premenstrual Dysphoric Disorder - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Anagrelide: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Peanut Allergy: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Cauda Equina Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Magnesium Citrate: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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Dermabrasion: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Septra: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

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

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

Hepatitis B - 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

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

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

B-Cell Lymphoma - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Butternut Squash: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

Premenstrual Dysphoric Disorder - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Anagrelide: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Peanut Allergy: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Cauda Equina Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Magnesium Citrate: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

Body Dysmorphic Disorder: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

Dermabrasion: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Septra: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

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

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

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