THE 2002 OFFICIAL PATIENT’S SOURCEBOOK
on
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 Ó2002 by ICON Group International, Inc. Copyright Ó2002 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: Tiffany LaRochelle 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 as a substitute for consultation with your physician. All matters regarding your health require medical supervision. 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, in close consultation with a qualified physician. The reader is advised to always check product information (package inserts) for changes and new information regarding dose and contraindications before taking 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., 1960The 2002 Official Patient’s Sourcebook on Hepatitis C: Revised and Updated for the Internet Age/James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary and index. ISBN: 0-597-83241-2 1. Hepatitis C-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 or as a substitute for consultation with licensed medical professionals. 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, or the authors are not responsible for the content of any Web pages nor publications referenced in this publication.
Copyright Notice If a physician wishes to copy limited passages from this sourcebook for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications are copyrighted. 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:
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Dedication To the healthcare professionals dedicating their time and efforts to the study of hepatitis C.
Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this sourcebook which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which directly or indirectly are dedicated to hepatitis C. All of the Official Patient’s Sourcebooks 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 sourcebook. 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 LaRochelle 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 the Official Patient’s Sourcebook series published 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 the Official Patient’s Sourcebook series published by ICON Health Publications.
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About ICON Health Publications In addition to hepatitis C, Official Patient’s Sourcebooks are available for the following related topics: ·
The Official Patient's Sourcebook on Alcoholism
·
The Official Patient's Sourcebook on Anabolic Steroid Dependence
·
The Official Patient's Sourcebook on Club Drug Dependence
·
The Official Patient's Sourcebook on Cocaine Dependence
·
The Official Patient's Sourcebook on Dextromethorphan Dependence
·
The Official Patient's Sourcebook on Dissociative Drug Dependence
·
The Official Patient's Sourcebook on Ghb Dependence
·
The Official Patient's Sourcebook on Heroin Dependence
·
The Official Patient's Sourcebook on Inhalants Dependence
·
The Official Patient's Sourcebook on Ketamine Dependence
·
The Official Patient's Sourcebook on Lsd Dependence
·
The Official Patient's Sourcebook on Marijuana Dependence
·
The Official Patient's Sourcebook on Mdma Dependence
·
The Official Patient's Sourcebook on Methamphetamine Dependence
·
The Official Patient's Sourcebook on Nicotine Dependence
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The Official Patient's Sourcebook on Pcp Dependence
·
The Official Patient's Sourcebook on Prescription Cns Depressants Dependence
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The Official Patient's Sourcebook on Prescription Drug Dependence
·
The Official Patient's Sourcebook on Prescription Opioids Dendedence
·
The Official Patient's Sourcebook on Prescription Stimulants Dependence
·
The Official Patient's Sourcebook on Rohypnol Dependence
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
Contents vii
Table of Contents INTRODUCTION ................................................................................................................................. 1 Overview ....................................................................................................................................... 1 Organization ................................................................................................................................. 3 Scope.............................................................................................................................................. 3 Moving Forward............................................................................................................................ 4 PART I: THE ESSENTIALS ............................................................................................................. 7 CHAPTER 1. THE ESSENTIALS ON HEPATITIS C: GUIDELINES ......................................................... 9 Overview ....................................................................................................................................... 9 What Is Hepatitis C? ................................................................................................................... 12 Hepatitis C Infection ................................................................................................................... 12 Transmission of Hepatitis C Virus.............................................................................................. 13 Injection Drug Use and Hepatitis C Infection ............................................................................ 14 Treatment .................................................................................................................................... 15 Screening and Prevention ........................................................................................................... 15 More Guideline Sources .............................................................................................................. 16 Vocabulary Builder...................................................................................................................... 33 CHAPTER 2. SEEKING GUIDANCE ................................................................................................... 37 Overview ..................................................................................................................................... 37 Associations and Hepatitis C....................................................................................................... 37 Finding More Associations ......................................................................................................... 43 Finding Drug Treatment and Alcohol Abuse Treatment Programs ........................................... 45 Finding Doctors........................................................................................................................... 46 Selecting Your Doctor ................................................................................................................. 47 Working with Your Doctor ......................................................................................................... 48 Broader Health-Related Resources .............................................................................................. 49 Vocabulary Builder...................................................................................................................... 50 CHAPTER 3. CLINICAL TRIALS AND HEPATITIS C.......................................................................... 51 Overview ..................................................................................................................................... 51 Recent Trials on Hepatitis C ....................................................................................................... 54 Benefits and Risks........................................................................................................................ 79 Keeping Current on Clinical Trials ............................................................................................. 82 General References....................................................................................................................... 83 Vocabulary Builder...................................................................................................................... 84 PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL ........................... 89 CHAPTER 4. STUDIES ON HEPATITIS C ........................................................................................... 91 Overview ..................................................................................................................................... 91 The Combined Health Information Database .............................................................................. 91 Federally-Funded Research on Hepatitis C ................................................................................. 97 E-Journals: PubMed Central ..................................................................................................... 110 The National Library of Medicine: PubMed.............................................................................. 129 Vocabulary Builder.................................................................................................................... 138 CHAPTER 5. PATENTS ON HEPATITIS C........................................................................................ 147 Overview ................................................................................................................................... 147 Patents on Hepatitis C............................................................................................................... 148 Patent Applications on Hepatitis C........................................................................................... 161 Keeping Current ........................................................................................................................ 175 Vocabulary Builder.................................................................................................................... 175 CHAPTER 6. BOOKS ON HEPATITIS C ........................................................................................... 179 Overview ................................................................................................................................... 179
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Book Summaries: Federal Agencies ........................................................................................... 179 Book Summaries: Online Booksellers ........................................................................................ 183 The National Library of Medicine Book Index........................................................................... 185 Chapters on Hepatitis C ............................................................................................................ 189 General Home References .......................................................................................................... 196 Vocabulary Builder.................................................................................................................... 196 CHAPTER 7. MULTIMEDIA ON HEPATITIS C................................................................................. 199 Overview ................................................................................................................................... 199 Video Recordings....................................................................................................................... 199 Audio Recordings ...................................................................................................................... 203 Bibliography: Multimedia on Hepatitis C ................................................................................. 204 Vocabulary Builder.................................................................................................................... 207 CHAPTER 8. PERIODICALS AND NEWS ON HEPATITIS C.............................................................. 209 Overview ................................................................................................................................... 209 News Services & Press Releases ................................................................................................ 209 Newsletter Articles .................................................................................................................... 219 Academic Periodicals covering Hepatitis C............................................................................... 221 CHAPTER 9. PHYSICIAN GUIDELINES AND DATABASES .............................................................. 223 Overview ................................................................................................................................... 223 NIH Guidelines ......................................................................................................................... 223 NIH Databases .......................................................................................................................... 224 Other Commercial Databases .................................................................................................... 236 The Genome Project and Hepatitis C ........................................................................................ 236 Specialized References ............................................................................................................... 241 Vocabulary Builder.................................................................................................................... 242 CHAPTER 10. DISSERTATIONS ON HEPATITIS C........................................................................... 243 Overview ................................................................................................................................... 243 Dissertations on Hepatitis C ..................................................................................................... 243 Keeping Current ........................................................................................................................ 245 PART III. APPENDICES .............................................................................................................. 247 APPENDIX A. RESEARCHING YOUR MEDICATIONS ..................................................................... 249 Overview ................................................................................................................................... 249 Your Medications: The Basics ................................................................................................... 250 Learning More about Your Medications ................................................................................... 251 Commercial Databases............................................................................................................... 253 Contraindications and Interactions (Hidden Dangers)............................................................. 255 A Final Warning ....................................................................................................................... 256 General References..................................................................................................................... 256 Vocabulary Builder.................................................................................................................... 257 APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE ............................................................... 259 Overview ................................................................................................................................... 259 What Is CAM? .......................................................................................................................... 259 What Are the Domains of Alternative Medicine? ..................................................................... 260 Can Alternatives Affect My Treatment?................................................................................... 263 Finding CAM References on Hepatitis C.................................................................................. 264 Additional Web Resources......................................................................................................... 279 General References..................................................................................................................... 281 Vocabulary Builder.................................................................................................................... 282 APPENDIX C. RESEARCHING NUTRITION..................................................................................... 283 Overview ................................................................................................................................... 283 Food and Nutrition: General Principles .................................................................................... 284 Finding Studies on Hepatitis C ................................................................................................. 288 Federal Resources on Nutrition................................................................................................. 292
Contents
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Additional Web Resources......................................................................................................... 293 Vocabulary Builder.................................................................................................................... 294 APPENDIX D. FINDING MEDICAL LIBRARIES ............................................................................... 297 Overview ................................................................................................................................... 297 Preparation ................................................................................................................................ 297 Finding a Local Medical Library ............................................................................................... 298 Medical Libraries Open to the Public ........................................................................................ 298 APPENDIX E. PRINCIPLES OF DRUG ADDICTION TREATMENT .................................................... 305 Overview ................................................................................................................................... 305 Principles of Effective Treatment .............................................................................................. 305 What Is Drug Addiction?.......................................................................................................... 308 Frequently Asked Questions ..................................................................................................... 309 Drug Addiction Treatment in the United States ...................................................................... 316 General Categories of Treatment Programs .............................................................................. 317 Treating Criminal Justice-Involved Drug Abusers and Addicts .............................................. 320 Scientifically-Based Approaches to Drug Addiction Treatment ............................................... 321 Resources ................................................................................................................................... 329 Selected NIDA Educational Resources on Drug Addiction Treatment .................................... 329 Vocabulary Builder.................................................................................................................... 333 APPENDIX F. MORE ON HEPATITIS C........................................................................................... 335 Overview ................................................................................................................................... 335 What Causes Hepatitis C?......................................................................................................... 336 How Could I Get Hepatitis C? .................................................................................................. 336 Could I Get Hepatitis C from a Blood Transfusion? ................................................................. 336 What Are the Symptoms? ......................................................................................................... 337 What Are the Tests for Hepatitis C? ......................................................................................... 337 How Is Hepatitis C Treated? ..................................................................................................... 337 How Can I Protect Myself?....................................................................................................... 338 For More Information................................................................................................................ 338 APPENDIX G. NIH CONSENSUS STATEMENT ON MANAGEMENT OF HEPATITIS C.................... 339 Overview ................................................................................................................................... 339 Abstract ..................................................................................................................................... 340 What Is Hepatitis C? ................................................................................................................. 341 What Is the Natural History of Hepatitis C? ............................................................................ 343 Diagnosing and Monitoring Hepatitis C .................................................................................. 346 What Is the Most Effective Therapy for Hepatitis C? ............................................................... 349 Which Patients With Hepatitis C Should Be Treated?.............................................................. 352 Prevent Transmission of Hepatitis C ........................................................................................ 353 Areas for Future Research ......................................................................................................... 355 Conclusions and Recommendations .......................................................................................... 356 Vocabulary Builder.................................................................................................................... 359 ONLINE GLOSSARIES ............................................................................................................... 361 Online Dictionary Directories................................................................................................... 365 HEPATITIS C GLOSSARY.......................................................................................................... 367 General Dictionaries and Glossaries ......................................................................................... 387 INDEX.............................................................................................................................................. 389
Introduction
1
INTRODUCTION Overview Dr. C. Everett Koop, former U.S. Surgeon General, once said, “The best prescription is knowledge.”1 The Agency for Healthcare Research and Quality (AHRQ) of the National Institutes of Health (NIH) echoes this view and recommends that every patient incorporate education into the treatment process. According to the AHRQ: Finding out more about your condition is a good place to start. By contacting groups that support your condition, visiting your local library, and searching on the Internet, you can find good information to help guide your treatment decisions. Some information may be hard to find—especially if you don’t know where to look.2 As the AHRQ mentions, finding the right information is not an obvious task. Though many physicians and public officials had thought that the emergence of the Internet would do much to assist patients in obtaining reliable information, 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.3
Quotation from http://www.drkoop.com. The Agency for Healthcare Research and Quality (AHRQ): http://www.ahcpr.gov/consumer/diaginfo.htm. 3 From the NIH, National Cancer Institute (NCI): http://cancertrials.nci.nih.gov/beyond/evaluating.html. 1 2
2
Hepatitis C
Since the late 1990s, physicians have seen a general increase in patient Internet usage rates. Patients frequently enter their doctor’s offices with printed Web pages of home remedies in the guise of latest medical research. This scenario is so common that doctors often spend more time dispelling misleading information than guiding patients through sound therapies. The 2002 Official Patient’s Sourcebook on Hepatitis C has been created for patients who have decided to make education and research an integral part of the treatment process. The pages that follow will tell you where and how to look for information covering virtually all topics related to hepatitis C, from the essentials to the most advanced areas of research. The title of this book includes the word “official.” This reflects the fact that the sourcebook draws from public, academic, government, and peerreviewed research. Selected readings from various agencies are reproduced to give you some of the latest official information available to date on hepatitis C. Given patients’ increasing sophistication in using the Internet, abundant references to reliable Internet-based resources are provided throughout this sourcebook. Where possible, guidance is provided on how to obtain free-ofcharge, primary research results as well as more detailed information via the Internet. E-book and electronic versions of this sourcebook are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). Hard copy users of this sourcebook can type cited Web addresses directly into their browsers to obtain access to the corresponding sites. Since we are working with ICON Health Publications, hard copy Sourcebooks are frequently updated and printed on demand to ensure that the information provided is current. In addition to extensive references accessible via the Internet, every chapter presents a “Vocabulary Builder.” Many health guides offer glossaries of technical or uncommon terms in an appendix. In editing this sourcebook, we have decided to place a smaller glossary within each chapter that covers terms used in that chapter. Given the technical nature of some chapters, you may need to revisit many sections. Building one’s vocabulary of medical terms in such a gradual manner has been shown to improve the learning process. We must emphasize that no sourcebook on hepatitis C should affirm that a specific diagnostic procedure or treatment discussed in a research study, patent, or doctoral dissertation is “correct” or your best option. This sourcebook is no exception. Each patient is unique. Deciding on appropriate
Introduction
3
options is always up to the patient in consultation with their physician and healthcare providers.
Organization This sourcebook is organized into three parts. Part I explores basic techniques to researching hepatitis C (e.g. finding guidelines on diagnosis, treatments, and prognosis), followed by a number of topics, including information on how to get in touch with organizations, associations, or other patient networks dedicated to hepatitis C. It also gives you sources of information that can help you find a doctor in your local area specializing in treating hepatitis C. Collectively, the material presented in Part I is a complete primer on basic research topics for patients with hepatitis C. Part II moves on to advanced research dedicated to hepatitis C. Part II is intended for those willing to invest many hours of hard work and study. It is here that we direct you to the latest scientific and applied research on hepatitis C. When possible, contact names, links via the Internet, and summaries are provided. It is in Part II where the vocabulary process becomes important as authors publishing advanced research frequently use highly specialized language. In general, every attempt is made to recommend “free-to-use” options. Part III provides appendices of useful background reading for all patients with hepatitis C or related disorders. The appendices are dedicated to more pragmatic issues faced by many patients with hepatitis C. Accessing materials via medical libraries may be the only option for some readers, so a guide is provided for finding local medical libraries which are open to the public. Part III, therefore, focuses on advice that goes beyond the biological and scientific issues facing patients with hepatitis C.
Scope While this sourcebook covers hepatitis C, your doctor, research publications, and specialists may refer to your condition using a variety of terms. Therefore, you should understand that hepatitis C is often considered a synonym or a condition closely related to the following: ·
Hcv
·
Nanb Hepatitis
·
Non-a Hepatitis
4
Hepatitis C
·
Non-a, Non-b Hepatitis
·
Non-b Hepatitis
In addition to synonyms and related conditions, physicians may refer to hepatitis C using certain coding systems. The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) is the most commonly used system of classification for the world’s illnesses. Your physician may use this coding system as an administrative or tracking tool. The following classification is commonly used for hepatitis C:4 ·
070 viral hepatitis
·
070.4 other specified viral hepatitis with hepatic coma
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070.41 acute or unspecified hepatitis c with hepatic coma
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070.44 chronic hepatitis c with hepatic coma
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070.5 other specified viral hepatitis without mention of hepatic coma
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070.51 acute or unspecified hepatitis c without mention of hepatic coma
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070.54 chronic hepatitis c without mention of hepatic coma
For the purposes of this sourcebook, we have attempted to be as inclusive as possible, looking for official information for all of the synonyms relevant to hepatitis C. You may find it useful to refer to synonyms when accessing databases or interacting with healthcare professionals and medical librarians.
Moving Forward Since the 1980s, the world has seen a proliferation of healthcare guides covering most illnesses. Some are written by patients or their family members. These generally take a layperson’s approach to understanding and coping with an illness or disorder. They can be uplifting, encouraging, and highly supportive. Other guides are authored by physicians or other healthcare providers who have a more clinical outlook. Each of these two styles of guide has its purpose and can be quite useful.
4 This list is based on the official version of the World Health Organization’s 9th Revision, International Classification of Diseases (ICD-9). According to the National Technical Information Service, “ICD-9CM extensions, interpretations, modifications, addenda, or errata other than those approved by the U.S. Public Health Service and the Health Care Financing Administration are not to be considered official and should not be utilized. Continuous maintenance of the ICD-9-CM is the responsibility of the federal government.”
Introduction
5
As editors, we have chosen a third route. We have chosen to expose you to as many sources of official and peer-reviewed information as practical, for the purpose of educating you about basic and advanced knowledge as recognized by medical science today. You can think of this sourcebook as your personal Internet age reference librarian. Why “Internet age”? All too often, patients diagnosed with hepatitis C will log on to the Internet, type words into a search engine, and receive several Web site listings which are mostly irrelevant or redundant. These patients are left to wonder where the relevant information is, and how to obtain it. Since only the smallest fraction of information dealing with hepatitis C is even indexed in search engines, a non-systematic approach often leads to frustration and disappointment. With this sourcebook, we hope to direct you to the information you need that you would not likely find using popular Web directories. Beyond Web listings, in many cases we will reproduce brief summaries or abstracts of available reference materials. These abstracts often contain distilled information on topics of discussion. While we focus on the more scientific aspects of hepatitis C, there is, of course, the emotional side to consider. Later in the sourcebook, we provide a chapter dedicated to helping you find peer groups and associations that can provide additional support beyond research produced by medical science. We hope that the choices we have made give you the most options available in moving forward. In this way, we wish you the best in your efforts to incorporate this educational approach into your treatment plan. The Editors
7
PART I: THE ESSENTIALS
ABOUT PART I Part I has been edited to give you access to what we feel are “the essentials” on hepatitis C. The essentials of a disease typically include the definition or description of the disease, a discussion of who it affects, the signs or symptoms associated with the disease, tests or diagnostic procedures that might be specific to the disease, and treatments for the disease. Your doctor or healthcare provider may have already explained the essentials of hepatitis C to you or even given you a pamphlet or brochure describing hepatitis C. Now you are searching for more in-depth information. As editors, we have decided, nevertheless, to include a discussion on where to find essential information that can complement what your doctor has already told you. In this section we recommend a process, not a particular Web site or reference book. The process ensures that, as you search the Web, you gain background information in such a way as to maximize your understanding.
Guidelines
CHAPTER 1. GUIDELINES
THE
ESSENTIALS
ON
HEPATITIS
9
C:
Overview Official agencies, as well as federally-funded institutions supported by national grants, frequently publish a variety of guidelines on hepatitis C. 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. The great advantage of guidelines over other sources is that they are often written with the patient in mind. Since new guidelines on hepatitis C 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.
The National Institutes of Health (NIH)5 The National Institutes of Health (NIH) is the first place to search for relatively current patient guidelines and fact sheets on hepatitis C. Originally founded in 1887, the NIH is one of the world’s foremost medical research centers and the federal focal point for medical research in the United States. At any given time, the NIH supports some 35,000 research grants at universities, medical schools, and other research and training institutions, both nationally and internationally. The rosters of those who have conducted research or who have received NIH support over the years include the world’s most illustrious scientists and physicians. Among them are 97 scientists who have won the Nobel Prize for achievement in medicine.
5
Adapted from the NIH: http://www.nih.gov/about/NIHoverview.html.
10 Hepatitis C
There is no guarantee that any one Institute will have a guideline on a specific disease, though the National Institutes of Health collectively publish over 600 guidelines for both common and rare diseases. The best way to access NIH guidelines is via the Internet. Although the NIH is organized into many different Institutes and Offices, the following is a list of key Web sites where you are most likely to find NIH clinical guidelines and publications dealing with hepatitis C and associated conditions: ·
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
·
National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines available at http://www.nlm.nih.gov/medlineplus/healthtopics.html
·
National Institute on Drug Abuse (NIDA); guidelines on abused drugs at http://www.nida.nih.gov/DrugAbuse.html
Among these, the National Institute on Drug Abuse is particularly noteworthy.6 NIDA was established in 1974, and in October 1992 it became part of the National Institutes of Health, Department of Health and Human Services. The Institute is organized into divisions and offices, each of which plays an important role in programs of drug abuse research. NIDA’s mission is to lead the Nation in bringing the power of science to bear on drug abuse and addiction. This charge has two critical components. The first is the strategic support and conduct of research across a broad range of disciplines. The second is to ensure the rapid and effective dissemination and use of the results of that research to significantly improve drug abuse and addiction prevention, treatment, and policy. NIDA supports over 85 percent of the world’s research on the health aspects of drug abuse and addiction. NIDA supported science addresses the most fundamental and essential questions about drug abuse, ranging from the molecule to managed care, and from DNA to community outreach research. NIDA is not only seizing upon unprecedented opportunities and technologies to further understanding of how drugs of abuse affect the brain and behavior, but also working to ensure the rapid and effective transfer of scientific data to policy makers, drug abuse practitioners, other health care practitioners and the general public. The NIDA web page is an important part of this effort (http://www.nida.nih.gov/). Before citing NIDA’s most
The section is reproduced or adapted from the NIDA: http://www.nida.nih.gov/NIDAWelcome.html#Mission. For the remainder of this book, “adapted” signifies attributed “reproduction” with formatting and other minimal editorial changes. 6
Guidelines 11
recent guideline on hepatitis C, the discussion below reproduces NIDA’s general overview of drug abuse and addiction. Understanding Drug Abuse and Addiction7 Many people view drug abuse and addiction as strictly a social problem. Parents, teens, older adults, and other members of the community tend to characterize people who take drugs as morally weak or as having criminal tendencies. They believe that drug abusers and addicts should be able to stop taking drugs if they are willing to change their behavior. These myths have not only stereotyped those with drug-related problems, but also their families, their communities, and the health care professionals who work with them. Drug abuse and addiction comprise a public health problem that affects many people and has wide-ranging social consequences. It is NIDA’s goal to help the public replace its myths and long-held mistaken beliefs about drug abuse and addiction with scientific evidence that addiction is a chronic, relapsing, and treatable disease. Addiction does begin with drug abuse when an individual makes a conscious choice to use drugs, but addiction is not just “a lot of drug use.” Recent scientific research provides overwhelming evidence that not only do drugs interfere with normal brain functioning creating powerful feelings of pleasure, but they also have long-term effects on brain metabolism and activity. At some point, changes occur in the brain that can turn drug abuse into addiction, a chronic, relapsing illness. Those addicted to drugs suffer from a compulsive drug craving and usage and cannot quit by themselves. Treatment is necessary to end this compulsive behavior. A variety of approaches are used in treatment programs to help patients deal with these cravings and possibly avoid drug relapse. NIDA research shows that addiction is clearly treatable. Through treatment that is tailored to individual needs, patients can learn to control their condition and live relatively normal lives. Treatment can have a profound effect not only on drug abusers, but on society as a whole by significantly improving social and psychological functioning, decreasing related criminality and violence, and reducing the spread of AIDS. It can also dramatically reduce the costs to society of drug abuse. 7
Adapted from http://165.112.78.61/Infofax/understand.html.
12 Hepatitis C
Understanding drug abuse also helps in understanding how to prevent use in the first place. Results from NIDA-funded prevention research have shown that comprehensive prevention programs that involve the family, schools, communities, and the media are effective in reducing drug abuse. It is necessary to keep sending the message that it is better to not start at all than to enter rehabilitation if addiction occurs. A tremendous opportunity exists to effectively change the ways in which the public understands drug abuse and addiction because of the wealth of scientific data NIDA has amassed. Overcoming misconceptions and replacing ideology with scientific knowledge is the best hope for bridging the “great disconnect” - the gap between the public perception of drug abuse and addiction and the scientific facts. The National Institutes of Health has recently published the following guideline for hepatitis C:
What Is Hepatitis C?8 Hepatitis C infection is caused by the hepatitis C virus, also known as HCV, a virus that infects cells in the liver. HCV is one of several viruses (hepatitis A, hepatitis B) that can cause an inflammation of the liver. Chronic infection with HCV can result in cirrhosis (liver scarring) or primary liver cancer (hepatocellular carcinoma).
Hepatitis C Infection ·
Hepatitis C infection is estimated to be responsible for most chronic liver disease in the United States and 8,000 to 10,000 deaths annually.
·
Acquisition of hepatitis C infection is very rapid among new drug injectors with 50 to 80 percent infected within 6 to 12 months.
·
Research has shown that hepatitis C infection is widespread in populations of experienced drug injectors, with rates in many areas of the United States exceeding 80 percent.
·
Is prevalent in many countries worldwide.
·
Is the most common chronic blood-borne infection in the United States, infecting an estimated 4 million Americans.
Adapted from The National Institute on Drug Abuse: http://165.112.78.61/HepatitisAlert/HepatitisAlert.html.
8
Guidelines 13
·
Is transmitted primarily through direct exposure to infected blood.
·
Is linked to injection drug use, which accounts for most HCV transmission in the United States.
·
Is estimated to be responsible for most chronic liver disease in the United States and 8,000 to 10,000 deaths annually.
·
Is the single most common reason for liver transplants in the United States.
·
The highest rates of new infection are among persons 20 to 39 years old and the highest rates of chronic infection are among persons 30 to 49 years old.
Transmission of Hepatitis C Virus Sharing contaminated needles is the most common route of infection. Injection drug use is responsible for at least 60 percent of HCV infection in the United States. The risk of sexual transmission of HCV is much lower than the risk associated with contaminated needles, but still present. Sexual transmission is estimated to account for less than 20 percent of HCV transmission. The highest rates of sexual transmission are associated with multiple sex partners, and the increased risk may be associated with traumatic sex that results in blood exposure. Long-term monogamous sexual partners of persons infected with HCV have very low rates of becoming infected (0 to 4 percent). Prior to the discovery of the virus and the development of a screening test for blood, many people were infected through contaminated blood transfusions. Since 1992, infection from blood transfusions is rare in the United States. The average rate of transmission from an infected pregnant mother to her infant is 5 to 6 percent (range 0 to 25 percent). This risk increases if the mother is infected with both HCV and HIV, with reported transmission rates of 5 to 36 percent. Other potential risks for transmission include sharing contaminated straws during intranasal use of cocaine, and sharing items such as razors and toothbrushes, which may be contaminated with infected blood. Data on exposure risks from tattooing or piercing in the United States are sparse.
14 Hepatitis C
Injection Drug Use and Hepatitis C Infection Although new infections among injection drug users in the United States have declined since 1989, both the incidence and prevalence of infection remain high. Studies have shown that infection is widespread in populations of experienced injectors, with rates in many areas of the United States exceeding 80 percent. Acquisition of hepatitis C infection is very rapid among new injectors following initiation of injection, with 50 to 80 percent infected within 6 to 12 months. Risks for infection include needle sharing, frequent daily injection, cocaine injection, and sharing needles with a long-term injector. Because of the efficiency of blood-to-blood transmission and the high prevalence of infection among injectors, anyone who has ever injected drugs, even if he or she may have experimented only once in the past, is at risk for infection. Due to common modes of transmission, a large proportion of injection drug users infected with HCV are also infected with hepatitis B virus and/or HIV.
Natural History of the Illness Following exposure to the virus, most people with acute infection display no symptoms and continue to feel well. However, some develop jaundice, and some people experience nonspecific symptoms such as anorexia (lack of appetite), malaise, and/or abdominal pain. Because specific symptoms are uncommon, the only way to determine whether infection is present is with a blood test for antibodies to the virus. The average incubation period for the virus is 6 to 7 weeks and antibodies to HCV can be detected in 80 percent of those infected by 15 weeks after exposure. A small proportion of those with acute infection are able to clear the virus naturally from the bloodstream. However, 75 to 85 percent of those infected develop chronic infection. While most people with chronic infection do not have any symptoms, complications can occur after 10 to 20 years of unapparent infection. As liver cells die, scar tissue forms in the liver (fibrosis), preventing normal blood flow. This leads to a condition called cirrhosis, which can be life-threatening. It is estimated that cirrhosis occurs in 10 to 20 percent of people with chronic infection, and 1 to 5 percent develop primary liver cancer (hepatocellular carcinoma). It is not yet known why some people are able to clear the virus, why disease severity varies from person to person, or how to predict who will develop disease. Unlike HIV, the amount of virus in a person’s blood is not a good
Guidelines 15
predictor of disease progression. Recent data show that alcohol consumption can increase the risk of progression, and studies indicate that persons infected with both HCV and HIV tend to have a more rapid decline in health.
Treatment While some antiviral treatment is available for HCV, it has not been found to be highly effective. It also has been shown to have toxic effects, and is often poorly tolerated. Research efforts to develop more effective treatment approaches that are appropriate for broader patient populations are ongoing. At present, the antiviral drug interferon, used alone or in combination with ribavirin, is approved for treatment of HCV. When interferon is combined with ribavirin, the effectiveness of treatment is improved. Studies indicate that the combination is effective in 30 to 40 percent of those treated, but that many patients relapse when therapy is stopped. Currently, treatment is recommended only for patients at greatest risk for progression to cirrhosis. Individuals found to be infected with HCV need to be assessed and monitored by a specialist for the presence and severity of chronic liver disease and for treatment eligibility. Infected persons should be advised to reduce alcohol intake and to abstain from using illicit drugs. Those using illicit drugs should be referred to drug treatment programs.
Screening and Prevention Unlike hepatitis A and hepatitis B, there is no vaccine to prevent hepatitis C infection. Thus, prevention efforts must rely on behavioral techniques. Persons who have injected illicit drugs, including those who injected only once or occasionally many years ago and who may not consider themselves to be drug users, should be tested for hepatitis C infection. Because of similar risk factors for infection, drug users should also be tested for HIV and hepatitis B. Those at risk should receive immunization for hepatitis A and B. Persons with known HIV infection should be screened for HCV as well. Regardless of test results, persons who use illicit drugs should be counseled to reduce their risk for acquiring infection or of potentially transmitting infection to others. Persons with multiple sex partners should be advised to use latex condoms.
16 Hepatitis C
Persons who test positive for HCV should be given information regarding the need for preventing further harm to the liver, reducing risks for transmitting HCV to others, and obtaining medical evaluation and follow-p for chronic liver disease and possible treatment. It is important that physicians know if a person is infected with HCV so that medications that may have side effects involving the liver can be avoided. To protect the liver from further harm, HCV-infected persons should be vaccinated against hepatitis A and B, if susceptible, and should be strongly advised that even moderate alcohol consumption may adversely affect disease progression. All persons should be advised not to use illicit drugs.
More Guideline Sources The guideline above on hepatitis C is only one example of the kind of material that you can find online and free of charge. The remainder of this chapter will direct you to other sources which either publish or can help you find additional guidelines on topics related to hepatitis C. Many of the guidelines listed below address topics that may be of particular relevance to your specific situation or of special interest to only some patients with hepatitis C. 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.
Topic Pages: MEDLINEplus For patients wishing to go beyond guidelines published by specific Institutes of the NIH, the National Library of Medicine has created a vast and patientoriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages.” You can think of a health topic page as a guide to patient guides. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. If you do not find topics of interest when browsing health topic pages, then you can choose to use the advanced search utility of MEDLINEplus at http://www.nlm.nih.gov/medlineplus/advancedsearch.html. This utility is similar to the NIH Search Utility, with the exception that it only includes material 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.
Guidelines 17
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 C and related conditions. One of the advantages of CHID over other sources is that it 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: ·
Understanding Hepatitis C and Your Therapy Choices Source: Thousand Oaks, CA: Amgen. 1999. 11 p. Contact: Available from COMPASS Program, Amgen, Inc. 1 Amgen Center Drive, Professional Services, Mailstop 36-2-A, Thousand Oaks, CA 91362. (888) 508-8088. Website: www.infergen.com. Price: Single copy free. Summary: This brochure helps people with hepatitis C understand the treatment options available to them. Written in a question and answer format, the brochure first reviews the symptoms and complications of hepatitis C and how it is transmitted. Even though hepatitis C can cause serious liver damage, many infected people don't have any symptoms and don't know they are infected. Hepatitis C is bloodborne and can be transmitted by blood transfusion, shared needles, improperly sterilized tattooing and body piercing instruments, sharing of personal items, and multiple sexual contacts, and can be passed from an infected pregnant mother to her unborn child; some of these routes of transmission are quite rare. People with hepatitis C are generally categorized in three groups, based on their history of treatment for the disease: naive patients who have never before been treated for hepatitis C; relapsers are patients who have received hepatitis C therapy before but, although the therapy worked for awhile, it stopped working for them; or nonresponders, patients who tried hepatitis C therapy before but it never worked for them. The brochure outlines the types of approved therapies for hepatitis C, notably different types of interferon therapies and discusses the safety precautions that must be used by patients on interferon therapies. The brochure includes a blank form for patients to fill out which helps them to summarize their history with hepatitis and can clarify doctor patient communication.
18 Hepatitis C
·
Hepatitis C: Living with a Silent, Chronic Disease Source: San Bruno, CA: StayWell Company. 1999. [2 p.]. Contact: Available from StayWell Company. Order Department, 1100 Grundy Lane, San Bruno, CA 94066-9821. (800) 333-3032. Fax (650) 2444512. E-mail:
[email protected]. Website: www.staywell.com. Price: $17.95 for pack of 50; plus shipping and handling. Summary: This patient education brochure describes hepatitis C and strategies for coping with this silent, chronic disease. Written in nontechnical language, the brochure first describes hepatitis as inflammation of the liver and then notes that hepatitis C is a variety of hepatitis that can spread and can lead to lifelong liver disease. Most people with hepatitis C have no symptoms until they develop liver diseases many years after their original infection. Common symptoms of hepatitis C can include flulike problems (fatigue, nausea, vomiting, diarrhea, and sore muscles and joints); tenderness in the upper right abdomen; and jaundice (yellowing skin), swelling in the abdomen, itching, and dark urine. Diagnosis is usually determined when routine liver tests are done on the blood, or when the patient donates blood. Once hepatitis C is discovered, a medical evaluation helps assess the health of the liver. Although hepatitis C is difficult to treat, the brochure recommends three approaches: avoid stressing the liver (do not use alcohol and unnecessary medications), eat a balanced diet, and take medications that are prescribed (interferon alpha 2b helps some patients). One section of the brochure reminds readers of how to stop the transmission of hepatitis C from themselves to others. The last page of the brochure reminds readers of the importance of regular followup care. The brochure is illustrated with full color line drawings. 7 figures.
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Hepatitis C: Viral Hepatitis Source: Santa Cruz, CA: ETR Associates. 1997. 4 p. Contact: Available from ETR Associates. P.O. Box 1830, Santa Cruz, CA 95061-1830. (800) 321-4407. Price: $16.00 for 50 copies. Summary: This patient education brochure provides basic information about viral hepatitis, the name given to several different diseases caused by viruses that damage the liver. Each of the seven types of viral hepatitis is a little different in how it is transmitted, its symptoms, and treatments. This brochure focuses on hepatitis C, the type of hepatitis that is most likely to develop into a chronic disease. Topics include transmission, relationship to sexual behavior, prevention, symptoms (fatigue, muscle and joint aches, vomiting, diarrhea, abdominal discomfort, dark urine or light-colored stool, jaundice), complications of infection, diagnostic tools,
Guidelines 19
and treatment options. Medications are available to treat the symptoms of chronic hepatitis C, but there is at present no cure. The brochure cautions that anyone who has chronic hepatitis C should avoid alcohol, since alcohol can speed up the disease process, making the person sicker more quickly. The brochure concludes with the toll-free telephone number of the American Liver Foundation (800-223-0179). ·
Pocket Guide for Women Living With HIV Contact: Canadian Public Health Association, Canadian HIV/AIDS Clearinghouse, 400-1565 Carling Ave Ste 400, Ottawa, (613) 725-3434, http://www.cpha.ca. Summary: This information package, for women, discusses living with the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS). It provides general information about HIV/AIDS, its affects on women, and how to locate a physician. It covers topics including medical treatment; alternative HIV therapies; HIV and pregnancy, injection drug use, and hepatitis C; proper nutrition for HIVpositive women; having safer sex with condoms; living as an HIVpositive mother; and where to find daycare for an HIV-positive child in Canada.
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HIV Positive People Packet Contact: CDC National Prevention Information Network, PO Box 6003, Rockville, MD, 20849-6003, (800) 458-5231, http://cdcnpin.org. Summary: This information kit, for persons with the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) is distributed only through the National HIV/sexually transmitted diseases (STD) Hotline. It contains several pamphlets including: (1) Preventing Infections From Pets, (2) Safe Food and Water, (3) You Can Prevent PCP, (3) You Can Prevent PCP in Children, (4) Living with HIV/AIDS, (5) Taking Part in Research Studies: What Questions Should You Ask? (6) You Can Prevent Cytomegalovirus (CMV), (7) Can Prevent Disseminated Mycobacterium Avium Complex Disease (MAC), (8) You Can Prevent Toxo (9) Tuberculosis : The Connection Between TB and HIV, (10) You Can Prevent Toxo, and (11) HIV Positive and Strong. It also contains a report titled Surgeon General's Report to the American Public on HIV Infection and AIDS, and an information sheet titled Frequently Asked Questions and Answers About Coinfection with HIV and Hepatitis C Virus.
20 Hepatitis C
·
[Hepatatis Foundation International Packet] Source: Cedar Grove, NJ: Hepatitis Foundation International. 199x. [40 p.]. 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: $10.00 each; discounts available for larger orders. Free with membership. Summary: This information packet provides a wealth of information to support educational programs about hepatitis and its prevention. The packet was created by the Hepatitis Foundation International, a group that provides updated information on new diagnostic measures and treatments, referral to physicians, and access to a telecommunications network of patients with similar ailments. The information stresses that understanding the disease process of viral hepatitis and its impact on the liver, and encouraging individuals to actively participate in their health care is vital. The packet includes fact sheets on hepatitis A, hepatitis B, vaccination, hepatitis C, diagnosis and treatment options, and liver care; copies of the foundation's newsletter; a curriculum for teachers on liver wellness, hepatitis B, and substance abuse prevention; information about the foundation; display information (miniposters) on preventing the sexual transmission of hepatitis B; and brochures on hepatitis B in children and on the physiology and role of the liver. The materials are compiled into a folder.
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Hepatitis C: What You Should Know. [Hepatitis C: Lo Que Usted Debe Saber] Source: South Deerfield, MA: Channing L. Bete Co., Inc. 2000. 7 p. Contact: Available from Channing L. Bete, Co., Inc. 200 State Road, South Deerfield, MA 01373-0200. (800) 628-7733. Fax (800) 499-6464. Price: $1.05 each; plus shipping and handling; quantity discounts available. Order number 42861 for English version; 42986 for Spanish version. Summary: Written in nontechnical language, this patient education booklet reviews hepatitis C, a liver disease caused by a virus in the blood. Hepatitis C can result in chronic damage to the liver, liver cancer and death. Many people do not realize that they have hepatitis C; although they remain without symptoms, they can still pass the infection to others. Early signs of hepatitis C may include fever, feeling tired, vomiting, headache, stomachache, and lack of appetite; later signs include dark colored urine and light colored bowel movements. The booklet reviews the ways that hepatitis C virus (HCV) is transmitted, including the use of shared needles or syringes to inject drugs, working at a job where blood
Guidelines 21
contact occurs, sharing personal items such as toothbrushes or razors, and sexual transmission. One section of the booklet describes the self care strategies for coping with hepatitis C, including getting plenty of rest, eating a healthy diet, avoiding alcohol consumption, and preventing transmission to others. The booklet concludes by recommending that readers learn about and practice safer sex, and by noting the toll-free helpline of the Center for Substance Abuse (800-662-HELP) for people who want to stop using drugs. The booklet is illustrated with line drawings. ·
Learn the Facts About Hepatitis C Source: South Deerfield, MA: Channing L. Bete Co., Inc. 2000. 15 p. Contact: Available from Channing L. Bete, Co., Inc. 200 State Road, South Deerfield, MA 01373-0200. (800) 628-7733. Fax (800) 499-6464. Price: $1.05 each plus shipping and handling; quantity discounts available. Order number 75447. Summary: This booklet offers basic information about hepatitis C, a viral infection that causes liver disease. Most people who get hepatitis C virus (HCV) become chronic carriers of the disease and must be careful to protect their own health and that of others (in order to avoid transmitting the disease). HCV is spread mainly through blood; risk factors for transmission of the virus include sharing needles or other equipment to inject drugs, having had a blood transfusion before 1992, exposure to blood on the job (e.g., health care workers), sharing personal care items, and sexual contact (a less frequent mode of transmission). HCV is not spread through casual contact or by food or water. The symptoms of HCV infection can resemble the flu and include fatigue, nausea, vomiting and abdominal pain, loss of appetite (anorexia) and weight loss, mild fever, and headaches; hepatitis C sometimes causes jaundice, dark urine, and light colored bowel movements. Most people with HCV have no symptoms, but they can still infect others and have liver damage resulting from their infection. Diagnosis of HCV is based on medical history, physical examination, and blood tests. Patients with chronic HCV are advised to get follow up tests, take medication as prescribed, avoid alcohol, get vaccinated against hepatitis A and hepatitis B, avoid or limit certain medications, and live a healthy lifestyle with a positive outlook. One section of the booklet encourages readers to help stop the spread of HCV and other viruses by never sharing needles or personal care items; abstaining from sex; using a latex condom for each act of vaginal, anal, or oral sex; and taking extra precautions if HCV infection is present. Detailed information on cleaning drug works (equipment) and on using condoms is provided. The booklet concludes with resources that can give
22 Hepatitis C
readers additional assistance. The booklet is illustrated with simple line drawings. ·
Double Jeopardy: The HIV/HCV Co-Infection Handbook Source: New York, NY: Community Prescription Service. 1999. 36 p. Contact: Available from Community Prescription Service. 349 West 12th Street, New York, NY 10014. (800) 842-0502. Price: Single copy free. Summary: This booklet was written to help people with HIV and hepatitis C virus (HCV) coinfection (people with both diseases) understand their illness and treatment options. Readers are reassured that HCV is a very slow developing, long term chronic disease and that like HIV, it can be treated. Topics discussed are risk behaviors for both diseases, testing for HIV and HCV, negative test results, positive HIV or HCV test results, questions to ask the physician, HIV or AIDS, strategies for maintaining optimum liver health, liver damage, treatment options for hepatitis C, drug interactions, methadone interactions, interferon drug therapy for HCV, combination therapy for HCV, HCV drugs undergoing trials, alternative or complementary therapies, groups that help, concerns about hepatitis A and B, and substance abuse and cessation issues. The booklet includes a liver damage control chart, an HIV drug chart, and lists of resources, including organizations that offer local chapters and support groups. The information in the booklet is presented in bold typefaces and colors to set off different sections.
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What I Need to Know About Hepatitis C. [Lo Que Necesito Saber Sobre la Hepatitis C] Source: Bethesda, MD: National Digestive Diseases Information Clearinghouse (NDDIC). 1999. 10 p. Contact: Available from National Digestive Diseases Information Clearinghouse (NDDIC). 2 Information Way, Bethesda, MD 20892-3570. (800) 891-5389 or (301) 654-3810. Fax (301) 907-8906. E-mail:
[email protected]. Price: Single copy free; bulk copies available. Summary: This brochure provides basic information about hepatitis C. Written in non-technical language, the brochure describes hepatitis C and the virus that causes it, explains how hepatitis C is transmitted, lists the symptoms of the disease, outlines the diagnostic tests used to confirm hepatitis C infection, describes the treatment, and focuses on preventing transmission of the disease. Hepatitis C, a liver disease caused by the hepatitis C virus (HCV), spreads through contact with an infected person's blood by such means as sharing drug needles, getting pricked with a needle that has infected blood on it, or having had a blood
Guidelines 23
transfusion before 1992. Hepatitis C is treated with a drug called interferon and, in chronic cases, with liver transplantation. The brochure lists two resource organizations (the American Liver Foundation and the Hepatitis Foundation International) for readers who wish to obtain more information. In addition, the contact information for the National Digestive Diseases Information Clearinghouse (NDDIC) is provided. The brochure is illustrated with simple line drawings. ·
One out of Every 50 Latinos is Infected with the Hepatitis C Virus: (A Deady Virus). [Uno de Cada 50 Latinos Esta Infectado Con El Virus De la Hepatitis C: (Un Virus Mortal)] Source: Bronx, NY: Latino Organization for Liver Awareness. 1999. [2 p.]. Contact: Available from Latino Organization for Liver Awareness. 1560 Mayflower Avenue, Bronx, NY 10461. (888) 367-5652. Price: Single copy free. Summary: Hepatitis C virus (HCV) infection is the most common chronic bloodborne infection in the United States. About 1 in every 50 Latinos in the United States has hepatitis C. This brochure offers simple facts about hepatitis C and the Latino community. The brochure notes that Latinos have more than a 40 percent greater chance of being infected with HCV than the general population in the United States. Hepatitis C, which causes inflammation of the liver, can result in cirrhosis (scarring of the liver), liver cancer and death, and is the leading cause of liver transplants in the United States. U.S. Census statistics show that by the year 2025, the Latino population in the United States is projected to double. As this population grows, hepatitis C threatens to affect more and more Latinos. The hepatitis C virus is spread primarily by direct contact with contaminated blood. People at high risk include those who received a blood transfusion or organ transplant before 1992, those who have injected illegal drugs (including only one time), hemophiliacs who received blood clotting factors before 1997, long term hemodialysis patients, and people whose blood tests show persistent abnormal ALT (alanine aminotransferase, a measure of liver function) levels. The reverse side of the brochure offers the same information in Spanish.
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About Hepatitis C Source: South Deerfield, MA: Channing L. Bete Co., Inc. 1998. 15 p. Contact: Available from Channing L. Bete, Co., Inc. 200 State Road, South Deerfield, MA 01373-0200. (800) 628-7733. Fax (800) 499-6464. Price: $0.89 each for 1-99 copies; plus shipping and handling; quantity discounts available. Order number: 20486A498.
24 Hepatitis C
Summary: This health promotion booklet reviews hepatitis C, an infection of the liver. People infected with hepatitis C virus (HCV) may not show any symptoms or may develop flulike symptoms or jaundice. In most cases, people who become infected with HCV carry the virus for the rest of their lives. Carriers may show no signs of illness but can still pass HBV to others and are at higher risk of liver damage (such as cirrhosis), liver cancer, and death from liver failure. The brochure describes how HCV is spread by body fluids (blood, semen, vaginal fluids) through activities such as receiving a blood transfusion before 1992, having sex, sharing needles, or sharing personal items with a person who has HCV. Some health care workers may also be exposed to HCV at work. The brochure outlines the symptoms, encourages readers to be tested, and notes the care strategies that can be used by people who test positive for the virus. The brochure outlines strategies for preventing the spread of HCV, including having safer sex, cleaning drug works, not sharing personal items, and seeking treatment for HCV infection. The brochure lists the telephone numbers of resource organizations from which readers can get more information. The brochure is written in nontechnical language and illustrated with line drawings of cartoon-like figures. ·
If You Have Hepatitis C Source: Atlanta, GA: Centers for Disease Control and Prevention (CDC). 1998. [2 p.]. Contact: Available from Centers for Disease Control and Prevention (CDC). 1600 Clifton Road, NE, Hepatitis Branch, Bldg. 6, MS G-37, Atlanta, GA 30333. (800) 443-7232. Fax (404) 639-1538. Website: www.cdc.gov. Price: Single copy free. Summary: This brochure provides information for patients with hepatitis C, a liver disease spread by contact with the blood of an infected person. Written in question and answer format, the brochure helps readers better understand what the disease is, how they may have contracted it, and how they can avoid passing hepatitis C virus (HCV) to others. Many people with long term (chronic) hepatitis C have no symptoms and feel well, but they should still be under the care of a physician for long term monitoring. The brochure includes a special section for readers who are pregnant, stressing that infants can become infected at birth if their mothers have HCV. A drug called interferon is licensed for the treatment of people with long term hepatitis C; however, only about 2 of every 10 people who are treated get rid of the virus. The brochure concludes with a section reminding readers to take care of their livers by seeing a physician regularly, avoiding alcohol, telling their physician about all the
Guidelines 25
medicines they are taking, and getting vaccinated against hepatitis A (for those people who already have liver damage from hepatitis C). The brochure includes the telephone number for the toll free Hepatitis Hotline (888 443 7232), as well as the Internet and the postal addresses. ·
Get Tested for Hepatitis C. [Hagase la Prueba de la Hepatitis C] Source: Atlanta, GA: Centers for Disease Control and Prevention (CDC). 1998. [2 p.]. Contact: Available from Centers for Disease Control and Prevention (CDC). 1600 Clifton Road, NE, Hepatitis Branch, MS G-37 Atlanta, GA 30333. (888) 443-7232 or (888) 4HEPCDC. Fax (404) 371-5488. Price: Single copy free. Also available at www.cdc.gov/ncidod/diseases/hepatitis/ resource/lbtinfo.htm. Summary: Hepatitis C is a liver disease caused by infection with the hepatitis C virus (HCV), which is found in the blood of persons who have this disease. This brochure, available in English or in Spanish, emphasizes that readers should be tested for hepatitis if they were notified that they received blood that possibly contained HCV or if they received blood before July 1992. The brochure briefly reviews the discovery of HCV and subsequent tests that were put into the blood donor system, then explains why it is important to be tested for the disease. Many persons who have hepatitis C have no symptoms and feel well; however, they can still infect others and they are still at risk for long term liver complications. People who have hepatitis C should protect their livers by seeing a physician regularly, not drinking alcohol, not starting any new medicines (including over the counter and herbal medicines), and getting vaccinated against hepatitis A. Antiviral medicines are approved for the treatment of persons with chronic hepatitis C; however, treatment is effective in only 20 to 30 percent of cases. Others at risk of getting hepatitis C are persons who have injected street drugs, health care workers exposed to blood in the workplace, and babies born to infected mothers. HCV also can be spread by sex, but this does not occur very often. The brochure concludes by offering practical strategies for everyday activities and how to prevent the transmission of HCV. The brochure offers the web site and Hepatitis Hotline (888-4437232) information of the Centers for Disease Control and Prevention (CDC).
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Hepatitis C Prevention Source: Atlanta, GA: Centers for Disease Control and Prevention (CDC). 1998. [2 p.].
26 Hepatitis C
Contact: Available from Centers for Disease Control and Prevention (CDC). 1600 Clifton Road, NE, Hepatitis Branch, MS G-37 Atlanta, GA 30333. (888) 443-7232 or (888) 4HEPCDC. Fax (404) 371-5488. Price: Single copy free. Also available at www.cdc.gov/ncidod/diseases/hepatitis/ resource/hepcprev.htm. Summary: Hepatitis C is a liver disease caused by the hepatitis C virus (HCV), which is found in the blood of persons who have this disease. This brochure describes hepatitis C, explains how to prevent getting the disease, and outlines who should have a blood test to diagnose hepatitis C. Hepatitis C is serious for some persons, but not for others. Some people with liver damage due to hepatitis C may develop cirrhosis (scarring) of the liver and liver failure (which may take many years to develop). The brochure outlines recommendations to prevent the transmission of hepatitis C, noting that HCV is spread primarily by exposure to human blood. The brochure recommends that readers be tested for HCV if they received a blood transfusion or solid organ transplant before July 1992; they were treated with a blood product for clotting problems before 1987; they ever injected street drugs; they were ever on long term kidney dialysis; or they ever had a sexually transmitted disease (STD). Early diagnosis of hepatitis C is important so patients can be counseled about how to prevent transmission of HCV to others and so patients can be checked for liver disease and get treatment, if indicated. The brochure offers the web site and Hepatitis Hotline (888-443-7232) information of the Centers for Disease Control and Prevention (CDC). ·
Hepatitis C: The Disease and How It Is Spread Source: Thousand Oaks, CA: Amgen, Inc. 1997. 5 p. Contact: Available from Amgen Professional Services. 1840 DeHavilland Drive, Thousand Oaks, CA 91320-1789. (800) 77-AMGEN. Price: Free to health professionals for distribution to patients. Summary: Hepatitis C is a liver disease caused by the hepatitis C virus (HCV); chronic HCV infection leads to inflammation of the liver and can cause serious liver damage. This brochure explains the nature of HCV infection and how to prevent its transmission. Topics include hepatitis C infection and treatment; the change from the acute to chronic phases of the disease; and how hepatitis C is transmitted. The brochure focuses on guidelines for how to protect family and friends from infection from a chronic HCV carrier. Precautions include the following: avoid sharing razors or toothbrushes, cover any cuts or wounds, dispose of wound dressings in a sealed bag in the trash, keep used syringes capped and in a needle disposal container, wear a condom if exposed to multiple sexual partners or if experiencing a genital herpes infection, and do not donate
Guidelines 27
blood. The authors suggest that spouses and sexual partners of people infected with HCV should also be tested for the virus. The authors also note that certain drugs, including some available without a prescription, can cause further damage to the liver of people with hepatitis C. ·
Inmate Release STD and HIV/AIDS Packet Contact: Virginia Department of Health, Division of HIV/STD, PO Box 2448, Richmond, VA, 23218-2448, (804) 225-4844, http://www.vdh.state.va.us/. Summary: This information package, for soon to be released incarcerated person in Virginia, discusses the human immunodeficiency (HIV)/acquired immune deficiency syndrome (AIDS), sexually transmitted diseases (STDs), and tuberculosis (TB). Fact sheets discuss hepatitis B virus (HBV), HIV/AIDS, and TB; define their symptoms; identify the means by which they can be transmitted; and advise individuals as to where they can get tested. A wallet card lists state-wide, toll-free telephone numbers for services such as substance abuse services, social services, job and career information, and legal services, and provides an HIV/STD hotline number. The information package makes recommendations about how to adjust to life outside of prison in such a manner as to be able to avoid a life of crime that can return individuals to the correctional setting. A brochure discusses the hepatitis C virus (HCV), its symptoms, how it is spread, and what one should do if infected with it. Another brochure outlines the facts about the Virginia AIDS Drug Assistance Program (ADAP) from which individuals with HIV/AIDS can receive financial aid for medications.
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Paquete de Informacion Sobre la Hepatitis C (VHC). [Hepatitis C (HCV) Information Packet] Contact: Hepatitis C Support Project, PO Box 427037, San Francisco, CA, 94142-7037, (415) 978-2400, http://www.hcvadvocate.org. Summary: This brochure, for the general public, provides information about the hepatitis C virus (HCV), a chronic liver disease. It discusses the epidemiology of HCV in the United States and it provides information on testing for HCV, its symptoms, and treatment. It discusses conditions linked to HCV, co-infection with HIV and HCV, and clinical trials. It presents treatment options from a western/conventional medicine and an alternative/complementry perspective. These treatments include interferon, rebetron, ribavirin, amantadine, infergen, pegylated (PEG), pegylated interferon and ribavirin, maxamine, ribozmes, new therapies, herbs, Traditional Chinese Medicine (TCM), acupuncture, and Qi Gong. The brochure provides information on managing HCV and discusses
28 Hepatitis C
hepatitis A and B vaccines, nutrition, and additional self-care suggestions. For individuals interested in learning more about HCV, contact information for several organizations is available. ·
Hepatitis C (HCV) Information Packet Contact: Hepatitis C Support Project, PO Box 427037, San Francisco, CA, 94142-7037, (415) 978-2400, http://www.hcvadvocate.org. Summary: This information packet, for the general public, provides information about the hepatitis C virus (HCV), which can cause chronic liver disease. It discusses the statistics of HCV incidents in the United States and it provides information on testing for HCV, its symptoms, treatment, and prevention. It discusses conditions linked to HCV, coinfection with HIV and HCV, and clinical trials. It presents treatment options from a western/conventional medicine and an alternative/complementary perspective. These treatments include interferon, rebetron, ribavirin, amantadine, infergen, pegylated (PEG), pegylated interferon, maxamine, ribozmes, new therapies, herbs, Traditional Chinese Medicine (TCM), acupuncture, and Qi Gong. The brochure provides information on managing HCV and discusses hepatitis A and B vaccines, nutrition, and additional self-care suggestions. For individuals interested in learning more about HCV, contact information for several organizations is provided.
The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search their site located at http://www.guideline.gov by using the keyword “hepatitis C” or synonyms. The following was recently posted: ·
Management of hepatitis C. Source: National Institutes of Health (NIH) Consensus Development Panel on Management of Hepatitis C.; 1997 March; 42 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 0421&sSearch_string=hepatitis+C
Guidelines 29
·
Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. Source: Centers for Disease Control and Prevention.; 1998 October; 40 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 0744&sSearch_string=hepatitis+C
·
Updated U.S. Public Health Service guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for postexposure prophylaxis. Source: Centers for Disease Control and Prevention/Food and Drug Administration (U.S.)/Health Resources and Services Administration/National Institutes of Health (U.S.).; 1998 May 15 (updated 2001 Jun); 43 pages http://www.guideline.gov/FRAMESETS/guideline_fs.asp?guideline=00 2088&sSearch_string=hepatitis+C
Healthfinder™ Healthfinder™ is an additional source sponsored by the U.S. Department of Health and Human Services which 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: ·
Chronic Hepatitis C: Current Disease Management Summary: This online health information document provides basic information about Hepatitis C. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=2298
30 Hepatitis C
·
Coping With HCV (Hepatitis C) Infection: Alternative or Complementary Approaches Summary: A patient guide to usage of alternative therapies for hepatitis C (HCV) infection. Source: Department of Veterans Affairs http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=5324
·
Hepatitis C (HCV) Patient Education Materials Summary: This web site presents materials for patients with hepatitis C. Source: Department of Veterans Affairs http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=5325
·
Hepatitis C (HCV) Provider Education Materials Summary: Materials about hepatitis C (HCV), written especially for physicians. Source: Department of Veterans Affairs http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=5327
·
Hepatitis C Education Campaign: Office of the U.S. Surgeon General Summary: The Office of the Surgeon General and some Members of Congress have formed a partnership to increase public awareness of who is at risk for hepatitis C infection, and what action they should take if Source: Office of the Surgeon General, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=5328
Guidelines 31
·
Hepatitis C Fact Sheet Summary: This fact sheet presents a general overview about hepatitis C including means of transmission, diagnosis, treatment, and prevention guideline. Source: World Health Organization http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=4715
·
Hepatitis C Virus (HCV) Summary: Written for clinicians, this Hepatitis C Virus (HCV) fact sheet presents basic information about the disorder that includes diagnosis, epidemiology, disease management guidelines, data on risk Source: Educational Institution--Follow the Resource URL for More Information http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=5316
·
Hepatitis C: New Treatment Helps Some, But Cure Remains Elusive Summary: This FDA Consumer magazine discusses Hepatitis C -- current treatment options, future options through clinical research, how patients are coping with the disease, and efforts at educating the medical Source: Office of Consumer Affairs, U.S. Food and Drug Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=4430
·
Hepatitis C: Treatment Alternatives Summary: This consumer health information brochure discusses research and research findings related to alternative therapy treatments for hepatitis C virus. Source: National Center for Complementary and Alternative Medicine, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=5349
32 Hepatitis C
·
Hepatitis C: What Clinicians and Other Health Professionals Need to Know Summary: A web-based training course on hepatitis C virus (HCV) infection designed for primary care physicians, infectious disease specialists, blood bank employees, public health professionals and other Source: Division of Viral Hepatitis, National Center for Infectious Diseases, Centers for Disease Control and Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&R ecordID=5314
The NIH Search Utility After browsing the references listed at the beginning of this chapter, you may want to explore the NIH Search Utility. This allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEBSPACE. 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 C. 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 conditions covered at the following Web site: http://www.icondata.com/health/pedbase/pedlynx.htm.
Guidelines 33
Additional Web Sources A number of Web sites that often link to government sites are available to the public. 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
·
drkoop.comÒ: http://www.drkoop.com/conditions/ency/index.html
·
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/
·
WebMDÒHealth: http://my.webmd.com/health_topics
Vocabulary Builder The material in this chapter may have contained a number of unfamiliar words. The following Vocabulary Builder introduces you to terms used in this chapter that have not been covered in the previous chapter: Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Pertaining to the abdomen. [EU] 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] Amantadine: An antiviral that is used in the prophylactic or symptomatic treatment of influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake. [NIH] Anorexia: Lack or loss of the appetite for food. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU]
34 Hepatitis C
Carcinoma: A malignant new growth made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. [EU] Chronic: Persisting over a long period of time. [EU] Cirrhosis: Liver disease characterized pathologically by loss of the normal microscopic lobular architecture, with fibrosis and nodular regeneration. The term is sometimes used to refer to chronic interstitial inflammation of any organ. [EU] 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] Condoms: A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. [NIH] Craving: A powerful, often uncontrollable desire for drugs. [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] Diarrhea: Passage of excessively liquid or excessively frequent stools. [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] Fibrosis: The formation of fibrous tissue; fibroid or fibrous degeneration [EU] Hepatocellular: Pertaining to or affecting liver cells. [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] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [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] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of
Guidelines 35
the skin and mucous membranes. [NIH] Malaise: A vague feeling of bodily discomfort. [EU] Methadone: A long-acting synthetic medication shown to be effective in treating heroin addiction. [NIH] Mycobacterium: An organism of the genus Mycobacterium. [EU] Nausea: An unpleasant sensation, vaguely referred to the epigastrium and abdomen, and often culminating in vomiting. [EU] 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] Prophylaxis: The prevention of disease; preventive treatment. [EU] 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] 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] Telecommunications: electronic means. [NIH]
Transmission of information over distances via
Toxic: Causing temporary or permanent effects that are detrimental to the functioning of a body organ or group of organs. [NIH] Transfusion: The introduction of whole blood or blood component directly into the blood stream. [EU] Transplantation: The grafting of tissues taken from the patient's own body or from another. [EU] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of mycobacterium. [NIH] Vaccination: The introduction of vaccine into the body for the purpose of inducing immunity. Coined originally to apply to the injection of smallpox vaccine, the term has come to mean any immunizing procedure in which vaccine is injected. [EU] Vaccine: A suspension of attenuated or killed microorganisms (bacteria, viruses, or rickettsiae), administered for the prevention, amelioration or treatment of infectious diseases. [EU] Vaginal: 1. of the nature of a sheath; ensheathing. 2. pertaining to the vagina. 3. pertaining to the tunica vaginalis testis. [EU] Viruses: Minute infectious agents whose genomes are composed of DNA or
36 Hepatitis C
RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. [NIH] World Health Organization: A specialized agency of the United Nations designed as a coordinating authority on international health work; its aim is to promote the attainment of the highest possible level of health by all peoples. [NIH]
Seeking Guidance 37
CHAPTER 2. SEEKING GUIDANCE Overview Some patients are comforted by the knowledge that a number of organizations dedicate their resources to helping people with hepatitis C. These associations can become invaluable sources of information and advice. Many associations offer aftercare support, financial assistance, and other important services. Furthermore, healthcare research has shown that support groups often help people to better cope with their conditions.9 In addition to support groups, your physician can be a valuable source of guidance and support. Therefore, finding a physician that can work with your unique situation is a very important aspect of your care. In this chapter, we direct you to resources that can help you find patient organizations and medical specialists. We begin by describing how to find associations and peer groups that can help you better understand and cope with hepatitis C. The chapter ends with a discussion on how to find a doctor that is right for you.
Associations and Hepatitis C As mentioned by the Agency for Healthcare Research and Quality, sometimes the emotional side of an illness can be as taxing as the physical side.10 You may have fears or feel overwhelmed by your situation. Everyone has different ways of dealing with disease or physical injury. Your attitude, your expectations, and how well you cope with your condition can all Churches, synagogues, and other houses of worship might also have groups that can offer you the social support you need. 10 This section has been adapted from http://www.ahcpr.gov/consumer/diaginf5.htm. 9
38 Hepatitis C
influence your well-being. This is true for both minor conditions and serious illnesses. For example, a study on female breast cancer survivors revealed that women who participated in support groups lived longer and experienced better quality of life when compared with women who did not participate. In the support group, women learned coping skills and had the opportunity to share their feelings with other women in the same situation. In addition to associations or groups that your doctor might recommend, we suggest that you consider the following list (if there is a fee for an association, you may want to check with your insurance provider to find out if the cost will be covered): ·
American Liver Foundation Address: American Liver Foundation 75 Maiden Lane, Suite 603, New York, NY 10038 Telephone: (212) 668-1000 Toll-free: (800) 465-4837 Fax: (973) 256-3214 Email:
[email protected] Web Site: http://www.liverfoundation.or Background: The American Liver Foundation is a national voluntary notfor-profit organization dedicated to the prevention, treatment, and cure of diseases of the liver through programs of research and education. Established in 1976, the Foundation's activities include support groups, patient advocacy, support of medical research, and patient and professional education. Educational materials include brochures on Hepatitis, Cirrhosis, Biliary Atresia, liver transplantation, gallstones, and Hereditary Hemochromatosis. Fact sheets are also available on a variety of liver diseases including Alagille Syndrome, Alpha-1-Antitrypsin Deficiency, Cancer of the Liver, Fatty Liver, Gilbert Syndrome, Primary Biliary Cirrhosis, Porphyria, and others. Videotapes produced by the Foundation include 'A Healthy Liver: A Happier Life,' 'Foundations for Decision Making,' 'Hepatitis B: Patient Information,' 'Hepatitis C: A Guide for Primary Care Physicians,' and 'The Visionaries.' The Foundation also offers liver wellness and substance abuse prevention programs to elementary schools and corporations. Relevant area(s) of interest: Hepatitis C
·
British Liver Trust Address: British Liver Trust Ransomes Europark, Ipswich, Suffolk, 1P3 9QG, United Kingdom Telephone: 01473 276326 Toll-free: 0808 800 1000
Seeking Guidance 39
Fax: 01473 276327 Web Site: http://www.britishlivertrust.org.u Background: The British Liver Trust is a nonprofit organization in the United Kingdom that is dedicated to helping adults with all forms of liver disease. The Trust is committed to promoting and funding liver disease research, publishing current information for affected individuals and family members, and supporting all individuals affected by liver disease and those who care for them. To fulfill its mission and objectives, the British Liver Trust offers a variety of programs and services including confidential telephone helplines, a nationwide network of support groups, annual national support group conferences, a web site on the Internet, and several publications, including informational leaflets and a regular newsletter entitled 'Liver Focus.' The Trust also supports training conferences for managers and health and safety officers concerning employee protection against infection from bloodborne viruses (i.e., including those that cause different forms of hepatitis) and has promoted the development of the British Liver Trust Liver Nurses' Forum, a national organization open to any nurse who works with liver patients or who has a special interest in liver disease. The Nurses' Forum is committed to conducting biannual meetings, offering an annual conference where nurses are encouraged to present their own research and to discuss issues of special relevance to liver nurses, promoting informal links between members, and publishing a regular newsletter. The British Liver Trust's web site discusses the organization's mission, goals, and services; offers news updates and access to research information; posts recent editions of its newsletter; and provides understandable information on different forms of liver disease. Relevant area(s) of interest: Hepatitis C ·
Canadian Liver Foundation Address: Canadian Liver Foundation 365 Bloor Street, Suite 200, Toronto, Ontario, M4W 3L4, Canada Telephone: (416) 964-4935 Toll-free: (800) 563-5483 Fax: (416) 964-0024 Email:
[email protected] Web Site: http://www.liver.c Background: The Canadian Liver Foundation (CLF) is a not-for-profit health organization committed to reducing the incidence and impact of liver disease by providing support for research and education into the causes, diagnosis, prevention and treatment of more than 100 diseases of
40 Hepatitis C
the liver. Established in 1969, the CLF has established 30 chapters across Canada and provides information in both English and French. Some of the liver diseases discussed in brochures and medical information sheets available from CLF include gallstones, hemochromatosis, primary biliary cirrhosis, several forms of hepatitis, porphyria, fatty liver, and liver cancer. Further information is provided on liver transplantation, the effects of sodium, and management of variceal bleeding. The Foundation also produces a newsletter and maintains World Wide Web site at http://www.liver.ca. Relevant area(s) of interest: Hepatitis C ·
Children's Liver Alliance Address: Children's Liver Alliance 3835 Richmond Avenue, Suite 190, Staten Island, NY 10312-3828 Telephone: (718) 987-6200 Fax: (718) 987-6200 Email:
[email protected] Web Site: http://livertx.or Background: The Children's Liver Alliance (formerly the Biliary Atresia and Liver Transplant Network) is an international not-for-profit voluntary health organization that was established in 1995. The mission of the Children's Liver Alliance (CLA) is to empower the hearts and minds of children with liver disease, their families, and the medical professionals who care for them. CLA disseminates educational information about pediatric liver diseases and transplantation via written publications, seminars, and the Internet. CLA provides a support network for families of children with liver disease (both pre- and postliver transplantation), acts as liaison between families and health care professionals, offers networking services, and promotes the importance of organ donation and tranplantation. CLA's publications include the bimonthly newsletter 'The Biliary Tree.'.
·
Children's Liver Disease Foundation (UK) Address: Children's Liver Disease Foundation (UK) AXA Equity and Law House, 35-37 Great Charles Street Queensway, Birmingham, B3 3JY, United Kingdom Telephone: 0121 212 3839 Toll-free: (800) 652-4372 Fax: 0121 212 4300 EWeb Site: http://www.childliverdisease.or
Seeking Guidance 41
Background: The Children's Liver Disease Foundation (UK) is a voluntary not- for-profit organization in the United Kingdom that was established in 1980. The Foundation is committed to providing emotional support to children, adolescents, and families affected by liver disease; promoting research into the causes of pediatric liver disease; creating a greater awareness of such disorders and conditions in the health care communities and the public; and promoting the development of means of early diagnosis and cure. The Children's Liver Disease Foundation is also dedicated to providing understandable information on pediatric liver disease through general informational brochures including 'A Guide to the Liver' and 'Signs and Symptoms of Liver Disease' as well as a leaflet series on specific pediatric liver diseases and conditions, such as Alagille syndrome; neonatal hepatitis; hepatitis A, B, C, and E; biliary atresia; and others. The Foundation's web site on the Internet discusses the organization's mission, goals, and services; enables interested individuals, family members, and health care professionals to make specific inquiries; and provides access to the Foundation's publication series. Relevant area(s) of interest: Hepatitis C ·
Hepatitis C Society of Canada Address: Hepatitis C Society of Canada 383 Huron Street, Toronto, Ontario, M5S 2G5, Canada Telephone: (416) 979-5855 Toll-free: (800) 652-4372 Fax: (416) 979-5856 Email:
[email protected] Web Site: http://web.idirect.com/~hepc Background: The Hepatitis C Society of Canada (HeCSC) is a national voluntary nonprofit organization dedicated to providing comfort and support to those infected with the hepatitis C virus, their family members, and other concerned individuals; promoting public awareness of hepatitis C and its transmission, care, and prevention; seeking fair treatment of all people living with and affected by hepatitis C; and promoting research that will help to prevent, treat, and cure hepatitis C. Viral hepatitis is inflammatory liver disease caused by viral infection. There are several forms of viral hepatitis that may be caused by different viruses. The virus responsible for hepatitis C, known as HCV, travels in the blood to the liver where it invades liver cells, multiples, and damages or destroys liver cells. Symptoms, which may range from mild to severe, may include fatigue, abdominal pain, nausea with or without vomiting, fever, itchy skin, and yellowish discoloration of the skin, whites of the
42 Hepatitis C
eyes, and mucous membranes (jaundice). The Hepatitis C Society of Canada was established in 1994 and currently has a network of over 20 support groups across Canada to promote mutual support and networking among affected individuals and family members. The Society also compiles and distributes information about hepatitis C to affected individuals and family members, the general public, the medical community, and policymakers and has established an ongoing dialogue with public health officials and government representatives to advocate for equality of access to disability pension plans, fair treatment from employers, and improvements in the security of Canada's blood supply. The Hepatitis C Society of Canada also offers local counseling, support, and referral services for affected individuals, family members, and friends via its 800 line; communicates on behalf of employees for fair treatment in the workplace; assists affected individuals in obtaining benefits from the disability pension plan; and provides representation at the Krever Commission Blood Inquiry on behalf of transfused carriers of hepatitis C. In addition, the Society conducts educational seminars, publishes a bimonthly newsletter, and maintains a web site on the Internet. Relevant area(s) of interest: HCV, Hepatitis C ·
Hepatitis Foundation International Address: Hepatitis Foundation International 30 Sunrise Terrace, Cedar Grove, NJ 07009-1423 Telephone: (973) 239-1035 Toll-free: (800) 891-0707 Fax: (973) 857-5044 Email:
[email protected] Web Site: http://www.hepFI.or Background: Hepatitis Foundation International (HFI) is a voluntary notfor- profit membership organization dedicated to increasing awareness of the worldwide problem of viral hepatitis and educating the public and health care providers about its prevention, diagnosis, and treatment. Viral hepatitis is inflammatory liver disease caused by viral infection. There are several different forms of viral hepatitis that may be caused by different viruses. Such forms of hepatitis include hepatitis A, hepatitis B, hepatitis C, hepatitis D, and hepatitis E. Depending upon the specific form of the disease and other factors, viral hepatitis may cause liver cell damage, associated scarring of the liver (cirrhosis), and, in some cases, an increased risk of liver cancer. In some cases, affected individuals may have no apparent symptoms. In other cases, some adults with hepatitis A may have dark urine and light stools and may experience fatigue, nausea,
Seeking Guidance 43
vomiting, fever, abdominal pain, and/or abnormal yellowing of the skin and the whites of the eyes (jaundice). Some individuals with hepatitis B, C, D, or E may have dark urine and light stools and experience mild flulike symptoms, fatigue, fever, and/or jaundice. Hepatitis Foundation International was established in 1995 and currently consists of approximately 35,000 members. The Foundation focuses exclusively on bringing viral hepatitis under control by supporting research to find cures; providing educational programs and materials to inform health professionals, affected individuals, family members, and the public concerning new diagnostic and treatment methods; and offering a support network for those who are affected by viral hepatitis. Hepatitis Foundation International also engages in patient advocacy and lobbying, provides appropriate referrals, and has a registry. The Foundation offers a wide range of educational materials including brochures, posters, information sheets, booklets, a primer for teachers concerning hepatitis B and substance abuse prevention, a coloring book for children, and a regular newsletter entitled 'Hepatitis Alert.' In addition, Hepatitis Foundation International has a web site on the Internet. Relevant area(s) of interest: HCV, Hepatitis C, NANB Hepatitis
Finding More Associations There are a number of directories that list additional medical associations that you may find useful. While not all of these directories will provide different information than what is listed above, by consulting all of them, you will have nearly exhausted all sources for patient associations.
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 C. 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.
DIRLINE A comprehensive source of information on associations is the DIRLINE database maintained by the National Library of Medicine. The database
44 Hepatitis C
comprises some 10,000 records of organizations, research centers, and government institutes and associations which primarily focus on health and biomedicine. DIRLINE is available via the Internet at the following Web site: http://dirline.nlm.nih.gov/. Simply type in “hepatitis C” (or a synonym) or the name of a topic, and the site will list information contained in the database on all relevant organizations.
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 C”. 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.” By making these selections and typing in “hepatitis C” (or synonyms) into the “For these words:” box, you will only receive results on organizations dealing with hepatitis C. You should check back periodically with this database since it is updated every 3 months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by specific diseases. You can access this database at the following Web site: http://www.rarediseases.org/cgi-bin/nord/searchpage. Select the option called “Organizational Database (ODB)” and type “hepatitis C” (or a synonym) in the search box.
Online Support Groups In addition to support groups, commercial Internet service providers offer forums and chat rooms for people with different illnesses and conditions. WebMDÒ, for example, offers such a service at their Web site: http://boards.webmd.com/roundtable. These online self-help communities can help you connect with a network of people whose concerns are similar to yours. Online support groups are places where people can talk informally. If you read about a novel approach, consult with your doctor or other
Seeking Guidance 45
healthcare providers, as the treatments or discoveries you hear about may not be scientifically proven to be safe and effective. The following Internet sites may be of particular interest: ·
National Hepatitis C Coalition online http://nationalhepatitis-c.org
·
Hepatitis Central http://hepatitis-central.com/
·
Hepatitia C Connection http://www.hepc-connection.org/
Finding Drug Treatment and Alcohol Abuse Treatment Programs To find the right drug abuse treatment program or alcohol abuse treatment program for you, two useful resources are available. National Drug and Treatment Referral Routing Service11 The U.S. Department of Health and Human Services (HHS) Substance Abuse and Mental Health Services Administration’s (SAMHSA) National Drug and Treatment Referral Routing Service provides a toll-free telephone number for alcohol and drug information/treatment referral assistance. The number is: 1-800-662-HELP. When you call the toll-free number, a recorded message gives you the following options: 1 - Printed materials on alcohol and drug information or 24-hour substance abuse treatment referral information in your area (Additional options guide you through information and referral choices, including a Spanish language message.) 2 - Location of a Substance Abuse Treatment Office in your State
11
Adapted from NIAAA: http://www.niaaa.nih.gov/other/referral.htm.
46 Hepatitis C
Substance Abuse Treatment Facility Locator12 Sponsored by the Substance Abuse and Mental Health Services Administration (SAMHSA), this searchable directory of drug and alcohol treatment programs shows the location of facilities around the country that treat alcoholism, alcohol abuse and drug abuse problems (http://findtreatment.samhsa.gov/). The Locator includes more than 11,000 addiction treatment programs, including residential treatment centers, outpatient treatment programs, and hospital inpatient programs for drug addiction and alcoholism. Listings include treatment programs for marijuana, cocaine, and heroin addiction, as well as drug and alcohol treatment programs for adolescents, and adults. SAMHSA endeavors to keep the Locator current. All information in the Locator is completely updated each year, based on facility responses to SAMHSA’s National Survey of Substance Abuse Treatment Services. New facilities are added monthly. Updates to facility names, addresses, and telephone numbers are made monthly, if facilities inform SAMHSA of changes. The search site is: http://findtreatment.samhsa.gov/facilitylocatordoc.htm.
Finding Doctors One of the most important aspects of your treatment will be the relationship between you and your doctor or specialist. All patients with hepatitis C must go through the process of selecting a physician. While this process will vary from person to person, the Agency for Healthcare Research and Quality makes a number of suggestions, including the following:13 ·
If you are in a managed care plan, check the plan’s list of doctors first.
·
Ask doctors or other health professionals who work with doctors, such as hospital nurses, for referrals.
·
Call a hospital’s doctor referral service, but keep in mind that these services usually refer you to doctors on staff at that particular hospital. The services do not have information on the quality of care that these doctors provide.
·
Some local medical societies offer lists of member doctors. Again, these lists do not have information on the quality of care that these doctors provide.
12 13
Adapted from SAMHSA: http://findtreatment.samhsa.gov/. This section is adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.
Seeking Guidance 47
Additional steps you can take to locate doctors include the following: ·
Check with the associations listed earlier in this chapter.
·
Information on doctors in some states is available on the Internet at http://www.docboard.org. This Web site is run by “Administrators in Medicine,” a group of state medical board directors.
·
The American Board of Medical Specialties can tell you if your doctor is board certified. “Certified” means that the doctor has completed a training program in a specialty and has passed an exam, or “board,” to assess his or her knowledge, skills, and experience to provide quality patient care in that specialty. Primary care doctors may also be certified as specialists. The AMBS Web site is located at http://www.abms.org/newsearch.asp.14 You can also contact the ABMS by phone at 1-866-ASK-ABMS.
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You can call the American Medical Association (AMA) at 800-665-2882 for information on training, specialties, and board certification for many licensed doctors in the United States. This information also can be found in “Physician Select” at the AMA’s Web site: http://www.amaassn.org/aps/amahg.htm.
If the previous sources did not meet your needs, you may want to log on to the Web site of the National Organization for Rare Disorders (NORD) at http://www.rarediseases.org/. NORD maintains a database of doctors with expertise in various rare diseases. The Metabolic Information Network (MIN), 800-945-2188, also maintains a database of physicians with expertise in various metabolic diseases.
Selecting Your Doctor15 When you have compiled a list of prospective doctors, call each of their offices. First, ask if the doctor accepts your health insurance plan and if he or she is taking new patients. If the doctor is not covered by your plan, ask yourself if you are prepared to pay the extra costs. The next step is to schedule a visit with your chosen physician. During the first visit you will have the opportunity to evaluate your doctor and to find out if you feel comfortable with him or her. Ask yourself, did the doctor: ·
Give me a chance to ask questions about hepatitis C?
While board certification is a good measure of a doctor’s knowledge, it is possible to receive quality care from doctors who are not board certified. 15 This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm. 14
48 Hepatitis C
·
Really listen to my questions?
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Answer in terms I understood?
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Show respect for me?
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Ask me questions?
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Make me feel comfortable?
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Address the health problem(s) I came with?
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Ask me my preferences about different kinds of treatments for hepatitis C?
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Spend enough time with me?
Trust your instincts when deciding if the doctor is right for you. But remember, it might take time for the relationship to develop. It takes more than one visit for you and your doctor to get to know each other.
Working with Your Doctor16 Research has shown that patients who have good relationships with their doctors tend to be more satisfied with their care and have better results. Here are some tips to help you and your doctor become partners: ·
You know important things about your symptoms and your health history. Tell your doctor what you think he or she needs to know.
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It is important to tell your doctor personal information, even if it makes you feel embarrassed or uncomfortable.
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Bring a “health history” list with you (and keep it up to date).
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Always bring any medications you are currently taking with you to the appointment, or you can bring a list of your medications including dosage and frequency information. Talk about any allergies or reactions you have had to your medications.
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Tell your doctor about any natural or alternative medicines you are taking.
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Bring other medical information, such as x-ray films, test results, and medical records.
This section has been adapted from the AHRQ: www.ahrq.gov/consumer/qntascii/qntdr.htm.
16
Seeking Guidance 49
·
Ask questions. If you don’t, your doctor will assume that you understood everything that was said.
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Write down your questions before your visit. List the most important ones first to make sure that they are addressed.
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Consider bringing a friend with you to the appointment to help you ask questions. This person can also help you understand and/or remember the answers.
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Ask your doctor to draw pictures if you think that this would help you understand.
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Take notes. Some doctors do not mind if you bring a tape recorder to help you remember things, but always ask first.
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Let your doctor know if you need more time. If there is not time that day, perhaps you can speak to a nurse or physician assistant on staff or schedule a telephone appointment.
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Take information home. Ask for written instructions. Your doctor may also have brochures and audio and videotapes that can help you.
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After leaving the doctor’s office, take responsibility for your care. If you have questions, call. If your symptoms get worse or if you have problems with your medication, call. If you had tests and do not hear from your doctor, call for your test results. If your doctor recommended that you have certain tests, schedule an appointment to get them done. If your doctor said you should see an additional specialist, make an appointment.
By following these steps, you will enhance the relationship you will have with your physician.
Broader Health-Related Resources In addition to the references above, the NIH has set up guidance Web sites that can help patients find healthcare professionals. These include:17 ·
Caregivers: http://www.nlm.nih.gov/medlineplus/caregivers.html
You can access this information at: http://www.nlm.nih.gov/medlineplus/healthsystem.html.
17
50 Hepatitis C
·
Choosing a Doctor or Healthcare Service: http://www.nlm.nih.gov/medlineplus/choosingadoctororhealthcareserv ice.html
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Hospitals and Health Facilities: http://www.nlm.nih.gov/medlineplus/healthfacilities.html
Vocabulary Builder The following vocabulary builder provides definitions of words used in this chapter that have not been defined in previous chapters: Biliary: Pertaining to the bile, to the bile ducts, or to the gallbladder. [EU] Membrane: A thin layer of tissue which covers a surface, lines a cavity or divides a space or organ. [EU] Neonatal: Pertaining to the first four weeks after birth. [EU] Porphyria: A pathological state in man and some lower animals that is often due to genetic factors, is characterized by abnormalities of porphyrin metabolism, and results in the excretion of large quantities of porphyrins in the urine and in extreme sensitivity to light. [EU]
Clinical Trials 51
CHAPTER 3. CLINICAL TRIALS AND HEPATITIS C Overview Very few medical conditions have a single treatment. The basic treatment guidelines that your physician has discussed with you, or those that you have found using the techniques discussed in Chapter 1, may provide you with all that you will require. For some patients, current treatments can be enhanced with new or innovative techniques currently under investigation. In this chapter, we will describe how clinical trials work and show you how to keep informed of trials concerning hepatitis C.
What Is a Clinical Trial?18 Clinical trials involve the participation of people in medical research. Most medical research begins with studies in test tubes and on animals. Treatments that show promise in these early studies may then be tried with people. The only sure way to find out whether a new treatment is safe, effective, and better than other treatments for hepatitis C is to try it on patients in a clinical trial.
The discussion in this chapter has been adapted from the NIH and the NEI: www.nei.nih.gov/netrials/ctivr.htm.
18
52 Hepatitis C
What Kinds of Clinical Trials Are There? Clinical trials are carried out in three phases: ·
Phase I. Researchers first conduct Phase I trials with small numbers of patients and healthy volunteers. If the new treatment is a medication, researchers also try to determine how much of it can be given safely.
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Phase II. Researchers conduct Phase II trials in small numbers of patients to find out the effect of a new treatment on hepatitis C.
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Phase III. Finally, researchers conduct Phase III trials to find out how new treatments for hepatitis C compare with standard treatments already being used. Phase III trials also help to determine if new treatments have any side effects. These trials--which may involve hundreds, perhaps thousands, of people--can also compare new treatments with no treatment. How Is a Clinical Trial Conducted?
Various organizations support clinical trials at medical centers, hospitals, universities, and doctors’ offices across the United States. The “principal investigator” is the researcher in charge of the study at each facility participating in the clinical trial. Most clinical trial researchers are medical doctors, academic researchers, and specialists. The “clinic coordinator” knows all about how the study works and makes all the arrangements for your visits. All doctors and researchers who take part in the study on hepatitis C carefully follow a detailed treatment plan called a protocol. This plan fully explains how the doctors will treat you in the study. The “protocol” ensures that all patients are treated in the same way, no matter where they receive care. Clinical trials are controlled. This means that researchers compare the effects of the new treatment with those of the standard treatment. In some cases, when no standard treatment exists, the new treatment is compared with no treatment. Patients who receive the new treatment are in the treatment group. Patients who receive a standard treatment or no treatment are in the “control” group. In some clinical trials, patients in the treatment group get a new medication while those in the control group get a placebo. A placebo is a harmless substance, a “dummy” pill, that has no effect on hepatitis C. In other clinical trials, where a new surgery or device (not a medicine) is being tested, patients in the control group may receive a “sham treatment.” This
Clinical Trials 53
treatment, like a placebo, has no effect on hepatitis C and does not harm patients. Researchers assign patients “randomly” to the treatment or control group. This is like flipping a coin to decide which patients are in each group. If you choose to participate in a clinical trial, you will not know which group you will be appointed to. The chance of any patient getting the new treatment is about 50 percent. You cannot request to receive the new treatment instead of the placebo or sham treatment. Often, you will not know until the study is over whether you have been in the treatment group or the control group. This is called a “masked” study. In some trials, neither doctors nor patients know who is getting which treatment. This is called a “double masked” study. These types of trials help to ensure that the perceptions of the patients or doctors will not affect the study results. Natural History Studies Unlike clinical trials in which patient volunteers may receive new treatments, natural history studies provide important information to researchers on how hepatitis C develops over time. A natural history study follows patient volunteers to see how factors such as age, sex, race, or family history might make some people more or less at risk for hepatitis C. A natural history study may also tell researchers if diet, lifestyle, or occupation affects how a disease or disorder develops and progresses. Results from these studies provide information that helps answer questions such as: How fast will a disease or disorder usually progress? How bad will the condition become? Will treatment be needed? What Is Expected of Patients in a Clinical Trial? Not everyone can take part in a clinical trial for a specific disease or disorder. Each study enrolls patients with certain features or eligibility criteria. These criteria may include the type and stage of disease or disorder, as well as, the age and previous treatment history of the patient. You or your doctor can contact the sponsoring organization to find out more about specific clinical trials and their eligibility criteria. If you are interested in joining a clinical trial, your doctor must contact one of the trial’s investigators and provide details about your diagnosis and medical history. If you participate in a clinical trial, you may be required to have a number of medical tests. You may also need to take medications and/or undergo
54 Hepatitis C
surgery. Depending upon the treatment and the examination procedure, you may be required to receive inpatient hospital care. Or, you may have to return to the medical facility for follow-up examinations. These exams help find out how well the treatment is working. Follow-up studies can take months or years. However, the success of the clinical trial often depends on learning what happens to patients over a long period of time. Only patients who continue to return for follow-up examinations can provide this important long-term information.
Recent Trials on Hepatitis C The National Institutes of Health and other organizations sponsor trials on various diseases and disorders. Because funding for research goes to the medical areas that show promising research opportunities, it is not possible for the NIH or others to sponsor clinical trials for every disease and disorder at all times. The following lists recent trials dedicated to hepatitis C.19 If the trial listed by the NIH is still recruiting, you may be eligible. If it is no longer recruiting or has been completed, then you can contact the sponsors to learn more about the study and, if published, the results. Further information on the trial is available at the Web site indicated. Please note that some trials may no longer be recruiting patients or are otherwise closed. Before contacting sponsors of a clinical trial, consult with your physician who can help you determine if you might benefit from participation. ·
Effect of a Change in HIV Therapy on Liver Steatosis, Inflammation, and Fibrosis Condition(s): HIV Infections; Hepatitis C Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to look at how 2 different anti-HIV drug treatments affect the liver. The use of anti-HIV drugs like the nucleoside reverse transcriptase inhibitors (NRTIs) may be linked to liver problems like fatty changes, scarring, abnormal liver function tests (LFTs), and lactic acidemia (an increase in lactic acid in the blood). Increased liver enzymes may mean liver damage. The way that the liver changes in people with abnormal LFTs and lactic acidemia is not completely understood. Study Type: Interventional Contact(s): see Web site below
19
These are listed at www.ClinicalTrials.gov.
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Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00023218 ·
Effects of Ribavirin on Zidovudine or Stavudine Condition(s): HIV Infections; Hepatitis C Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to see how treatment of hepatitis C (HCV) patients with ribavirin (RBV) affects the anti-HIV drugs stavudine (d4T) or zidovudine (ZDV). Studies have shown that RBV may interfere with the action of ZDV and d4T. There is little information about the way these drugs interact in the body. This study will examine how the drug RBV affects levels of ZDV or d4T in patients who are currently on stable anti-HIV therapy. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00021632
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Epidemiology, Infectivity and Natural History of Hepatitis C Virus Infection Condition(s): Hepatitis C Study Status: This study is currently recruiting patients. Sponsor(s): Warren G Magnuson Clinical Center (CC) Purpose - Excerpt: This study will evaluate hepatitis C virus (HCV) infection in blood donors who test positive for antibodies to this virus. Most HCV-infected people do not become ill and are not aware that they have hepatitis or have had it in the past. Some infected people recover completely, whereas others remain chronically infected. The study will try to define infectivity of anti-HCV positive individuals, routes of transmission of the virus, and the number of HCV-infected persons who have evidence of liver disease. Blood donors at the NIH Clinical Center or the Central Maryland Chapter of the American Red Cross who test positive for HCV may be eligible for this study. Participants will have a physical examination and history, including questions about socioeconomic status and current sexual practices. They will have 100 milliliters (ml) (6 tablespoons) of blood drawn at the first visit and 50 ml (3 tablespoons) drawn 3, 6, 9 and 12 months after the initial visit. Some participants may undergo plasmapheresis, a procedure for collecting additional plasma (the liquid portion of the blood). For this procedure, whole blood is collected through a needle placed in an arm vein. The
56 Hepatitis C
blood circulates through a machine that separates it into its components. The plasma is then removed, and the red and white cells and platelets are returned to the body, either through the same needle used to draw the blood or through a second needle placed in the other arm. In some individuals, other body fluids (saliva, urine or semen) may also be collected. Participants may be asked to bring their household contacts and sexual partners to NIH for interview and blood testing for evidence of HCV infection and liver disease. Although this is not required for participation in the study, it would provide additional valuable information. Participants found to have chronic viral infection will be seen more often and will provide additional blood samples for routine medical care. Further medical evaluation may include X-rays or liver scans and referral to a specialist for additional tests or therapy. Ten people in this study will be recruited to participate in a secondary investigation to analyze changes in the level of HCV and the immune response to it, and to relate these changes to the degree of liver damage. In addition to blood collected for the primary study, participants in this investigation will have an additional 50 ml (3 tablespoons) of blood drawn from an arm vein every week for 10 weeks to measure levels of virus, ALT (a liver enzyme), and immune response. Study Type: Observational Contact(s): Maryland; Warren G. Magnuson Clinical Center (CC), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800-411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004850 ·
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
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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): Maryland; Warren G. Magnuson Clinical Center (CC), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800-411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00001712 ·
Gamma Interferon Therapy for Chronic Hepatitis C Condition(s): Chronic Hepatitis C Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: This study will test whether gamma interferon is effective in treating chronic hepatitis C infection-a long-lasting viral infection affecting the liver. One-third of patients with hepatitis C infection develop cirrhosis of the liver, which can lead to liver failure or liver cancer. The current treatment for hepatitis C infection is peglyated alpha interferon (peginterferon) plus ribavirin; however, this treatment is successful in only about half of patients. Gamma interferon works similarly to alpha interferon, but through different pathways, and therefore might be helpful in patients who do not respond to alpha interferon. Patients 18 years of age and older with chronic hepatitis C infection, genotype 1, who did not respond to alpha interferon and ribavirin therapy may be eligible for this study. (Genotype 1 is a strain of
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hepatitis C virus that has a lower treatment success rate.) Potential participants will be admitted to the NIH Clinical Center for 2 to 3 days for a medical evaluation to determine eligibility for the study and, if enrolled, to begin gamma interferon therapy. Screening will include a medical history and physical examination, blood and urine tests, and possibly chest X-ray, abdominal ultrasound, and psychiatric evaluation. Participants will receive injections of gamma interferon under the skin 3 times a week for 4 weeks (a total of 12 injections). They will be randomly assigned to receive either 100 or 200 micrograms of drug per injection. Blood will be drawn just before the first injection and then 6, 12, 24 and 48 hours later to monitor changes in the levels of hepatitis C virus and immune responses to treatment. The amount and rapidity of decrease in virus will be compared with what occurs with alpha interferon treatment to define the relative effectiveness of gamma interferon. (Patients may leave the hospital at any time after the first day, but must return in time for the final blood test.) Patients will be seen in the clinic each week during treatment to report symptoms and drug side effects and to have blood drawn for routine tests and viral levels. After the 4-week treatment is completed, patients will return for follow-up visits at weeks 6 and 8 for routine blood tests. Phase(s): Phase II Study Type: Interventional Contact(s): Maryland; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800-411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00028275 ·
Genetics of Hepatitis C Virus Infection Condition(s): Hepatitis C; Liver Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: The course of hepatitis C varies among people infected with the virus. Some people respond to treatment while many do not; some recover completely while others remain chronically infected; and among those who remain infected, some have mild symptoms while others' symptoms are severe. This study will look for genetic factors that may contribute to these differences. Children over 2 years of age and adults with hepatitis C virus infection or with other kinds of liver disease
Clinical Trials 59
(such as hepatitis B virus infection, primary biliary cirrhosis, Wilson's disease and others), and normal volunteers may be eligible for this study. Participants will provide 40 to 60 centiliters (1 to 2 ounces) of blood. DNA will be isolated from the white blood cells for analysis of genes involved in certain immune functions. The genetic findings from patients with hepatitis C, patients with other forms of liver disease, and normal volunteers will be compared to try to learn how the differences may influence the symptoms and course of hepatitis C and to understand how the virus causes disease. The results of this study may provide information useful for developing a vaccine and better treatments for hepatitis C. Study Type: Observational Contact(s): Maryland; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800-411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00005657 ·
Immune Response to Hepatitis C Virus Condition(s): Hepatitis C Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: This study will identify and characterize immune factors involved in hepatitis C infection and elimination of the virus. Individual responses to hepatitis C infection vary; some people are able to eliminate the virus, whereas others remain chronically infected. This study may identify factors important in preventing infection that may be of help in developing a vaccine or more effective treatments. People over 18 years old who have been exposed to hepatitis C virus may participate in this study. Subjects will be recruited from the National Institutes of Health, Inova Fairfax Hospital, Occupational Medical Services-IDP P.C., Washington Hospital Center and Holy Cross Hospital, all in the Washington, D.C. metropolitan area. Individual patients from other centers will also be recruited on a case by case basis. Participants will have 40 to 60 cc (1 to 2 ounces) of blood drawn at seven intervals. The first collection will be as soon as possible after exposure to hepatitis C virus and then again at 2, 4, 6, 12, 24, and 48 weeks after exposure. The white blood cells will be studied for their response to the virus, and markers for infection will be followed. If infection develops, additional samples of blood may be requested, and patients will be offered
60 Hepatitis C
evaluation for treatment. Test results will be kept confidential and will not be entered into any medical records. Study Type: Observational Contact(s): Maryland; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800-411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00006301 ·
Interleukin-2 (IL-2), Pegylated Interferon (PEG-IFN alfa-2b), and Ribavirin (RBV) Treatment in Patients with Hepatitis C and HIV Coinfection Condition(s): HIV Infections; Hepatitis C Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will test the safety and effectiveness of a new treatment for hepatitis C (HCV) in patients who also have HIV. The usual treatment for HCV in people who are not HIV-infected is interferon-alfa (IFN) with ribavirin (RBV), an approved treatment by the Food and Drug Administration (FDA). This study will use a new, longer acting form of IFN called PEG-IFN alfa-2b. PEG-IFN alfa-2b is approved by the FDA for use in treating HCV but has not yet been approved for use with RBV. This study also will use IL-2, which is a substance that the body naturally produces. People with HIV infection usually do not make enough IL-2. IL-2 is being tested in this study to see if it will "boost" the immune system's response to HCV. The FDA has approved IL-2 for the treatment of some cancers. (The name PEG-IFN alfa-2b was changed from PEG-INTRON .) Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00015652
·
ISIS 14803-CS2, Treatment with ISIS 14803, Administered IV in Patients with Chronic Hepatitis C Virus Infections Condition(s): Hepatitis C, Chronic Study Status: This study is currently recruiting patients. Sponsor(s): Isis Pharmaceuticals; Hepasense, Ltd.; Elan International Services, Ltd.; Elan Corporation, Plc
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Purpose - Excerpt: Purpose of this study is to evaluate the safety, tolerability, antiviral activity, and pharmacokinetic behavior of ISIS 14803 administered for up to 12 weeks by intravenous infusions in patients with chronic hepatitis C. Phase(s): Phase II Study Type: Interventional Contact(s): California; Isis Pharmaceuticals, Carlsbad, California, 92008, United States; Recruiting; Chin Yin Lim 800-679-4747 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00035945 ·
Long Term Interferon for Patients Who Did Not Clear Hepatitis C Virus with Standard Treatment Condition(s): Chronic Hepatitis C; Cirrhosis, Liver; Fibrosis, Liver; Hepatic Cirrhosis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institute of Allergy and Infectious Diseases (NIAID); National Center on Minority Health and Health Disparities (NCMHD); National Cancer Institute (NCI); Hoffmann-LaRoche Purpose - Excerpt: The HALT-C Trial is a National Institute of Diabetes and Digestive and Kidney Diseases sponsored, randomized clinical trial of long-term use of Peginterferon alfa-2a (pegylated interferon) in patients who failed to respond to prior interferon treatment. All patients who enter the trial will be treated for 6 months with Peginterferon alfa-2a and Ribavirin. Patients who respond to this 6 month treatment will continue to be treated for an additional 6 months. Patients who do not respond to this treatment will be eligible for the long-term maintenance phase of this study where patients will be randomly selected to be treated with Peginterferon alfa-2a or to discontinue treatment for 3.5 years. Patients in both arms of this study will be followed closely with quarterly study visits. The combination of peginterferon plus ribavirin has recently been approved by the FDA for treatment of chronic HCV. Patients who remain HCV-RNA positive after being treated for at least 6 months with peginterferon and ribavirin outside of this study may be eligible to directly enter the randomized portion of the HALT-C Trial. The HALT-C study is designed to determine if continuing interferon long-term over several years will suppress Hepatitis C virus, prevent progression to cirrhosis, prevent liver cancer and reduce the need for liver transplantation. Phase(s): Phase III
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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00006164 ·
Long-Term Therapy with Ribavirin for Chronic Hepatitis C Condition(s): Chronic Hepatitis C Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Chronic hepatitis C is a disease of the liver caused by the hepatitis C virus. The disease can be serious and even fatal. Approximately 25% of patients with chronic hepatitis C will develop cirrhosis and some of these patients will develop cancer of the liver or liver failure. Presently the disease is treated with a combination of alpha interferon (an antiviral and immune stimulating drug) and ribavirin (an antiviral drug). Alpha interferon is given by injection three times a week and ribavirin is given as a tablet by mouth twice a day. The combination therapy lasts 12 months. Less than half of the patients given these medications will receive a lasting benefit and many patients do not respond well to the combination therapy. This study will select up to 50 patients will chronic hepatitis C who have not responded to combination therapy or who could not stand the side effects associated with combination therapy. These subjects will be evaluated and undergo liver biopsy to determine their present liver condition. If selected as subjects they will be started on single drug therapy with ribavirin. The drug will be given orally twice a day at a dose based on the patient's body weight. The patients will be followed on an out-patient basis. They will we asked to return for regular check-ups and blood tests every 2 to 8 weeks for the duration of the study. After 6 months, the medication will be stopped or adjusted based on the results of the subject's blood tests (liver enzymes). A response is considered if a decrease of 50% or more of the initial liver enzyme (alanine aminotransferase, ALT) is noted. A complete response will be considered if liver enzymes return to normal levels. Therapy will be discontinued after 6 months if patients do not respond. However, patients that respond to the single drug therapy will continue to receive the medication at a decreased dose. The patients will remain on an appropriate dose for up to 4 years with repeat liver biopsies at 2 and 4 years to assess progress. This study will determine if long-term therapy with ribavirin is safe and effective. Phase(s): Phase IV
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Study Type: Interventional Contact(s): Maryland; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800-411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00001854 ·
Nucleic Acid Amplification Testing (NAT) of Blood Donors for HCV and HIV Condition(s): Hepatitis C; HIV Infection Study Status: This study is currently recruiting patients. Sponsor(s): Warren G Magnuson Clinical Center (CC) Purpose - Excerpt: This study will evaluate the accuracy of an experimental test method called nucleic acid amplification technology (NAT) in detecting human immunodeficiency virus (HIV) and hepatitis C virus (HCV). This test amplifies the nucleic acid in a virus more than a million-fold, allowing early detection of minute quantities of virus in the blood. Blood donors to the National Institutes of Health's Department of Transfusion Medicine (blood bank) will have their blood screened with transcription mediated amplification, a type of NAT test. Donors whose blood is found positive for HIV or HCV by NAT testing will be notified and asked to participate in this study. Those who agree will provide a blood sample about once a week for 3 months. The samples will be tested with additional assays to detect evidence of HIV or HCV infection. If the test results are confirmed positive, no more blood samples will be collected. The results of the tests and their significance will be explained to participants. It is anticipated that NAT screening will reduce the risk of transfusion-related HIV transmission from the current 1 in 650,000 to 1 in a million and the risk of HCV transmission from the current 1 in 100,000 to 1 in 350,000. It is possible that these tests will completely eliminate the risk of transmitting these diseases through blood transfusion. Study Type: Observational Contact(s): Maryland; Warren G. Magnuson Clinical Center (CC), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800-411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004846
64 Hepatitis C
·
Peginterferon alpha-2b And Ribavirin to Treat Hepatitis C in HIVInfected Patients Condition(s): Hepatitis C; HIV Infections Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will evaluate the safety and effectiveness of combination therapy with peginterferon alpha-2b and ribavirin for treating hepatitis C virus (HCV) infection in HIV-infected patients. In studies of patients with hepatitis C alone, interferon alpha-2b plus ribavirin treatment eradicated the HCV in almost half the patients. Peginterferon alpha-2b is a compound that results from attaching a polyethylene glycol molecule to interferon alpha-2b. This compound stays in the blood longer than unmodified interferon alpha-2b, causing a higher blood concentration and thus maintaining activity against the hepatitis C virus. HIV-infected patients 21 years of age and older with chronic hepatitis C infection and a viral load greater than 2000 copies/mL may be eligible for this 2 1/2-year study. Candidates will be screened with blood and urine tests and possibly a liver biopsy, if a recent one is not available. The liver biopsy is done to determine the severity of liver disease. For this test, patients are admitted to the NIH Clinical Center for 1 to 2 days. A sedative is injected into an arm vein, the skin in the area over the biopsy site is numbed with a local anesthetic, and a needle is inserted rapidly into and out of the liver to obtain a small tissue sample. The patient remains in the hospital overnight for monitoring. A chest Xray, electrocardiogram (EKG) and liver ultrasound are also done. Within 4 weeks of the screening tests, candidates who appear eligible for the study will have a physical examination, medical history and repeat blood tests. Women who can become pregnant will have serial pregnancy tests throughout the study. Patients who meet the study criteria and decide to participate will begin treatment with weekly injections under the skin of peginterferon alpha-2b and take ribavirin pills twice a day by mouth. In addition, patients will continue to take all other medications prescribed by their doctor. Clinic visits will be scheduled as follows: - Days 1, 3, 5, 7, 10 and 21 - Blood will be drawn for safety tests and to measure blood levels of HIV and HCV. - Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 52, 56 and 64 - Blood and urine tests will be done to determine the side effects of treatment and its effect on the HCV infection. - Week 48 or end of treatment - Treatment will stop after 48 weeks. At this time, or earlier for those who do not complete the 48 weeks, patients will return to the clinic for a routine clinic visit, blood tests (including tests for hepatitis B and D) and abdominal ultrasound. Patients will be hospitalized for 2 days for a repeat liver biopsy. - Week 72 and extended follow-up visits -
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At week 72, patients will return for blood tests and a routine clinic visit. HCV viral load will be measured. Follow-up visits every 3 months for an additional year will include a blood test to measure HCV viral load and a complete physical examination. Phase(s): Phase II Study Type: Interventional Contact(s): Maryland; National Institute of Allergy and Infectious Diseases (NIAID), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00018031 ·
PEG-Intron Plus Rebetol Treatment of Chronic Hepatitis C Patients with Liver Fibrosis Who Failed to Respond to alpha-Interferon Plus Ribavirin Condition(s): Chronic Hepatitis C; Liver Fibrosis; Cirrhosis Study Status: This study is currently recruiting patients. Sponsor(s): Schering-Plough Purpose - Excerpt: The objective of this study is to determine the effectiveness of PEG-Intron 1.5 ug/kg/wk plus REBETOL 800-1400 mg/day in adults with chronic hepatitis C with moderate to severe liver fibrosis or cirrhosis who failed to respond to previous treatment with an a interferon in combination with ribavirin. Patients who do not respond to PEG-Intron plus Rebetol will be enrolled in a long-term maintenance study to evaluate the effectiveness of PEG-intron therapy monotherapy versus no treatment for the prevention of disease progression (Protocols P02569 and P02570). Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00039871
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Pegylated Interferon and Ribavarin to Treat Chronic Hepatitis C with and without Kidney Disease Condition(s): Hepatitis C Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
66 Hepatitis C
Purpose - Excerpt: This study will examine the effectiveness of pegylated interferon, or peginterferon (a long-acting form of alpha interferon) plus ribavirin in treating hepatitis C (genotype 1) infection with and without kidney disease. (Genotype 1 is a strain of hepatitis C virus that has a lower success rate of therapy.) Combination therapy with alpha interferon and ribavirin is the recommended treatment for hepatitis C infection in patients without kidney disease. However, it is not successful in all patients. An early predictor of who is or is not likely to respond to therapy would allow treatment to be stopped in non-responders within 2 to 4 weeks rather than 6 or 12 months. This study will determine whether early changes in viral levels with treatment predict the ultimate outcome. It will also compare responses in patients without and with kidney disease to better evaluate problems of therapy in the latter group. Ribavirin is not given to people with kidney disease because of possible severe drug side effects. However, because patients with kidney disease are poor treatment responders and because ribavirin increases the success of therapy in patients without kidney disease 2- to 3-fold, however, this study will look for a dose of the drug that can safely be given to patients with kidney disease. Patients 18 years of age and older with hepatitis C, genotype 1, with or without kidney disease may be eligible for this study. Candidates will be screened with a medical history and physical evaluation, blood tests, symptom questionnaires, 24-hour urine collection, chest X-ray, electrocardiogram, and liver ultrasound. A liver biopsy (removal of a small piece of liver tissue) will be done in patients who have not had one within the last year. Additional procedures, such as eye examination, treadmill stress test, hearing test, or others may be required depending on the individual's medical condition. Patients without kidney disease will be randomly assigned to one of two treatment groups: Group A will take both peginterferon (by injection under the skin once a week) and ribavirin (capsules by mouth) from the start of therapy; Group B will start treatment with peginterferon alone and add ribavirin after 4 weeks. Patients with kidney disease (Group C) will start with peginterferon alone and add ribavirin 4 weeks later. All patients will be admitted to the NIH Clinical Center for a few days when treatment starts in order to draw blood at precise intervals (6, 12, 24, 48, and 72 hours after the first peginterferon injection) for measurements of viral levels. Blood will then be drawn once a week for 4 weeks (just before each injection) to determine how rapidly viral levels decrease with treatment and to measure blood levels of interferon and ribavirin. After 4 weeks of therapy, patients will have a blood test and check of symptoms and side effects every 4 weeks for 24 weeks (every 2 weeks for Group C patients until the optimum ribavirin dose is found) and then every 8 weeks for the remainder of the study. They will have a physical
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examination and urine test every 12 weeks. Patients will be tested for hepatitis virus RNA after 24 weeks of therapy to determine if they are a responder or non-responder. Responders will be advised to continue therapy for a full 48 weeks to ensure a continued response when treatment stops. Non-responders-whose chances for a lasting response are estimated at only 2%-will be offered the option to continue treatment, to stop treatment and continue being followed without treatment, or to enroll in other studies of non-responders. At the end of the 72-week treatment and follow-up, patients will have the same blood and urine tests as were done at the beginning of the study and a repeat liver ultrasound. Phase(s): Phase IV Study Type: Interventional Contact(s): Maryland; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800-411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00028093 ·
Pegylated Interferon to Treat Chronic Hepatitis D Condition(s): Hepatitis D Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: This study will evaluate the safety and effectiveness of a long-acting form of alpha interferon called pegylated interferon in treating hepatitis D virus (HDV) infection. HDV only infects people who already have hepatitis B infection. HDV is often severe and progressive. Alpha interferon is the standard treatment for HDV, given by injection once a day or three times a week for up to 12 months. However, this treatment does not work for everyone, and those who respond usually relapse when the drug is stopped. The sustained-release form of the drug, pegylated interferon, is given just once a week. Pegylated interferon is more effective than standard interferon in hepatitis C patients, with patients experiencing longer-term improvement. This study will evaluate the effects of pegylated interferon on hepatitis D and hepatitis B. It will determine whether long-term therapy with this drug improves inflammation and scarring of the liver, thereby delaying or reversing cirrhosis, and whether the improvement can be maintained. Patients with chronic hepatitis D over 6 years old may be eligible for this study.
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Participants will have a medical evaluation, including a history and physical examination, blood tests, routine urinalysis and 24-hour urine collection. Chest X-ray, electrocardiogram, abdominal ultrasound and liver biopsy will be done if these tests have not been done within the last year. In addition, depending on their age and individual health status, some patients may have exercise stress testing, an eye examination, hearing test, and psychiatric consultation. All patients will fill out a health-related quality of life questionnaire. Patients will receive pegylated interferon by injection once a week and have blood tests to measure the effects of treatment on the liver and on HBV and HDV levels. The medical examination and liver biopsy will be repeated at the end of 12 months. Patients who improved with treatment may continue therapy long-term. Medical evaluations and liver biopsies will be repeated at 3 years and at 5 years. Phase(s): Phase II Study Type: Interventional Contact(s): Maryland; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800-411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00023322 ·
Rituximab Vasculitis
to
Treat
Hepatitis
C-Associated
Cryoglobulinemic
Condition(s): Hepatitis C; Vasculitis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will examine the safety and effectiveness of the drug Rituximab in treating hepatitis C-associated cryoglobulinemic vasculitis. About 5 percent of patients with hepatitis C develop cryoglobulinemic vasculitis. This syndrome, characterized by inflammation of blood vessels (vasculitis), may involve the skin, joints, kidneys, nerves and other sites, and cause skin rashes, joint pain, weakness, fatigue, and numbness. About 10 to 30 percent of patients develop kidney disease, which, in some cases, can lead to kidney failure. Although the cause of cryoglobulinemic vasculitis is not known, a critical component is the presence of cryoglobulins-abnormal proteins that white blood cells called B lymphocytes produce in response to the chronic hepatitis C infection. Rituximab decreases the number of B cells. The Food and Drug Administration approved Rituximab in 1997 for the
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treatment of B-cell non-Hodgkin's lymphoma. Patients between 18 and 75 years of age with hepatitis C and signs and symptoms of cryoglobulinemic vasculitis may be eligible for this study. They must have failed, or been unable to tolerate, treatment with IFN-a and ribavirin. Candidates will be screened with a history and physical examination, electrocardiogram (ECG), blood and urine tests, 24-hour urine collection and chest X-ray, if clinically indicated. Participants will be randomly assigned to receive Rituximab upon entering the study or 6 months after entering the study. Those whose treatment is delayed 6 months will be followed once a month at NIH for disease evaluation and blood tests during that time. Patients will be given Rituximab intravenously (through a vein) once a week for 4 weeks. For the first dose, patients will be admitted to the hospital for at least 24 hours after the infusion for monitoring. Subsequent infusions will be given on an inpatient or outpatient basis, depending on how the infusion is tolerated. The day before each infusion they will have a history and physical examination, blood work, and other tests, such as X-rays, as clinically indicated. After the four infusions, patients will be followed for drug side effects and response to treatment. They will have blood tests every week for 4 weeks and will then return to NIH for 1 day every month for 12 months for a physical examination, blood tests, and X-rays, if medically indicated. Visits may be more frequent, if necessary, and patients may be asked to stay longer than a day if test findings require further investigation. Patients whose cryoglobulinemic vasculitis improves and remains inactive for 12 months after completing Rituximab therapy will have completed the study. Those who benefit from treatment but have a later worsening of disease may receive a second course of four infusions, with follow-up for 12 months after the last infusion. Patients who do not respond to treatment and whose disease worsens will be advised of other treatment options, but will be asked to return to NIH monthly for 12 months for follow-up. Phase(s): Phase II Study Type: Interventional Contact(s): Maryland; National Institute of Allergy and Infectious Diseases (NIAID), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00029107
70 Hepatitis C
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The Impact of HAART on Response to Hepatitis C Treatment in Patients Taking Peginterferon alpha-2b and Ribavirin Condition(s): HIV Infections; Hepatitis C Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will evaluate how controlling HIV infection with HAART (highly active antiretroviral therapy) affects the response to hepatitis C treatment with peginterferon alpha-2b and ribavirin in HIVinfected patients with chronic hepatitis C. HIV worsens liver disease caused by hepatitis C. Since treatment of HIV infection with HAART improves immune function, it may be beneficial to start HAART before treating HCV. HIV-infected patients 18 years of age and older with chronic hepatitis C infection may be eligible for this study. Patients must have an HCV viral load greater than 2000 copies/mL and a CD4 count that is either more than 500 cells/mm3, or more than 350 cells/mm3 with an HIV viral load no greater than 40,000 particles/mL. Candidates will be screened for current or previous diseases, conditions or treatments that may exclude them from this study. Screening includes a medical history and physical examination, eye examination, blood and urine tests, chest X-ray, electrocardiogram (EKG), liver ultrasound, and, possibly, a liver biopsy, if a recent one is not available. The liver biopsy is optional and is done to determine the severity of liver disease. Patients will be sedated for this test. The skin in the area over the biopsy site is numbed with a local anesthetic, and a needle is inserted rapidly into and out of the liver to obtain a small tissue sample. Patients remain in the hospital overnight for monitoring. Women of childbearing age will have a pregnancy test. Patients enrolled in the study will be randomly assigned to one of the following treatment groups: 1) pegylated interferon and ribavirin for 48 weeks (control group); or 2) HAART for 6 months, followed by 48 weeks of pegylated interferon and ribavirin. HAART group - Patients taking HAART will be followed in the clinic every 2 weeks for the first month and then monthly for the next 5 months. After 6 months of HAART they will begin taking pegylated interferon and ribavirin and will follow the dosing and follow-up schedule outlined below for patients in the control group. Control group - Patients will have weekly injections under the skin of peginterferon alpha-2b and ribavirin pills daily by mouth. Clinic visits will be scheduled as follows: - Days 1, 3, 7, and 21 - Blood will be drawn for safety tests and to measure blood levels of HIV and HCV. HCV medications will be injected on days 7 and 21. - Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 52, 56, and 64 - Blood and urine tests will be done to determine the side effects of pegylated interferon and ribavirin treatment and its effect on the HCV infection. Eye examinations will be
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done every 3 months. - Week 48 or end of treatment - Treatment with pegylated interferon and ribavirin will stop after 48 weeks. At this time (or earlier for those who do not complete the 48 weeks of treatment), patients will return to the clinic for a routine visit, blood tests (including a test for hepatitis B) and abdominal ultrasound. Patients may also be hospitalized for 2 days for a repeat optional liver biopsy. - Week 72 and extended follow-up visits - At week 72, patients will return for blood tests and a routine clinic visit. HCV viral load will be measured. Follow-up visits every 3 months for an additional year will include a blood test to measure HCV viral load and a complete physical examination. Phase(s): Phase II Study Type: Interventional Contact(s): Maryland; National Institute of Allergy and Infectious Diseases (NIAID), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting; Patient Recruitment and Public Liaison Office 1-800411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00031343 ·
Thymosin Plus PEG-Interferon in Hepatitis C Patients with Cirrhosis Who Did Not Respond to Interferon or Interferon Plus Ribavirin Condition(s): Hepatitis C; Hepatitis C, Chronic Study Status: This study is currently recruiting patients. Sponsor(s): SciClone Pharmaceuticals Purpose - Excerpt: Chronic hepatitis C infection is one of the leading causes of chronic liver disease in the United States. Approximately onethird of patients with hepatitis C infection develop cirrhosis of the liver, which can lead to liver failure or liver cancer. The current treatment for hepatitis C infection in previously untreated patients is successful in only about half of patients. There is no established therapy for nonresponders. This is a randomized, double-blind, multicenter trial to determine the effectiveness of thymosin alpha 1 (thymalfasin) 1.6 mg twice weekly plus PEGinterferon alfa-2a 180 ug/wk compared to placebo plus PEGinterferon alfa-2a in adults with chronic hepatitis C with early cirrhosis or progression to cirrhosis who are non-responders to previous treatment with interferon or interferon plus ribavirin. The definition of non-response requires a positive HCV RNA test at the end of a course of at least 3 months of therapy. Patients will receive treatment for 12 months, and will be followed-up for a further 6 months after the end of therapy Phase(s): Phase III
72 Hepatitis C
Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00039962 ·
A Comparison of the Effectiveness, Safety, and Tolerability of Two Different Hepatitis C Treatments in Patients Infected with Both HIV and Hepatitis C Virus (HCV) Condition(s): HIV Infections; Hepatitis C Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to see if treatment with PEG-interferon-alfa-2a (PEG-IFN) plus ribavirin is a more effective treatment for hepatitis C virus (HCV) than interferon-alfa-2a (IFN) plus ribavirin for patients infected with both HCV and HIV. The study will also compare the 2 regimens to see which has fewer side effects. HCV infection is common in patients infected with HIV. Patients infected with both HIV and HCV viruses seem to have more severe hepatitis C. A combination of IFN and ribavirin has been shown to lessen the severity of HCV. PEG-IFN is a modified form of IFN that stays in the blood longer, which means that patients would not have to take the treatment as often. This study will compare the safety and effectiveness of PEG-IFN to IFN when each is combined with ribavirin. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00008463
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A Study to Evaluate the Effects of Anti-HIV Drugs in HIV-Positive Patients Who Also Have Hepatitis C Infection Condition(s): HIV Infections; Hepatitis C Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study evaluates patients infected with both HIV and Hepatitis C virus (HCV) who are receiving anti-HIV drugs. The purpose of this study is to learn more about HCV infection in patients whose HIV blood level decreases to less than 500 copies/ml. Phase(s): Phase II Study Type: Observational
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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00001117 ·
Combination Drug Therapy for Patients with Hepatitis C Condition(s): Chronic Hepatitis C; Fibrosis; Hemolytic Anemia Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Hepatitis C is a major cause of liver disease in the United States and leads to cirrhosis of the liver in approximately onethird of patients some of whom will ultimately suffer from liver failure or liver cancer. At present, the recommended therapy of hepatitis C is the combination of alpha interferon and ribavirin given for 6 to 12 months. Ribavirin is a antiviral drug that is given by mouth. Interferon is both an antiviral and an immune medication which must be given by injections (three times a week) and has many difficult side effects. The purpose of this study is to determine whether the combination of ribavirin and interferon improve the liver disease of hepatitis C and whether improvements can be maintained by continuing ribavirin therapy longterm. This study will take 100 to 120 patients suffering from hepatitis C and place them under combination drug therapy with alpha interferon and ribavirin. The course of drug therapy is scheduled to last 6 to 12 months. Patients will be selected after appropriate screening for hepatitis C virus and elevated liver enzymes are conducted and liver biopsy shows chronic hepatitis with some degree of injury and scarring. During the first 6 months of the study, subjects will be asked to return to the outpatient clinic for routine check-ups and blood tests every 2 to 4 weeks. Blood tests will include tests for hepatitis C virus. If the virus test becomes negative on treatment, the therapy will be considered successful and will be continued for a full 6 or 12 months (depending upon the strain of virus). If the virus test does not become negative during the first six months of treatment, subjects will be considered "non-responders" and will stop taking interferon but will continue on ribavirin alone or an identically appearing placebo tablet. These non-responsive subjects will continue this therapy for an additional 12 months. (A year-and-a-half total). Upon completion of the drug therapies, subjects will be requested to submit blood samples and undergo a liver biopsy to determine if the therapy was successful. Test results that reveal a loss of hepatitis C antibodies or normal levels of liver enzymes will be deemed successful. Patients that have successful laboratory test results will be considered for
74 Hepatitis C
continuation of ribavirin therapy. Patients that received placebo for a year will be eligible to receive ribavirin long-term at the end of the study. Phase(s): Phase III Study Type: Interventional Contact(s): Maryland; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Patient Recruitment and Public Liaison Office 1-800411-1222
[email protected]; TTY 1-866-411-1010 Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00001729 ·
Comparing Single Photon Emission Computed Tomography (SPECT) and Liver Biopsy to Evaluate the Liver in Patients with HIV and Hepatitis C Virus Condition(s): HIV Infections; Hepatitis C Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to find if the Single Photon Emission Computed Tomography (SPECT) scan is as effective as a liver biopsy (using a special needle to remove tissue from the liver) in examining liver damage in patients with HIV and hepatitis C virus (HCV). A standard way to examine the liver for disease has been to perform a liver biopsy. The SPECT scan, which takes a picture of the liver, has been found to be effective in determining liver damage but studies need to be done in patients with hepatitis. This study will compare the effectiveness of the liver biopsy and SPECT scan in determining liver disease in patients with HIV and HCV. The SPECT scan might be a good replacement for the liver biopsy if it is found to be as good as or better than liver biopsies. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00006643
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Evaluating Silymarin for Chronic Hepatitis C Condition(s): Hepatitis C, Chronic Study Status: This study is no longer recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM)
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Purpose - Excerpt: To investigate the effect of silymarin, derived from the milk thistle plant, Silybum marianum, in preventing and reversing the complications of chronic infection with hepatitis C virus and/or clearing hepatitis C infections. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00030030 ·
Hepatitis C in Clinically Discordant Hemophilic Siblings Condition(s): Blood Disease; Hemophilia A; Hepatitis, Viral, Human Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To define the natural history, immunologic, and genetic factors that influence the clinical outcome of hepatitis C in a cohort of hemophilic siblings. Study Type: Epidemiology Contact(s): Fried, Michael W. Chapel Hill, North Carolina, United States . Study chairs or principal investigators: Fried, Michael W., Study Chair; University of North Carolina Chapel Hill, North Carolina, United States Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00007371
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Herbal Treatment of Hepatitis C in Methadone Maintained Patients Condition(s): Hepatitis C Study Status: This study is no longer recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: Hepatitis C (HCV) is a chronic viral illness leading to progressive liver damage that has emerged as a major public health issue in the United States. While HCV affects all population groups, individuals with a history of intravenous drug use form the largest known risk group. Between 90 and 100 percent of long term intravenous drug use will eventually test positive for HCV, and there is substantial risk that even short term experimentation will result in infection. Studies suggest that HCV will be the major cause of cirrhosis and liver cancer in the next century. Currently, approved therapy includes recombinant interferons, which lead to sustained remission in a minority of patients. However, patients abusing other substances, including alcohol, are not
76 Hepatitis C
eligible for interferon therapy. The need for investigation into other potential therapies is clear. Current practice patterns in the Far East include the use of traditional herbal remedies for symptomatic chronic viral hepatitis. This study is intended to examine the effect of commonly used herbal remedies for the treatment of symptomatic HCV. Phase(s): Phase II Study Type: Interventional Contact(s): Minnesota; Hennepin County Medical Center, Minneapolis, Minnesota, United States. Study chairs or principal investigators: Jeff Albrecht, MD, Principal Investigator; Hennepin County Medical Center Minneapolis Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00010816 ·
Hepatitis C Antiviral Resistance in African-Americans Condition(s): Hepatitis C Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: This study is designed to test the hypothesis that African-Americans respond less well to combination pegylated interferon and ribavirin therapy than Caucasian-Americans who have chronic hepatitis C genotype 1 and who were not previously treated with either interferon or ribavirin. Reasons for differences in response, regardless of race, will be studied. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00038974
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Phase III Randomized Study of High vs Standard Dose of Interferon alfa for Chronic Hepatitis C Condition(s): Hepatitis C Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); Tulane University School of Medicine Purpose - Excerpt: Objectives: I. Determine whether the initial response to interferon alfa (IFN-A) can be increased by starting at a dose of 5 MU three times a week in patients with chronic hepatitis C. II. Determine
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whether patients who had normalized alanine aminotransferase (ALT) levels can maintain normal ALT during stepwise dose reduction from 5 MU to 3 MU to 1.5 MU. Phase(s): Phase III Study Type: Interventional Contact(s):. Study chairs or principal investigators: Anna S. F. Lok, Study Chair; Tulane University School of Medicine Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00004804 ·
Prevalence of Hepatitis C Virus Infection in HIV-Infected Children Condition(s): HIV Infections; Hepatitis C Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to find out how many children who are infected with HIV are also infected with hepatitis C virus (HCV). HCV infection is a major health concern. HIV-infected adults who are co-infected with HCV appear to have more rapid HIV disease progression. There is little data on how widespread HCV is among children who are HIV-infected. This study wants to find out how widespread HCV is among HIV-infected children. This information will help determine the need for future HCV studies. This study also will obtain blood samples for future testing for other hepatitis viruses such as hepatitis G virus (HGV or GB virus C). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00037076
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Risk of Post Transfusion Hepatitis C Virus Infection Condition(s): Hepatitis, Viral, Human; Blood Transfusion; Blood donors Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the risk of transfusion-transmitted hepatitis C virus (HCV) in cardiac surgery patients before and after donor screening for anti-HCV and surrogate markers of non-A, non-B hepatitis (NANBH). Also, to characterize donors who were HCV seronegative and who lacked surrogate markers at the time of donation, but whose recipient seroconverted to HCV. Study Type: Epidemiology
78 Hepatitis C
Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00005339 ·
The Safety and Effectiveness of a Two-Drug Combination in the Treatment of Patients with Hepatitis C Plus Advanced HIV Infections Condition(s): HIV Infections; Hepatitis C Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID); Schering-Plough Purpose - Excerpt: To investigate the toxicity of interferon alfa-2b ( IFN alfa-2b ) in combination with nucleoside analog therapy in HIV-positive patients with chronic hepatitis C. To determine the efficacy of treatment with IFN alfa-2b for chronic hepatitis C in patients with advanced HIV infections treated with nucleoside analog therapy. IFN alfa-2b has HIV inhibitory properties and has also been approved for treatment of chronic hepatitis C. Studies have shown that IFN alfa-2b is effective in asymptomatic HIV-positive patients with chronic hepatitis C, but the drug's benefit against hepatitis C in patients with advanced HIV infection has not been determined. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00001035
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To determine the prevalence of HIV and other related infections such as Hepatitis C, along with associated risk behaviors, in patients with severe mental illness (SMI). Condition(s): HIV Infections; Hepatitis C; Mental Disorders Study Status: This study is completed. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Cooperative Studies Program Purpose - Excerpt: It is suspected, but not well documented, that persons with severe mental illness (SMI) represent a significant transmission source of serious infectious diseases. SMI diagnoses are defined as schizophrenia, schizoaffective disorder, bipolar disorder, or posttraumatic stress disorder (PTSD). Severely mentally ill persons are at high risk for Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS). To assess the risk of HIV and related infections among these individuals, the National Institute of
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Mental Health (NIMH) Office on AIDS funded the HIV/SMI five site collaborative study "Assessing HIV/AIDS and Associated Health Risks in People with Severe Mental Illness". This Durham ERIC study supplements the NIMH HIV/SMI study with a four-year longitudinal cohort study of 300-plus SMI veterans in order to estimate the prevalence of HIV risk behaviors and HIV infection, as well as to measure utilization of health services over time. The Durham VA is the only VA site represented in the study and is collaborating with four non-VA sites including Dartmouth, University of New Hampshire, University of Connecticut and Duke University. As such, we have the additional goals of investigating health and health-care-service issues relevant to veterans with SMI and of establishing a database for the longitudinal study of veterans with SMI. Study Type: Observational Contact(s): North Carolina; VAMC - DURHAM, NC, Durham, North Carolina, 27705, United States; Marion I. Butterfield, MD, MPH 919-2866936
[email protected] Web Site: http://clinicaltrials.gov/ct/gui/show/NCT00007709
Benefits and Risks20 What Are the Benefits of Participating in a Clinical Trial? If you are interested in a clinical trial, it is important to realize that your participation can bring many benefits to you and society at large: ·
A new treatment could be more effective than the current treatment for hepatitis C. Although only half of the participants in a clinical trial receive the experimental treatment, if the new treatment is proved to be more effective and safer than the current treatment, then those patients who did not receive the new treatment during the clinical trial may be among the first to benefit from it when the study is over.
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If the treatment is effective, then it may improve health or prevent diseases or disorders.
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Clinical trial patients receive the highest quality of medical care. Experts watch them closely during the study and may continue to follow them after the study is over.
This section has been adapted from ClinicalTrials.gov, a service of the National Institutes of Health: http://www.clinicaltrials.gov/ct/gui/c/a1r/info/whatis?JServSessionIdzone_ct=9jmun6f291. 20
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People who take part in trials contribute to scientific discoveries that may help other people with hepatitis C. In cases where certain diseases or disorders run in families, your participation may lead to better care or prevention for your family members. The Informed Consent
Once you agree to take part in a clinical trial, you will be asked to sign an “informed consent.” This document explains a clinical trial’s risks and benefits, the researcher’s expectations of you, and your rights as a patient.
What Are the Risks? Clinical trials may involve risks as well as benefits. Whether or not a new treatment will work cannot be known ahead of time. There is always a chance that a new treatment may not work better than a standard treatment. There is also the possibility that it may be harmful. The treatment you receive may cause side effects that are serious enough to require medical attention.
How Is Patient Safety Protected? Clinical trials can raise fears of the unknown. Understanding the safeguards that protect patients can ease some of these fears. Before a clinical trial begins, researchers must get approval from their hospital’s Institutional Review Board (IRB), an advisory group that makes sure a clinical trial is designed to protect patient safety. During a clinical trial, doctors will closely watch you to see if the treatment is working and if you are experiencing any side effects. All the results are carefully recorded and reviewed. In many cases, experts from the Data and Safety Monitoring Committee carefully monitor each clinical trial and can recommend that a study be stopped at any time. You will only be asked to take part in a clinical trial as a volunteer giving informed consent.
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What Are a Patient’s Rights in a Clinical Trial? If you are eligible for a clinical trial, you will be given information to help you decide whether or not you want to participate. As a patient, you have the right to: ·
Information on all known risks and benefits of the treatments in the study.
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Know how the researchers plan to carry out the study, for how long, and where.
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Know what is expected of you.
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Know any costs involved for you or your insurance provider.
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Know before any of your medical or personal information is shared with other researchers involved in the clinical trial.
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Talk openly with doctors and ask any questions.
After you join a clinical trial, you have the right to: ·
Leave the study at any time. Participation is strictly voluntary. However, you should not enroll if you do not plan to complete the study.
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Receive any new information about the new treatment.
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Continue to ask questions and get answers.
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Maintain your privacy. Your name will not appear in any reports based on the study.
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Know whether you participated in the treatment group or the control group (once the study has been completed).
What about Costs? In some clinical trials, the research facility pays for treatment costs and other associated expenses. You or your insurance provider may have to pay for costs that are considered standard care. These things may include inpatient hospital care, laboratory and other tests, and medical procedures. You also may need to pay for travel between your home and the clinic. You should find out about costs before committing to participation in the trial. If you have health insurance, find out exactly what it will cover. If you don’t have health insurance, or if your insurance company will not cover your costs, talk to the clinic staff about other options for covering the cost of your care.
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What Should You Ask before Deciding to Join a Clinical Trial? Questions you should ask when thinking about joining a clinical trial include the following: ·
What is the purpose of the clinical trial?
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What are the standard treatments for hepatitis C? Why do researchers think the new treatment may be better? What is likely to happen to me with or without the new treatment?
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What tests and treatments will I need? Will I need surgery? Medication? Hospitalization?
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How long will the treatment last? How often will I have to come back for follow-up exams?
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What are the treatment’s possible benefits to my condition? What are the short- and long-term risks? What are the possible side effects?
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Will the treatment be uncomfortable? Will it make me feel sick? If so, for how long?
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How will my health be monitored?
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Where will I need to go for the clinical trial? How will I get there?
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How much will it cost to be in the study? What costs are covered by the study? How much will my health insurance cover?
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Will I be able to see my own doctor? Who will be in charge of my care?
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Will taking part in the study affect my daily life? Do I have time to participate?
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How do I feel about taking part in a clinical trial? Are there family members or friends who may benefit from my contributions to new medical knowledge?
Keeping Current on Clinical Trials Various government agencies maintain databases on trials. The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide patients, family members, and physicians with 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
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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 their Web site (www.clinicaltrials.gov) and search by “hepatitis C” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: ·
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For 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
General References The following references describe clinical trials and experimental medical research. They have been selected to ensure that they are likely to be available from your local or online bookseller or university medical library. These references are usually written for healthcare professionals, so you may consider consulting with a librarian or bookseller who might recommend a particular reference. The following includes some of the most readily available references (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·
A Guide to Patient Recruitment : Today’s Best Practices & Proven Strategies by Diana L. Anderson; Paperback - 350 pages (2001), CenterWatch, Inc.; ISBN: 1930624115; http://www.amazon.com/exec/obidos/ASIN/1930624115/icongroupinterna
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A Step-By-Step Guide to Clinical Trials by Marilyn Mulay, R.N., M.S., OCN; Spiral-bound - 143 pages Spiral edition (2001), Jones & Bartlett Pub; ISBN: 0763715697; http://www.amazon.com/exec/obidos/ASIN/0763715697/icongroupinterna
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·
The CenterWatch Directory of Drugs in Clinical Trials by CenterWatch; Paperback - 656 pages (2000), CenterWatch, Inc.; ISBN: 0967302935; http://www.amazon.com/exec/obidos/ASIN/0967302935/icongroupinterna
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The Complete Guide to Informed Consent in Clinical Trials by Terry Hartnett (Editor); Paperback - 164 pages (2000), PharmSource Information Services, Inc.; ISBN: 0970153309; http://www.amazon.com/exec/obidos/ASIN/0970153309/icongroupinterna
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Dictionary for Clinical Trials by Simon Day; Paperback - 228 pages (1999), John Wiley & Sons; ISBN: 0471985961; http://www.amazon.com/exec/obidos/ASIN/0471985961/icongroupinterna
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Extending Medicare Reimbursement in Clinical Trials by Institute of Medicine Staff (Editor), et al; Paperback 1st edition (2000), National Academy Press; ISBN: 0309068886; http://www.amazon.com/exec/obidos/ASIN/0309068886/icongroupinterna
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Handbook of Clinical Trials by Marcus Flather (Editor); Paperback (2001), Remedica Pub Ltd; ISBN: 1901346293; http://www.amazon.com/exec/obidos/ASIN/1901346293/icongroupinterna
Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Analog: A chemical compound that is similar to another drug in its effects but differs slightly in its chemical structure. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthetic: An agent that causes insensitivity to pain. [NIH] Antibiotic: A chemical substance produced by a microorganism which has the capacity, in dilute solutions, to inhibit the growth of or to kill other microorganisms. Antibiotics that are sufficiently nontoxic to the host are used as chemotherapeutic agents in the treatment of infectious diseases of man, animals and plants. [EU] Anxiety: The unpleasant emotional state consisting of psychophysiological responses to anticipation of unreal or imagined danger, ostensibly resulting from unrecognized intrapsychic conflict. Physiological concomitants include increased heart rate, altered respiration rate, sweating, trembling, weakness, and fatigue; psychological concomitants include feelings of impending danger, powerlessness, apprehension, and tension. [EU]
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Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Showing or causing no symptoms. [EU] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biopsy: The removal and examination, usually microscopic, of tissue from the living body, performed to establish precise diagnosis. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Chemotherapy: The treatment of disease by means of chemicals that have a specific toxic effect upon the disease - producing microorganisms or that selectively destroy cancerous tissue. [EU] Confusion: Disturbed orientation in regard to time, place, or person, sometimes accompanied by disordered consciousness. [EU] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Pertaining to the skin; dermal; dermic. [EU] Effusion: The escape of fluid into a part or tissue, as an exudation or a transudation. [EU] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Enzyme: A protein molecule that catalyses chemical reactions of other substances without itself being destroyed or altered upon completion of the reactions. Enzymes are classified according to the recommendations of the Nomenclature Committee of the International Union of Biochemistry. Each enzyme is assigned a recommended name and an Enzyme Commission (EC) number. They are divided into six main groups; oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. [EU] Fatal: Causing death, deadly; mortal; lethal. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Hepatic: Pertaining to the liver. [EU] Herpesviridae: A family of enveloped, linear, double-stranded DNA viruses infecting a wide variety of animals. There are three subfamilies based on biological characteristics: alphaherpesvirinae, betaherpesvirinae, and gammaherpesvirinae. [NIH] Infusion: The therapeutic introduction of a fluid other than blood, as saline
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solution, solution, into a vein. [EU] Interferons: Proteins secreted by vertebrate cells in response to a wide variety of inducers. They confer resistance against many different viruses, inhibit proliferation of normal and malignant cells, impede multiplication of intracellular parasites, enhance macrophage and granulocyte phagocytosis, augment natural killer cell activity, and show several other immunomodulatory functions. [NIH] 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] Lesion: Any pathological or traumatic discontinuity of tissue or loss of function of a part. [EU] Lymphoma: Any neoplastic disorder of the lymphoid tissue, the term lymphoma often is used alone to denote malignant lymphoma. [EU] Microgram: A unit of mass (weight) of the metric system, being onemillionth of a gram (10-6 gm.) or one one-thousandth of a milligram (10-3 mg.). [EU] Monotherapy: A therapy which uses only one drug. [EU] Palliative: 1. affording relief, but not cure. 2. an alleviating medicine. [EU] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] 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] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] 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] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH]
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Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Recombinant: 1. a cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Remission: A diminution or abatement of the symptoms of a disease; also the period during which such diminution occurs. [EU] Resection: Excision of a portion or all of an organ or other structure. [EU] 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] Sarcoma: A tumour made up of a substance like the embryonic connective tissue; tissue composed of closely packed cells embedded in a fibrillar or homogeneous substance. Sarcomas are often highly malignant. [EU] Schizophrenia: A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, hallucinations, emotional disharmony, and regressive behavior. [NIH] Sedative: 1. allaying activity and excitement. 2. an agent that allays excitement. [EU] Silymarin: A mixture of flavonoids extracted from seeds of the milk thistle, Silybum marianum. It consists primarily of three isomers: silicristin, silidianin, and silybin, its major component. Silymarin displays antioxidant and membrane stabilizing activity. It protects various tissues and organs against chemical injury, and shows potential as an antihepatoxic agent. [NIH] Stavudine: A dideoxynucleoside analog that inhibits reverse transcriptase and has in vitro activity against HIV. [NIH] Surgical: Of, pertaining to, or correctable by surgery. [EU] Symptomatic: 1. pertaining to or of the nature of a symptom. 2. indicative (of a particular disease or disorder). 3. exhibiting the symptoms of a particular disease but having a different cause. 4. directed at the allying of symptoms, as symptomatic treatment. [EU] Thymosin: 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] Tomography: The recording of internal body images at a predetermined plane by means of the tomograph; called also body section roentgenography. [EU]
Urinalysis:
Examination of urine by chemical, physical, or microscopic
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means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH] Vasculitis: Inflammation of a vessel, angiitis. [EU]
Your Rights and Insurance 89
PART II: ADDITIONAL RESOURCES AND ADVANCED MATERIAL
ABOUT PART II In Part II, we introduce you to additional resources and advanced research on hepatitis C. All too often, patients who conduct their own research are overwhelmed by the difficulty in finding and organizing information. The purpose of the following chapters is to provide you an organized and structured format to help you find additional information resources on hepatitis C. In Part II, as in Part I, our objective is not to interpret the latest advances on hepatitis C or render an opinion. Rather, our goal is to give you access to original research and to increase your awareness of sources you may not have already considered. In this way, you will come across the advanced materials often referred to in pamphlets, books, or other general works. Once again, some of this material is technical in nature, so consultation with a professional familiar with hepatitis C is suggested.
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CHAPTER 4. STUDIES ON HEPATITIS C Overview Every year, academic studies are published on hepatitis C or related conditions. Broadly speaking, there are two types of studies. The first are peer reviewed. Generally, the content of these studies has been reviewed by scientists or physicians. Peer-reviewed studies are typically published in scientific journals and are usually available at medical libraries. The second type of studies is non-peer reviewed. These works include summary articles that do not use or report scientific results. These often appear in the popular press, newsletters, or similar periodicals. In this chapter, we will show you how to locate peer-reviewed references and studies on hepatitis C. We will begin by discussing research that has been summarized and is free to view by the public via the Internet. We then show you how to generate a bibliography on hepatitis C and teach you how to keep current on new studies as they are published or undertaken by the scientific community.
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 C, 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
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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 in “hepatitis C” (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 a sample of what you can expect from this type of search: ·
Hepatitis C Source: HRSA Care Action September 1999;1-12. Contact: US Department of Health and Human Services, Public Health Service, Health Resources and Services Administration, Office of Communications, HIV/AIDS Bureau, 5600 Fishers Ln 7-46, Rockville, MD, 20857, (301) 443-6652, http://www.hrsa.dhhs.gov/hab. Summary: This newsletter for health professionals discusses hepatitis C. Topics include acute and chronic infection, epidemiology, transmission, hepatitis C virus (HCV) testing (i.e., the enzyme immuno assay and the recombinant immuno blot assay), treatment (i.e., alfa interferon monotherapy and interferon and ribavirin), and HCV and the human immunodeficiency virus (HIV) co-infection. Specific types of transmission discussed include injection drug use, other drug use, transfusions and transplants, sexual transmission, vertical transmission, nosocomial transmission, occupational exposure, household contact, and tattooing and body-piercing. Other specific topics include testing for HCV antibodies in HIV-positive patients, assessment of liver damage, side effects of interferon and ribavirin, and initiating treatment. The newsletter includes a table with the following information regarding hepatitis A, B, C, D, and E viruses: what each is, incubation periods, methods of transmission, symptoms, available treatments, available vaccinations, populations at risk, and methods of prevention. The newsletter also identifies populations who should be tested for HCV and discusses genotypic and phenotypic tests for measuring resistance to antiretroviral therapy.
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Hepatitis C-Associated Autoimmune Disorders Source: Rheumatic Disease Clinics of North America. 24(2): 353-374. May 1998. Summary: This journal article provides health professionals with information on hepatitis C virus (HCV) infection, HCV-associated immune and autoimmune disorders, and therapeutic strategies and
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toxicities documented in patients with HCV-associated disorders. The article begins with a discussion of the possible role of the immune system in HCV infection and an explanation of how the HCV infection is diagnosed. This is followed by data on the prevalence of HCV-associated autoimmunity. The article then describes the serologic and clinical correlates of HCV infection to illustrate an emerging picture of autoimmune disease spectra. Correlates include autoantibody formation, cryoglobulinemic manifestation, vasculitis, vascular thrombosis and antiphospholipid antibody syndrome, glomerulonephritis, systemic lupus erythematosus, rheumatoid arthritis, polymyositis, dermatomyositis, Sjogren's syndrome, autoimmune thyroid disease, and autoimmune hepatitis. In addition, the article discusses the treatment of HCV infection with interferon alpha. Although this drug has been shown to reduce cryoglobulins and improve associated proteinuria, vasculitis, and neuropathy, it may have no effect on, precipitate, or exacerbate other autoimmune diseases. The article concludes that further epidemiologic and virologic investigations controlling for HCV risk factors, HCV subtype, human leukocyte antigen genotype, and geographic and environmental variables will be needed to clarify a potential causal relationship for HCV infection in autoimmune disease. 1 figure, 2 tables, and 177 references. ·
Progress Against Hepatitis C Infection Source: Patient Care. 36(3): 11-12, 14-15, 19-20. February 15, 2002. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Fax (201) 573-4956. Summary: Hepatitis C virus (HCV) infection, the most frequently encountered cause of chronic viral hepatitis in the developed world, often results in the development of chronic infection (in 55 to 85 percent of patients infected). This article reports on progress against hepatitis C infection. The most common method of detecting HCV infection is via elevated liver enzyme levels, often discovered in conjunction with a routine physical examination. However, many people do not have routine physical examinations, and HCV infection may be present for decades before symptoms or physical signs are noted, so screening of high risk persons is key to detection. Treatment of HCV infection is aimed primarily at prevention of progressive liver disease, which may culminate in cirrhosis or liver cancer. Quality of life can be affected at an earlier disease stage, making therapy an option even for patients whose disease is not progressing quickly. As treatment efficacy continues to improve, some experts now offer treatment to all patients with HCV infection. The best results have been achieved with a regimen of
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peginterferon plus ribavirin given for 6 months to 1 year. Such an approach makes early detection by the primary care physician more important than ever. 1 figure. 2 tables. 20 references. ·
Hepatitis C Virus Infection in a Community in the Nile Delta: Risk Factors for Seropositivity Source: Hepatology. 33(1): 248-253. January 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: This article reports on a study undertaken to identify risk factors for hepatitis C virus (HCV) infection in a rural village in the Nile Delta with a high prevalence of antibodies to HCV (anti HCV). One half of the village households were systematically selected, tested for anti HCV, and interviewed. Of this group (n = 3999), 973 (24.3 percent) were anti HCV positive, reflecting prior HCV infection but not necessarily current liver disease, with nearly equal prevalence among males and females. Anti HCV prevalence increased sharply with age among both males and females, from 9.3 percent in those 20 years of age and younger to greater than 50 percent in those older than 35 years of age. Among those over 20 years of age, the following risk factors were significantly associated with seropositivity: age, male gender, marriage, anti schistosomiasis injection treatment, blood transfusion, invasive medical procedure (surgery, catheterization, endoscopy, or dialysis), receipt of injections from 'informal' health care provider, and cesarean section or abortion. Exposures not significantly related to anti HCV positivity in adults included history of, or active infection with, Schistosoma mansoni; sutures or abscess drainage; goza smoking in a group; and shaving by community barbers. Among those 20 years old or younger, no risk factors were clearly associated with anti HCV positivity; however, circumcision for boys by informal health care providers was marginally associated with anti HCV. The authors note that prevention programs focused primarily on culturally influenced risks in rural Egyptian communities are being implemented and evaluated. 7 tables. 32 references.
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Outcome of Hospital Care of Liver Disease Associated with Hepatitis C in the United States Source: Hepatology. 33(1): 201-206. January 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: This study describes mortality and resource utilization for inpatient (hospital) care of hepatitis C (HCV) in comparison to alcohol
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induced liver disease (ALD) in the United States. The study also identifies factors that affect outcomes. The Healthcare Cost and Utilization Project database, a national inpatient sample was used to identify hospitalization records with diagnoses related to liver disease from HCV and ALD. Outcomes of hospitalizations was analyzed in terms of inhospital deaths and health care resource utilization. For 1995, the authors estimate that there were 26,700 hospitalizations and 2,600 deaths in acute, nonfederal hospitals in the United States for liver diseases caused by HCV. Total charges for these hospitalizations were $514 million. In comparison, ALD was associated with 101,200 hospitalizations; 13,400 deaths, and $1.8 billion in charges. Simultaneous HCV and alcohol abuse was associated with younger ages at the time of hospitalization and death compared with HCV or ALD alone. In analyses, alcohol abuse and HIV infection were associated with an increased risk of death among those with HCV. Liver transplantation and patient death were associated with the largest increase in hospitalization charges. Major complications of cirrhosis (such as variceal bleeding, encephalopathy, and hepatorenal syndromes) and sociodemographic factors (such as race and health insurance) were also significantly associated with the risk of death and hospitalization charges, which were similar in HCV and ALD. The authors provide new estimates regarding the public health impact of HCV, for use in health policy decision and cost effectiveness analyses of preventive and therapeutic interventions. 6 tables. 21 references. ·
Role of Liver Biopsy in Chronic Hepatitis C Source: Hepatology. 33(1): 196-200. January 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide, affecting 175 million people globally. Over 80 percent of acutely infected patients go on to develop chronicity, but only 20 to 25 percent will develop end stage liver disease and its complications. This article considers the role of liver biopsy in chronic hepatitis C. The authors stress that liver biopsy is indicated to exclude other forms of liver pathologies and to establish the stage of liver disease. In this study, the authors calculated a discriminant score to predict cirrhosis in chronic hepatitis C infection; 111 patients were included. The results showed that additional diagnoses or unsuspected diagnoses are less frequent than clinicians suspected. Unsuspected additional diagnoses were rare and consisted only of fatty liver disease. The authors confirmed that the discriminant score for predicting cirrhosis is inferior to liver biopsy. Only
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in 23 percent of this sample could the presence or absence of cirrhosis be predicted reliably by the use of the clinical discriminant score. The authors conclude that the majority of patients with chronic hepatitis C will require a liver biopsy, which has an important implication on staging of the liver disease, prognosis, and possibly further management options. 1 figure. 5 tables. 28 references. ·
Hepatitis C Virus in Blood and Dialysate in Hemodialysis Source: American Journal of Kidney Diseases. 37(1): 38-42. January 2001. Contact: Available from W.B. Saunders Company. Periodicals Department, 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 6542452 or (407) 345-4000. Summary: The prevalence of hepatitis C virus (HCV) positivity among hemodialysis patients remains high compared with that of the healthy population, and thus the issue of safety and environmental protection must be addressed. This article reports on a study undertaken to evaluate the dynamics of prehemodialysis and posthemodialysis blood HCV levels and HCV escape to spent dialysate (and thus to the environment). A serine protease inhibitor (nafamostat mesilate) was used as the anticoagulant for hemodialysis. High flux polysulfone membrane dialyzers were used; dialyzer reuse was not performed. A portion of total spent dialysate (the fluid used for dialysis) was continuously extracted to measure for HCV. No HCV extravasation to spent dialysis was found, although HCV copy numbers were reduced to a statistically significant level in postdialysis blood compared with predialysis levels. The need to establish standards for risk management in dialysis centers is evident. The data obtained in this study strongly suggest that to minimize the risk for HCV transmission, lower transmembrane pressure (TMP) should be used in the hemodialysis of HCV positive patients, with fresh polysulfone dialyzers and dialysis settings of 180 to 250 milliliters per minute for blood flow, 500 milliliters per minute for dialysate flow, and less than 1.872 mm Hg for TMP. 1 figure. 23 references.
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Chronic Hepatitis C: Implications for the Primary Care Clinician Source: JAAPA. Journal of the American Academy of Physician Assistants. 14(2): 41-44, 47-48, 63. February 2001. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Fax (201) 573-4956. Summary: Chronic hepatitis C rarely causes acute illness, and may progress slowly without overt symptoms until the liver has been irreparably damaged. This article reviews the primary care
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considerations for managing patients with chronic hepatitis C. The authors cover the mechanism, natural history, and progression of infection with the hepatitis C virus (HCV); encourage readers to learn when to have a high index of suspicion for HCV infection; and summarize the clinical tools available to confirm diagnosis of HCV. The authors note that HCV is most often detected when elevated liver enzyme levels are found during a routine workup, health insurance screen, or preoperative evaluation. Risk factors for HCV infection include body piercing, child born to mother who has hepatitis C, hemodialysis, incarceration, injury with contaminated needles, intranasal cocaine use, IV drug use (even once), multiple sexual partners, sexual partners of hepatitis C patients, tattoos, and transfusion or infusion of blood products before 1992. Once infection has been diagnosed, liver biopsy is performed to assess the severity of disease. One of the most important roles of the primary care provider is to offer adequate patient education and support. The most important lifestyle modification for the patient is abstinence from alcohol. Alcohol kills liver cells and accelerates the progression to fibrosis and cirrhosis, and no amount of alcohol has been found safe for a patient who has chronic hepatitis C. Major lifestyle changes are not recommended, but patients should be counseled not to share razors, toothbrushes, or other items that may be contaminated with blood. Treatment (with interferon injections) is expensive, associated with multiple side effects, and varies widely in its effectiveness in eradicating the virus. The authors review five variables that can be considered to predict an individual's response to therapy and to guide the aggressiveness of that therapy. Appended to the article is a posttest with which readers can earn continuing education credit. 2 tables.
Federally-Funded Research on Hepatitis C The U.S. Government supports a variety of research studies relating to hepatitis C and associated conditions. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.21 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. Visit the CRISP Web site at 21 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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http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket. You can perform targeted searches by various criteria including geography, date, as well as topics related to hepatitis C and related conditions. 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 C and related conditions. In some cases, therefore, it may be difficult to understand how some basic or fundamental research could eventually translate into medical practice. The following sample is typical of the type of information found when searching the CRISP database for hepatitis C: ·
Project Title: Hepatitis C Clearance and Host Genetic Factors Principal Investigator & Institution: Thio, Chloe L.; Assistant Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2000; Project Start 0-SEP-2000; Project End 1-AUG2005 Summary: (Applicant's Abstract) The candidate is completing a three year Infectious Diseases fellowship and has devoted the last two years to studying associations of the human leukocyte antigen complex to hepatitis B virus outcomes in a multi-cohort study. Through this grant, the candidate will use molecular genetics tools in an epidemiologic setting and will thus bridge the gap between the epidemiologists and basic scientists in an effort to understand immunopathogenic mechanisms of infectious diseases. Long-term, the candidate would like to establish herself as a faculty member interested in understanding infectious disease outcomes by examining the genetically-determined variability of the host response. In particular, in the short-term, this candidate is interested in studying host genetic factors that affect hepatitis C outcomes to elucidate mechanisms of hepatitis C virus pathogenesis, which eventually may have therapeutic and vaccine implications. The work will be performed under the guidance of Dr. David Thomas who has expertise in hepatitis C and epidemiology. In collaboration with Dr. David Vlahov, the epidemiologist who established the ALIVE cohort, and with Dr. Mary Carrington, a leader in the field of genetics, the candidate will have the collaborative resources necessary for the successful completion of this project. The candidate will complement her research by attending 2 hours per week of infectious diseases and hepatitis related conferences, attending weekly hepatitis C research meetings, and seeing patients in an infectious diseases/hepatitis clinic
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one half-day per week. She also plans to take courses in epidemiology, genetics, and virology. Over 170 million people worldwide are infected with hepatitis C virus (HCV), 85 percent of them have a persistent infection and the remainder clear the virus. This heterogeneous outcome difference is not explained by viral or environmental factors. As has been shown in other chronic viral infections, it is likely that host factors, which may be genetically programmed determine these outcomes. In the past, these host-virus interactions have been difficult to explore because of limited knowledge of HCV biology and lack of molecular tools to explore the human genome. However, HCV biology is unfolding and the recent advances in molecular biology permit detection of human genomic variability on a large scale. Using the ALIVE cohort of injection drug users, the candidate will study 131 individuals who have cleared the virus and 262 matched controls with persistent HCV infection. She will test polymorphisms in the human leukocyte antigen alleles and putative pathogenic genes for distortions in allele frequency between the clearance and persistently infected individuals. Where possible, the allele frequencies will be checked for Hardy-Weinberg equilibrium distortions. Chi-square analysis and univariate and multivariate conditional logistic regression will be performed. The associations will also be assessed with regards to HCV genotype. Success is anticipated since the cohort is wellcharacterized, the molecular tools exist, and the collaborations have proven to be productive in HBV studies. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Hepatitis C Clinical Trial-Clinical Centers Principal Investigator & Institution: Bisceglie, Adrian; Internal Medicine; St. Louis University 221 N Grand Blvd St. Louis, Mo 63103 Timing: Fiscal Year 2000; Project Start 1-MAY-1999; Project End 0-APR2007 Summary: This project is aimed at developing practical, safe and effective means of preventing the progression of liver disease in patients with chronic hepatitis C virus (HCV) infection. Approximately 800 patients with chronic hepatitis C who have failed to respond to therapy with alpha interferon (with or without ribavirin) and who have significant fibrosis on liver biopsy will be enrolled in a study of the efficacy and safety of a continuous long-term antiviral therapy (for as long as four years). The objective of the Trial is to evaluate whether continuous therapy with long-term antiviral therapy can slow the progression of liver disease, preventing cirrhosis or preventing worsening of cirrhosis, decompensation, development of hepatocellular carcinoma (HCC) and death from liver disease. The Trial will also evaluate the natural history
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of hepatitis C and the factors that predict or correlate with disease progression. The major focus will be to evaluate whether antiviral therapy, despite not leading to eradication of HCV, can suppress hepatocellular injury, necrosis and fibrosis. Patients with chronic hepatitis C who have previously been treated with alpha interferon without a sustained virological and biochemical response will be eligible to enter the Trial. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Hepatitis C in Clinically Discordant Hemophilic Siblings Principal Investigator & Institution: Fried, Michael W.; Associate Professor of Medicine; Medicine; University of North Carolina Chapel Hill Box 2688, 910 Raleigh Rd Chapel Hill, Nc 27515 Timing: Fiscal Year 2000; Project Start 0-SEP-1999; Project End 1-AUG2003 Summary: The clinical spectrum of hepatitis C is variable and the factors responsible for these divergent outcomes with chronic hepatitis C infection remain unknown. We propose to study a cohort of hemophilic siblings infected with hepatitis C to define the natural history, immunologic, and genetic factors that influence its clinical outcome. Patients with hemophilia have a prevalence rate of hepatitis C as high as 90 percent. The sex-linked pattern of inheritance of hemophilia allows us to identify a cohort of siblings both of who have been infected with hepatitis C. Hemophilic siblings are an attractive population to study because: 1) They are all males; 2) Siblings will be relatively close in age; 3) The mode of HCV acquisition is identical; 4) The age at acquisition of hepatitis C is similar 5) The date of acquisition can be confidently estimated upon their factor replacement history; 6) Hemophilic sibs share significant amounts of genetic material. Hemophilic siblings with hepatitis C will undergo a detailed clinical evaluation to stage their liver disease and to identify sibling pairs with clinically and/or histologically discordant levels of disease activity. These siblings pairs will be further studied to define antigen recognition patterns of peripheral CD8 plus CTL and CD4 plus cells and determine their functional significance. Using peripheral blood mononuclear cells, CD8 plus cells will be assayed for CTL activity against three overlapping vaccinia/HCV constructs covering the entire HCV genome followed by fine cloning to identify HCV-specific CTL epitopes. Peripheral CD4 plus cells will be tested for their ability to proliferate to HCV antigens. Using stimulation index, we will quantitate the presence and magnitude of this response. We will also try to identify immunodominant regions targeted by cytotoxic T cells using HLA class I matched hemophilic siblings. Finally, we will identify
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specific host genes that are preferentially expressed or repressed in patients with delayed progression of their HCV disease. We will quantitate the expression of mRNAs encoding host antiviral defense and immunoregulatory elements in peripheral blood mononuclear cells (PBMCs) and liver tissue from sibling pairs that have discordant chronic hepatitis C using mRNA libraries that will be screened by high density oligonucleotide arrays. The expression levels of these genes (including, but not limited to, interferon alpha, beta, and gamma; IRF-1 and IRF-2; interferon induced protein kinase; the cellular protein activator of PKR (PACT) RNase L; interferon-inducible RNA-specific adenosine deaminase; a ribonuclease specific for inosine- containing RNA; chemokine receptors CCR1, CCR3, CCR5, and their signal transduction elements; 2'-5'-oligoadenylate synthetase; tumor necrosis factor; FAS receptor; signal transduction components of these antiviral pathways, and both type 1 and 2 cytokines) will be correlated with delayed progression and diminished pathogenesis in paired hemophilic siblings. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Hepatitis C Virus and Hepatocellular Carcinoma Principal Investigator & Institution: Dash, Srikanta A.; Associate Professor; Pathology; Tulane University of Louisiana New Orleans, La 70118 Timing: Fiscal Year 2001; Project Start 1-JUL-2001; Project End 0-JUN2006 Summary: (provided by applicant): Hepatitis C virus infection causes long-term inflammation of the liver which frequently leads to chronic liver disease, liver fibrosis and hepatocellular carcinoma. Treatment for liver cancer and liver cirrhosis is transplantation. Therefore, development of novel therapies to eradicate hepatitis C can save some of these end stage liver diseases and hepatocellular carcinomas. Concepts of designing innovative anti-viral therapies, which will stop virus replication and basic studies on several aspects of virus replication, have been hampered due to the lack of a reliable cell culture model to replicate HCV. Recently, we reported replication of HCV in a human hepatocellular carcinoma cell line and in a lymphoblastoid cell line after transfecting them with fulllength HCV RNA. We demonstrated that these two transfected cell lines produced infectious HCV particles for over 2 months. In addition, we showed that we could transmit HCV to a chimpanzee after intravenous inoculation of HCV derived from transfected HepG2 cells. Furthermore, avoid potential problems of low levels of HCV in the RNA transfection models, we developed an inducible model to study HCV replication and expression by biochemical means without the use of RT-PCR. On the
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basis of these preliminary results, we propose to extend our studies and establish infectious cell culture for HCV genotype la using a bonafide chimpanzee infectious clone prepared by Jens Bukh at the National Institute of Health. It is our hypothesis that efficient transfection of fulllength HCV RNA from a chimpanzee infectious HCV clone to HepG2 cells will result in replication of HCV in cell culture. Establishment of such cell culture systems for la and lb strains of HCV should facilitate studies to test therapeutic potential of interferons, ribozymes and protease inhibitors. The non-structural protein NS3 possess multiple enzyme activities (protease, helicase and NTPase) which appear to be important for HCV replication. We generated several adenoviral constructs containing single-chain antibody fragments derived from human which target core, E2, NS3 and NS4 proteins. Furthermore, we postulate that intracellular expression of single-chain antibodies targeted to structural proteins should inhibit virus formation and those antibodies targeted to non-structural proteins, NS3 and NS4, may block protease, helicase and NTPase activities and thus interfere with the processing of HCV proteins and replication. To directly test our hypotheses, we have developed three Specific Aims: 1) To study replication, expression and morphogenesis of hepatitis C virus genotype la in human hepatocellular carcinoma cell line (HepG2) transfected with chimpanzee infectious clone and determine whether the level of replication can be comparable to that of infected human liver with or without hepatocellular carcinoma and utilize the HCV cell culture models to identify therapeutic potential of interferons, ribozymes and protease inhibitors that may block one or more steps of hepatitis C replication cycle. 2) To study the molecular biology of the protease, helicase and NTPase domains of the NS3 protein and its role in negative strand RNA synthesis using an inducible expression system that utilizes T7 RNA polymerase and a transcription plasmid. We propose to establish a more robust RNA replication and expression system as an alternative to low levels of HCV in the RNA transfection model. 3) To determine whether intracellular expression of single-chain antibodies (scFv) targeted to structural proteins, core and E2, interfere with virus morphogenesis and antibodies targeted to NS3 and NS4 proteins could inhibit protease, helicase and NTPase activities and replication of HCV. Accomplishment of these aims will promote development of novel therapies to treat chronic hepatitis C infection and may reduce the potential risk of developing liver cirrhosis and hepatocellular carcinoma. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket
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Project Title: Iron Depletion (Phlebotomy) and Interferon Alpha Therapy in Chronic Hepatitis C Principal Investigator & Institution: Flamm, Steven; Northwestern University 303 E Chicago Ave Chicago, Il 60611 Timing: Fiscal Year 2000 Summary: Hepatitis C virus (HCV) is the major etiologic agent of posttransfusion, non-A, non-B hepatitis and is an important worldwide health problem. Since HCV results in chronic infection in as many as 90% of infected individuals of which up to 50% develop cirrhosis (with its complications or portal hypertension, ascites, encephalopathy, and bleeding disorders), the seriousness of the disease is apparent. In addition, chronic HCV infection can lead to highly lethal hepatocellular carcinoma. The only approved therapy of chronic HCV infection is interferon alpha. 50% of patients respond to this medication with normalization of serum liver enzymes (ALT) but only 10-20% continue to show benefit one year after starting therapy. It is currently unclear why some respond to alpha interferon while others do not. Van Thiel, et al. have suggested that hepatic iron concentrations are higher in those patients with chronic hepatitis C who do not respond to alpha interferon. Olynyk, et al. further investigated this relationship in patient with chronic hepatitis C. They discovered that while all patients in the study had a normal hepatic iron index (hepatic iron concentration/age), responders to alpha interferon had a significantly lower hepatic iron index than those who did not. They concluded that hepatic iron may impair the action of interferon or act synergistically with the hepatitis C virus affecting inflammatory activity. Bacon, et al. examined the effect in patients who had previously failed to respond to interferon. In the eight patients studied, there was a significant decrease in serum ALT after phlebotomy. Furthermore, six patients received a second course of alpha interferon for at least four months, and the ALT normalized in two of them. They concluded that hepatic iron may have synergistic effects with HCV on hepatocellular injury in chronic hepatitis C. We propose a trial to further examine these potentially important relationships in chronic hepatitis C patients who have failed alpha interferon therapy. We will investigate the hypotheses that hepatic iron may act synergistically with the hepatitis C virus affecting inflammatory activity. We propose phlebotomizing patients (the induction phase) to decrease hepatic iron stores and determining effects on biochemical parameters (serum ALT and AST) as a primary endpoint, and hepatic histology as a secondary endpoint. These endpoints allow evaluation of iron depletion (phlebotomy) on virologic activity and inflammation. It is possible that decreasing hepatic iron concentration may have favorable effects on
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hepatic inflammation and viral activity and thus may serve as a primary treatment modality. A complete response is defined as normalization of serum aminotransferases and negative hepatitis virologic titers (PCR). Patients will then be randomized (the treatment phase) to an iron depletion (phlebotomy) group which will also serve as a control group or to a group which will undergo iron depletion and additionally receive interferon alpha, the current standard therapy for chronic hepatitis C. The patients will be followed in prospective fashion. This will allow comparison of iron depletion alone to alpha interferon in the setting or iron depletion as a treatment modality in those with hepatitis C who have already failed a standard course of interferon therapy. The treatment phase will last 24 weeks. A complete response will be defined as described above. All patients undergo a 6 month period of observation to assess sustained resonse rates. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Role of Cd81 in Hepatitis C Virus Infection Principal Investigator & Institution: Geisert, Eldon E.; University of Tennessee Health Sci Ctr Health Science Center Memphis, Tn 38163 Timing: Fiscal Year 2000; Project Start 1-AUG-2000; Project End 1-JUL2005 Summary: Hepatitis C is a major health problem within the United States and the world. Recently, considerable progress was made in understanding the nature of this disease. Recently considerable progress was made by identifying CD81 as a putative ligand of the Hepatitis C virus. For the past several years, our laboratory has focused on the role of CD81 in the regulation of cell growth. The overall goal of the present proposal is to investigate the molecular associations of CD81 in the liver that may contribute to binding or entry of the hepatitis C virus. We hypothesize the CD81 is part of a molecular complex which varies between different body tissues. By defining components of this complex in the liver and comparing this to other tissues, we will begin to reveal specific molecular interactions critical to the virus interactions with CD81. The present proposal is designed to answer three questions related to hepatitis C infections. 1) What tissues and cells within the human body express CD81? 2) Is CD81 part of a molecular complex within the plane of t he membrane, and does the components of this complex change from tissue to tissue? 3) Is it possible to block or alter the interaction of hepatitis C with CD81 by altering cis interactions within the plane of the membrane or trans interactions with the E2 protein on the hepatitis C virus. This information will define the potential targets for Hepatitis C. By comparing the cells expressing CD81 and t he cells capable of the
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binding the virus, we will use subtractive methods to identify potential co- receptor molecules on the surface of the cell. This information can then be used to examine potential allelic variation in populations of patients that either spontaneously recover from hepatitis C infection or that are predestined to develop chronic infections. Once we identify genetic differences that result in alterations in alterations in the progression of hepatitis C infection or that are predest8ned to develop chronic infections. Once we identify genetic difference that result in alterations in the progression of hepatitis C infections, we may be able to develop treatment protocols to better treat this disease. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Studies of the Natural History of Hepatitis C in Liver Principal Investigator & Institution: Carithers, Robert L.; Professor; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2000; Project Start 0-SEP-1999; Project End 1-AUG2003 Summary: Chronic hepatitis C virus infection has emerged as the most important form of viral hepatitis in the United States. Although the disease often remains indolent for many years, approximately 20 percent of patients with chronic hepatitis C progress to cirrhosis within 20 years. As a consequence, liver failure from chronic hepatitis C has become the leading indication for liver transplantation both in the United States and Europe. Despite remarkable progress in our understanding of many aspects of this disease, the mechanism of hepatocellular injury in patients with chronic hepatitis C is not well understood. Unfortunately, neither efficient cell culture systems nor animal models are available to study the pathogenesis of the liver disease. Given these limitations, we have systematically examined the evolution of liver injury in patients with recurrent hepatitis C after liver transplantation. By correlating the degree of injury to the transplanted organ with detailed analyses of viral replication we hope to provide insights into the pathogenesis of liver cell injury in these chronically infected patients. This proposal is designed to examine the hypothesis that differing patterns of mutation in the genomic sequence of HCV RNA have a profound influence on the severity of liver injury in patients with recurrent hepatitis C after liver transplantation. Our Specific Aim 1 is to prospectively determine the relationship between evolution of HCV quasispecies and hepatocellular injury in patients with recurrent hepatitis C. In Specific Aim 2 we plan to intensively investigate the clonal evolution of quasispecies and to determine the tissue origin of these viral strains both in patients with severe recurrent hepatitis C and in those with mild hepatocellular injury
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after liver transplantation. We plan to test the hypothesis that the primary site of quasispecies replication is critical to the development of hepatocellular injury. We propose that emergence of nonpathogenic strains of virus after liver transplantation result from continuous extrahepatic replication of HCV, whereas pathogenic strains of HCV originate from intrahepatic replication of the virus. In Specific Aim 3 we plan to assess in impact of HCV genotype, circulating levels of virus, and evolution of HCV quasispecies on the long term evolution of histologic injury in the transplanted liver. By carefully correlating the evolution of the virus with the degree of hepatocellular injury experienced by patients who develop recurrent hepatitis C after liver transplantation, we hope to provide insights into to the pathogenesis of this important liver disease. From these detailed analyses we also hope to isolate pathogenic strains of virus which can later be tested in cell culture systems. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Transgenic Mouse Model for Hepatitis C Principal Investigator & Institution: Hoffman, Harold A.; Biocon, Inc. 15801 Crabbs Branch Way Rockville, Md 20855 Timing: Fiscal Year 2000; Project Start 5-MAY-2000; Project End 0-APR2002 Summary: Progress toward developing more effective therapeutic regimens for chronic hepatitis C, including antiviral, immunomodulatory, or antifibrotic agents, has been stymied by two major technical deficiencies, both of which represent critical bottlenecks to drug discovery and evaluation. These include the absence of a cell culture system that is permissive for efficient replication of hepatitis C virus (HCV), and the lack of a readily available small animal model that mimics the pathogenesis of chronic hepatitis G in humans. The overarching aim of the work proposed in this application is to ameliorate the second of these technical deficiencies by the commercial development of transgenic mice that express hepatitis C proteins and/or viral RNAs in a liver-specific fashion and that either manifest hepatic pathology similar to that observed in human disease. The long range goal of these studies is to make available appropriately validated animal models that can be used in preclinical studies aimed at defining the therapeutic efficacy of novel interventions. In preliminary work, we have established several lines of transgenic mice that express either the complete open reading frame (ORF) of HCV or the segment of the ORF encoding the structural proteins under control of the liver-specific mouse albumin promoter/enhancer. In one relatively well characterized lineage (FLN/35), we have observed enhanced hepatic steatosis in both males and
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females, and hepatocellular carcinoma in males over the age of 13 months. These histologic endpoints mimic findings in chronic hepatitis G, and provide substantial support for the utility of transgenic mice as models of hepatitis C in humans. In Specific Aim 1, we propose development of additional transgenic lineages, and further characterization of the phenotypes of mice expressing these HGV transgenes. In Specific Aim 2, we propose experiments aimed at elucidating the genetic and1or molecular requirements for steatosis and hepatocellular carcinoma in these mice. In Specific Aim 3, we propose the development of mice with inducible HGV transgenes, as the induction of HCV protein expression in immunologically mature mice will allow development of a model of the immunopathologically-mediated manifestations of hepatitis C. PROPOSED COMMERCIAL APPLICATIONS: The goal is to develop mouse models for use in preclinical studies of therapeutic interventions for hepatitis C. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Treatment of Chronic Hepatitis C with Amantadine Hydrochloride Principal Investigator & Institution: Smith, Jill; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2001 Summary: Treatment of chronic hepatitis C with interferon has been disappointing, with less than one-third achieving a sustained response and most experiencing significant side effects. A prospective openlabeled study was conducted to test the safety and efficacy of the antiviral drug amantadine-HCL, in patients with chronic hepatitis C infection who had previously failed therapy with interferon. Patients were treated with amantadine-HCL 100mg given orally twice daily for six months. Thirty percent achieved a complete response (normalization of alanine aminotransferase, ALT, and loss of hepatitis C RNA), 40% a partial response (> 50% reduction in ALT and RNA), and 30% did not respond to amantadine-HCL. Response to therapy was significantly greater with amantadine-HCL compared to two time intervals of no treatment or therapy with interferon. The purpose of this study is to expand these findings to a larger trial designed as a randomized double-blind placebo controlled cross-over study. Eligible patients with hepatitis C will be randomized to receive either amantadine -HCL or placebo by mouth twice daily for six months. After six months, patients on placebo will be crossed over to amantadine treatment for the next six months and those on amantadine will be continued for an additional six months. Response
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to therapy will be assessed by a reduction in the hepatitis C viral RNA level and hepatic alanine aminotransferase levels. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Interferon-Gamma to Treat Chronic HCV Infection Principal Investigator & Institution: Muir, Andrew; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 1-SEP-2001; Project End 1-AUG2003 Summary: (adapted from the application) Current treatment options for chronic hepatitis C infection remain limited and unsatisfactory. Treatment with interferon-alpha and ribavirin leads to a sustained response in the minority of patients, and many patients may not be eligible for treatment due to side effects associated with these medications. Other treatment options are clearly necessary for chronic hepatitis C infection. A major complication of chronic hepatitis C infection is fibrogenesis, ultimately leading to development of cirrhosis. Animal models have demonstrated that interferon-gamma reduces fibrogenesis through its effect on stellate cells. A recent report in patients with idiopathic pulmonary fibrosis found that interferon-gamma was well-tolerated and led to improved pulmonary function, ostensibly due to a reduction in fibrogenesis. Given these data, we postulate not only that interferon-gamma will be effective for treatment of hepatitis C mediated fibrogenesis, but also that it will be safe. We have therefore proposed a phase I study to assess the effectiveness of interferon-gamma in twenty patients with chronic hepatitis C infection. The patients will include those who have failed previous therapy with interferon-alpha or are not candidates for interferon-alpha therapy. Men or women 18 years of age or older are eligible. Other inclusion criteria are serum positive for hepatitis C virus by PCR; liver biopsy consistent with chronic hepatitis and with a fibrosis score of at least one on the Knodell scale; compensated liver disease; and informed, written consent obtained prior to entry. All patients will receive 200 micrograms of interferon-gamma three times a week for twelve months. Patients will undergo liver biopsy prior to treatment and at the end of treatment. Safety and tolerance will be evaluated at weeks 1, 2, 4, 8 and then every 4 weeks during treatment and at weeks 4 and 12 following the completion of therapy. Serum HCVRNA will be evaluated prior to initiating therapy and at the end of therapy. The primary endpoint of this study will be the histological response of patients with chronic hepatitis C infection to treatment with interferon-gamma. Secondary endpoints include the biochemical
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response, inflammatory and regulatory cytokine levels, and quality of life during treatment. Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket ·
Project Title: Young Adult Very Low Birthweight--Neonatal Blood Transfusion Principal Investigator & Institution: Hack, Maureen; Professor of Pediatrics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2000; Project Start 1-DEC-1978; Project End 0-NOV2003 Summary: Prior to 1986 risk factors for hepatitis C, or non A, non B hepatitis as it was then called, included transfusions of blood and blood products, needle sharing and intravenous drug abuse, health care employment with frequent exposure to blood, sexual contact with, or household exposure to a person who had hepatitis C, and possibly sexual contact. The overall prevalence of hepatitis C infection ranges from 0.5% for low risk blood donors to 60%-90% for drug users and hemophiliacs who have received multiple blood transfusions. Five to 15% of persons transfused prior to 1986 contracted hepatitis C. In examining these results, it is important to take into account that the majority of reports between 1990 and 1992 pertain to results obtained using first generation type radioimmunoassay tests, which, as noted above, have a poor sensitivity and predictive value. There is very little known of the natural history of HCV infections in childhood. High risk groups include children requiring multiple blood transfusions and/or pooled blood products, as well as those born to Hepatitis C positive mothers. It is postulated that the natural history and risk of progression to liver disease in children will vary depending on the underlying condition for which the blood products were received, but that it is likely that 40% of infected children will develop chronic hepatitis with progression at some time to cirrhosis, and that they will be at increased risk of developing hepatocellular carcinoma. This progression may extend over 30 to 40 years. The Specific Aims are: 1) to examine the prevalence of Hepatitis C infection in a cohort of very low birthweight young adults. 2) to estimate the risk of hepatitis C infection according to the total volume of blood received, and the number of different donors. 3) among Hepatitis C positive VLBW subjects, to identify the neonatal risk factors and childhood and adolescent health and behavioral risk factors associated with both the development of Hepatitis C liver disease and its severity. 4) to refer the Hepatitis C positive VLBW subjects for the best possible treatment currently available, to prevent the development of disease
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and/or deterioration of the liver associated with viral infection. 5) to inform the Hepatitis C positive VLBW subjects of the results of their tests, and to counsel them concerning health risk behaviors (such as drinking alcohol) and hepatotoxic medications, and precautions they might need to take to prevent transmission to close intimate partners. Hypotheses: 1) That 10-15% of the very low birthweight subjects who received neonatal blood transfusions will be Hepatitis C positive at 20 years of age. 2) That the probability of testing Hepatitis C positive will depend on the number of transfusions from different donors and the total volume of blood received during the neonatal and behavioral risk factors. We propose, initially, a pilot study to examine the prevalence of Hepatitis C infection among the 20 year-old subjects in our main study born in 1977 who received blood (n=87). If the hypothesized Hepatitis C infection rate of 10-15% is found, we plan to extend the study to examine the prevalence of Hepatitis C infection among the total cohort of 20 year-old very low birthweight subjects who received blood (n=198/156 seen at age 20). All subjects will be screened with the anti-HCV 3.0 enzyme immunoassay. We also plan to test for ALT as an indicator of ongoing hepatitis associated with HCV infection and for other transfusion-transmitted disease associated markers including HbsAg, anti-HBc and HIV. The pilot project will be implemented by initially sending a letter to the subjects who received neonatal blood transfusions informing them that they received blood as infants, that prior to 1986 blood was not screened for Hepatitis C, and that the Center for Disease Control suggests screening all persons who received blood transfusions prior to this time. Blood tests will be free of charge. Since the subjects were seen a year ago, the only additional information which will be required is an update on health and a question as to whether they ever received blood transfusions after the neonatal period. The subjects will be informed of the results, and if positive for Hepatitis C they will be referred for counseling and further testing for potential liver disease. " Website: http://commons.cit.nih.gov/crisp3/CRISP.Generate_Ticket
E-Journals: PubMed Central22 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
22
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Information (NCBI) at the U.S. National Library of Medicine (NLM).23 Access to this growing archive of e-journals is free and unrestricted.24 To search, go to http://www.pubmedcentral.nih.gov/index.html#search, and type “hepatitis C” (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 C in the PubMed Central database: ·
In vivo analysis of the 3[prime prime or minute] untranslated region of the hepatitis C virus after in vitro mutagenesis of an infectious cDNA clone by Masayuki Yanagi, Marisa St. Claire, Suzanne U. Emerson, Robert H. Purcell, and Jens Bukh; 1999 March 2 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=26776
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A Quantitative Test to Estimate Neutralizing Antibodies to the Hepatitis C Virus: Cytofluorimetric Assessment of Envelope Glycoprotein 2 Binding to Target Cells by D Rosa, S Campagnoli, C Moretto, E Guenzi, L Cousens, M Chin, C Dong, AJ Weiner, JYN Lau, Q Choo, D Chien, P Pileri, M Houghton, and S Abrignani; 1996 March 5 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=39854
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A Second Hepatitis C Virus-Encoded Proteinase by A Grakoui, DW McCourt, C Wychowski, SM Feinstone, and CM Rice; 1993 November 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=47821
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Assessment of Viral Loads in Patients with Chronic Hepatitis C with Amplicor HCV Monitor Version 1.0, Cobas HCV Monitor Version 2.0, and Quantiplex HCV RNA Version 2.0 Assays by Michele MartinotPeignoux, Veronique Le Breton, Sandrine Fritsch, Gaelle Le guludec, Nathalie Labouret, Francoise Keller, and Patrick Marcellin; 2000 July http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87008&ren dertype=external
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Assessment, by Transcription-Mediated Amplification, of Virologic Response in Patients with Chronic Hepatitis C Virus Treated with Peginterferon [alpha]-2a by Christoph Sarrazin, David A. Hendricks, Farhad Sedarati, and Stefan Zeuzem; 2001 August http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88249&ren dertype=external
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. 24 The value of PubMed Central, in addition to its role as an archive, lies 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. 23
112 Hepatitis C
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At Least 12 Genotypes of Hepatitis C Virus Predicted by Sequence Analysis of the Putative E1 Gene of Isolates Collected Worldwide by J Bukh, RH Purcell, and RH Miller; 1993 September 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=47323
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At Least Five Related, but Distinct, Hepatitis C Viral Genotypes Exist by T Cha, E Beall, B Irvine, J Kolberg, D Chien, and MS Urdea; 1992 August 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=49662
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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 Q. Meng, C. Wong, A. Rangachari, S. Tamatsukuri, M. Sasaki, E. Fiss, L. Cheng, T. Ramankutty, D. Clarke, H. Yawata, Y. Sakakura, T. Hirose, and C. Impraim; 2001 August http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88264&ren dertype=external
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Automated Specific Capture of Hepatitis C Virus RNA with Probes and Paramagnetic Particle Separation by Hayato Miyachi, Atsuko Masukawa, Toshio Ohshima, Toru Hirose, Chaka Impraim, and Yasuhiko Ando; 2000 January http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=86008&ren dertype=external
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Changes in anti-viral effectiveness of interferon after dose reduction in chronic hepatitis c patients: a case control study by Frank C. Bekkering, Avidan U. Neumann, Johannes T. Brouwer, Rachel S. Levi-Drummer, and Solko W. Schalm; 2001 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=64636
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Characterization of the Terminal Regions of Hepatitis C Viral RNA: Identification of Conserved Sequences in the 5' Untranslated Region and Poly(A) Tails at the 3' End by JH Han, V Shyamala, KH Richman, MJ Brauer, B Irvine, MS Urdea, P Tekamp-Olson, G Kuo, Q Choo, and M Houghton; 1991 March 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=51094
Studies 113
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Classification of Hepatitis C Virus Type 2 Isolates by Phylogenetic Analysis of Core and NS5 Regions by Mauro Pistello, Fabrizio Maggi, Claudia Fornai, Alessandro Leonildi, Antonietta Morrica, Maria Linda Vatteroni, and Mauro Bendinelli; 1999 June http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85058&ren dertype=external
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Classification of Hepatitis C Viruses Based on Phylogenetic Analysis of the Envelope 1 and Nonstructural 5B Regions and Identification of Five Additional Subtypes by L Stuyver, WV Arnhem, A Wyseur, F Hernandez, E Delaporte, and G Maertens; 1994 October 11 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=44972
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Clinical course of hepatitis C virus during the first decade of infection: cohort study by Helen E Harris, Mary E Ramsay, Nick Andrews, and Keith P Eldridge; 2002 February 23 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=65664
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Clinical Evaluation of the Automated COBAS AMPLICOR HCV MONITOR Test Version 2.0 for Quantifying Serum Hepatitis C Virus RNA and Comparison to the Quantiplex HCV Version 2.0 Test by Ming-Lung Yu, Wan-Long Chuang, Chia-Yen Dai, Shinn-Cherng Chen, Zu-Yau Lin, Ming-Yuh Hsieh, Liang-Yen Wang, and Wen-Yu Chang; 2000 August http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87152&ren dertype=external
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Clinical Update:Early treatment of acute hepatitis C infection may lead to cure by John Hoey; 2001 November 27 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=81686&ren dertype=external
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Comparison and Application of a Novel Genotyping Method, Semiautomated Primer-Specific and Mispair Extension Analysis, and Four Other Genotyping Assays for Detection of Hepatitis C Virus Mixed-Genotype Infections by Yu-Wen Hu, Evan Balaskas, Milena Furione, Pei-Hua Yen, Garry Kessler, Vito Scalia, Linda Chui, and Graham Sher; 2000 August http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87116&ren dertype=external
114 Hepatitis C
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Correlation between Mutations in the Interferon SensitivityDetermining Region of NS5A Protein and Viral Load of Hepatitis C Virus Subtypes 1b, 1c, and 2a by Maria I. Lusida, Motoko Nagano-Fujii, Chairul A. Nidom, Soetjipto, Retno Handajani, Tsunenori Fujita, Kiyomasa Oka, and Hak Hotta; 2001 November http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88455&ren dertype=external
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Correlation Between the Infectivity of Hepatitis C Virus In vivo and Its Infectivity In vitro by YK Shimizu, RH Purcell, and H Yoshikura; 1993 July 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=46862
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Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus by Stephane Bressanelli, Licia Tomei, Alain Roussel, Ilario Incitti, Rosa Letizia Vitale, Magali Mathieu, Raffaele De Francesco, and Felix A. Rey; 1999 November 9 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=23895
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Detection of Acute Hepatitis C Virus Infection by ELISA Using a Synthetic Peptide Comprising a Structural Epitope by GJ Kotwal, BM Baroudy, IK Kuramoto, FF McDonald, GM Schiff, PV Holland, and JB Zeldis; 1992 May 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=49107
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Detection of Antibody Against Antigen Expressed by Molecularly Cloned Hepatitis C Virus cDNA: Application to Diagnosis and Blood Screening for Posttransfusion Hepatitis by T Miyamura, I Saito, T Katayama, S Kikuchi, A Tateda, M Houghton, Q Choo, and G Kuo; 1990 February 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=53394
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Detection of Intrahepatic Replication of Hepatitis C Virus RNA by In situ Hybridization and Comparison with Histopathology by F Negro, D Pacchioni, Y Shimizu, RH Miller, G Bussolati, RH Purcell, and F Bonino; 1992 March 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=48634
Studies 115
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Determination of Hepatitis C Virus Genotype by Direct Sequence Analysis of Products Generated with the Amplicor HCV Test by Jeff J. Germer, Paul N. Rys, Jill N. Thorvilson, and David H. Persing; 1999 August http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85299&ren dertype=external
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Development of a Simple and Highly Sensitive Enzyme Immunoassay for Hepatitis C Virus Core Antigen by Katsumi Aoyagi, Chiharu Ohue, Kumiko Iida, Tatsuji Kimura, Eiji Tanaka, Kendo Kiyosawa, and Shintaro Yagi; 1999 June http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=84955&ren dertype=external
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Diagnosis of Hepatitis C Virus (HCV) Infection Using an Immunodominant Chimeric Polyprotein to Capture Circulating Antibodies: Reevaluation of the Role of HCV in Liver Disease by DY Chien, Q Choo, A Tabrizi, C Kuo, J McFarland, K Berger, C Lee, JR Shuster, T Nguyen, DL Moyer, M Tong, S Furuta, M Omata, G Tegtmeier, H Alter, E Schiff, L Jeffers, M Houghton, and G Kuo; 1992 November 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=50267
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Early Events in Hepatitis C Virus Infection of Chimpanzees by YK Shimizu, AJ Weiner, J Rosenblatt, DC Wong, M Shapiro, T Popkin, M Houghton, HJ Alter, and RH Purcell; 1990 August 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=54550
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Effect of Multiple Freeze-Thaw Cycles on Hepatitis B Virus DNA and Hepatitis C Virus RNA Quantification as Measured with BranchedDNA Technology by Mel Krajden, James M. Minor, Oretta Rifkin, and Lorraine Comanor; 1999 June http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=84922&ren dertype=external
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Effects of Storage and Type of Blood Collection Tubes on Hepatitis C Virus Level in Whole Blood Samples by Harald H. Kessler, Evelyn Stelzl, Reinhard B. Raggam, Josef Haas, Franz Kirchmeir, Karin Hegenbarth, Elisabeth Daghofer, Brigitte I. Santner, Egon Marth, and Rudolf E. Stauber; 2001 May http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88026&ren dertype=external
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Evidence for Immune Selection of Hepatitis C Virus (HCV) Putative Envelope Glycoprotein Variants: Potential Role in Chronic HCV Infections by AJ Weiner, HM Geysen, C Christopherson, JE Hall, TJ
116 Hepatitis C
Mason, G Saracco, F Bonino, K Crawford, CD Marion, KA Crawford, M Brunetto, PJ Barr, T Miyamura, J McHutchinson, and M Houghton; 1992 April 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=48889 ·
Evidence for In vitro Replication of Hepatitis C Virus Genome in a Human T-Cell Line by YK Shimizu, A Iwamoto, M Hijikata, RH Purcell, and H Yoshikura; 1992 June 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=49315
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Functional Measurement of Hepatitis C Virus Core-Specific CD8 + TCell Responses in the Livers or Peripheral Blood of Patients by Using Autologous Peripheral Blood Mononuclear Cells as Targets or Stimulators by Shih-Hua Fang, Bor-Luen Chiang, Mei-Hua Wu, Hideo Iba, Ming-Yang Lai, Pei-Ming Yang, Ding-Shinn Chen, and Lih-Hwa Hwang; 2001 November http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88461&ren dertype=external
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Gene Mapping of the Putative Structural Region of the Hepatitis C Virus Genome by In Vitro Processing Analysis by M Hijikata, N Kato, Y Ootsuyama, M Nakagawa, and K Shimotohno; 1991 July 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=51914
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Genetic Organization and Diversity of the Hepatitis C Virus by Q Choo, KH Richman, JH Han, K Berger, C Lee, C Dong, C Gallegos, D Coit, A Medina-Selby, PJ Barr, AJ Weiner, D w. Bradley, G Kuo, and M Houghton; 1991 March 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=51250
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Genomic and Phylogenetic Analysis of Hepatitis C Virus Isolates from Argentine Patients: a Six-Year Retrospective Study by J. F. Quarleri, B. H. Robertson, V. L. Mathet, M. Feld, L. Espinola, M. P. Requeijo, O. Mando, G. Carballal, and J. R. Oubina; 2000 December http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87637&ren dertype=external
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Genomic Structure of the Human Prototype Strain H of Hepatitis C Virus: Comparison with American and Japanese Isolates by G Inchauspe, S Zebedee, D Lee, M Sugitani, M Nasoff, and AM Prince; 1991 November 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=52914
Studies 117
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Genotype Dependence of Hepatitis C Virus Load Measurement in Commercially Available Quantitative Assays by Janet Mellor, Anna Hawkins, and Peter Simmonds; 1999 August http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85273&ren dertype=external
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Genotyping of Hepatitis C Virus Isolates using CLIP Sequencing by R. S. Ross, S. O. Viazov, C. D. Holtzer, A. Beyou, A. Monnet, C. Mazure, and M. Roggendorf; 2000 October http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87440&ren dertype=external
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Hepatitis C virus and other Flaviviridae viruses enter cells via low density lipoprotein receptor by Vincent Agnello, Gyorgy Abel, Mutasim Elfahal, Glenn B. Knight, and Qing-Xiu Zhang; 1999 October 26 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=23090
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Hepatitis C virus core protein shows a cytoplasmic localization and associates to cellular lipid storage droplets by G. Barba, F. Harper, T. Harada, M. Kohara, S. Goulinet, Y. Matsuura, G. Eder, Zs. Schaff, M. J. Chapman, T. Miyamura, and C. Brechot; 1997 February 18 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=19768
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Hepatitis C Virus Genotyping Based on 5[prime prime or minute] Noncoding Sequence Analysis (Trugene) by P. Halfon, P. Trimoulet, M. Bourliere, H. Khiri, V. de Ledinghen, P. Couzigou, J. M. Feryn, P. Alcaraz, C. Renou, H. J. A. Fleury, and D. Ouzan; 2001 May http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88023&ren dertype=external
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Hepatitis C Virus Infection is Associated with the Development of Hepatocellular Carcinoma by I Saito, T Miyamura, A Ohbayashi, H Harada, T Katayama, S Kikuchi, Y Watanabe, S Koi, M Onji, Y Ohta, Q Choo, M Houghton, and G Kuo; 1990 September 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=54573
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Hepatitis C virus internal ribosome entry site RNA contains a tertiary structural element in a functional domain of stem --loop II by Alita J. Lyons, J. Robin Lytle, Jordi Gomez, and Hugh D. Robertson; 2001 June 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=55737&ren dertype=external
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Hepatitis C virus lacking the hypervariable region 1 of the second envelope protein is infectious and causes acute resolving or persistent infection in chimpanzees by Xavier Forns, Robert Thimme, Sugantha
118 Hepatitis C
Govindarajan, Suzanne U. Emerson, Robert H. Purcell, Francis V. Chisari, and Jens Bukh; 2000 November 21 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=27222 ·
Hepatitis C virus replication is directly inhibited by IFN-[alpha] in a full-length binary expression system by Raymond T. Chung, Wenping He, Afroz Saquib, Ana M. Contreras, Ramnik J. Xavier, Ashish Chawla, Timothy C. Wang, and Emmett V. Schmidt; 2001 August 14 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=55541
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Hepatitis C Virus RNA in Southern African Blacks with Hepatocellular Carcinoma by J Bukh, RH Miller, MC Kew, and RH Purcell; 1993 March 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=45977
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Hepatitis C Virus Shares Amino Acid Sequence Similarity with Pestiviruses and Flaviviruses as Well as Members of Two Plant Virus Supergroups by RH Miller and RH Purcell; 1990 March 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=53625
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Hepatitis C Virus Variants From Vietnam are Classifiable Into the Seventh, Eighth, and Ninth Major Genetic Groups by H Tokita, H Okamoto, F Tsuda, P Song, S Nakata, T Chosa, H Iizuka, S Mishiro, Y Miyakawa, and M Mayumi; 1994 November 8 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=45158
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High-Throughput Real-Time Reverse Transcription-PCR Quantitation of Hepatitis C Virus RNA by Maria Martell, Jordi Gomez, Juan I. Esteban, Silvia Sauleda, Josep Quer, Beatriz Cabot, Rafael Esteban, and Jaime Guardia; 1999 February http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=84298&ren dertype=external
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Host cell factor requirement for hepatitis C virus enzyme maturation by Lloyd Waxman, Michael Whitney, Brian A. Pollok, Lawrence C. Kuo, and Paul L. Darke; 2001 November 20 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=61144
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How Escherichia coli can bias the results of molecular cloning: Preferential selection of defective genomes of hepatitis C virus during the cloning procedure by Xavier Forns, Jens Bukh, Robert H. Purcell, and Suzanne U. Emerson; 1997 December 9 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=28406
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Human hepatitis C virus NS5A protein alters intracellular calcium levels, induces oxidative stress, and activates STAT-3 and NF-[kappa]B
Studies 119
by Guozhong Gong, Gulam Waris, Rasheeda Tanveer, and Aleem Siddiqui; 2001 August 14 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=55498 ·
Identification of an Immunodominant Epitope within the Capsid Protein of Hepatitis C Virus by MS Nasoff, SL Zebedee, G Inchauspe, and AM Prince; 1991 June 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=51893
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Identification of eIF2B[gamma] and eIF2[gamma] as cofactors of hepatitis C virus internal ribosome entry site-mediated translation using a functional genomics approach by Martin Kruger, Carmela Beger, Qiang-Xin Li, Peter J. Welch, Richard Tritz, Mark Leavitt, Jack R. Barber, and Flossie Wong-Staal; 2000 July 18 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=26988
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Imino sugars inhibit the formation and secretion of bovine viral diarrhea virus, a pestivirus model of hepatitis C virus: Implications for the development of broad spectrum anti-hepatitis virus agents by Nicole Zitzmann, Anand S. Mehta, Sandra Carrouee, Terry D. Butters, Frances M. Platt, John McCauley, Baruch S. Blumberg, Raymond A. Dwek, and Timothy M. Block; 1999 October 12 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=18380
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Importance of Primer Selection for the Detection of Hepatitis C Virus RNA with the Polymerase Chain Reaction Assay by J Bukh, RH Purcell, and RH Miller; 1992 January 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=48201
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Improved Serodiagnosis of Hepatitis C Virus Infection with Synthetic Peptide Antigen from Capsid Protein by B Hosein, CT Fang, MA Popovsky, J Ye, M Zhang, and CY Wang; 1991 May 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=51509
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Improved Version 2.0 Qualitative and Quantitative AMPLICOR Reverse Transcription-PCR Tests for Hepatitis C Virus RNA: Calibration to International Units, Enhanced Genotype Reactivity, and Performance Characteristics by Sung C. Lee, Anisha Antony, Nitta Lee, Jeff Leibow, Jian Q. Yang, Stephen Soviero, Karen Gutekunst, and Maurice Rosenstraus; 2000 November http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87559&ren dertype=external
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Incidence of hepatitis C virus infection among injection drug users during an outbreak of HIV infection by David M. Patrick, Mark W.
120 Hepatitis C
Tyndall, Peter G.A. Cornelisse, Kathy Li, Chris H. Sherlock, Michael L. Rekart, Steffanie A. Strathdee, Sue L. Currie, Martin T. Schechter, and Michael V. O'Shaughnessy; 2001 October 2 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=81496 ·
Incidence of seroconversion to positivity for hepatitis C antibody in repeat blood donors in England, 1993-5 by K Soldan, J A J Barbara, and J Heptonstall; 1998 May 9 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=28537
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Infection with HIV and hepatitis C virus among injecting drug users in a prevention setting: retrospective cohort study by Ingrid van Beek, Robyn Dwyer, Gregory J Dore, Kehui Luo, and John M Kaldor; 1998 August 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=28635
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Interaction of Immune Sera with Synthetic Peptides Corresponding to the Structural Protein Region of Hepatitis C Virus by W Ching, C Wychowski, MJ Beach, H Wang, CL Davies, M Carl, DW Bradley, HJ Alter, SM Feinstone, and JW Shih; 1992 April 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=48831
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Interferon alfa with or without ribavirin for chronic hepatitis C: systematic review of randomised trials by Lise L Kjaergard, Kim Krogsgaard, and Christian Gluud; 2001 November 17 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=59848
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Low prevalence of liver-kidney microsomal autoantibodies of type 1 (LKM1) in hepatitis C seropositive subjects on Crete, Greece by Dimitrios Drygiannakis, Christos Lionis, Ioannis Drygiannakis, Georgios Pappas, and Elias Kouroumalis; 2001 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=33343
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Molecular Cloning of the Human Hepatitis C Virus Genome From Japanese Patients with Non-A, Non-B Hepatitis by N Kato, M Hijikata, Y Ootsuyama, M Nakagawa, S Ohkoshi, T Sugimura, and K Shimotohno; 1990 December 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=55204
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Molecular Evidence of Male-to-Female Sexual Transmission of Hepatitis C Virus after Vaginal and Anal Intercourse by Philippe Halfon, Herve Riflet, Christophe Renou, Yves Quentin, and Patrice Cacoub; 2001 March http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87908&ren dertype=external
Studies 121
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Molecular Model of the Specificity Pocket of the Hepatitis C Virus Protease: Implications for Substrate Recognition by E Pizzi, A Tramontano, L Tomei, NL Monica, C Failla, M Sardana, T Wood, and RD Francesco; 1994 February 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=43057
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Mother to child transmission of hepatitis C virus: prospective study of risk factors and timing of infection in children born to women seronegative for HIV-1 by Massimo Resti, Chiara Azzari, Francesco Mannelli, Maria Moriondo, Elio Novembre, Maurizio de Martino, Alberto Vierucci, and Tuscany Study Group on Hepatitis C Virus Infection in Children; 1998 August 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=28636
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Nested Restriction Site-Specific PCR To Detect and Type Hepatitis C Virus (HCV): a Rapid Method To Distinguish HCV Subtype 1b from Other Genotypes by Laura Krekulova, Vratislav Rehak, Adil E. Wakil, Eva Harris, and Lee W. Riley; 2001 May http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88024&ren dertype=external
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Note:Can Pooling Be Used for Seroprevalence Studies of Hepatitis C? by G. M. Stephens, J. M. Raboud, L. Karakas, and C. H. Sherlock; 2000 November http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87579&ren dertype=external
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Note:Definition of False-Positive Reactions in Screening for Hepatitis C Virus Antibodies by Matthias Schroter, Heinz-Hubert Feucht, Peter Schafer, Bernhard Zollner, Susanne Polywka, and Rainer Laufs; 1999 January http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=84219&ren dertype=external
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Note:Detection and Quantitation of Hepatitis C Virus RNA in Feces of Chronically Infected Individuals by Marcel Beld, Roel Sentjens, Sjoerd Rebers, Jan Weel, Pauline Wertheim-van Dillen, Cees Sol, and Rene Boom; 2000 September http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87401&ren dertype=external
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Note:Detection of Antibodies to Hepatitis C Virus in Dried Blood Spot Samples from Mothers and Their Offspring in Lahore, Pakistan by S. P. Parker, H. I. Khan, and W. D. Cubitt; 1999 June http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85032&ren dertype=external
122 Hepatitis C
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Note:Diagnostic Value of Anti-Hepatitis C Virus (HCV) Core Immunoglobulin M in Recurrence of HCV Infection after Orthotopic Liver Transplantation by Carmela Casino, Daniela Lilli, Daniela Rivanera, Antonella Comanducci, Massimo Rossi, Giovanni Casciaro, Irene Pecorella, Dario Alfani, and Carlo Mancini; 1999 August http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85330&ren dertype=external
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Note:Existence of Hepatitis C Virus in Culex quinquefasciatus after Ingestion of Infected Blood: Experimental Approach to Evaluating Transmission by Mosquitoes by Ting-Tsung Chang, Tsuey-Yu Chang, Cheng-Chen Chen, Kung-Chia Young, Jun-Neng Roan, Yen-Chien Lee, Pin-Nan Cheng, and Hua-Lin Wu; 2001 September http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88344&ren dertype=external
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Note:Hepatitis C Virus Core Mutations Reduce the Sensitivity of a Fluorescence Enzyme Immunoassay by Hajime Tokita, Gilbert R. Kaufmann, Mamoru Matsubayashi, Isao Okuda, Tsukasa Tanaka, Hideharu Harada, Motokazu Mukaide, Kazuo Suzuki, and David A. Cooper; 2000 September http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87404&ren dertype=external
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Note:Hepatitis C Virus Quantitation: Optimization of Strategies for Detecting Low-Level Viremia by Wolfgang T. Hofgartner, Jeffrey A. Kant, and Karen E. Weck; 2000 February http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=86236&ren dertype=external
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Note:Molecular Epidemiology of Hepatitis C Virus Infection in an Area of Hyperendemicity in Southern Italy: a Population-Based Study by Alberto R. Osella, Laura Sonzogni, Aldo Cavallini, Luciana Foti, Vito Guerra, Alfredo Di Leo, Mario U. Mondelli, Giovanni Misciagna, and Enrico M. Silini; 1999 July http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85170&ren dertype=external
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Note:Phylogenetic Characterization of Genotype 4 Hepatitis C Virus Isolates from Argentina by Victoria Alfonso, Diego Flichman, Silvia Sookoian, Viviana Andrea Mbayed, and Rodolfo Hector Campos; 2001 May http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88066&ren dertype=external
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Note:Quantitative Detection of Hepatitis C Virus RNA by Light Cycler PCR and Comparison with Two Different PCR Assays by Matthias
Studies 123
Schroter, Bernhard Zollner, Peter Schafer, Rainer Laufs, and HeinzHubert Feucht; 2001 February http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87816&ren dertype=external ·
Note:Relevance of Reactivity in Commercially Available Hepatitis C Virus Antibody Assays by Susanne Polywka, Matthias Schroter, HeinzHubert Feucht, Bernhard Zollner, and Rainer Laufs; 2001 April http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87996&ren dertype=external
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Note:Second Generation of the Automated Cobas Amplicor HCV Assay Improves Sensitivity of Hepatitis C Virus RNA Detection and Yields Results That Are More Clinically Relevant by Alain Doglio, Catherine Laffont, Francois X. Caroli-Bosc, Pascale Rochet, and J.-Claude Lefebvre; 1999 May http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=84830&ren dertype=external
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Novel Approach To Reduce the Hepatitis C Virus (HCV) Window Period: Clinical Evaluation of a New Enzyme-Linked Immunosorbent Assay for HCV Core Antigen by Giancarlo Icardi, Filippo Ansaldi, Bianca Marisa Bruzzone, Paolo Durando, Stephen Lee, Carla de Luigi, and Pietro Crovari; 2001 September http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88305&ren dertype=external
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NS5A, a nonstructural protein of hepatitis C virus, binds growth factor receptor-bound protein 2 adaptor protein in a Src homology 3 domain /ligand-dependent manner and perturbs mitogenic signaling by SengLai Tan, Haruhisa Nakao, Yupeng He, Sangeetha Vijaysri, Petra Neddermann, Bertram L. Jacobs, Bruce J. Mayer, and Michael G. Katze; 1999 May 11 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=21894
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Nucleotide Sequence and Mutation Rate of the H Strain of Hepatitis C Virus by N Ogata, HJ Alter, RH Miller, and RH Purcell; 1991 April 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=51453
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Performance of the COBAS AMPLICOR HCV MONITOR Test, Version 2.0, an Automated Reverse Transcription-PCR Quantitative System for Hepatitis C Virus Load Determination by G. Gerken, T. Rothaar, M. G. Rumi, R. Soffredini, M. Trippler, M. J. Blunk, A. Butcher, S. Soviero, and G. Colucci; 2000 June http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=86766&ren dertype=external
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Persistent Hepatitis C Virus Infection in a Chimpanzee is Associated with Emergence of a Cytotoxic T Lymphocyte Escape Variant by A Weiner, AL Erickson, J Kansopon, K Crawford, E Muchmore, AL Hughes, M Houghton, and CM Walker; 1995 March 28 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=42297
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Physicians' preference values for hepatitis C health states and antiviral therapy: A survey by Raj Patil, Scott J. Cotler, Geraldine BanaadOmiotek, Robert A. McNutt, Michael D. Brown, Sheldon Cotler, and Donald M. Jensen; 2001 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=37537
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Poliovirus Chimeras Replicating under the Translational Control of Genetic Elements of Hepatitis C Virus Reveal Unusual Properties of the Internal Ribosomal Entry Site of Hepatitis C Virus by H Lu and E Wimmer; 1996 February 20 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=39952
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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 Jean Long, Shane Allwright, Joseph Barry, Sheilagh Reaper Reynolds, Lelia Thornton, Fiona Bradley, and John V Parry; 2001 November 24 http://www.pubmedcentral.nih.gov/articlerender.fcgi?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 Shane Allwright, Fiona Bradley, Jean Long, Joseph Barry, Lelia Thornton, and John V Parry; 2000 July 8 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=27426
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Prevention of Hepatitis C Virus Infection in Chimpanzees After Antibody-Mediated in vitro Neutralization by P Farci, HJ Alter, DC Wong, RH Miller, S Govindarajan, R Engle, M Shapiro, and RH Purcell; 1994 August 2 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=44488
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Prevention of hepatitis C virus infection in chimpanzees by hyperimmune serum against the hypervariable region 1 of the envelope 2 protein by Patrizia Farci, Atsushi Shimoda, Doris Wong, Teresa Cabezon, Daniela De Gioannis, Antonello Strazzera, Yohko Shimizu, Max Shapiro, Harvey J. Alter, and Robert H. Purcell; 1996 December 24 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=26415
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Prophylactic DNA vaccine for hepatitis C virus (HCV) infection: HCVspecific cytotoxic T lymphocyte induction and protection from HCVrecombinant vaccinia infection in an HLA-A2.1 transgenic mouse model by Tatsumi Arichi, Takafumi Saito, Marian E. Major, Igor M. Belyakov, Mutsunori Shirai, Victor H. Engelhard, Stephen M. Feinstone, and Jay A. Berzofsky; 2000 January 4 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=26657
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Prospective Comparison of Whole-Blood- and Plasma-Based Hepatitis C Virus RNA Detection Systems: Improved Detection Using Whole Blood as the Source of Viral RNA by Jack T. Stapleton, Donna Klinzman, Warren N. Schmidt, Michael A. Pfaller, Ping Wu, Douglas R. LaBrecque, Jian-qiu Han, Mary Jeanne Perino Phillips, Robert Woolson, and Beth Alden; 1999 March http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=84440&ren dertype=external
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Prospective Multicenter Clinical Evaluation of AMPLICOR and COBAS AMPLICOR Hepatitis C Virus Tests by Frederick S. Nolte, Michael W. Fried, Mitchell L. Shiffman, Andrea Ferreira-Gonzalez, Carlton T. Garrett, Eugene R. Schiff, Stephen J. Polyak, and David R. Gretch; 2001 November http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88479&ren dertype=external
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Proteolytic Processing and Membrane Association of Putative Nonstructural Proteins of Hepatitis C Virus by M Hijikata, H Mizushima, Y Tanji, Y Komoda, Y Hirowatari, T Akagi, N Kato, K Kimura, and K Shimotohno; 1993 November 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=47860
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Quantitative analysis of hepatitis C virus-specific CD8 + T cells in peripheral blood and liver using peptide-MHC tetramers by Xiao-Song He, Barbara Rehermann, F. Xavier Lopez-Labrador, Judie Boisvert, Ramsey Cheung, John Mumm, Heiner Wedemeyer, Marina Berenguer, Teresa L. Wright, Mark M. Davis, and Harry B. Greenberg; 1999 May 11 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=21922
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Risk factors for acquisition of hepatitis C virus infection: a case series and potential implications for disease surveillance by Leland J. Yee, Heidi L. Weiss, Rebecca G. Langner, Jorge Herrera, Richard A. Kaslow, and Dirk J. van Leeuwen; 2001 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=37546
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Risk factors for hepatitis C virus infection among street youths by Elise Roy, Nancy Haley, Pascale Leclerc, Jean-Francois Boivin, Lyne Cedras, and Jean Vincelette; 2001 September 4 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=81413
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Screening for Hepatitis C Virus in Human Immunodeficiency VirusInfected Individuals by Chloe L. Thio, Karen R. Nolt, Jacquie Astemborski, David Vlahov, Kenrad E. Nelson, and David L. Thomas; 2000 February http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=86151&ren dertype=external
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Sequence Analysis of the 5' Noncoding Region of Hepatitis C Virus by J Bukh, RH Purcell, and RH Miller; 1992 June 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=49204
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Sequence Analysis of the Core Gene of 14 Hepatitis C Virus Genotypes by J Bukh, RH Purcell, and RH Miller; 1994 August 16 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=44581
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Serodiagnosis of Hepatitis C Virus (HCV) Infection with an HCV Core Protein Molecularly Expressed by a Recombinant Baculovirus by J Chiba, H Ohba, Y Matsuura, Y Watanabe, T Katayama, S Kikuchi, I Saito, and T Miyamura; 1991 June 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=51721
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Serological Determination of Hepatitis C Virus Subtypes 1a, 1b, 2a, 2b, 3a, and 4a by a Recombinant Immunoblot Assay by Matthias Schroter, Heinz-Hubert Feucht, Peter Schafer, Bernhard Zollner, and Rainer Laufs; 1999 August http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85286&ren dertype=external
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Sialadenitis histologically resembling Sjogren syndrome in mice transgenic for hepatitis C virus envelope genes by Kazuhiko Koike, Kyoji Moriya, Kotaro Ishibashi, Hiroshi Yotsuyanagi, Yoshizumi Shintani, Hajime Fujie, Kiyoshi Kurokawa, Yoshiharu Matsuura, and Tatsuo Miyamura; 1997 January 7 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=19297
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Simplified Hepatitis C Virus Genotyping by Heteroduplex Mobility Analysis by Peter A. White, Xinyan Zhai, Ian Carter, Yue Zhao, and William D. Rawlinson; 2000 February http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=86128&ren dertype=external
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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 J.-P. Defoort, M. Martin, B. Casano, S. Prato, C. Camilla, and V. Fert; 2000 March http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=86341&ren dertype=external
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The Hepatitis C Virus NS3 Serine Proteinase and NS4A Cofactor: Establishment of a Cell-Free Trans-Processing Assay by C Lin and CM Rice; 1995 August 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=41197
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The La antigen binds 5[prime prime or minute] noncoding region of the hepatitis C virus RNA in the context of the initiator AUG codon and stimulates internal ribosome entry site-mediated translation by Naushad Ali and Aleem Siddiqui; 1997 March 18 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=20073
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The Physical State of the Negative Strand of Hepatitis C Virus RNA in Serum of Patients with Chronic Hepatitis C by M Shindo, AMD Bisceglie, T Akatsuka, T Fong, L Scaglione, M Donets, JH Hoofnagle, and SM Feinstone; 1994 August 30 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=44678
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Transcripts from a single full-length cDNA clone of hepatitis C virus are infectious when directly transfected into the liver of a chimpanzee by Masayuki Yanagi, Robert H. Purcell, Suzanne U. Emerson, and Jens Bukh; 1997 August 5 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=23104
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Transient Immunoglobulin M Antibody Response to Hepatitis C Virus Capsid Antigen in Posttransfusion Hepatitis C: Putative Serological Marker for Acute Viral Infection by P Chen, J Wang, L Hwang, Y Yang, C Hsieh, J Kao, J Sheu, M Lai, T Wang, and D Chen; 1992 July 1 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=49419
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Transmission of Hepatitis C Virus in a Gynecological Surgery Setting by Marco Massari, Nicola Petrosillo, Giuseppe Ippolito, Laura Solforosi, Lucio Bonazzi, Massimo Clementi, and Aldo Manzin; 2001 August http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88251&ren dertype=external
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Two Successive Hepatitis C Virus Infections in an Intravenous Drug User by Barbara Proust, Frederic Dubois, Yannick Bacq, Sophie Le Pogam, Sylvie Rogez, Romuald Levillain, and Alain Goudeau; 2000 August http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87209&ren dertype=external
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Unwinding of nucleic acids by HCV NS3 helicase is sensitive to the structure of the duplex by Alan J. Tackett, Lai Wei, Craig E. Cameron, and Kevin D. Raney; 2001 January 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=29657&ren dertype=external
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Use of a Novel Hepatitis C Virus (HCV) Major-Epitope Chimeric Polypeptide for Diagnosis of HCV Infection by David Y. Chien, Phillip Arcangel, Angelica Medina-Selby, Doris Coit, Mark Baumeister, Steve Nguyen, Carlos George-Nascimento, Alexander Gyenes, George Kuo, and Pablo Valenzuela; 1999 May http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=84783&ren dertype=external
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Use of Whole Blood Specimens for Routine Clinical Quantitation of Hepatitis C Virus RNA Does Not Increase Assay Sensitivity by Linda Cook, Angela M. Ross, Glenn B. Knight, and Vincent Agnello; 2000 December http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87600&ren dertype=external
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Vaccination of Chimpanzees Against Infection by the Hepatitis C Virus by Q Choo, G Kuo, R Ralston, A Weiner, D Chien, GV Nest, J Han, K Berger, K Thudium, C Kuo, J Kansopon, J McFarland, A Tabrizi, K Ching, B Moss, LB Cummins, M Houghton, and E Muchmore; 1994 February 15 http://www.pubmedcentral.nih.gov/articlerender.fcgi?rendertype=abst ract&artid=43144
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Vitamin B12 and hepatitis C: Molecular biology and human pathology by William B. Lott, Seyedtaghi S. Takyar, Joseph Tuppen, Darrell H. G. Crawford, Michael Harrison, Theo P. Sloots, and Eric J. Gowans; 2001 April 24 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=33138
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Whole-Blood Hepatitis C Virus RNA Extraction Methods by Warren Schmidt and Jack T. Stapleton; 2001 October http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88445&ren dertype=external
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. 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 the public.25 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. To generate your own bibliography of studies dealing with hepatitis C, simply go to the PubMed Web site at www.ncbi.nlm.nih.gov/pubmed. Type “hepatitis C” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for “hepatitis C” (hyperlinks lead to article summaries): ·
Large dose natural interferon alpha therapy for patients with chronic hepatitis C. Author(s): Ohmiya M, Hayashi J, Furusyo N, Ueno K, Kishihara Y, Nabeshima S, Kashiwagi S. Source: Fukuoka Igaku Zasshi. 1997 December; 88(12): 380-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9465478&dopt=Abstract
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Licorice for hepatitis C: yum-yum or just ho-hum? Author(s): Lewis JH.
PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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130 Hepatitis C
Source: The American Journal of Gastroenterology. 2001 August; 96(8): 2291-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11513162&dopt=Abstract ·
Low prevalence of hepatitis C virus infection among hospital staff and acupuncturists in Kyushu, Japan. Author(s): Nakashima K, Kashiwagi S, Hayashi J, Noguchi A, Hirata M, Ikeda S, Sakota I, Shingu T. Source: The Journal of Infection. 1993 January; 26(1): 17-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7681088&dopt=Abstract
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Management of viral hepatitis C. Author(s): Leung NW. Source: Journal of Gastroenterology and Hepatology. 2002 February; 17 Suppl 1: 146-154. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12000600&dopt=Abstract
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Medicinal herbs for hepatitis C virus infection. Author(s): Liu JP, Manheimer E, Tsutani K, Gluud C. Source: Cochrane Database Syst Rev. 2001; (4): Cd003183. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11687177&dopt=Abstract
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Molecular analysis of intraspousal transmission of hepatitis C virus. Author(s): Chayama K, Kobayashi M, Tsubota A, Koida I, Arase Y, Saitoh S, Ikeda K, Kumada H. Source: Journal of Hepatology. 1995 April; 22(4): 431-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7665861&dopt=Abstract
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Natural history and treatment of Hepatitis C. Author(s): Highleyman L. Source: Beta. 1999; 12(4): 16-29. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11367245&dopt=Abstract
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Oral thymic extract for chronic hepatitis C in patients previously treated with interferon. A randomized, double-blind, placebo-
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controlled trial. Author(s): Raymond RS, Fallon MB, Abrams GA. Source: Annals of Internal Medicine. 1998 November 15; 129(10): 797-800. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9841585&dopt=Abstract ·
Oral thymic extract to treat hepatitis C. Author(s): Frossard JL. Source: Annals of Internal Medicine. 1999 August 17; 131(4): 312. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10454958&dopt=Abstract
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Past and present hepatitis G virus infections in areas where hepatitis C is highly endemic and those where it is not endemic. Author(s): Tanaka E, Tacke M, Kobayashi M, Nakatsuji Y, Kiyosawa K, Schmolke S, Engel AM, Hess G, Alter HJ. Source: Journal of Clinical Microbiology. 1998 January; 36(1): 110-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9431931&dopt=Abstract
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Pharmacokinetics, safety, and antiviral effects of hypericin, a derivative of St. John's wort plant, in patients with chronic hepatitis C virus infection. Author(s): Jacobson JM, Feinman L, Liebes L, Ostrow N, Koslowski V, Tobia A, Cabana BE, Lee D, Spritzler J, Prince AM. Source: Antimicrobial Agents and Chemotherapy. 2001 February; 45(2): 517-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11158749&dopt=Abstract
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Plastic microchip electrophoresis for analysis of PCR products of hepatitis C virus. Author(s): Chen YH, Wang WC, Young KC, Chang TT, Chen SH. Source: Clinical Chemistry. 1999 November; 45(11): 1938-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10545063&dopt=Abstract
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Preliminary report of a randomized, double-blind placebo-controlled trial of a Chinese herbal medicine preparation CH-100 in the treatment of chronic hepatitis C. Author(s): Batey RG, Bensoussan A, Fan YY, Bollipo S, Hossain MA.
132 Hepatitis C
Source: Journal of Gastroenterology and Hepatology. 1998 March; 13(3): 244-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9570235&dopt=Abstract ·
Preliminary results of individual therapy of chronic hepatitis C by Ukrain and interferon-alpha. Author(s): Voltchek I, Sologub T, Nowicky JW, Grigoryeva T, Belozyorova L, Belopolskaya M, Semenyako N, Lamanova E. Source: Drugs Exp Clin Res. 2000; 26(5-6): 261-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11345036&dopt=Abstract
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Prevalence and risk factors of hepatitis C virus infection among Koreans in rural area of Korea. Author(s): Shin HR, Kim JY, Ohno T, Cao K, Mizokami M, Risch H, Kim SR. Source: Hepatology Research : the Official Journal of the Japan Society of Hepatology. 2000 June; 17(3): 185-196. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10794972&dopt=Abstract
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Prevalence of anti-hepatitis C antibodies in a rural community without high mortality from liver disease in Niigata prefecture. Author(s): Kayaba K, Igarashi M, Okamoto H, Tsuda F. Source: J Epidemiol. 1998 October; 8(4): 250-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9816817&dopt=Abstract
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Prevalence of anti-hepatitis C virus antibody and chronic liver disease among atomic bomb survivors. Author(s): Fujiwara S, Kusumi S, Cologne J, Akahoshi M, Kodama K, Yoshizawa H. Source: Radiation Research. 2000 July; 154(1): 12-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10856960&dopt=Abstract
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Prevalence, infectivity, and risk factor analysis of hepatitis C virus infection in prostitutes. Author(s): Wu JC, Lin HC, Jeng FS, Ma GY, Lee SD, Sheng WY.
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Source: Journal of Medical Virology. 1993 April; 39(4): 312-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8492103&dopt=Abstract ·
Primary hepatic high-grade non-Hodgkin's lymphoma and chronic hepatitis C infection. Author(s): Mohler M, Gutzler F, Kallinowski B, Goeser T, Stremmel W. Source: Digestive Diseases and Sciences. 1997 November; 42(11): 2241-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9398801&dopt=Abstract
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Prospective multicenter clinical evaluation of AMPLICOR and COBAS AMPLICOR hepatitis C virus tests. Author(s): Nolte FS, Fried MW, Shiffman ML, Ferreira-Gonzalez A, Garrett CT, Schiff ER, Polyak SJ, Gretch DR. Source: Journal of Clinical Microbiology. 2001 November; 39(11): 4005-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11682522&dopt=Abstract
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Risk factors for hepatitis C virus infection. A case-control study of blood donors in the Trent Region (UK). Author(s): Neal KR, Jones DA, Killey D, James V. Source: Epidemiology and Infection. 1994 June; 112(3): 595-601. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8005225&dopt=Abstract
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Rural support for hepatitis C. Author(s): Westrup M. Source: Australian Nursing Journal (July 1993). 1998 March; 5(8): 19. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9592406&dopt=Abstract
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Side effects of high-dose interferon therapy for chronic hepatitis C. Author(s): Okanoue T, Sakamoto S, Itoh Y, Minami M, Yasui K, Sakamoto M, Nishioji K, Katagishi T, Nakagawa Y, Tada H, Sawa Y, Mizuno M, Kagawa K, Kashima K. Source: Journal of Hepatology. 1996 September; 25(3): 283-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8895006&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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Stability of hepatitis C virus RNA during specimen handling and storage prior to NASBA amplification. Author(s): Damen M, Sillekens P, Sjerps M, Melsert R, Frantzen I, Reesink HW, Lelie PN, Cuypers HT. Source: Journal of Virological Methods. 1998 June; 72(2): 175-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9694325&dopt=Abstract
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Storage conditions of blood samples and primer selection affect the yield of cDNA polymerase chain reaction products of hepatitis C virus. Author(s): Cuypers HT, Bresters D, Winkel IN, Reesink HW, Weiner AJ, Houghton M, van der Poel CL, Lelie PN. Source: Journal of Clinical Microbiology. 1992 December; 30(12): 3220-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1333489&dopt=Abstract
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The hepatitis C virus internal ribosome entry site adopts an iondependent tertiary fold. Author(s): Kieft JS, Zhou K, Jubin R, Murray MG, Lau JY, Doudna JA. Source: Journal of Molecular Biology. 1999 September 24; 292(3): 513-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10497018&dopt=Abstract
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The long term efficacy of glycyrrhizin in chronic hepatitis C patients. Author(s): Arase Y, Ikeda K, Murashima N, Chayama K, Tsubota A, Koida I, Suzuki Y, Saitoh S, Kobayashi M, Kumada H. Source: Cancer. 1997 April 15; 79(8): 1494-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9118029&dopt=Abstract
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The N-terminal region of NS3 serine proteinase of hepatitis C virus is important to maintain its enzymatic integrity. Author(s): Mori A, Yuasa S, Yamada K, Nagami Y, Miyamura T. Source: Biochemical and Biophysical Research Communications. 1997 February 24; 231(3): 738-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9070884&dopt=Abstract
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The prevalence of hepatitis C in different countries of the ERA/EDTA area. Author(s): Kohler H. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1995; 10(4): 468-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7542750&dopt=Abstract
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The treatment of hepatitis C: emerging evidence of the need for change. Author(s): Patrick L. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 1999 August; 4(4): 219. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10468646&dopt=Abstract
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The use of alternative medicine in the treatment of hepatitis C. Author(s): Bean P. Source: Am Clin Lab. 2002 May; 21(4): 19-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12087634&dopt=Abstract
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Time course of total cysteine, glutathione and homocysteine in plasma of patients with chronic hepatitis C treated with interferon-alpha with and without supplementation with N-acetylcysteine. Author(s): Bernhard MC, Junker E, Hettinger A, Lauterburg BH. Source: Journal of Hepatology. 1998 May; 28(5): 751-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9625308&dopt=Abstract
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Transmission of hepatitis C by ozone enrichment of autologous blood. Author(s): Gabriel C, Blauhut B, Greul R, Schneeweis B, Roggendorf M.
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Source: Lancet. 1996 February 24; 347(9000): 541. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8596287&dopt=Abstract ·
Transmission of hepatitis C in an isolated area in Japan: communityacquired infection. The South Kiso Hepatitis Study Group. Author(s): Kiyosawa K, Tanaka E, Sodeyama T, Yoshizawa K, Yabu K, Furuta K, Imai H, Nakano Y, Usuda S, Uemura K, et al. Source: Gastroenterology. 1994 June; 106(6): 1596-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8194707&dopt=Abstract
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Transmission of hepatitis C virus in Asia: past and present perspectives. Author(s): Kao JH, Chen DS. Source: Journal of Gastroenterology and Hepatology. 2000 May; 15 Suppl: E91-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10921389&dopt=Abstract
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Transmission of hepatitis C virus in Taiwan: prevalence and risk factors based on a nationwide survey. Author(s): Sun CA, Chen HC, Lu CF, You SL, Mau YC, Ho MS, Lin SH, Chen CJ. Source: Journal of Medical Virology. 1999 November; 59(3): 290-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10502258&dopt=Abstract
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Treatment of chronic hepatitis C virus infection. Author(s): Malnick SD, Beergabel M, Lurie Y. Source: The Annals of Pharmacotherapy. 2000 October; 34(10): 1156-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11054985&dopt=Abstract
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Treatment strategies for chronic hepatitis C virus infection. Author(s): Kasahara A. Source: Journal of Gastroenterology. 2000; 35(6): 411-23. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10864347&dopt=Abstract
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Two cases of hepatitis C treated with herbs and supplements. Author(s): Stern E. Source: Journal of Alternative and Complementary Medicine (New York, N.Y.). 1997 Spring; 3(1): 77-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9395695&dopt=Abstract
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Viral hepatitis C. Author(s): Leevy CB, Zierer KG, Leevy CM. Source: J Assoc Acad Minor Phys. 1998; 9(4): 59-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10825999&dopt=Abstract
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What should we advise about adjunctive therapies, including herbal medicines, for hepatitis C? Author(s): Sarin SK. Source: Journal of Gastroenterology and Hepatology. 2000 May; 15 Suppl: E164-71. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10921401&dopt=Abstract
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Zinc supplementation enhances the response to interferon therapy in patients with chronic hepatitis C. Author(s): Takagi H, Nagamine T, Abe T, Takayama H, Sato K, Otsuka T, Kakizaki S, Hashimoto Y, Matsumoto T, Kojima A, Takezawa J, Suzuki K, Sato S, Mori M. Source: Journal of Viral Hepatitis. 2001 September; 8(5): 367-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11555194&dopt=Abstract
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A novel high throughput screening assay for HCV NS3 helicase activity. Author(s): Hicham Alaoui-Ismaili M, Gervais C, Brunette S, Gouin G, Hamel M, Rando RF, Bedard J. Source: Antiviral Research. 2000 June; 46(3): 181-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10867156&dopt=Abstract
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Effects of the Japanese herbal medicine "Sho-saiko-to" (TJ-9) on interleukin-12 production in patients with HCV-positive liver cirrhosis.
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Author(s): Yamashiki M, Nishimura A, Huang XX, Nobori T, Sakaguchi S, Suzuki H. Source: Dev Immunol. 1999; 7(1): 17-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10636475&dopt=Abstract ·
HCV/HIV co-infection II: sobriety and treatment. Author(s): Moreno G. Source: Posit Aware. 2002 March-April; 13(2): 27-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12001925&dopt=Abstract
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Plasma collected from heparinized blood is not suitable for HCV-RNA detection by conventional RT-PCR assay. Author(s): Willems M, Moshage H, Nevens F, Fevery J, Yap SH. Source: Journal of Virological Methods. 1993 April; 42(1): 127-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7686556&dopt=Abstract
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Presence of lower temperature-dependent antibody with low avidity to C100-3 (HCV) antigen in voluntary blood donors. Author(s): Yamaki M, Shimada T, Matsumoto C, Watanabe J, Nishioka K. Source: Jpn J Med Sci Biol. 1992 February; 45(1): 1-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=1322472&dopt=Abstract
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The epidemiology and infection route of asymptomatic HCV carriers detected through blood donations. Author(s): Shimoyama R, Sekiguchi S, Suga M, Sakamoto S, Yachi A. Source: Gastroenterol Jpn. 1993 May; 28 Suppl 5: 1-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7689501&dopt=Abstract
Vocabulary Builder Abortion: 1. the premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions,
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uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. premature stoppage of a natural or a pathological process. [EU] Abscess: A localized collection of pus caused by suppuration buried in tissues, organs, or confined spaces. [EU] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Aggressiveness: The quality of being aggressive (= characterized by aggression; militant; enterprising; spreading with vigour; chemically active; variable and adaptable). [EU] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [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 Tlymphocytes, 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] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antioxidant: One of many widely used synthetic or natural substances added to a product to prevent or delay its deterioration by action of oxygen in the air. Rubber, paints, vegetable oils, and prepared foods commonly contain antioxidants. [EU] Ascites: Effusion and accumulation of serous fluid in the abdominal cavity; called also abdominal or peritoneal dropsy, hydroperitonia, and hydrops
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abdominis. [EU] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Calibration: Determination, by measurement or comparison with a standard, of the correct value of each scale reading on a meter or other measuring instrument; or determination of the settings of a control device that correspond to particular values of voltage, current, frequency or other output. [NIH] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH] Catechin: Extracted from Uncaria gambier, Acacia catechu and other plants; it stabilizes collagen and is therefore used in tanning and dyeing; it prevents capillary fragility and abnormal permeability, but was formerly used as an antidiarrheal. [NIH] Chelation: Combination with a metal in complexes in which the metal is part of a ring. [EU] Chimera: An individual that contains cell populations derived from different zygotes. [NIH] Chloroquine: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. [NIH] Circumcision: Excision of the prepuce or part of it. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. [NIH] Cytotoxic: Pertaining to or exhibiting cytotoxicity. [EU] Decompensation: Failure of compensation; cardiac decompensation is marked by dyspnea, venous engorgement, and edema. [EU] Deferoxamine: Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the form of its mesylate. [NIH] Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH]
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Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH] Encephalopathy: Any degenerative disease of the brain. [EU] Endoscopy: Visual inspection of any cavity of the body by means of an endoscope. [EU] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] Escherichia: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria whose organisms occur in the lower part of the intestine of warmblooded animals. The species are either nonpathogenic or opportunistic pathogens. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Flaviviridae: A family of RNA viruses, some formerly classified under Togoviridae, many of which cause disease in humans and domestic animals. The three genera are flavivirus, pestivirus, and hepatitis c-like viruses. [NIH] 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] Glomerulonephritis: A variety of nephritis characterized by inflammation of the capillary loops in the glomeruli of the kidney. It occurs in acute, subacute, and chronic forms and may be secondary to haemolytic streptococcal infection. Evidence also supports possible immune or autoimmune mechanisms. [EU] Glycyrrhiza: A genus of leguminous herbs or shrubs whose roots yield glycyrrhetinic acid and its derivatives, carbenoxolone for example. Licorice toxicity is manifested as hypokalemia, low blood potassium. Licorice is used as flavoring and aromatic in pharmaceuticals and as candy. [NIH] Granule: A small pill made from sucrose. [EU] Haemodialysis: The removal of certain elements from the blood by virtue of the difference in the rates of their diffusion through a semipermeable membrane, e.g., by means of a haemodialyzer. [EU]
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Haemolysis: Disruption of the integrity of the red cell membrane causing release of haemoglobin. Haemolysis may be caused by bacterial haemolysins, by antibodies that cause complement-dependent lysis, by placing red cells in a hyptonic solution, or by defects in the red cell membrane. [EU] Hepatotoxic: Toxic to liver cells. [EU] 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] Hypertension: Persistently high arterial blood pressure. Various criteria for its threshold have been suggested, ranging from 140 mm. Hg systolic and 90 mm. Hg diastolic to as high as 200 mm. Hg systolic and 110 mm. Hg diastolic. Hypertension may have no known cause (essential or idiopathic h.) or be associated with other primary diseases (secondary h.). [EU] Iatrogenic: Resulting from the activity of physicians. Originally applied to disorders induced in the patient by autosuggestion based on the physician's examination, manner, or discussion, the term is now applied to any adverse condition in a patient occurring as the result of treatment by a physician or surgeon, especially to infections acquired by the patient during the course of treatment. [EU] Idiopathic: Of the nature of an idiopathy; self-originated; of unknown causation. [EU] Incarceration: Abnormal retention or confinement of a body part; specifically : a constriction of the neck of a hernial sac so that the hernial contents become irreducible. [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] Ingestion: The act of taking food, medicines, etc., into the body, by mouth. [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] 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]
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Localization: 1. the determination of the site or place of any process or lesion. 2. restriction to a circumscribed or limited area. 3. prelocalization. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH]
Metabolite: process. [EU]
Any substance produced by metabolism or by a metabolic
Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU]
Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Necrosis: The sum of the morphological changes indicative of cell death and caused by the progressive degradative action of enzymes; it may affect groups of cells or part of a structure or an organ. [EU] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuropathy: A general term denoting functional disturbances and/or pathological changes in the peripheral nervous system. The etiology may be known e.g. arsenical n., diabetic n., ischemic n., traumatic n.) or unknown. Encephalopathy and myelopathy are corresponding terms relating to involvement of the brain and spinal cord, respectively. The term is also used to designate noninflammatory lesions in the peripheral nervous system, in contrast to inflammatory lesions (neuritis). [EU] 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] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH]
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Pharmacokinetics: The pattern of absorption, distribution, and excretion of a drug over time. [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] 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] Preclinical: Before a disease becomes clinically recognizable. [EU] Preoperative: Preceding an operation. [EU] Prisons: Penal institutions, or places of confinement for war prisoners. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Pulmonary: Pertaining to the lungs. [EU] Radiotherapy: The treatment of disease by ionizing radiation. [EU] Receptor: 1. a molecular structure within a cell or on the surface characterized by (1) selective binding of a specific substance and (2) a specific physiologic effect that accompanies the binding, e.g., cell-surface receptors for peptide hormones, neurotransmitters, antigens, complement fragments, and immunoglobulins and cytoplasmic receptors for steroid hormones. 2. a sensory nerve terminal that responds to stimuli of various kinds. [EU] Rheumatoid: Resembling rheumatism. [EU] Sarin: An organophosphorous ester compound that produces potent and irreversible inhibition of cholinesterase. It is toxic to the nervous system and is a chemical warfare agent. [NIH] Schistosoma: A genus of trematode flukes belonging to the family Schistosomatidae. There are over a dozen species. These parasites are found in man and other mammals. Snails are the intermediate hosts. [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] 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
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glutathione peroxidase. [NIH] Serine: A non-essential amino acid occurring in natural form as the Lisomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Seroconversion: The change of a serologic test from negative to positive, indicating the development of antibodies in response to infection or immunization. [EU] Serum: The clear portion of any body fluid; the clear fluid moistening serous membranes. 2. blood serum; the clear liquid that separates from blood on clotting. 3. immune serum; blood serum from an immunized animal used for passive immunization; an antiserum; antitoxin, or antivenin. [EU] 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] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] Substrate: A substance upon which an enzyme acts. [EU] Systemic: Pertaining to or affecting the body as a whole. [EU] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Thrombocytopenia: Decrease in the number of blood platelets. [EU] Thrombosis: The formation, development, or presence of a thrombus. [EU] Tolerance: A condition in which higher doses of a drug are required to produce the same effect as during initial use; often is associated with physical dependence. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH] Urinary: Pertaining to the urine; containing or secreting urine. [EU] Vaccinia: The cutaneous and sometimes systemic reactions associated with vaccination with smallpox vaccine. [EU]
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CHAPTER 5. PATENTS ON HEPATITIS C Overview You can learn about innovations relating to hepatitis C by reading recent patents and patent applications. 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.26 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 to patients with hepatitis C 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 to patients with hepatitis C. 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.
26Adapted
from The U. S. Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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Patents on Hepatitis C By performing a patent search focusing on hepatitis C, 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 example of the type of information that you can expect to obtain from a patent search on hepatitis C: ·
Treatment of hepatitis C by administration of anti-IL-2 receptor monoclonal antibody Inventor(s): Pinna; Antonio (Miami, FL), Ricordi; Camillo (Miami, FL), Tzakis; Andreas G. (Miami, FL) Assignee(s): University of Miami (Miami, FL) Patent Number: 6,406,695 Date filed: October 29, 1999 Abstract: A novel method using anti-interleukin 2 receptor monoclonal antibodies for treating patients having severe viral hepatitis C is described. The inventive method may be used to treat recurrent hepatitis C following liver transplantation, thereby reducing complications in recipients of liver allografts. Excerpt(s): The invention relates to a new use for existing monoclonal antibodies known to prevent or treat immunological rejection of transplanted organ and tissues. Specifically, the invention provides for the first time a method of using an anti-IL-2 receptor monoclonal antibody for reversing severe viral hepatitis C. ... Recurrence of hepatitis C following liver transplantation remains a feared complication in recipients of liver allografts. Frequent recurrence of hepatitis C infection following orthotopic liver transplantation (OLT) is common, affecting up to 75% of transplant recipients (1). Hepatitis C viral RNA is detected in 95% to 100% of liver transplant patients suffering from recurrent hepatitis C. Traditionally, severe hepatitis C recurrence following liver transplantation is treated by reduction or discontinuation of immunosuppressive therapy and a combination of antiviral drugs such as alpha interferon and ribavirin, a regimen which has proven to be ineffective. Severe hepatitis C or cirrhosis secondary to hepatitis C
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continue to be complicating factors in liver transplantation. ... As noted herein, antiviral therapy for recurrent hepatitis C viral infection postorthotopic liver transplantation has failed miserably to date. Cholestatic hepatitis has an incidence of 8% to 13% with a high morbidity level. Characteristics indicative of cholestatic hepatitis include early hepatitis C virus recurrence, moderate to high bilirubin levels, renal insufficiency, ascites, and elevated serum hepatitis C viral RNA concentrations (3). Web site: http://www.delphion.com/details?pn=US06406695__ ·
Hepatitis C surrogate virus for testing the activity of hepatitis C virus protease, a recombinant gene and a use thereof Inventor(s): Jang; Sung Key (Pohang, KR), Hahm; Bumsuk (Pohang, KR) Assignee(s): LG Chemicals Co. Ltd. (KR) Patent Number: 6,395,471 Date filed: December 23, 1998 Abstract: The present invention provides a hybrid virus comprising poliovirus and the hepatitis C virus protease NS3 and a target site for NS3. The hybrid virus is useful for screening for drugs against hepatitis C virus. Excerpt(s): The present invention relates to a hepatitis C virus (HCV), more particularly, is related to a hepatitis C surrogate virus which comprises poliovirus genome, HCV protease and its target site, and is suitable for testing efficacy of anti-HCV drugs and screening the same, a recombinant gene and a use thereof. ... Hepatitis C virus (HCV) is the major etiologic agent of non-A, non-B hepatitis (Alter et al, N. Engl. J. Med. 321, 1494-1500, 1989; Choo et al., Science, 244, 359-362, 1989; Kuo et al., Science 244, 362-364, 1989). This virus has been implicated in liver cirrhosis and hepatocellular carcinoma (Bruix et al., Lancet ii, 1004-1006, 1989; Saito et al., Proc. Natl. Acad. Sci. USA, 87, 6547-6549, 1990). At present, .alpha.-interferon is widely used for treating HCV patients. However, only about half of the patients respond to .alpha.-interferon, and about half of the responders suffer from a recurrence of the virus (Hino et al., C. J. Med. Virol., 42, 299-305, 1994; Tsubota et al., Hepatology, 19, 1088-1094, 1994). Development of other anti-HCV drugs is, therefore, necessary. ... An embodiment of the present invention is a recombinant gene coding hepatitis C surrogate virus comprising a virus gene coding picornavirus, a protease gene coding hepatitis C virus protease NS3 which is in an open reading frame (ORF) of said picornavirus, and a target gene coding target sites of said hepatitis C
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virus protease NS3 which is in said open reading frame of said picornavirus. Web site: http://www.delphion.com/details?pn=US06395471__ ·
Synthesis and purification of hepatitis C virus-like particles Inventor(s): Liang; T. Jake (Potomac, MD), Baumert; Thomas F. (Bethesda, MD) Assignee(s): The United States of America as represented by the Department of Health & (Washington, DC) Patent Number: 6,387,662 Date filed: April 21, 1999 Abstract: Production of enveloped RNA virus-like particles intracellularly in vitro in insect cells using a recombinant baculovirus vector containing a cDNA coding for viral structural proteins is disclosed. In vitro production and purification of hepatitis C virus (HCV)-like particles containing HCV core protein, E1 protein and E2 protein is disclosed. Production of antibodies in vivo to the purified HCV-like particles is disclosed. Excerpt(s): Hepatitis C virus (HCV) is a major causative agent of posttransfusion and community-acquired non-A, non-B hepatitis world-wide (Kuo, G. et al., Science 244:362-364, 1989; Choo O. L. et al., Science 244:359-362, 1989; Alter H. J. et al., N. Engl. J. Med. 321:1494-1500, 1989; Kato N. et al., Proc. Natl. Acad. Sci. USA 87: 9524-9528, 1990). The majority of HCV infected individuals develop chronic hepatitis which progresses eventually to liver cirrhosis and hepatocellular carcinoma (Tong M. J. et al., N. Engl. J. Med. 332:1463-1466, 1995). Currently, no effective vaccine to prevent HCV infection or treatment for chronic HCV infection exists (Lemon, S. M. & Thomas, D. L., New Engl. J. Med. 336:177-203, 1997; Hoofuagle, J. & DiBisceclie, New Engl. J. Med. 336:347356, 1997). Development of an effective vaccine and/or treatment has been hampered by the inability to propagate HCV efficiently in cultured cells and the lack of a small animal model. ... Although the viral genomic organization has been characterized in detail, morphologic analysis of hepatitis C virus has been hampered by low levels of HCV particles in infected patients and the inability to propagate efficiently the virus in cultured cells. The levels of the viral particles present in infected patient plasma and/or liver tissues are very low, making it difficult to visualize the virus. By analogy to other members of the Flaviviridae, the HCV genomic organization suggests a virus consisting of a nucleocapsid comprising a viral genome and core protein coated by a lipid envelope
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containing the envelope glycoproteins E1 and E2. Studies of HCV infection in chimpanzees, a reliable animal model for hepatitis C, have provided evidence that HCV is inactivated by chloroform, indicating that it contains essential lipids and therefore is probably enveloped (Feinstone, S. M. et al., Infect. Immun. 41:816-821, 1983). Filtration studies have estimated the virion particle size to be about 30-60 nm in diameter (He et al., J. Infect. Dis. 156:636-640, 1987). ... According to one aspect of the invention, there is provided a method of producing virus-like particles in vitro comprising the steps of providing a vector comprising an expression system capable of producing proteins in insect cells, cloning a cDNA that codes for structural proteins of an enveloped RNA virus into the vector such that the cDNA is capable of being expressed in transfected or infected insect cells, transfecting or infecting insect cells with the vector containing the cloned cDNA that codes for the structural proteins of an enveloped RNA virus, maintaining the transfected or infected insect cells in culture for sufficient time to allow expression of the cDNA to produce the structural proteins of an enveloped RNA virus, and allowing the structural proteins to form intracellular virus-like particles. In one embodiment, the method further comprises the step of purifying the intracellular virus-like particles from the cultured cells. In a preferred embodiment, the purifying step comprises lysing the cells to produce a lysate and subjecting the lysate to gradient centrifugation. In another embodiment, the purifying step comprises lysing the cells to produce a lysate and subjecting the lysate to immunoadsorption using an immunoreagent that specifically recognizes a viral protein contained within the virus-like particles. In one embodiment, the method further comprises the step of generating an immune response in a mammal by introducing an effective amount of purified virus-like particles into the mammal in a pharmaceutically acceptable carrier. In a preferred embodiment, the immunizing step is performed in a mammal selected from the group consisting of a mouse, rat, rabbit, goat, sheep, horse and human. In one embodiment of the method, the cloned cDNA is produced from an enveloped RNA virus that is a member of the Sindbis-like superfamily or a member of the Flavivirus-like superfamily. Preferrably, the cloned cDNA is produced from a member of the group consisting of Togaviridae, Bromovirus, Cucumovirus, Tobavirus, Ilarvirus, Tobravirus, Potexvirus, Flaviviridae, and Pestivirus. In one embodiment of the method, the cloning step comprises cloning a cDNA comprising a 5' untranslated region and sequences coding for hepatitis C virus (HCV) core protein, HCV envelope 1 (E1) protein, HCV envelope 2 (E2) protein and p7 protein, such that the cDNA is capable of being expressed in transfected or infected insect cells, and the maintaining step comprises maintaining the transfected or infected insect cells in culture for about 72
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hr to 120 hr, to allow expression of the cDNA to produce HCV structural proteins and allow the HCV structural proteins to form intracellular HCV-like particles. The cloned cDNA may also include sequence that codes for a few amino acids of non-structural protein NS2. One embodiment of the invention is HCV-like particles produced according to this method. In one embodiment, the HCV-like particles further comprise a portion of HCV RNA transcript. The HCV-like particles are about 40 nm to about 60 nm in diameter and have a density of about 1.14 g/cm.sup.3 to about 1.18 g/cm.sup.3. Another embodiment of the invention is a vaccine comprising the HCV-like particles in a pharmaceutically acceptable carrier. One more embodiment is a therapeutic agent comprising HCV-like particles in a pharmaceutically acceptable carrier. Another embodiment is antibodies produced by immunizing an animal with HCV-like particles, and the antibodies can be monoclonal antibodies. Another embodiment of the invention is a diagnostic kit for detecting HCV infection in an individual comprising HCV-like particles and a, means for detecting antibodies that bind to the HCV-particles. Web site: http://www.delphion.com/details?pn=US06387662__ ·
Combination therapy for chronic hepatitis C infection Inventor(s): Albrecht; Janice K. (Winter Park, FL), Grint; Paul C. (Basking Ridge, NJ) Assignee(s): Schering Corporation (Kenilworth, NJ) Patent Number: 6,387,365 Date filed: May 19, 1995 Abstract: There is disclosed a method for treating chronic hepatitis C infection in patients in need of such treating comprising administering an amount of alpha interferon in association with an amount of ribavirin effective to treat chronic hepatitis C infection with the absence or substantial reduction of side effects associated with administration of ribavirin and alpha interferon. Excerpt(s): Chronic infection with hepatitis C virus is an insidious and slow-progressing disease having a significant impact on the quality of life. It can eventually result in cirrhosis of the liver, decompensated liver disease and/or hepatocelluar carcinoma. ... Alpha interferon monotherapy is commonly used to treat chronic hepatitis C infection. However this treatment is not always effective and sometimes results in intolerable side effects related to the dosage and duration of therapy. Ribavirin has been proposed as a monotherapy treatment for chronic
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hepatitis C infection (Thomas et al. AASLD Abstracts, Hepatology Vol. 20, NO. 4, Pt 2, Number 440, 1994). However, this monotherapy treatment has usually been found relatively ineffective and has its own undesirable side effects. ... There is a need for a method for treating chronic hepatitis C infection with a combination of alpha interferon and ribavirin in the substantial absence of side effects normally associated with either compound. Web site: http://www.delphion.com/details?pn=US06387365__ ·
Method for producing in vitro the RNA-dependent RNA polymerase and terminal nucleotidyl transferase activities encoded by hepatitis C virus (HCV) Inventor(s): De Francesco; Raffaele (Rome, IT), Tomei; Licia (Rome, IT), Behrens; Sven-Erik (Weimar, DE) Assignee(s): Istituto di Ricerehe di Biologia Molecolare P. Angeletti S.p.A. (Pomezia, IT) Patent Number: 6,383,768 Date filed: March 23, 1998 Abstract: This is a method for reproducing in vitro the RNA-dependent RNA polymerase activity associated with hepatitis C virus. The method is characterized in that sequences contained in NS5B are used in the reaction mixture. The terminal nucleotidyl transferase activity, a further property of the NS5B protein, can also be reproduced using this method. The method takes advantage of the fact that the NS5B protein, either purified to apparent homogeneity or present in extracts of overproducing organisms, can catalyze the addition of ribonucleotides to the 3'-termini of exogenous or endogenous RNA molecules. The invention also relates to a composition of matter that comprises sequences contained in NS5B, and to the use of these compositions for the set up of an enzymatic test capable of selecting, for therapeutic purposes, compounds that inhibit the enzymatic activity associated with NS5B. Excerpt(s): The present invention relates to the molecular biology and virology of the hepatitis C virus (HCV). More specifically, this invention has as its object the RNA-dependent RNA polymerase (RdRp) and the nucleotidyl terminal transferase (TNTase) activities produced by HCV, methods of expression of the HCV RdRp and TNTase, methods for assaying in vitro the RdRp and TNTase activities encoded by HCV in order to identify, for therapeutic purposes, compounds that inhibit these enzymatic activities and therefore might interfere with the replication of the HCV virus. ... As is known, the hepatitis C virus (HCV) is the main
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etiological agent of non-A, non-B hepatitis (NANB). It is estimated that HCV causes at least 90% of post-transfusional NANB viral hepatitis and 50% of sporadic NANB hepatitis. Although great progress has been made in the selection of blood donors and in the immunological characterization of blood used for transfusions, there is still a high number of HCV infections among those receiving blood transfusions (one million or more infections every year throughout the world). Approximately 50% of HCV-infected individuals develop cirrhosis of the liver within a period that can range from 5 to 40 years. Furthermore, recent clinical studies suggest that there is a correlation between chronic HCV infection and the development of hepatocellular carcinoma. Web site: http://www.delphion.com/details?pn=US06383768__ ·
Modified forms of Hepatitis C NS3 protease for facilitating inhibitor screening and structural studies of protease: inhibitor complexes Inventor(s): Wittekind; Michael (Doylestown, PA), Weinheimer; Steven (Northford, CT), Zhang; Yaqun (Holland, PA), Goldfarb; Valentina (Franklin Park, NJ) Assignee(s): Bristol-Myers Squibb Company (Princeton, NJ) Patent Number: 6,333,186 Date filed: January 6, 2000 Abstract: The present invention relates to modified Hepatitis C NS3 proteases and modified Hepatitis C NS4a-NS3 fusion proteases. These proteins are highly soluble and are useful for NMR spectroscopy, X-ray crystallography, and inhibitor screening. DNA constructs are also provided. Excerpt(s): The present invention relates to modified forms of the Hepatitis C NS3 protease. The wild type protease is essential in vivo for viral replication of Hepatitis C. The novel proteins of this invention are useful for screening for inhibitors of the protease and for structural studies of the protease and protease:inhibitor complexes. ... Hepatitis C virus (HCV) infection is the suspected cause of 90% of all cases of non-A, non-B hepatitis (Choo et al., 1989, Kuo et al., 1989). HCV infection is more common than HIV infection with an incidence rate of 2-15% worldwide. Over 4 million people are infected with HCV in the United States alone. While primary infection with HCV is often asymptomatic, almost all HCV infections progress to a chronic state that persists for decades. A staggering 20-50% are thought to eventually develop chronic liver disease (e.g. cirrhosis) and 20-30% of these cases will lead to liver failure or liver cancer. Up to 12,000 people in the U.S. will die this year from sequelae
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associated with HCV infection. As the current population ages over the next two decades, the morbidity and mortality associated with HCV are expected to triple. The development of safe and effective treatment(s) for HCV infection is a major unmet medical need. ... Hepatitis C virus is a positive-strand RNA virus of the family Flaviviridae. The HCV genome encodes a single polyprotein of 3033 amino acids, of which residues 1027 to 1657 (631 amino acids) represent the NS3 protein (Choo et al., 1991). The HCV NS3 protein is a site-specific protease that cleaves the HCV polyprotein selectively at four sites related by their primary amino acid sequences (Grakoui et al., 1993a). These cleavages give rise to the mature non-structural (replicative) proteins of HCV, including NS3, NS4A, NS4B, NS5A, and NS5B (Bartenschlager et al., 1993; Grakoui et al., 1993b; Hijikata, et al., 1993a,b; Tomei et al., 1993; Bartenschlager et al., 1994; Eckart et al., 1994; Lin et al., 1994; Manabe, et al 1994). Genetic studies have demonstrated that the homologous NS3 proteases of related viruses (e.g Yellow Fever Virus and Bovine viral diarrhea virus) are absolutely essential for viral replication (Chambers et al., 1990; Xu et al., 1997). Thus, inhibitors of NS3 protease should inhibit HCV replication and would be useful for the discovery and development of effective antiviral treatments for HCV infection. Web site: http://www.delphion.com/details?pn=US06333186__ ·
Hepatitis C E1 and E2 truncated polypeptides and methods of obtaining the same Inventor(s): Selby; Mark (San Francisco, CA), Houghton; Michael (Danville, CA) Assignee(s): Chiron Corporation (Emeryville, CA) Patent Number: 6,326,171 Date filed: October 8, 1999 Abstract: Novel Hepatitis C E1 and E2 truncated polypeptides and complexes comprising these polypeptides, are disclosed. The polypeptides are C-terminally truncated to remove all or a portion of their membrane spanning domains. Hence, the polypeptides are capable of secretion when expressed recombinantly. Excerpt(s): The present invention pertains generally to viral proteins. In particular, the invention relates to truncated, secreted forms of hepatitis C virus E1 and E2 proteins and the isolation and recombinant production of the same. ... Hepatitis C Virus (HCV) is the principal cause of parenteral non-A, non-B hepatitis which is transmitted largely through blood transfusion and sexual contact. The virus is present in between 0.4 to
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2.0% of blood donors. Chronic hepatitis develops in approximately 50% of infections and of these, approximately 20% of infected individuals develop liver cirrhosis which sometimes leads to hepatocellular carcinoma. Accordingly, the study and control of the disease is of medical importance. Web site: http://www.delphion.com/details?pn=US06326171__ ·
Screening methods to identify agents that selectively inhibit hepatitis C virus replication Inventor(s): Katze; Michael G. (Seattle, WA), Gale; Michael J. (Monroe, WA) Assignee(s): University of Washington (Seattle, WA) Patent Number: 6,326,151 Date filed: February 25, 2000 Abstract: The present invention relates to novel methods for identifying antiviral agents which selectively interfere with viral proteins that override the interferon(IFN)-induced cellular defense mechanisms against viral infection. In particular, the present invention relates to screening assays that identify agents which selectively inhibit the interaction between viral proteins containing an interferon sensitivity determining region (ISDR) and IFN-induced PKR protein kinase. The present invention more particularly relates to screening assays that identify agents which selectively inhibit the interaction between hepatitis C virus (HCV) nonstructural 5A protein (NS5A), which contains an ISDR, and IFN-induced PKR protein kinase. The interaction between the viral ISDR and IFN-induced PKR protein kinase results in the override of IFNinduced cellular defense mechanisms to combat viral infection. Therefore the agents identified using the assays of the invention may have utility as antiviral agents. Excerpt(s): The present invention relates to novel methods for identifying antiviral agents which selectively interfere with viral proteins that override the interferon(IFN)-induced cellular defense mechanisms against viral infection. In particular, the present invention relates to screening assays that identify agents which selectively inhibit the interaction between viral proteins containing an interferon sensitivity determining region (ISDR) and IFN-induced PKR protein kinase. The present invention more particularly relates to screening assays that identify agents which selectively inhibit the interaction between hepatitis C virus (HCV) nonstructural 5A protein (NS5A), which contains an ISDR, and IFN-induced PKR protein kinase. The interaction between the viral
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ISDR and IFN-induced PKR protein kinase results in the override of IFNinduced cellular defense mechanisms to combat viral infection. Therefore the agents identified using the assays of the invention may have utility as antiviral agents. ... Hepatitis C virus (HCV) infection is an important clinical problem worldwide. In the United States alone, an estimated four million individuals are chronically infected with HCV. HCV, the major etiologic agent of non-A, non-B hepatitis, is transmitted primarily by transfusion of infected blood and blood products (Cuthbert et al., 1994, Clin. Microbiol. Rev. 7:505-532; Mansell et al., 1995, Semin. Liver Dis. 15:15-32). Prior to the introduction of anti-HCV screening in mid-1990, HCV accounted for 80-90% of posttransfusion hepatitis cases in the United States. Currently, injection drug use is probably the most common risk factor for HCV infection, with approximately 80% of this population seropositive for HCV. A high rate of HCV infection is also seen in individuals with bleeding disorders or chronic renal failure, groups that have frequent exposure to blood and blood products. Web site: http://www.delphion.com/details?pn=US06326151__ ·
Hepatitis C virus protease-dependent chimeric pestivirus Inventor(s): Hong; Zhi (Nanuet, NY), Lai; Vicki C. H. (North Plainfield, NJ), Lau; Johnson Y. N. (Warren, NJ) Assignee(s): Schering Corporation (Kenilworth, NJ) Patent Number: 6,326,137 Date filed: June 25, 1999 Abstract: A chimeric bovine viral diarrhea virus (BVDV) that depends on a hepatitis C virus (HCV). The invention further relates to using the chimeric, infectious virus to screen for HCV NS3 inhibitor compounds in cell culture models or in animal models of viral infection. Excerpt(s): The present invention relates to a chimeric pestivirus, such as bovine viral diarrhea virus (BVDV), that depends on a hepatitis C virus (HCV) protease function. The invention further relates to using the chimeric, infectious virus to screen for HCV NS3 inhibitor compounds in cell culture systems or in animal models of viral infection. ... Infection by hepatitis C virus (HCV) is a compelling human medical problem. HCV is recognized as the causative agent for most cases of non-A and non-B hepatitis, with an estimated prevalence of 170 million cases (i.e., 2-3%) globally [Choo, et al., Science, 244: 359-362 (1989); Kuo, et al., Science, 244: 362-364 (1989); Purcell, FEMS Microbiology Reviews, 14: 181-192 (1994); Van der Poel, C. L., Current Studies in Hematology and Blood Transfusion, H. W. Reesink, Ed., (Basel: Karger), pp. 137-163 (1994)]. Four
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million individuals may be infected in the United States alone [Alter, and Mast, Gastroenterol. Clin. North Am., 23: 437-455 (1994)]. ... Experiments using transient expression of various forms of HCV NS polyproteins in mammalian cells have established that the NS3 serine protease is necessary but not sufficient for efficient processing of all of these cleavages. HCV NS3 protease requires a cofactor to catalyze some of these cleavage reactions. Efficient proteolytic processing at NS3/4A, NS4A/4B, NS4B/5A, and NS5A/5B sites within the non-structural domain of hepatitis C virus requires a heterodimeric complex of the NS3 serine protease and the NS4A protein. [Bartenschlager et al. 1995, J. Virol. 67:3835-3844; Failla et al., 1994, J. Virol. 68:3753-3760]. A 13-amino acid synthetic NS4A peptide, corresponding to the central hydrophobic domain of NS4A protein, spanning residues 21-33 has been shown to be sufficient for activation of NS3 protease [Butkiewicz et al., 1996, Virology, 225: 328-338]. A smaller domain (amino acid residues 22-30) of NS4A has been shown to be sufficient for activation of the protease [Lin et al., 1995, J. Virol 69:4377-80]. Web site: http://www.delphion.com/details?pn=US06326137__ ·
Viral specific requirements for self-priming RNA replication of hepatitis C virus replicase Inventor(s): Zhong; Weidong (40 Elmar Cir., Royersford, PA 19468), Hong; Zhi (100 Briar Rd., Nanuet, NY 10954), Lau; Johnson Y. N. (17 Mattben Dr., Warren, NJ 07059) Assignee(s): none reported Patent Number: 6,322,966 Date filed: May 11, 1999 Abstract: The present invention relates to identification of the features of an RNA template that provide for efficient "copy-back" self-priming activity of hepatitis C virus replicase. This activity can be used to screen for anti-HCV replicase compounds, or to characterize the biological relevance of lead compounds that have already been identified. The specific features of the optimal RNA templates can be used for developing a system to characterize HCV NS5B polymerase mechanistically and kinetically, and for designing small RNA molecules to co-crystallize with HCV NS5B polymerase. Excerpt(s): The present invention relates to identification of optimal properties of an RNA template for "copy-back" self-priming RNA synthesis of hepatitis C virus replicase. This activity can be used to screen for anti-HCV replicase compounds, or to characterize the biological
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relevance of lead compounds that have already been identified. ... Infection by hepatitis C virus (HCV) is a compelling human medical problem. HCV is recognized as the causative agent for most cases of nonA and non-B hepatitis, with an estimated prevalence of 170 million cases (i.e., 2-3%) globally [Choo, et al., Science, 244: 359-362 (1989); Kuo, et al., Science, 244: 362-364 (1989); Purcell, FEMS Microbiology Reviews, 14: 181-192 (1994); Van der Poel, C. L., Current Studies in Hematology and Blood Transfusion, H. W. Reesink, Ed., (Basel: Karger), pp. 137-163 (1994)]. Four million individuals may be infected in the United States alone [Alter, and Mast, Gastroenterol. Clin. North Am., 23: 437-455 (1994)]. ... The ability of recombinant HCV NS5B to initiate RNA synthesis by a primer-independent mechanism has recently been observed [U.S. patent application Ser. No. 09/305,185 filed May 4, 1999, entitled "De Novo Priming Activity of Hepatitis C Virus Replicase,". De novo priming was also observed with bovine viral diarrhea virus [Kao et al., Virology, 23, pp. 1-7(1999)]. De novo initiation of RNA synthesis is likely to be the mode of initiation of HCV replication in an infected cell. Web site: http://www.delphion.com/details?pn=US06322966__ ·
De novo priming activity of hepatitis C virus replicase Inventor(s): Zhong; Weidong (Royersford, PA), Hong; Zhi (Nanuet, NY), Uss; Annette Schettino (Lebanon Township, NJ), Lau; Johnson Y. N. (Warren, NJ) Assignee(s): Schering Corporation (Kenilworth, NJ) Patent Number: 6,297,005 Date filed: May 4, 1999 Abstract: The present invention relates to identification of a novel, de novo priming activity of hepatitis C virus replicase. This activity can be used to screen for anti-HCV replicase compounds, or to characterize the biological relevance of lead compounds that have already been identified. Excerpt(s): The present invention relates to identification of a novel, de novo priming activity of hepatitis C virus replicase. This activity can be used to screen for anti-HCV replicase compounds, or to characterize the biological relevance of lead compounds that have already been identified. ... Infection by hepatitis C virus (HCV) is a compelling human medical problem. HCV is recognized as the causative agent for most cases of nonA and non-B hepatitis, with an estimated prevalence of 170 million cases (i.e., 2-3%) globally [Choo, et al., Science, 244: 359-362 (1989); Kuo, et al., Science, 244: 362-364 (1989); Purcell, FEMS Microbiology Reviews, 14: 181-192 (1994); Van der Poel, C. L., Current Studies in Hematology and
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Blood Transfusion, H. W. Reesink, Ed., (Basel: Karger), pp. 137-163 (1994)]. Four million individuals may be infected in the United States alone [Alter, and Mast, Gastroenterol. Clin. North Am., 23: 437-455 (1994)]. ... The present invention advantageously establishes that hepatitis C virus (HCV) replicase activity can proceed in a primer-independent mode, e.g, by de novo priming. This priming activity, which depends on the template sequence and, critically, on the concentration of the initial one to two complementary nucleotide triphosphates, can be harnessed for various primary, and especially secondary, screening assays for antiHCV compounds. In particular, the present invention permits one to determine whether an HCV NS5B binding compound or inhibitor is capable of selectively blocking de novo priming and primer independent replicase activity, without adversely affecting host cell replication and transcription processes. Web site: http://www.delphion.com/details?pn=US06297005__ ·
Methods for the detection of a novel hepatitis C virus (HCV) terminal 3' noncoding region Inventor(s): Rice; Charles M. (University City, MO), Kolykhalov; Alexander A. (St. Louis, MO) Assignee(s): Washington University (St. Louis, MO) Patent Number: 6,297,003 Date filed: July 18, 1997 Abstract: The invention relates to the discovery of a novel RNA sequence at the 3' terminal sequence of hepatitis C virus (HCV) genome RNA. Included in the invention are the 3' sequence, its complement, and their use for nucleic-acid based diagnostics and for developing and evaluating novel anti-HCV therapies. This sequence element, which is conserved among HCV genotypes, is likely to be essential for viral replication, and required for construction of full-length HCV cDNA clones capable of yielding infectious RNA, progeny virus or replication-competent HCV replicons. Such functional clones are useful tools for evaluation of therapeutic approaches and as substrates for developing candidate attenuated or inactivated HCV derivatives for vaccination against HCV. Excerpt(s): The present invention relates generally to a novel nucleotide sequence element identified at or near the 3' terminus of the hepatitis C virus (HCV) viral genome RNA. This element is highly conserved among HCV genotypes and may be essential for HCV replication. ... After the development of diagnostic tests for hepatitis A virus and hepatitis B virus, an additional agent, which could be experimentally transmitted to
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chimpanzees (Alter et al, 1978; Hollinger et al, 1978; Tabor et al, 1978), became recognized as the major cause of transfusion-acquired hepatitis. cDNA clones corresponding to the causative non-A non-B (NANB) hepatitis agent, called hepatitis C virus (HCV), were reported in 1989 (Choo et al, 1989). This breakthrough has led to rapid advances in diagnostics, and in our understanding of the epidemiology, pathogenesis and molecular virology of HCV (see Houghton et al, 1994 for review). Evidence of HCV infection is found throughout the world and the prevalence of anti-HCV antibodies ranges from 0.4-2% in most developed countries to more than 14% in Egypt (Hibbs et al, 1993). Besides transmission via blood or blood products, or less frequently by sexual and congenital routes, sporadic cases, not associated with known risk factors, occur and account for more than 40% of HCV cases (Alter et al, 1990; Mast and Alter, 1993). Infections are usually chronic (Alter et al, 1992) and clinical outcomes range from an inapparent carrier state to acute hepatitis, chronic active hepatitis, and cirrhosis which is strongly associated with the development of hepatocellular carcinoma. Although alpha IFN has been shown to be useful for the treatment of some patients with chronic HCV infections (Davis et al, 1989; DiBisceglie et al, 1989) and subunit vaccines show some promise in the chimpanzee model (Choo et al, 1994), future efforts are needed to develop more effective therapies and vaccines. The considerable diversity observed among different HCV isolates (for review, see Bukh et al, 1995), the emergence of genetic variants in chronically infected individuals (Enomoto et al, 1993; Hijikata et al, 1991; Kato et al, 1992; Kato et al, 1993; Kurosaki et al, 1993; Lesniewski et al, 1993; Ogata et al, 1991; Weiner et al, 1991; Weiner et al, 1992), and the lack of protective immunity elicited after HCV infection (Farci et al, 1992; Prince et al, 1992) present major challenges towards these goals. ... 2. Alter, M. J.; Hadler, S. C.; Judson, F. N.; Mares, A.; Alexander, W. J.; Hu, P. Y.; Miller, J. K.; Moyer, L. A.; Fields, H. A.; Bradley, D. W.; and Margolis, H. S. (1990). Risk factors for acute non-A, non-B hepatitis in the United States and association with hepatitis C virus infection. J. Am. Med. Assoc. 264:2231-2235. Web site: http://www.delphion.com/details?pn=US06297003__
Patent Applications on Hepatitis C As of December 2000, U.S. patent applications are open to public viewing.27 Applications are patent requests which have yet to be granted (the process to 27
This has been a common practice outside the United States prior to December 2000.
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achieve a patent can take several years). The following patent applications have been filed since December 2000 relating to hepatitis C: ·
Diagnostic reagent for hepatitis C virus infection Inventor(s): Takahama, Yoichi ; (Hyogo-ken, JP), Shiraishi, Junichi ; (Hyogo-ken, JP) Correspondence: Bruce D. Grant; Morrison & Foerstre LLP; Suite 500; 3811 Valley Centre Drive; San Diego; CA; 92130; US Patent Application Number: 20020081630 Date filed: December 21, 2001 Abstract: A diagnostic reagent for hepatitis C virus infection obtained by sensitizing a solid phase with HCV antigen and a conjugated antigen prepared by chemical bonding of HCV antigen and a carrier protein, and a method of diagnosing hepatitis C virus infection, which comprises adding the diagnostic reagent for hepatitis C virus infection to a sample, and measuring the degree of agglutination of carrier particles as the solid phase. The diagnostic reagent and the method of diagnosis enable many samples to be measured with higher sensitivity and rapidity. Excerpt(s): The present invention relates to a diagnostic reagent for detecting hepatitis C virus (HCV) infection by utilizing immunoagglutination. ... In regard to hepatitis C, HCV gene was detected by the research group of Chiron Corporation, U.S.A., in 1988 prior to the detection of HCV. To detect antibodies to HCV, various recombinant antigens or synthetic peptides have been investigated, and kits for detecting HCV-associated antibodies have been developed. The methods of detection now available are agar diffusion, counterimmunoelectrophoresis, radioimmunoassay, enzyme immunoassay, passive hemagglutination, and latex agglutination. ... The present invention provides a diagnostic reagent for hepatitis C virus infection obtained by sensitizing a solid phase with HCV antigen and a conjugated antigen prepared by chemical bonding of HCV antigen and a carrier protein. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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·
Hepatitis C virus gene products Inventor(s): Ou, Jing-Hsiung ; (San Gabriel, CA), Xu, Zhenming ; (Buena Park, CA) Correspondence: McCutchen, Doyle, Brown & Enersen, LLP; Three Embarcadero Center; San Francisco; CA; 94111; US Patent Application Number: 20020076415 Date filed: December 14, 2000 Abstract: The present invention provides heretofore unidentified proteins and smaller peptides of HCV, which are produced by translation of the HCV core RNA through a frameshifting mechanism. In one embodiment the invention provides a protein that is about 125 to about 161 amino acids long depending on the HCV genotypes. The smaller peptides of the invention range in length from about 13 amino acids to over 50 amino acids. The invention also includes DNA sequences that encode the polypeptides of the invention, antibodies directed against the polypeptides of the invention, and therapeutic compositions including vaccines and anti-viral compositions. Additionally, the invention provides for methods for diagnosing, preventing and treating hepatitis C using the compounds and compositions of the invention. Excerpt(s): This invention relates to hepatitis C virus (HCV) and, in particular, to compositions and methods for treating and diagnosing hepatitis C. ... Recently a new viral species, hepatitis C virus (HCV) has been identified as the primary (if not only) cause of blood-associated NANBH (BA-NANBH). Hepatitis C appears to be the major form of transfusion-associated hepatitis in a number of countries, including the United States and Japan. The major problem in this disease is the frequent progression to chronic liver damage (25-55%). There is also evidence implicating HCV in induction of hepatocellular carcinoma. ... Therefore, there is a need for reliable diagnostic and prognostic tools to detect nucleic acids, antigens, and antibodies related to HCV. In addition, there is also a need for effective vaccines and immunotherapeutic agents for the prevention and/or treatment of hepatitis C. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Preventive and therapeutic antiviral drug for aids, hepatitis B, hepatitis C and influenza Inventor(s): Fujisaki, Shigemi ; (Nishinomiya-shi, JP), Honda, Mitsuo ; (Mitaka-shi, JP) Correspondence: Nixon Peabody, LLP; 8180 Greensboro Drive; Suite 800; McLean; VA; 22102; US Patent Application Number: 20020068055 Date filed: August 21, 2001 Abstract: The present invention provides a preventive and therapeutic antiviral drug for AIDS, hepatitis B, hepatitis c and influenza containing MEP-F (metalloendopeptidase-F) and proteases (protein decomposition enzymes) as effective ingredients.Viruses should pass through CD4 receptors on the surface of the cell membrane for invading into the cell. However, since MEP-F extinguishes the activity of CD4 to prevent the viruses from invading into the cell, growth and proliferation of the virus are inhibited, manifesting preventive and therapeutic efficacy for viral infection. Excerpt(s): The present invention relates to a preventive and therapeutic antiviral drug for AIDS, hepatitis B, hepatitis C and influenza. ... The therapeutic and preventive antiviral drug according to the present invention contains MEP-F and other proteases as effective ingredients, and their efficacy is applicable to AIDS, hepatitis B, hepatitis C and influenza. ... (iv) Results of tests for viral infections: No symptoms of hepatitis B and hepatitis C and no abnormal findings were noted in serologic tests for HBV, HCV and antigens. Positive responses were noted in the HIV test and ELISA test, and the result of reconfirmation by the western blot technique also positive. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Ribavirin-interferon alfa combination therapy for eradicating detectable HCV-RNA in patients having chronic hepatitis C infection Inventor(s): Ganguly, Ashit K. ; (Upper Montclair, NJ), McCormick, Jinping ; (Edison, NJ), Lovey, Raymond G. ; (West Caldwell, NJ), Bennett, Frank ; (Piscataway, NJ), Saksena, Anil K. ; (Upper Montclair, NJ), Girijavallabhan, Viyyoor M. ; (Parsippany, NJ) Correspondence: Schering-Plough Corporation; Patent Department (K-61, 1990); 2000 Galloping Hill Road; Kenilworth; NJ; 07033-0530; US Patent Application Number: 20020055473 Date filed: April 18, 2001 Abstract: Ribavirin derivatives represented by the formula II, pharmaceutical compositions containing them as well as methods of using the ribavirin derivatives represented by the formula II for the treatment of susceptible viral infections, for example, chronic hepatitis C infections administrating, the ribavirin derivatives being represented by formula II 1are disclosed. Excerpt(s): Chronic infection with hepatitis C virus is an insidious and slow-progressing disease having a significant impact on the quality of life. It can eventually result in cirrhosis of the liver, decompensated liver disease and/or hepatocelluar carcinoma. ... Combination treatment with interferon alfa-2b and ribavirin of patients with chronic hepatitis C is disclosed by Reichard et al.(The Lancet 1998; 351;83-87; and T. Poynard et al.( The Lancet ,1998, Vol. 352, October 31, p 1426-1432). See also J. G. McHutchinson et al. (N. Engl. J. Med.,1998, 339:1485-1492); and G. L. Davis et al. (N. Engl. J. Med., 1998, 339:1493-1499).However, this combination therapy is not always effective due to side effects associated ribavirin such as ribavirin-related hemolysis, and anemia. ... There is a definite need for more potent, safer ribavirin derivatives having fewer side effects for use as monotherapy or in combination with antiviral agents, e.g., interferon-alpha, to treat patients having susceptible viral infections, e.g., chronic hepatitis C infections, in a long-term, effective manner. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Crystallizable compositions comprising a hepatitis C virus NS3 protease domain/NS4A complex Inventor(s): Kim, Joseph L. ; (Natick, MA), Morgenstern, Kurt A. ; (Derry, NH), Lin, Chao ; (Cambridge, MA), Fox, Ted ; (Maynard, MA), Thomson, John A. ; (Belmont, MA) Correspondence: Fish & Neave; 1251 Avenue Of The Americas; 50TH Floor; New York; NY; 10020-1105; US Patent Application Number: 20020042046 Date filed: September 14, 2001 Abstract: The present invention relates to compositions and crystals of a hepatitis C virus protease in complex with its viral cofactor. This invention also relates to methods of using the structure coordinates of hepatitis C virus protease in complex with a synthetic NS4A to solve the structure of similar or homologous proteins or protein complexes. Excerpt(s): The present invention relates to compositions and crystals of a hepatitis C virus protease in complex with its viral cofactor. This invention also relates to methods of using the structure coordinates of hepatitis C virus protease in complex with a synthetic NS4A to solve the structure of similar or homologous proteins or protein complexes. ... Infection by hepatitis C virus (HCV) is a compelling human medical problem. HCV is recognized as the causative agent for most cases of nonA, non-B hepatitis, with an estimated human seroprevalence of 1% globally [Choo, Q.-L. et al., "Isolation of a cDNA Clone Derived From a Blood-Borne Non-A, Non-B Viral Hepatitis Genome", Science, 244, pp. 359-362 (1989); Kuo, G. et al., "An Assay for Circulating Antibodies to a Major Etiologic Virus of Human Non-A, Non-B Hepatitis", Science, 244, pp. 362-364 (1989); Purcell, R. H., "Hepatitis C virus: Historical perspective and current concepts", FEMS Microbiology Reviews, 14, pp. 181-192 (1994); Van der Poel, C. L., "Hepatitis C Virus. Epidemiology, Transmission and Prevention in Hepatitis C virus. Current Studies in Hematology and Blood Transfusion, H. W. Reesink, Ed., (Basel: Karger), pp. 137-163 (1994)]. Four million individuals may be infected in the United States alone [Alter, M. J. and Mast, E. E., "The Epidemiology of Viral Hepatitis in the United States, Gastroenterol. Clin. North Am., 23, pp. 437-455 (1994)]. ... Upon first exposure to HCV only about 20% of infected individuals develop acute clinical hepatitis while others appear to resolve the infection spontaneously. In most instances, however, the virus establishes a chronic infection that persists for decades [Iwarson, S. "The Natural Course of Chronic Hepatitis", FEMS Microbiology Reviews, 14, pp. 201-204 (1994)]. This usually results in recurrent and progressively worsening liver inflammation, which often leads to more severe disease
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states such as cirrhosis and hepatocellular carcinoma [Kew, M. C., "Hepatitis C and Hepatocellular Carcinoma", FEMS Microbiology Reviews, 14, pp. 211-220 (1994); Saito, I., et al. "Hepatitis C Virus Infection is Associated with the Development of Hepatocellular Carcinoma", Proc. Natl. Acad. Sci. USA 87, pp. 6547-6549 (1990)]. Currently, there are no broadly effective treatments for the debilitating progression of chronic HCV. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·
Method for detecting hepatitis C Inventor(s): Budkowska, Agata ; (Clamart, FR), Maillard, Patrick ; (Montlhery, FR), Bronnert, Christian ; (Fresnes, FR), Gounon, Pierre ; (Noiseau, FR), Nitkiewicz, Jadwiga ; (Komorow, PL), Grainic, Radu ; (Jouy En Josas, FR) Correspondence: Oblon Spivak Mcclelland Maier & Neustadt PC; Fourth Floor; 1755 Jefferson Davis Highway; Arlington; VA; 22202; US Patent Application Number: 20020037868 Date filed: June 15, 2001 Abstract: The present invention provides methods of detecting hepatitis C virus. Excerpt(s): The present invention relates to a methods for detecting hepatitis C virus. ... Hepatitis C virus (HCV) is an enveloped positive strand RNA virus, recognized as the major etiologic agent of blood-borne and sporadic non-A, non-B hepatitis. Due to the propensity of this virus to cause chronic infections, and its association with liver cirrhosis and hepatocellular carcinoma, HCV is a significant world-wide health problem. ... The above objects and others are provided by a method of directly detecting hepatitis C virus in serum of a patient by detecting the virus with primers corresponding to viral RNA encoding core protein which RNA is a light fraction of the total viral RNA, the light fraction being isolated after ultracentifugation in a CsCl gradient of human serum containing HCV virus, the light fraction containing most of the circulating infectious HCV virus particles, which method entails precipitating RNA, effecting reverse transcription and then effecting amplification with the primers described herein. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Treatment of hepatitis C using hyperthermia Inventor(s): Groth, Karl Emil ; (St. Paul, MN), Kelly, Theodore Charles ; (Minnetonka, MN), Westerbeck, Todd L. ; (Burnsville, MN), Blick, Gary ; (Stamford, CT) Correspondence: Thomas E. Popovich; Popovich & Wiles, PA; IDS Center, Suite 1902; 80 South 8th Street; Minneapolis; MN; 55402; US Patent Application Number: 20020033181 Date filed: September 13, 2001 Abstract: The invention provides a method of treating a patient infected with hepatitis C virus (HCV) comprising raising the core temperature of the patient and then returning the core temperature of the patient to normal at least one time, wherein the core temperature is raised to a temperature range and a duration sufficient to reduce or eliminate the patient's viral load of HCV. Excerpt(s): This invention relates to hyperthermic treatment of hepatitis C. ... Injected drug users are the largest group of people with hepatitis C infection. People who received a blood transfusion or kidney transplant before a diagnostic test became available form another large group of those infected. ... Since human immunodeficiency virus (HIV) is also common among injected drug users and is transmitted sexually, about forty percent of HIV infected patients are co-infected with HCV. Various types of HIV such as HIV-1 and HIV-2 exist. Hepatitis C virus occurs in six known genotypes and more than fifty subtypes. The hepatitis C virus is harbored in the liver and most people infected with HCV eventually will develop cirrhosis or liver carcinoma. HCV can cause an acute or chronic infection. In chronic infection, the infected person can exhibit signs of chronic hepatitis or be a chronic asymptomatic carrier. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Administration system for seronegative of hepatitis C virus Inventor(s): Okushin, Hiroaki ; (Himeji-shi, JP) Correspondence: Crowell & Moring, L.L.P.; P.O. Box 14300; Washington; DC; 20044-4300; US Patent Application Number: 20020022015 Date filed: September 13, 2001 Abstract: The present invention provides an effective therapeutic agent for chronic hepatitis C, as well as a drug administration system for
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treating chronic hepatitis C by use of said therapeutic agent.Specifically, the present invention provides a therapeutic agent for negation of hepatitis C virus (HCV)-RNA wherein the daily effective dosage of interferon (IFN) is administered once per day, or divided and administered in portions per day. The present invention also provides a drug administration system for administering said therapeutic agent, and a method for negation of HCV-RNA by said drug administration system, as well as a therapeutic method for chronic hepatitis C. The IFN is IFN.alpha. or IFN-.beta.. Excerpt(s): The present invention relates to an effective therapeutic agent for chronic hepatitis C by negating hepatitis C virus(HCV)-RNA. Specifically, the present invention provides the effective therapeutic agent used for interferon (IFN) therapy, a drug administration system (drug administration unit), a method for negating HCV-RNA by said administration system, and further a therapeutic method for chronic hepatitis C by negation of HCV-RNA. ... In general, hepatitis is understood to be an inflammation in the liver caused by viral infection in many cases, and hepatitis A caused by hepatitis A virus (HAV) and hepatitis B by hepatitis B virus (HBV) have been known for a long time. However, the presence of hepatitis non-A and non-B judged to be neither hepatitis A nor B came to be regarded as problematic, and thereafter, the presence of hepatitis C virus (HCV) as a major causative virus was revealed to be attributable to hepatitis non-A and non-B, and attention is now paid to chronic hepatitis C caused by HCV. ... The characteristics of hepatitis C caused by HCV are high chronic degrees from acute hepatitis, as compared with other types of hepatitis. If chronic hepatitis C is unattended, the risk of progress through cirrhosis to hepatocellular carcinoma is high, so therapy effective against HCV should be conducted at an early stage. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·
Human Monoclonal Antibodies Specific for Hepatitis C Virus (HCV) E2 Antigen Inventor(s): Persson, Mats Axel Atterdag ; (Stockholm, SE), Allander, Tobias Erik ; (Stockholm, SE) Correspondence: Alisa A. Harbin; Chiron Corporation; Intellectual Property R440; P O Box 8097; Emeryville; CA; 946628097 Patent Application Number: 20020016445 Date filed: April 17, 1997
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Abstract: The present invention relates to compositions derived from immunoglobulin molecules specific for the hepatitis C virus (HCV). More particularly, the invention is related to molecules which are capable of specifically binding with HCV E2 antigen. The molecules are useful in specific binding assays, affinity purification schemes and pharmaceutical compositions for the prevention and treatment of HCV infection in mammalian subjects. The invention thus relates to novel human monoclonal antibodies specific for HCV E2 antigen, fragments of such monoclonal antibodies, polypeptides having structure and function substantially homologous to antigen-binding sites obtained from such monoclonal antibodies, nucleic acid molecules encoding those polypeptides, and expression vectors comprising the nucleic acid molecules. Excerpt(s): The present invention relates to compositions derived from immunoglobulin molecules specific for the hepatitis C virus (HCV). More particularly, the invention is related to recombinant human monoclonal antibodies which are capable of specifically binding with HCV E2 antigen. ... Hepatitis C virus (HCV) infection occurs throughout the world and is the major cause of transfusion-associated hepatitis. There are an estimated 150,000 new cases of HCV infection each year in the United States. The seroprevalence of anti-HCV antibodies in blood donors from around the world has been shown to vary between 0.02 and 1.23%, with rates in some countries as high as about 19%. In addition to being the predominate cause of transfusion-induced hepatitis, HCV is also a common cause of hepatitis in individuals exposed to blood or blood products. Thus, recipients of blood or blood products, intravenous drug users, renal dialysis patients and needle-stick victims represent high-risk groups for HCV infection. Alter et al. (1993) Infect Agents Dis 2:155-166. Further, heterosexual transmission of HCV across the urogenital tract, and mother-to-baby transmission, has been well documented. Ohto et al. (1994) N Engl J Med 330:744-750. Other risk factors associated with HCV infection include familial or household contact with an HCV-infected individual and health-care employment with occupational exposure to blood and hemodialysis. Alter et al. (1990) JAMA 264:2231-2235. Chronic hepatitis develops in approximately 62% of infections. Alter et al. (1992) N Engl J Med 327:1899-1905. ... The only currently available treatment for chronic hepatitis C infection consists of a-interferon (.alpha.-IFN) therapy. However, long-term response to interferon therapy only occurs in 10% to 30% of treated individuals, and there is evidence that the different HCV strains vary greatly in their responsiveness to interferon therapy, with the type 1 viruses being the most refractive. Furthermore, flu-like side effects are commonly encountered with interferon therapy (occurring in approximately 60% to
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80% of treated individuals), as well as other less common side effects such as nausea, depression, fatigue and thrombocytopenia. Interferon therapy is also not indicated for immunocompromised individuals. Accordingly, there exists a need for more effective therapeutic approaches in the treatment of chronic HCV infection. In this regard, some effect has been seen using ribivirin, or combination therapies with ursodiol and .alpha.-IFN. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·
Enzymatic nucleic acid treatment of disases or conditions related to hepatitis c virus infection Inventor(s): Blatt, Lawrence ; (Boulder, CO), McSwiggen, James A. ; (Boulder, CO), Roberts, Elisabeth ; (Federal Heights, CO), Pavo, Pamela A. ; (Lafayette, CO), Macejack, Dennis ; (Arvada, CO) Correspondence: McDonnell Boehnen Hulbert & Berghoff; 300 South Wacker Drive; Suite 3200; Chicago; IL; 60606; US Patent Application Number: 20020013458 Date filed: February 15, 2000 Abstract: Enzymatic nucleic acid molecules which modulate the expression and/or replication of hepatitis C virus (HCV). Excerpt(s): This patent application is a continuation-in-part of Blatt et al., U.S. Ser. No. 09/274,553, filed Mar. 22, 1999 and Blatt et al., U.S. Ser. No. 09/257,608, filed Feb. 24, 1999, which both claim the benefit of Blatt et al., U.S. Ser. No. 60/100,842, filed Sep. 18, 1998, and McSwiggen et al., U.S. Ser. No. 60/083,217 filed Apr. 27, 1998, all of these earlier applications are entitled "Enzymatic Nucleic Acid Treatment of Diseases or Conditions Related to Hepatitis C Virus Infection". Each of these applications are hereby incorporated by reference herein in their entirety including the drawings. ... This invention relates to methods and reagents for the treatment of diseases or conditions relating to the hepatitis C virus (HCV) infection. ... Chronic Hepatitis C is a slowly progressing inflammatory disease of the liver, mediated by a virus (HCV) that can lead to cirrhosis, liver failure and/or hepatocellular carcinoma over a period of 10 to 20 years. In the US, it is estimated that infection with HCV accounts for 50,000 new cases of acute hepatitis in the United States each year (NIH Consensus Development Conference Statement on Management of Hepatitis C March 1997). The prevalence of HCV in the United States is estimated at 1.8% and the CDC places the number of chronically infected Americans at approximately 4.5 million people. The CDC also estimates that up to 10,000 deaths per year are caused by chronic HCV infection.
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The prevalence of HCV in the United States is estimated at 1.8% and the CDC places the number of chronically infected Americans at approximately 4.5 million people. The CDC also estimates that up to 10,000 deaths per year are caused by chronic HCV infection. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·
Whole Blood/Mitogen Assay for the Early Detection of a Subject Infected with Hepatitis C Virus and Kit Inventor(s): Cohen, Tamar Jehuda. ; (Mercaz, IL) Correspondence: Eitan, Pearl, Latzer & Cohen-Zedek; One Crystal Park, Suite 210; 2011 Crystal Drive; Arlington; VA; 22202-3709; US Patent Application Number: 20020006608 Date filed: November 22, 1996 Abstract: This invention provides a method of detection of antibodies directed against Hepatitis C virus, comprising the following steps: a) obtaining a whole blood sample from the subject; b) incubating the whole blood sample in a culture in the presence of media containing mitogen, so as to induce polyclonal activation of lymphocytic cells to produce antibodies to Hepatitis C virus; c) exposing the resultant culture of step b) to a Hepatitis C virus antigen, thereby allowing an antigen-antibody immune complex to form; and d) detecting the presence of antigenantibody immune complex of step c); wherein the presence of Hepatitis C virus specific antibodies is indicative of the subject being exposed to Hepatitis C virus.Lastly, this invention provides a kit for the detection of specific Hepatitis C virus specific antibodies from the subject. Excerpt(s): Hillings et al. reported on the transmission of non-A, non-B hepatitis (presumably hepatitis C) to chimpanzees by inoculation with leucocytes, most probably T leucocytes, derived from either acutely or chronically infected patents or chimpanzees (Hellings, J. A. et al., J. Virol. Methods, 1985). ... Lastly, this invention provides a kit for the detection of specific Hepatitis C virus antibodies from the subject. ... The present invention relates to an improved assay for detecting a subject infected with Hepatitis C virus. This invention is contemplated for use as: 1) a diagnostic to determine if an individual has been infected with Hepatitis C virus, 2) a prognostic indicator, and 3) a method to monitor the effectiveness of anti-viral treatment (or effectiveness of a new potential anti-Hepatitis C virus drug. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Hepatitis C virus asialoglycoproteins Inventor(s): Ralston, Robert O. ; (Danville, CA), Marcus, Frank ; (Danville, CA), Thudium, Kent B. ; (Oakland, CA), Gervase, Barbara A. ; (Vallejo, CA), Hall, John A. ; (Rohnert Park, CA), Berger, Kim M. ; (Lafayette, CA), Choo, Qui-Lim ; (El Cerrito, CA), Houghton, Michael ; (Danville, CA), Kuo, George ; (San Francisco, CA) Correspondence: Chiron Corporation; Intellectual Property; P.O. Box 8097; Emeryville; CA; 94662-8097; US Patent Application Number: 20020004048 Date filed: August 13, 2001 Abstract: Two Hepatitis C Virus envelope proteins (E1 and E2) are expressed without sialylation. Recombinant expression of these proteins in lower eukaryotes, or in mammalian cells in which terminal glycosylation is blocked, results in recombinant proteins which are more similar to native HCV glycoproteins. When isolated by GNA lectin affinity, the E1 and E2 proteins aggregate into virus-like particles. Excerpt(s): This invention relates to the general fields of recombinant protein expression and virology. More particularly, the invention relates to glycoproteins useful for diagnosis, treatment, and prophylaxis of Hepatitis C virus (HCV) infection, and methods for producing such glycoproteins. ... Non-A, Non-B hepatitis (NANBH) is a transmissible disease (or family of diseases) that is believed to be virally induced, and is distinguishable from other forms of virus-associated liver disease, such as those caused by hepatitis A virus (HAV), hepatitis B virus (HBV), delta hepatitis virus (HDV), cytomegalovirus (CMV) or Epstein-Barr virus (EBV). Epidemiologic evidence suggests that there may be three types of NANBH: the water-borne epidemic type; the blood or needle associated type; and the sporadically occurring community acquired type. The number of causative agents is unknown. However, a new viral species, hepatitis C virus (HCV) has recently been identified as the primary (if not only) cause of blood-borne NANBH (BB-NANBH). See for example PCT W089/046699 and U.S. patent application Ser. No. 07/355,002, filed May. 18 1989.Hepatitis C appears to be the major form of transfusionassociated hepatitis in a number of countries or regions, including the United States, Europe, and Japan. There is also evidence implicating HCV in induction of hepatocellular carcinoma. Thus, a need exists for an effective method for preventing and treating HCV infection. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for treating hepatitis C Inventor(s): Graves, Mary ; (Welwyn Garden City, GB), Pappas, Stephen C. ; (Clifton, NJ), Zahm, Friederike ; (Freiburg, DE) Correspondence: Hoffmann-La Roche Inc.; Patent Law Department; 340 Kingsland Street; Nutley; NJ; 07110 Patent Application Number: 20010046957 Date filed: June 20, 2001 Abstract: A method of treating a patient infected with a hepatitis C virus to decrease the severity of the viral infection. The method comprises concomitantly administering over a given period of time to the patient a first component and a second component. The first component consists of a pharmaceutical composition containing as an active ingredient a pharmaceutically acceptable salt or prodrug of mycophenolic acid in a therapeutically effective amount to decrease the severity of the viral infection. The second component consists of an injection solution containing as an active ingredient interferon-.alpha. or pegylated interferon-.alpha. in a therapeutically effective amount to decrease the severity of the viral infection. The components are concomitantly administered over a period of time at least sufficient to reduce the amount of HCV-RNA present in the peripheral blood of said patient to less than 100 copies/ml at 24 weeks after the end of treatment. Excerpt(s): The invention relates to the field of treating liver diseases, in particular hepatitis C infections, by administering (i) interferon-.alpha. or pegylated interferon-.alpha. and (ii) a pharmaceutically acceptable salt or a prodrug of mycophenolic acid. ... Hepatitis C virus (HCV) is a liver damaging infection that can lead to cirrhosis, liver failure or liver cancer. It is currently estimated that there are 170 -200 million people infected with this virus worldwide. ... In accordance with the present invention, administration of the two components synergistically enhances the treatment of hepatitis C provided by administering each component separately. The synergistic effect results in a sustained response. By "sustained response" is meant that the amount of HCV in peripheral blood set forth as copies of HCV-RNA in peripheral blood is less than 100 copies/ml, for example when measured at 24 weeks after the end of administration of the two components. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Keeping Current In order to stay informed about patents and patent applications dealing with hepatitis C, you can access the U.S. Patent Office archive via the Internet at no cost to you. This archive is available at the following Web address: http://www.uspto.gov/main/patents.htm. Under “Services,” click on “Search Patents.” You will see two broad options: (1) Patent Grants, and (2) Patent Applications. To see a list of granted patents, perform the following steps: Under “Patent Grants,” click “Quick Search.” Then, type “hepatitis C” (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 C. You can also use this procedure to view pending patent applications concerning hepatitis C. Simply go back to the following Web address: http://www.uspto.gov/main/patents.htm. Under “Services,” click on “Search Patents.” Select “Quick Search” under “Patent Applications.” Then proceed with the steps listed above.
Vocabulary Builder 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] Asialoglycoproteins: Endogenous glycoproteins from which sialic acid has been removed by the action of sialidases. They bind tightly to their cell surface receptor which is located on hepatocyte plasma membranes. After internalization by adsorptive endocytosis they are delivered to lysosomes for degradation. Therefore receptor-mediated clearance of asialoglycoproteins is an important aspect of the turnover of plasma glycoproteins. They are elevated in serum of patients with hepatic cirrhosis or hepatitis. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Bromovirus: A genus of tripartite plant viruses in the family bromoviridae. Transmission is by beetles. [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] Conjugated: Acting or operating as if joined; simultaneous. [EU] Counterimmunoelectrophoresis: Immunoelectrophoresis in which immunoprecipitation occurs when antigen at the cathode is caused to
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migrate in an electric field through a suitable medium of diffusion against a stream of antibody migrating from the anode as a result of endosmotic flow. [NIH]
Cucumovirus: A genus of plant viruses of the family bromoviridae, which infect cucurbits and solanaceous plants. Transmission occurs via aphids in a non-persistent manner, and also via seeds. The type species cucumber mosaic virus, a cucumovirus, should not be confused with cucumber green mottle mosaic virus, a tobamovirus. [NIH] Diffusion: The process of becoming diffused, or widely spread; the spontaneous movement of molecules or other particles in solution, owing to their random thermal motion, to reach a uniform concentration throughout the solvent, a process requiring no addition of energy to the system. [EU] Endogenous: Developing or originating within the organisms or arising from causes within the organism. [EU] 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 health-related event occurring in such outbreaks. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. [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] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [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] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hyperthermia: Abnormally high body temperature, especially that induced for therapeutic purposes. [EU] Ilarvirus: A genus of the family bromoviridae which infects mainly woody
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plants. Species are divided into ten subgroups. Tobacco streak virus is the type species. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] 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] Lymphocytic: Pertaining to, characterized by, or of the nature of lymphocytes. [EU] 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] Polyproteins: Proteins which are synthesized as a single polymer and then cleaved into several distinct proteins. [NIH] Potexvirus: A genus of plant viruses that cause mosaic and ringspot symptoms. Transmission occurs mechanically. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU]
Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [NIH]
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CHAPTER 6. BOOKS ON HEPATITIS C Overview This chapter provides bibliographic book references relating to hepatitis C. You have many options to locate books on hepatitis C. The simplest method is to go to your local bookseller and inquire about titles that they have in stock or can special order for you. Some patients, however, feel uncomfortable approaching their local booksellers and prefer online sources (e.g. www.amazon.com and www.bn.com). In addition to online booksellers, excellent sources for book titles on hepatitis C include the Combined Health Information Database and the National Library of Medicine. Once you have found a title that interests you, visit your local public or medical library to see if it is 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 to 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 C” (or synonyms) into the “For these words:” box. You will only receive results on books. You should check back periodically with this database which is updated every 3 months. The following is a typical result when searching for books on hepatitis C:
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Hepatitis C Contact: Hazelden Foundation, Educational Materials, PO Box 176, Center City, MN, 55012-0176, (651) 213-4000, http://www.hazelden.org. Summary: This monograph, for individuals with hepatitis C, discusses living and coping with this infectious disease. The monograph provides facts about hepatitis C transmission, diagnosis, symptoms, drug treatment, and high-risk groups. It presents a spiritual program to help individuals cope with the emotional effects of living with hepatitis C. It also discusses the importance of good nutrition, liver transplantation, and complementary and alternative treatments for hepatitis C.
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Living With Hepatitis C: A Survivor's Guide Contact: Hatherleigh Press, 5-22 46 Ave Ste 200, Long Island City, NY, 11101, (800) 367-2550, http://www.hatherleigh.com. Summary: This monograph, for individuals with hepatitis C, offers guidance and answers for individuals infected with hepatitis C. It provides guidance and answers to individuals infected with hepatitis C, their friends and family. It discusses the nature of the disease and how it affects the body; how to understand blood tests and biopsies; how to avoid infecting others; healthy nutrition; what to expect if a liver transplant is needed; how to deal with emotions and grief; children with Hepatitis C; how an individual can protect him/herself from enormous medical costs; and what to expect in the future regarding new research and new drugs.
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Management of Hepatitis C: NIH Consensus Development Conference Program and Abstracts Source: Bethesda, MD: National Institutes of Health. 1997. 139 p. Contact: Available from NIH Consensus Program Information Center. P.O. Box 2577, Kensington, MD 20891. (888) 644-2667. Fax (301) 816-2494. Price: Single copy free. Summary: This document presents abstracts of the NIH Consensus Development Conference on the Management of Hepatitis C, held in March 1997 in Bethesda, Maryland. It notes the conference's agenda, panel, speakers, and planning committee members. The document was designed for the use of panelists and participants in the conference and as a pertinent reference document for anyone interested in the conference deliberations. The abstracts are presented in four sections: the natural history of hepatitis C, diagnostic considerations, the epidemiology and spread of hepatitis C, and therapeutic issues. Specific topics covered
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include the clinical spectrum of disease, blood donors with hepatitis C, hepatitis C and hepatocellular carcinoma (liver cancer), hepatitis C and alcohol, diagnostic tests for hepatitis C, the role of liver biopsy, the epidemiology of hepatitis C, the sexual and perinatal spread of hepatitis C virus infection, the use of interferon alfa-2b, ribavirin treatment, drug side effects, predictive factors for a beneficial response to drug therapy in hepatitis C, the treatment of patients with liver cirrhosis, retreatment with interferon, and cost effectiveness considerations. Each abstract includes brief references. ·
Hepatitis C Handbook Source: Berkeley, CA: North Atlantic Books and Frog, Ltd. 1999. 473 p. Contact: Available from North Atlantic Books and Frog, Ltd. P.O. Box 12327, Berkeley, CA 94712. (800) 337-2665 or (510) 559-8277. Fax (510) 5598279. E-mail:
[email protected]. Website: www.northatlanticbooks.com. Price: $25.00 plus shipping and handling. ISBN: 1556433131. Summary: Hepatitis C is a common, recently discovered viral infection usually contracted from the use of intravenous drugs, often decades previously, or less commonly by blood or blood products prior to the introduction of blood screening protocols. This handbook offers an overview of hepatitis C virus (HCV) and focuses on the significance of the diagnosis and on lifestyle changes that may prove helpful. The author guides the patient to an informed and balanced choice between the currently available range of treatment options, including interferon and other antiviral agents as well as Chinese herbal remedies. The author hopes to empower readers and so provides detailed medical information about symptoms, lifestyle changes, real life experiences with the disease, and treatment strategies. The first chapter offers facts and figures about the virus and its prevalence; transmission, epidemiology, and the origins of the virus are discussed in Chapter 2, along with professional briefings regarding the prevention of the further proliferation of HCV. Information regarding the various tests that patients are likely to encounter are covered in Chapter 3, together with a discussion of the implications of a diagnosis and whether or not to get tested. Other chapters in the first section cover special situations, including coinfection with other types of hepatitis, children, hemophilia, and Cooley's anemia. The second section offers three chapters that concentrate on the response to having HCV. This section is designed to enable the reader to go through the process of coming to terms with their condition, to better participate as a member of their own health care team, and to deal with members of the medical profession. The third section summarizes the main treatment options
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open to HCV patients. Chapters cover conventional treatments, traditional Chinese medicine, Western herbal medicine (including medicinal mushrooms), Ayurvedic medicine, vitamins and minerals (and amino acids), homeopathy, miscellaneous treatments, and naturopathy (the 'no treatment' option). The fourth section covers lifestyle options, including diet, alcohol, drugs, exercise, yoga, Qu Gong, and stress management. The final section offers a wealth of resources for readers, including additional technical information, a glossary, a list of resources, and a subject index. Each chapter also includes references. ·
Hepatitis C: From Pathogenesis to Prognosis Source: Thousand Oaks, CA: Amgen, Inc. 1997. 32 p. Contact: Available from Amgen Professional Services. 1840 DeHavilland Drive, Thousand Oaks, CA 91320-1789. (800) 77-AMGEN. Price: Single copy free to health professionals. Summary: This document summarizes the current understanding of hepatitis C virus (HCV), from its pathogenesis to present research on treatment and cure options. HCV infection results in a chronic disease state in 50 to 70 percent of cases and is now the most common cause of chronic liver disease in the United States. It is highly infectious; known routes of transmission include blood and blood products, injection drug use, and sexual contacts. The virus has been cloned and is now well characterized with respect to both structural and nonstructural proteins. Molecular cloning technology has resulted in the development of specific and sensitive screening, diagnostic, and monitoring assays for HCV. In addition, tests to determine the quantity of viral RNA in blood and to define areas of the viral genome have been developed. Both viral load and genome have been suggested to be predictive of patient response to therapy. Other factors associated with response to treatment include age, presence of iron overload, duration of infection, mode of transmission, and the level of serum bile salts. The development of effective vaccines against hepatitis C is difficult, in part because of the quasispecies nature of HCV. The authors conclude that increased knowledge of the epidemiology and natural history of hepatitis C, coupled with greater understanding of how these diagnostic assays can guide the use of available and future therapies, is crucial in combatting this disease. 8 figures. 4 tables. 53 references. (AA-M).
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Hepatitis C: Diagnostic Techniques and Monitoring Strategies Source: Thousand Oaks, CA: Amgen, Inc. 1997. 32 p.
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Contact: Available from Amgen Professional Services. 1840 DeHavilland Drive, Thousand Oaks, CA 91320-1789. (800) 77-AMGEN. Price: Single copy free to health professionals. Summary: This document summarizes the present diagnostic techniques and monitoring strategies used as part of the management of hepatitis C virus (HCV). HCV infection results in a chronic disease state in 50 to 70 percent of cases and is now the most common cause of chronic liver disease in the United States. It is highly infectious; known routes of transmission include blood and blood products, injection drug use, and sexual contacts. The virus has been cloned and is now well characterized with respect to both structural and nonstructural proteins. Molecular cloning technology has resulted in the development of specific and sensitive screening, diagnostic, and monitoring assays for HCV. In addition, tests to determine the quantity of viral RNA in blood and to define areas of the viral genome have been developed. Both viral load and genome have been suggested to be predictive of patient response to therapy. The authors review HCV diagnostic and monitoring tests, including liver enzymes, serological assays, virological assays, genotyping and serotyping, and liver biopsy. The discovery of antibodies to HCV or elevated ALT in a patient with or without symptoms of liver disease frequently culminates in the diagnosis of hepatitis C. The sequence of tests used to confirm the diagnosis may depend on the patient's known risk factors and the type of test (ALT, anti-HCV, or both) that initially established the likelihood of infection. The authors conclude that once the diagnosis of HCV infection is confirmed, determination of the presence or absence of cirrhosis, HCV RNA concentration, and genotype or serotype are important predictive factors in determining which patients are most likely to respond to therapy. 8 figures. 8 tables. 66 references. (AA-M).
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes & Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in PrintÒ). The following have been recently listed with online booksellers as relating to hepatitis C (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com):
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Viral Hepatitis C, d and E: Proceedings of the International Meeting on Non-A, Non-B Hepatitis, Tokyo, 27-30 September, 1989 (International Congress) by Toshio Shikata, et al (1991); ISBN: 0444811176; http://www.amazon.com/exec/obidos/ASIN/0444811176/icongroupin terna
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Hepatitis C by G. Csmos, et al (1994); ISBN: 0387548238; http://www.amazon.com/exec/obidos/ASIN/0387548238/icongroupin terna
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Recent Advances in the Study of Hepatitis C Virus (Intervirology, Vol 37, No 2) by O. Hino (Editor) (1994); ISBN: 3805560591; http://www.amazon.com/exec/obidos/ASIN/3805560591/icongroupin terna
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Hepatitis C Virus (Current Studies in Hematology and Blood Transfusion, No 61) by H.W. Reesink (Editor) (1994); ISBN: 380555866X; http://www.amazon.com/exec/obidos/ASIN/380555866X/icongroupi nterna
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Hepatitis C: Directory of New Medical & Scientific Reviews With Subject Index by Science, Life Consults (1995); ISBN: 0788305700; http://www.amazon.com/exec/obidos/ASIN/0788305700/icongroupin terna
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Natural Liver Therapy by Christopher Hobbs, et al (1997); ISBN: 0961847026; http://www.amazon.com/exec/obidos/ASIN/0961847026/icongroupin terna
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Hepatitis C Protocols (Methods in Molecular Medicine, No 19) by Johnson Y. N. Lau (Editor) (1998); ISBN: 0896035212; http://www.amazon.com/exec/obidos/ASIN/0896035212/icongroupin terna
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Hepatitis C: The Silent Killer by Carol Turkington, et al (1998); ISBN: 0809229587; http://www.amazon.com/exec/obidos/ASIN/0809229587/icongroupin terna
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Hepatitis C: The Silent Epidemic by Carol Turkington (1999); ISBN: 0809229579; http://www.amazon.com/exec/obidos/ASIN/0809229579/icongroupin terna
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Hepatitis C: A Personal Guide to Good Health by Beth Ann Petro Roybal, Emmet B. Keeffe (Introduction) (1999); ISBN: 1569751838; http://www.amazon.com/exec/obidos/ASIN/1569751838/icongroupin terna
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The Hepatitis C Handbook by Matthew Dolan, et al (1999); ISBN: 1556433131; http://www.amazon.com/exec/obidos/ASIN/1556433131/icongroupin terna
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Hepatitis C (A Volume in the Biomedical Research Reports) by T. Jake Liang (Editor), et al (2000); ISBN: 0124478700; http://www.amazon.com/exec/obidos/ASIN/0124478700/icongroupin terna
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My Mom Has Hepatitis C by Hedy Weinberg, et al (2000); ISBN: 1578260752; http://www.amazon.com/exec/obidos/ASIN/1578260752/icongroupin terna
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Living With Hepatitis C: Everything You Need to Know (Your Personal Health) by Jenny Heathcote (Editor), et al (2001); ISBN: 1552096122; http://www.amazon.com/exec/obidos/ASIN/1552096122/icongroupin terna
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The Hepatitis C Help Book: A Groundbreaking Treatment Program Combining Western and Eastern Medicine for Maximum Wellness and Healing by Misha Ruth Cohen, et al (2001); ISBN: 0312263368; http://www.amazon.com/exec/obidos/ASIN/0312263368/icongroupin terna
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Living with Hepatitis C: A Survivor's Guide, Third Revised Edition by Gregory T. Everson, Hedy Weinberg (2002); ISBN: 1578261082; http://www.amazon.com/exec/obidos/ASIN/1578261082/icongroupin terna
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Bible Cure for Hepatitis C (Bible Cure Series) by Don, MD Colbert (2002); ISBN: 0884198294; http://www.amazon.com/exec/obidos/ASIN/0884198294/icongroupin terna
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Hepatitis C Virus: From Laboratory to Clinic by Mark A. Feitelson (2002); ISBN: 0521799597; http://www.amazon.com/exec/obidos/ASIN/0521799597/icongroupin terna
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
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LOCATORplus.” Once you are in the search area, simply type “hepatitis C” (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:28 ·
Anti-HCV commercial panel data: comparative performance data for anti-HCV assays using commercial seroconversion and other panels. Author: Keith R. Perry ... [et al.]; Year: 1999; London: Medical Devices Agency, c1999; ISBN: 1841820806
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Antiviral therapy for chronic hepatitis C. Author: J. C. Smith, N. L. Greer; Year: 1998; Minneapolis, MN: ICSI, 1998
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C-change: report of the enquiry into hepatitis C related discrimination. Author: New South Wales. Anti-Discrimination Board; Year: 2001; [Sydney]; The Board, [2001]; ISBN: 0731353870
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Chronic hepatitis: new concepts of pathogenesis, diagnosis and treatment: proceedings of the Falk Workshop held in Cologne, Germany, 27-28 January 2000. Author: edited by H.P. Dienes ... [et al.]; Year: 2000; Dordrecht; Boston: Kluwer Academic, c2000; ISBN: 0792387635 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/0792387635/icongroupin terna
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Combination therapy (ribavirin and interferon alfa) to replace interferon alfa alone for the treatment of patients with moderate hepatitis C. Author: Wessex Institute for Health Research and Development; Year: 1999; Bristol, UK: South and West Regional Health Authority, 1999
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Critical issues in gastroenterology. Author: edited by Gary Gitnick; Year: 1998; Baltimore, Md.: Williams & Wilkins, c1998; ISBN: 0683305557 http://www.amazon.com/exec/obidos/ASIN/0683305557/icongroupin terna
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HCV and related liver diseases. Author: K. Okita, (ed.); Year: 1999; Toyko; New York: Springer, c1999; ISBN: 4431702350 (alk. paper)
In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is 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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http://www.amazon.com/exec/obidos/ASIN/4431702350/icongroupin terna ·
Health emergency 2001: the spread of drug-related AIDS and hepatitis C among African Americans and Latinos. Author: Dawn Day, with a forewrod by Joycelyn Elders; Year: 2001; Princeton, NJ: Dogwood Center, [2001]
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Hepatitis & health: a survey of high school students in New South Wales. Author: Paul Van de Ven ... [et al.]; Year: 2001; Sydney, NSW: National Centre in HIV Social Research, Faculty of Arts and Social Sciences, University of New South Wales, c2001; ISBN: 1875978453
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Hepatitis B and C: management and treatment. Author: Thierry Poynard; Year: 2002; London: Martin Dunitz; Florence, KY: Distributed in the USA by Taylor & Francis, 2002; ISBN: 1841840777 http://www.amazon.com/exec/obidos/ASIN/1841840777/icongroupin terna
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Hepatitis C: an Australian perspective. Author: edited by Nick Crofts, Greg Dore, Stephen Locarnini; Year: 2001; Melbourne: IP Communications, 2001; ISBN: 0957861729
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Hepatitis C: biomedical research reports. Author: volume editor[s], Jake T. Liang, Jay H. Hoofnagel; Year: 2000; San Diego: Academic Press, 2000; ISBN: 0124478700 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/0124478700/icongroupin terna
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Hepatitis C protocols. Author: edited by Johnson Yui-Nam Lau; forewords by T. Jake Liang ... [et al.]; Year: 1998; Totowa, N.J.: Humana Press, c1998; ISBN: 0896035212 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/0896035212/icongroupin terna
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Hepatitis C viral load testing: assessment report. Author: [prepared by Medicare Services Advisory Committee (MSAC)]; Year: 2000; Canberra: Medicare Services Advisory Committee, Dept. of Health and Aged Care, c2000; ISBN: 0642446490
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Hepatitis C virus: from laboratory to clinic. Author: Mark A. Feitelson; Year: 2002; Cambridge; New York: Cambridge University Press, 2002; ISBN: 0521799597 (pbk.) http://www.amazon.com/exec/obidos/ASIN/0521799597/icongroupin terna
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Hepatitis C virus. Author: volume editor, H.W. Reesink; Year: 1998; Basel; New York: Karger, 1998; ISBN: 3805565429 (hardcover: alk. paper) http://www.amazon.com/exec/obidos/ASIN/3805565429/icongroupin terna
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Hepatitis C viruses. Author: edited by C.H. Hagedorn and C.M. Rice; Year: 2000; Berlin; New York: Springer, c2000; ISBN: 3540653589 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/3540653589/icongroupin terna
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Hepatitis C, silent epidemic, mute public health response: seventh report by the Committee on Government Reform and Oversight. Author: United States. Congress. House. Committee on Government Reform and Oversight; Year: 1998; Washington: U.S. G.P.O., 1998
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Hepatitis C, the silent epidemic: the authoritative guide. Author: Fred K. Askari; illustrations by Daniel S. Cutler; Year: 1999; New York: Kluwer Academic / Plenum, c1999; ISBN: 0306460122 http://www.amazon.com/exec/obidos/ASIN/0306460122/icongroupin terna
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Herbs for hepatitis C and the liver. Author: Stephen Harrod Buhner; Year: 2000; Pownal, Vt.: Storey Books, c2000; ISBN: 1580172555 (pbk.) http://www.amazon.com/exec/obidos/ASIN/1580172555/icongroupin terna
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Management of chronic viral hepatitis. Author: edited by Stuart C. Gordon; Year: 2002; New York: M. Dekker, c2002; ISBN: 0824705823 (alk. paper) http://www.amazon.com/exec/obidos/ASIN/0824705823/icongroupin terna
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Management of hepatitis C: January 1989 through January 1997: 2200 citations. Author: prepared by Ronald L. Gordner, Tommie Sue Tralka; Year: 1997; Bethesda, Md. (8600 Rockville Pike): U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, National Library of Medicine, Reference Section; Pittsburgh, PA.: Sold by the Supt. of Docs., U.S. G.P.O., 1997
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Non-responding hepatitis C patient: options and variables. Author: edited by Bruce R. Bacon; Year: 2000; London: Royal Society of Medicine Press, c2000; ISBN: 1853154377
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Nucleic acid amplification technology (NAT) for the detection of hepatitis C virus (HCV) in plasma pools: validation report. Author: Giulio Pisani ... [et al.]; Year: 2000; Roma: Istituto superiore di sanità, c2000
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Public health 2000 [microform]: hepatitis C--the silent epidemic: hearing before the Subcommittee on Human Resources of the Committee on Government Reform and Oversight, House of Representatives, One Hundred Fifth Congress, second session, March 5, 1998. Author: United States. Congress. House. Committee on
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Government Reform and Oversight. Subcommittee on Human Resources; Year: 1998; Washington: U.S. G.P.O.: For sale by the U.S. G.P.O., Supt. of Docs., Congressional Sales Office, 1998; ISBN: 0160572347 http://www.amazon.com/exec/obidos/ASIN/0160572347/icongroupin terna ·
Report of the Tribunal of Inquiry into the Blood Transfusion Service Board. Author: Ireland. Tribunal of Inquiry into the Blood Transfusion Service Board; Year: 1997; Dublin: Stationery Office, c1997; ISBN: 0707638372 http://www.amazon.com/exec/obidos/ASIN/0707638372/icongroupin terna
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Reproductive care of women living with hepatitis C infection. Author: Principal authors: Marc Boucher, Andrée Gruslin; Year: 2000; Ottawa, ON: SOGC, 2000
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Surveillance and prevention of hepatitis C infection in Australian prisons: a discussion paper. Author: Kate Dolan; Year: 2000; [Kensington, N.S.W.]: National Drug and Alcohol Research Centre, [2000]; ISBN: 0733407099
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Through the looking glass: the health and socioeconomic status of hepatitis C positive transfusion recipients, 1986-1990. Author: Robert S. Hogg ... [et al.]; Year: 1999; Vancouver, BC: Centre for Health Evaluation & Outcome Sciences, [1999?]
Chapters on Hepatitis C Frequently, hepatitis C will be discussed within a book, perhaps within a specific chapter. In order to find chapters that are specifically dealing with hepatitis C, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and hepatitis C using the “Detailed Search” option. Go directly 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.” By making these selections and typing in “hepatitis C” (or synonyms) into the “For these words:” box, you will only receive results on chapters in books. The following is a typical result when searching for book chapters on hepatitis C:
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Hepatitis C Source: in Hagan, P.T., ed. Mayo Clinic Guide to Self-Care: Answers for Everyday Health Problems. New York, NY: Kensington Publishers. 1999. p. 178-179. Contact: Available from Mayo Clinic. 200 First Street, S.W., Rochester, MN 55905. (800) 291-1128 or (507) 284-2511. Fax (507) 284-0161. Website: www.mayo.edu. Price: $16.95 plus shipping and handling. ISBN: 0962786578. Summary: This chapter on hepatitis C is from a self care handbook on everyday health problems published by the Mayo Clinic. The handbook offers readers a guide to symptoms, diagnosis, and treatment for common problems (particularly self care strategies and tips for handling these problems in children). Hepatitis C is a virus that causes inflammation of the liver. Nearly 4 million Americans have the virus, but many of them don't know it as the symptoms can be very subtle. Generally, hepatitis C is spread through contact with blood contaminated with the virus (in rare cases, it's transmitted sexually). About 15 to 20 percent of people infected with hepatitis C fight off the virus on their own without liver damage. For the rest, the disease settles in and slowly attacks the liver. Anywhere from 20 to 50 percent of people with chronic hepatitis develop cirrhosis (scarring) of the liver, usually within the first 2 decades after infection. Ultimately, liver cancer or liver failure occurs in about half of those people who develop cirrhosis. Recommended lifestyle changes for people with hepatitis C can include eliminating alcohol consumption, avoiding medications that may carry a risk of liver damage, and maintaining a healthful lifestyle (diet, exercise, and rest). One section discusses the use of interferon alpha, a drug that inhibits viral replication and that can be effective in approximately 20 percent of people with hepatitis C. One sidebar reviews the people who should be tested or screened for hepatitis C. The book is focused on how to prevent illness, how to detect illness before it becomes a serious and costly problem, and how to avoid unnecessary trips to the clinic or emergency room.
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What Is Hepatitis C?: An Introduction Source: in Everson, G.T. and Weinberg, H. Living with Hepatitis C: A Survivor's Guide. New York, NY: Hatherleigh Press. 1999. p. 1-14. Contact: Available from Hatherleigh Company, Ltd. 1114 First Avenue, Suite 500, New York, NY 10021. (800) 367-2550 or (212) 832-1039. Website: hatherleigh.com. Price: $14.95 plus shipping and handling. ISBN: 1578260345.
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Summary: Hepatitis C is a viral infection that causes inflammation, injury, and ultimately scarring of the liver (cirrhosis). This chapter introducing hepatitis C is from a book that offers information and guidance for people living with hepatitis C. The authors explain in nontechnical language some basic facts and statistics about hepatitis C, its history and discovery, and information about viruses and other forms of viral hepatitis. Hepatitis C is primarily a blood to blood virus, so loved ones cannot easily be infected by the patient with hepatitis C. However, hepatitis C can put a heavy strain on relationships. The authors portray the hepatitis C virus as a slow moving time bomb that can lurk in the liver for decades, silently injuring the liver and setting the stage for complications. The earlier the diagnosis, the better the choices that are available for long term care and supportive measures such as good nutrition. The chapter concludes with information about research into a potential cure for hepatitis C. The chapter includes lengthy quotes from patients with hepatitis, which offer the patients' perspectives, insights, and experiences to the reader. 1 figure. 1 reference. ·
Treatment for Hepatitis C: The Interferon Story and Ribavirin Source: in Everson, G.T. and Weinberg, H. Living with Hepatitis C: A Survivor's Guide. New York, NY: Hatherleigh Press. 1999. p. 128-147. Contact: Available from Hatherleigh Company, Ltd. 1114 First Avenue, Suite 500, New York, NY 10021. (800) 367-2550 or (212) 832-1039. Website: hatherleigh.com. Price: $14.95 plus shipping and handling. ISBN: 1578260345. Summary: Hepatitis C is a viral infection that causes inflammation, injury, and ultimately scarring of the liver (cirrhosis). This chapter reviewing the treatments for hepatitis C is from a book that offers information and guidance for people living with hepatitis C. Patients living with chronic hepatitis C may experience fatigue, a loss of energy, loss of concentrating ability, and a sense of inadequacy in performing their daily activities. The authors explain in nontechnical language some of the issues that hepatitis C patients must consider as they undertake treatment for the disease. Topics include interferon monotherapy, the types of interferon, measuring response to interferon, ribavirin, patient selection for mono or combination therapy, the patient's experience (injections, interferon side effects, ribavirin side effects), treatment tips from patients, and information for nonresponders. The author encourages all patients to remain physically active, pursue their occupation, socialize, and maintain proper nutrition, regardless of other treatment choices. For responders, a sustained response is the most desirable outcome after interferon treatment. Most patients with a
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sustained response have cleared the virus from their blood and have improvement in their liver biopsy. However, general medical advice includes ongoing physical examinations by a physician and biochemical tests of liver function. The chapter includes quotes from patients with hepatitis, which offer the patients' perspectives, insights, and experiences to the reader. 3 figures. 1 reference. ·
HIV-AIDS and Hepatitis C Co-Infection: Double Trouble Source: in Everson, G.T. and Weinberg, H. Living with Hepatitis C: A Survivor's Guide. New York, NY: Hatherleigh Press. 1999. p. 186-198. Contact: Available from Hatherleigh Company, Ltd. 1114 First Avenue, Suite 500, New York, NY 10021. (800) 367-2550 or (212) 832-1039. Website: hatherleigh.com. Price: $14.95 plus shipping and handling. ISBN: 1578260345. Summary: Hepatitis C is a viral infection that causes inflammation, injury, and ultimately scarring of the liver (cirrhosis). This chapter addressing hepatitis C and HIV coinfection is from a book that offers information and guidance for people living with hepatitis C. The authors explain in nontechnical language some of the issues that patients with HIV must struggle with after they learn they also have hepatitis C. The author notes that until a few years ago, doctors did not focus on treating hepatitis C in people with AIDS because patients had limited years to live and interferon treatment affected the immune system. Now the introduction of new AIDS drugs has produced a growing number of HIV infected patients with strengthened immune systems who are enjoying longer lifespans. Topics include a definition of HIV and AIDS, risk factors for co infection, testing considerations and problems, population trends, the treatment of HIV infection with highly active antiretroviral therapies (HAART), the complications of therapy in coinfection, how coinfection affects the rate of progression of liver disease, antiviral therapy of hepatitis C for coinfected patients, and liver transplantation. The chapter includes lengthy quotes from patients with hepatitis and HIV, which offer the patients' perspectives, insights, and experiences to the reader. 1 figure.
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Hepatitis C Virology: Antigen, Antibody, and Molecular Testing Source: in Gordon, S.C. Management of Chronic Viral Hepatitis. New York, NY: Marcel Dekker Inc. 2002. p. 33-64. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. Website:
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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. 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 authors focus on antigen, antibody, and molecular testing for hepatitis C virology. The case patient is a 54 year old male physician with a history of acute myelogenous leukemia who received multiple transfusions in August 1989 who developed abnormal liver chemistries in March 1990. Serological (blood) testing revealed that he was anti-HCV negative by the ELISA 1 assay; anti-HAV (total) was positive, but anti HAV IgM was negative. HBsAg and anti HBc were negative and anti HBs positive. Both the antinuclear antibodies (ANA) and the anti smooth muscle antibody tests were negative. This case illustrates a number of points that relate to the history of the hepatitis C virus and its associated serological assays. The first generation test for anti HCV was released in the United States in May 1990, although it was available in Europe as early as 1989. This patient had hepatitis C in 1990, but it was not until later with the development of more refined assays that his serological profile became defined. Later, as the patient underwent treatment with antiviral agents, the development of increasingly more sophisticated molecular based assays assisted in his clinical management. 11 figures. 2 tables. 53 references. ·
When You Have Hepatitis C, Understanding the Diagnosis: Blood Tests and Biopsies Source: in Everson, G.T. and Weinberg, H. Living with Hepatitis C: A Survivor's Guide. New York, NY: Hatherleigh Press. 1999. p. 15-30. Contact: Available from Hatherleigh Company, Ltd. 1114 First Avenue, Suite 500, New York, NY 10021. (800) 367-2550 or (212) 832-1039. Website: hatherleigh.com. Price: $14.95 plus shipping and handling. ISBN: 1578260345. Summary: Hepatitis C is a viral infection that causes inflammation, injury, and ultimately scarring of the liver (cirrhosis). This chapter discussing the diagnosis of hepatitis C is from a book that offers information and guidance for people living with hepatitis C. The authors explain in nontechnical language some basic facts about the testing process for hepatitis C from diagnosis through the years of ongoing care. Diagnostic tests described include: ELISA I, ELISA II, and III; RIBA; HCV RNA assays; PCR quantitative assay; branched chain DNA assay;
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genotyping and quasispecies; radiologic imaging; ultrasound; CT scan; and liver biopsy. The authors also discuss testing limits, interpreting biopsy results, and monitoring tests, including liver enzymes, bilirubin, albumin, clotting factors, and complete blood count (CBC). The authors note that one predictor of response to therapy may be the number of quasispecies of hepatitis C circulating in the patient's blood. The virus mutates freely, so patients often have multiple copies of the hepatitis C virus that vary genetically; these are called quasispecies. In addition, the subtypes of hepatitis C respond differently to therapy, so it can be useful to have the subtype diagnosed. The authors recognize that many readers fear even the word 'biopsy,' but they stress that only a biopsy can give the doctor a true idea of the condition of the liver. They detail exactly what the patient can expect during and after the biopsy. The chapter includes lengthy quotes from patients with hepatitis, which offer the patients' perspectives, insights, and experiences to the reader. 2 figures. 1 table. ·
Children with Hepatitis C: A Growing Problem Source: in Everson, G.T. and Weinberg, H. Living with Hepatitis C: A Survivor's Guide. New York, NY: Hatherleigh Press. 1999. p. 199-210. Contact: Available from Hatherleigh Company, Ltd. 1114 First Avenue, Suite 500, New York, NY 10021. (800) 367-2550 or (212) 832-1039. Website: hatherleigh.com. Price: $14.95 plus shipping and handling. ISBN: 1578260345. Summary: Hepatitis C is a viral infection that causes inflammation, injury, and ultimately scarring of the liver (cirrhosis). This chapter addressing children with hepatitis C is from a book that offers information and guidance for people living with hepatitis C. The authors explain in nontechnical language some of the issues that parents of children with hepatitis C patients must struggle with. Topics include statistics regarding the incidence of hepatitis C in infants and children; diagnostic issues, including antibody testing and HCV RNA assays; strategies to prevent infection; pregnancy and breastfeeding concerns of women with hepatitis C; the impact of chronic disease on the family; the course of the infection in children; and treatment options and decision making. The chapter includes lengthy quotes from parents of children with hepatitis, which offer the patients' perspectives, insights, and experiences to the reader. 1 figure.
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Hepatitis C: Diagnosis and Treatment Source: in McDonald, J.W.D.; Burroughs, A.K.; Feagan, B.G., eds. Evidence Based Gastroenterology and Hepatology. London, UK: BMJ Publishing Group. 1999. p. 294-304.
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Contact: Available from BMJ Publishing Group. BMA Books, BMA House, Tavistock Square, London WCIH 9JR. Fax 44 (0)20 7383 6402. Email:
[email protected]. Website: www.bmjbooks.com. Price: Contact publisher for price. Summary: Hepatitis C is often characterized by a progression to chronic disease. This chapter on the diagnosis and treatment of hepatitis C is from a book that emphasizes the approaches of evidence based medicine in gastroenterology (the study of the gastrointestinal tract and gastrointestinal diseases) and hepatology (the study of the liver and liver diseases). The author of this chapter notes that since chronic hepatitis C is generally silent, its diagnosis often happens in conjunction with investigation for another disease. Systematic screening should be recommended in subjects who have a history of blood transfusion or intravenous drug addiction. The ELISA is the appropriate test for screening. In ELISA positive subjects, the presence of chronic infection is established by the detection of serum HCV RNA by polymerase chain reaction (PCR). A liver biopsy is recommended in patients who are HCV RNA positive with increased ALT levels in order to assess the severity of the liver disease and determine whether there is an indication for therapy. Combination therapy with interferon and ribavirin is now standard therapy, and results in a sustained response in approximately 40 percent of patients. Genotyping of the virus and the measure of baseline viral load are useful to assess the probability of sustained response and to determine the appropriate duration of combination therapy. 5 tables. 66 references. ·
Hepatitis C: An Overview Source: in Coggins, C.H., et al, eds. Annual Review of Medicine: Selected Topics in the Clinical Sciences. Palo Alto, CA: Annual Review, Inc. 1995. Volume 46: 309-317. Contact: Available from Annual Reviews, Inc. 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303. (800) 347-8007 or (415) 259-5017 for reprints of individual articles; (800) 523-8635 for subscriptions. E-mail
[email protected]. Price: $47 including shipping and handling. ISBN: 0824305450. ISSN: 0066-4219. Summary: This entry from the Annual Review of Medicine provides readers with an overview of hepatitis C virus (HCV). Topics include structure and genotypes; diagnostic tests; epidemiology; HCV related hepatitis and cirrhosis; HCV associated hepatocellular carcinoma; treatment options, including the use of interferon and liver transplantation; and HCV vaccines. 1 figure. 41 references.
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Non-A, Non-B Hepatitis Viruses Source: in Hollinger, F.B., et al. Viral Hepatitis: Biological and Clinical Features, Specific Diagnosis, and Prophylaxis. 2nd ed. New York, NY: Raven Press, Ltd. 1991. p. 139-173. Contact: Available from Raven Press. 1185 Avenue of the Americas, Dept. 5B, New York, NY 10036. (800) 777-2836 or (212) 930-9500. Fax (212) 8693495. Price: $91.50 plus shipping (as of 1995). ISBN: 0881677272. Summary: This chapter, from a book that examines the fundamental aspects of viral hepatitis, discusses the non-A, non-B hepatitis viruses. Two sections cover parenteral and sporadic non-A, non-B hepatitis and enterically-transmitted non-A, non-B hepatitis. Each section discusses history, infectious agents, clinical features and management, transmission, epidemiology, immunodiagnosis, and prevention. One section also focuses on the prevention of transfusion-associated hepatitis C. 10 figures. 7 tables. 359 references.
General Home References In addition to references for hepatitis C, you may want a general home medical guide that spans all aspects of home healthcare. The following list is a recent sample of such guides (sorted alphabetically by title; hyperlinks provide rankings, information, and reviews at Amazon.com): · Drugs (Health Issues) by Sarah Lennard-Brown; Library Binding - 64 pages (March 2002), Raintree/Steck Vaughn; ISBN: 0739847732; http://www.amazon.com/exec/obidos/ASIN/0739847732/icongroupinterna · The Encyclopedia of Drugs and Alcohol (Reference) by Greg Roza; School & Library Binding - 199 pages (September 2001); Franklin Watts, Incorporated; ISBN: 0531118991; http://www.amazon.com/exec/obidos/ASIN/0531118991/icongroupinterna
Vocabulary Builder 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] Gastrointestinal: Pertaining to or communicating with the stomach and intestine, as a gastrointestinal fistula. [EU]
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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] 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]
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CHAPTER 7. MULTIMEDIA ON HEPATITIS C Overview Information on hepatitis C can come in a variety of formats. Among multimedia sources, video productions, slides, audiotapes, and computer databases are often available. In this chapter, we show you how to keep current on multimedia sources of information on hepatitis C. 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. If you see an interesting item, visit your local medical library to check on the availability of the title.
Video Recordings Most diseases do not have a video dedicated to them. If they do, they are often rather technical in nature. An excellent source of multimedia information on hepatitis C is the Combined Health Information Database. You will need to limit your search to “video recording” and “hepatitis C” 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.).” By making these selections and typing “hepatitis C” (or synonyms) into the “For these words:” box, you will only receive results on video productions. The following is a typical result when searching for video recordings on hepatitis C: ·
Hepatitis C: A Viral Mystery Source: Boston, MA: Fanlight Productions. 2000. (videocassette).
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Contact: Available from Fanlight Productions. 4196 Washington Street, Boston, MA 02131. (800) 937-4113 or (617) 469-4999. Fax (617) 469-3379. Email:
[email protected]. Website: www.fanlight.com. Price: $195.00 plus shipping and handling. Summary: Hepatitis C is a viral disease of the liver which affects nearly four million Americans. The virus is primarily spread through blood contamination. There is no vaccine and no definite cure for the infection. This documentary videotape profiles several individuals who are living with this serious, chronic illness. In addition to discussing the available medical treatments, the program explores alternative options for treatment, including dietary changes, herbal therapies, meditation, guided imagery, and Qi Gong. The program reviews the modes of transmission of hepatitis C virus (HCV), including through blood transfusions, IV drug use, unsafe sex practices or multiple sexual partners, and tattooing and body piercing. The program interviews Dr. Stephen Steady, a hepatologist (liver specialist) who reminds viewers that many people with HCV infections are asymptomatic, but complications can be rampant, affecting other organ systems and overall quality of life (primarily through fatigue). The program reviews the drug therapy options (interferon and ribavirin, predominantly), noting that these treatments are effective only in 40 percent of the patients with hepatitis C, yet they can cause many side effects of their own. The program concludes with a look at the need for liver transplantation for some patients with hepatitis C, the important role of hepatitis C education for prevention, and support groups for patients with the illness. ·
Update on Management of Hepatitis C Source: Kansas City, MO: American Academy of Family Physicians. 2000. (videocassette). Contact: Available from American Academy of Family Physicians. 8880 Ward Parkway, Kansas City, MO 64114-2797. (800) 274-2237. Price: $17.95 for members; $25.00 for non-members, plus shipping and handling. Summary: Viral hepatitis remains the most common cause of liver disease worldwide and infection with the hepatitis C virus (HCV) has become a serious health problem in the United States. This continuing education program assists family physicians in this new challenge of the identification and diagnosis of patients at greatest risk of HCV infection. While there is, as yet, no known cure for HCV, early medical intervention and lifestyle changes can significantly improve the prognosis. Infection with HCV can lead to chronic hepatitis, cirrhosis (liver scarring), and hepatocellular carcinoma (HCC, liver cancer). Unlike hepatitis A and B, there is no vaccination available to prevent hepatitis C, nor are there any
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preexposure or postexposure prophylaxis (prevention) options. This program reviews the epidemiology of HCV, identification of patients at risk, diagnosis, HCV related liver disease, and management approaches, including interferon monotherapy, combination therapy, side effects, contraindications, and ongoing medical monitoring. The program includes a video tape and a study guide; the latter includes references and a patient education handout, as well as a posttest with which viewers can qualify for continuing education credit. 6 figures. 13 tables. 31 references. ·
Hepatitis C: Unknown Epidemic Source: Princeton, NJ: Films for the Humanities and Sciences. 1998. (videocassette). Contact: Available from Films for the Humanities and Sciences. P.O. Box 2053, Princeton, NJ 08543-2053. (800) 257-5126 or (609) 275-1400. Fax (609) 275-3767. E-mail:
[email protected]. Website: www.films.com. Price: $99.00 to purchase; $75.00 for rental; plus shipping and handling. Order number BVL9342. Summary: This videotape offers a segment of ABC's Nightline program that explores the epidemic of hepatitis C virus (HCV) infection in the United States. In this program, ABC News anchor Forrest Sawyer investigates the virus with Dr. Miriam Alter, epidemiologist at the Centers for Disease Control and Prevention; Dr. Jerome Groopman, professor at Harvard Medical School; and Andi Thomas, founder of the advocacy group Hep-C ALERT. Together they examine topics including risk factors associated with the disease, improvements in blood screening, the results of targeted looks back at past blood recipients, and the need for additional funding to increase research. Hepatitis C is characterized as a definite health epidemic: 15 percent of the people who get infected successfully fight it off; in 80 percent of those infected, the disease becomes chronic; and in 5 percent of those infected, HCV results in liver cirrhosis (scar tissue), which can then lead to cancer and death. It is virtually impossible to predict who will be in which category. The disease is spread predominantly through needle sharing, sexual contact, and blood transfusions occurring prior to the 1990's. The disease has been called the silent epidemic because it was only identified 10 years ago and the infection remains symptomless for decades. The three panelists interviewed share their information and differences of opinions on the wisdom of getting tested for HCV, the magnitude of the public health problem of the disease, the need for targeted look back for people who received blood transfusions, and the emotions of dealing with the disease.
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·
Hepatitis C: The Silent Scourge Source: Princeton, NJ: Films for the Humanities and Sciences. 1996. (videocassette). Contact: Available from Films for the Humanities and Sciences. P.O. Box 2053, Princeton, NJ 08543-2053. (800) 257-5126 or (609) 275-1400. Fax (609) 275-3767. E-mail:
[email protected]. Website: www.films.com. Price: $99.00 plus shipping and handling. Order number CAF6419. Summary: Hepatitis C virus (HCV) is a disease that is transmitted primarily by contact with infected blood and that manifests few symptoms. As many as 3.5 million people in the United States are believed to carry the virus, and many are not even aware that they have been exposed; 10,000 die from it each year. This program, hosted by Drs. Miriam Alter and Harold Margolis of the Centers for Disease Control and Prevention (CDC), explains current knowledge about the newest strain of the hepatitis virus, and its causes, treatment, and prevention. The program is designed like a news report and begins with an overview of the role and functions of the liver. The program then reviews the various forms of the hepatitis virus, noting that all of them cause liver inflammation and cirrhosis and can lead to symptoms like the flu, dark urine, or jaundice (yellowing of the skin). The narrators review the ways each type is transmitted, the symptoms, the treatment and side effects, prognostic factors, the availability of immunization, and risk factors. The program goes into more depth on hepatitis C, interviewing patients and health care providers. A brief section describes the use of liver transplantation as the final option for end stage liver failure caused by hepatitis. Another section interviews Thelma King Theil, the chair of the Hepatitis Foundation International, who focuses on the activities of the organization, particularly those related to prevention.
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Cutting Edge Medical Report: Hepatitis C 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: $19.95 plus $5.00 shipping and handling. Summary: This video presents a health update on hepatitis C. 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 C,
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offering details about transmission, symptoms, risk factors and behaviors, complications, epidemiology, and the progression of HCV to chronic, carrier state. Additional sections describe liver transplantation for people with hepatitis C and the psychosocial impact of chronic HCV 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.
Audio Recordings The Combined Health Information Database contains abstracts on audio productions. To search CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find audio productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Sound Recordings.” By making these selections and typing “hepatitis C” (or synonyms) into the “For these words:” box, you will only receive results on sound recordings (again, most diseases do not have results, so do not expect to find many). The following is a typical result when searching for sound recordings on hepatitis C: ·
[1991 Digestive Disease Week Sessions Audiocassettes] Source: Timonium, MD: Milner-Fenwick, Inc. 1991. (audiocassettes). Contact: Available from AGA Audiovisual Materials in Gastroenterology and Liver Disease. c/o Milner-Fenwick, Inc., 2125 Greenspring Drive, Timonium, MD 21093-3100. (800) 432-8433. Price: $14.95 per cassette; discount available for complete series. Summary: These audiocassettes reproduce clinical symposia, research forums, and lectures from the Digestive Disease Week (DDW) 1991 conference, held in New Orleans, LA. Topics available include Helicobacter pylori, gastrointestinal tract disorders in pregnancy, new approaches to biliary tract disease, controversies in the management of pancreatitis, an update on hepatitis C, controversies in the management of pancreatic pseudocysts, the management of irritable bowel syndrome (IBS), the use of somatostatin to treat diarrheal disorders, and recurrent Crohn's disease. Topics in the lectures include: the diagnosis and management of recurrent acute pancreatitis, the regulation of human pancreatic secretion, the use of interleukin 1, the pathophysiology of osmotic and carbohydrate-induced diarrhea, and the management of intractable ascites.
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Hepatitis C: Diagnosis, Clinical Management, and Prevention Source: Cedar Grove, NJ: Hepatitis Foundation International. November 22, 1997. (videocassette, audiocassette, manual). Contact: Available from Hepatitis Foundation International. 30 Sunrise Terrace, Cedar Grove, NJ 07009. (800) 891-0707. Price: $15.00 each for videotape and reference text; $10.00 for audiocassette tape. Summary: These materials on hepatitis C are from a satellite video conference sponsored by the Hepatitis Foundation International and the Centers for Disease Control and Prevention. The packet includes a videotape of the conference itself, an audiotape of the discussions from the conference, and the accompanying reference manual. The program featured speakers on eight topics: burden and prevalence, risk factors and epidemiology, serology, chronic hepatitis C infection in children, followup laboratory tests and clinical evaluation, the natural history of hepatitis C virus infection, treatment, and counseling messages. One case study is also presented. The slides from the program are reproduced in the manual. The manual includes a section on risk assessment with examples of questions to identify patients at risk for HCV infection and to determine whether serologic testing may be indicated. Screening recommendations for HCV infection are provided in chart format. An additional section compiles some concerns expressed by patients diagnosed with hepatitis C. The manual concludes with a reprint of the 1997 National Institutes of Health Consensus Statement and an article on advising patients who seek alternative medical therapies such as chiropractic, acupuncture, homeopathy, and herbal remedies. Additional handouts to stimulate and support physician patient communication are provided, as well as a list of resources noting organizations that can provide patients with information on hepatitis. The manual is spiral bound.
Bibliography: Multimedia on Hepatitis C 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 C (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
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date, author, or relevance. The following multimedia has been indexed on hepatitis C. For more information, follow the hyperlink indicated: ·
Acute and chronic hepatitis C. Source: Glaxo Pharmaceuticals; Year: 1993; Format: Slide; [New York, N.Y.: HP Pub. Co.], 1993
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Bloodborne pathogens : protect yourself. Source: produced by Coastal Training Technologies Corp; Year: 1999; Format: Videorecording; Virginia Beach, VA: Coastal Training Technologies, c1999
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Bloodborne pathogens. Source: CLMI, Comprehensive Loss Management, Inc.; produced by Media Productions, Inc; Year: 1995; Format: Videorecording; Minneapolis, Minn.: Comprehensive Loss Management, c1995
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Case studies in clinical infection : hepatitis. Source: a presentation of Films for the Humanities & Sciences; Sheffield University Television; produced for the Department of Medical Microbiology, University of Sheffield; Year: 2001; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c2001
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Epidemiology and prevention of viral hepatitis A, B, C, D, E : an overview. Source: CDC, Centers for Disease Control and Prevention; Year: 1996; Format: Slide; [Atlanta, Ga.: The Centers, 1996]
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Epidemiology of the hepatitis c virus. Source: Nick Crofts, Sandy Thompson, John Kaldor; Year: 1999; Format: Electronic resource; Canberra: Commonwealth Department of Health and Aged Care, 1999
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Ethical issues and considerations surrounding genetics ; Polymerase chain reaction (PCR): technology in infectious diseases. Source: HSTN; Year: 2002; Format: Videorecording; Carrollton, TX: PRIMEDIA Workplace Learning, c2002
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Expert opinions on contemporary clinical issues in hepatitis C. Source: Willis C. Maddrey, Eugene R. Schiff; Year: 1999; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, c1999
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Expert perspectives on contemporary clinical issues in hepatitis C. Source: co-chairs: Willis C. Maddrey, Eugene R. Schiff; Year: 1999; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, c1999
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Fighting hepatitis C. Source: a presentation of Films for the Humanities & Sciences; a production of Dartmouth-Hitchcock Medical Center; Year: 2002; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c2002
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Hepatitis & you as a healthcare worker. Part 2 : hepatitis B & C. Year: 2001; Format: Videorecording; Carrollton, TX: HSTN, c2001
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Hepatitis A, B, & C : viruses and their detection. Source: presented by Department of Medicine, Emory University, School of Medicine; Year: 1980; Format: Videorecording; Atlanta: Emory Medical Television Network, 1980
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Hepatitis A, B, C, D, and E. Source: [presented by] the Emory Medical Television Network and the Emory University School of Medicine; Year: 1990; Format: Videorecording; Atlanta, Ga.: The University, c1990
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Hepatitis and the nurse practitioner : satellite symposium, 5th Annual National Conference for Nurse Practitioners, Washington D.C., November 12, 1999. Source: sponsored by Postgraduate Institute for Medicine; Year: 2000; Format: Electronic resource; [Colorado?]: Postgraduate Institute for Medicine, c2000
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Hepatitis C : a review of Australia's response. Source: prepared by David Lowe and Ruth Cotton for the Department of Health and Aged Care; Year: 1999; Format: Electronic resource; Canberra: Commonwealth of Australia, 1999
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Hepatitis C : a viral mystery. Source: produced & directed by Terry Strauss; executive producer, Stephen Steady; Year: 2000; Format: Videorecording; Boston, MA: Fanlight Productions, c2000
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Hepatitis C : an update: recorded at DDW 1991 in New Orleans. Year: 1991; Format: Sound recording; [Bethesda, Md.]: American Gastroenterological Association, [1991]
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Hepatitis C : silent scourge. Source: a presentation of Films for the Humanities & Sciences; ITV, Information Television Network; Year: 1996; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c1996
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Hepatitis C : the silent epidemic. Source: EduMed Corporation and Allina Health System; Year: 1999; Format: Videorecording; Minnetonka, MN: EduMed Corp., c1999
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Hepatitis C. Source: a presentation of Films for the Humanities & Sciences; Nightline, ABCNEWS; Year: 1999; Format: Videorecording; Princeton, N.J.: Films for the Humanities and Sciences, c1999
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Hijacking the ribosome : functional insights into protein synthesis by internal ribosome entry in hepatitis C virus. Source: Office of Research Services, Medical Arts and Photography Branch; Year: 2001; Format: Videorecording; [Bethesda, Md.]: National Institutes of Health, [2001]
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Primary care : hepatitis C. Source: a co-production of Audio Visual Communication Resources and Physician Education & Development; Year: 1998; Format: Videorecording; [Oakland, Calif.]: Kaiser Foundation Health Plan, c1998
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Simplified approach to the management of patients with hepatitis C . Year: 2001; Format: Electronic resource; [Winnipeg, Manitoba, Canada]: Mayer Zev Enterprises, [2001?]
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Transfusion transmitted diseases. Source: [presented by] the American Association of Blood Banks, Abbott Diagnostics Educational Services; Year: 1987; Format: Slide; [Arlington, Va.]: The Association, [1987]
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Treatment of chronic hepatitis. Source: [presented by] Marshfield Clinic, Saint Joseph's Hospital, [and] Marshfield Medical Research Foundation; Year: 1991; Format: Videorecording; Marshfield, WI: Marshfield Regional Video Network, [1991]
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Universal precautions : 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 ColumbiaPresbyterian Medical Center; Year: 1989; Format: Videorecording; Garden Grove, CA: Medcom/Trainex, c1989
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Universal precautions. Source: St. Joseph Mercy Hospital, Pontiac, MI; Year: 1989; Format: Videorecording; Pontiac, MI: SJMH, c1989
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Update on management of hepatitis C. Source: American Academy of Family Physicians; Year: 2000; Format: Videorecording; Leawood, KS: American Academy of Family Physicians, c2000
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Update on non-A, non-B hepatitis. Source: with Richard D. Aach; Year: 1990; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, c1990
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Viral hepatitis : recorded at DDW 1995 in San Diego. Source: AGA, American Gastroenterological Association; Year: 1995; Format: Sound recording; [Bethesda, Md.]: The Association, [1995?]
Vocabulary Builder 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-, poly- and heterosaccharides. [EU] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Helicobacter: A genus of gram-negative, spiral-shaped bacteria that is pathogenic and has been isolated from the intestinal tract of mammals,
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including humans. [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] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Serology: The study of serum, especially of antigen-antibody reactions in vitro. [NIH] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH]
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CHAPTER 8. PERIODICALS AND NEWS ON HEPATITIS C Overview Keeping up on the news relating to hepatitis C can be challenging. Subscribing to targeted periodicals can be an effective way to stay abreast of recent developments on hepatitis C. Periodicals include newsletters, magazines, and academic journals. In this chapter, we suggest a number of news sources and present various periodicals that cover hepatitis C beyond and including those which are published by patient associations mentioned earlier. We will first focus on news services, and then on periodicals. News services, press releases, and newsletters generally use more accessible language, so if you do chose to subscribe to one of the more technical periodicals, make sure that it uses language you can easily follow.
News Services & Press Releases Well before articles show up in newsletters or the popular press, they may appear in the form of a press release or a public relations announcement. One of the simplest ways of tracking press releases on hepatitis C is to search the news wires. News wires are used by professional journalists, and have existed since the invention of the telegraph. Today, there are several major “wires” that are used by companies, universities, and other organizations to announce new medical breakthroughs. 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.
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PR Newswire Perhaps the broadest of the wires is PR Newswire Association, Inc. To access this archive, simply go to http://www.prnewswire.com. Below the search box, select the option “The last 30 days.” In the search box, type “hepatitis C” or synonyms. The search results are shown by order of relevance. When reading these press releases, do not forget that the sponsor of the release may be a company or organization that is trying to sell a particular product or therapy. Their views, therefore, may be biased. The following is typical of press releases that can be found on PR Newswire: ·
Schering-Plough Commends NIH for Consensus Statement On Management of Hepatitis C Summary: KENILWORTH, N.J., June 12 /PRNewswire-FirstCall/ -Schering-Plough Corporation (NYSE: KENILWORTH, N.J., June 12 /PRNewswire-FirstCall/ -- Schering-Plough Corporation (NYSE:
Reuters The Reuters’ Medical News database can be very useful in exploring news archives relating to hepatitis C. While some of the listed articles are free to view, others can be purchased for a nominal fee. To access this archive, go to http://www.reutershealth.com/frame2/arch.html and search by “hepatitis C” (or synonyms). The following was recently listed in this archive for hepatitis C: ·
Chronic HCV infection does not affect survival after kidney transplantation Source: Reuters Medical News Date: May 23, 2002 http://www.reuters.gov/archive/2002/05/23/professional/links/20020 523clin007.html
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Hepatitis C may be transmitted via toothbrushes Source: Reuters Health eLine Date: May 22, 2002 http://www.reuters.gov/archive/2002/05/22/eline/links/20020522elin 018.html
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HCV-3 identified as risk factor for liver enzyme elevation after HAART Source: Reuters Medical News Date: May 21, 2002 http://www.reuters.gov/archive/2002/05/21/professional/links/20020 521clin011.html
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Idun reports positive phase I results for hepatitis C drug Source: Reuters Industry Breifing Date: May 20, 2002 http://www.reuters.gov/archive/2002/05/20/business/links/20020520 drgd005.html
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Dual PI therapy does not increase hepatotoxicity risk in HCV-infected patients Source: Reuters Industry Breifing Date: May 15, 2002 http://www.reuters.gov/archive/2002/05/15/business/links/20020515 clin009.html
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Liver transplant feasible for HIV-infected patients with HCV Source: Reuters Medical News Date: April 29, 2002 http://www.reuters.gov/archive/2002/04/29/professional/links/20020 429clin021.html
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Immunity to hepatitis C may be possible: study Source: Reuters Health eLine Date: April 26, 2002 http://www.reuters.gov/archive/2002/04/26/eline/links/20020426elin 005.html
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Prior HCV infection may provide some protection against reinfection Source: Reuters Medical News Date: April 25, 2002 http://www.reuters.gov/archive/2002/04/25/professional/links/20020 425epid005.html
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Immtech selects independent tester of HCV drug candidates Source: Reuters Industry Breifing Date: June 19, 2002 http://www.reuters.gov/archive/2002/06/19/business/links/20020619 drgd005.html
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Chiron licenses hepatitis C technology to Merck Source: Reuters Industry Breifing Date: June 19, 2002 http://www.reuters.gov/archive/2002/06/19/business/links/20020619 inds011.html
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Combo treatment best for hepatitis C, panel says Source: Reuters Health eLine Date: June 13, 2002 http://www.reuters.gov/archive/2002/06/13/eline/links/20020613elin 018.html
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Consensus panel deems interferon/ribavirin best treatment for Hepatitis C Source: Reuters Medical News Date: June 12, 2002 http://www.reuters.gov/archive/2002/06/12/professional/links/20020 612prof001.html
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Iron removal may improve effectiveness of interferon for chronic hepatitis C Source: Reuters Industry Breifing Date: June 04, 2002 http://www.reuters.gov/archive/2002/06/04/business/links/20020604 clin014.html
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Hepatitis C transmission via toothbrush deemed possible Source: Reuters Medical News Date: May 27, 2002 http://www.reuters.gov/archive/2002/05/27/professional/links/20020 527epid004.html
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Preclinical study validates activity of Maxim's Ceplene in hepatitis C Source: Reuters Industry Breifing Date: April 22, 2002 http://www.reuters.gov/archive/2002/04/22/business/links/20020422 drgd002.html
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Isis, Merck extend hepatitis C alliance Source: Reuters Industry Breifing Date: April 22, 2002 http://www.reuters.gov/archive/2002/04/22/business/links/20020422 inds007.html
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Schering-Plough profits rise slightly on hepatitis C-drug sales Source: Reuters Industry Breifing Date: April 18, 2002 http://www.reuters.gov/archive/2002/04/18/business/links/20020418 inds013.html
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Roche touts results of Pegasys hepatitis C study Source: Reuters Industry Breifing Date: April 18, 2002 http://www.reuters.gov/archive/2002/04/18/business/links/20020418 drgd006.html
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High sustained virologic response to hepatitis C with pegylated interferon alfa plus ribavirin Source: Reuters Medical News Date: April 18, 2002 http://www.reuters.gov/archive/2002/04/18/professional/links/20020 418drgd007.html
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Hepatitis C emerging as important factor in outcome of HIV-infected patients Source: Reuters Industry Breifing Date: April 18, 2002 http://www.reuters.gov/archive/2002/04/18/business/links/20020418 epid001.html
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Drug cuts hepatitis C levels in blood Source: Reuters Health eLine Date: April 18, 2002 http://www.reuters.gov/archive/2002/04/18/eline/links/20020418elin 037.html
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NIH to begin phase I testing of Nabi hepatitis C therapy Source: Reuters Industry Breifing Date: April 17, 2002 http://www.reuters.gov/archive/2002/04/17/business/links/20020417 drgd008.html
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Citalopram safely relieves depression in patients with hepatitis C Source: Reuters Industry Breifing Date: April 12, 2002 http://www.reuters.gov/archive/2002/04/12/business/links/20020412 clin015.html
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Smoking can aggravate hepatitis C liver damage Source: Reuters Health eLine Date: April 10, 2002 http://www.reuters.gov/archive/2002/04/10/eline/links/20020410elin 009.html
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Drug use, STDs related to HCV infection in young, low-income women Source: Reuters Medical News Date: April 09, 2002 http://www.reuters.gov/archive/2002/04/09/professional/links/20020 409publ001.html
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Sharing injection equipment spreads hepatitis C Source: Reuters Health eLine Date: April 02, 2002 http://www.reuters.gov/archive/2002/04/02/eline/links/20020402elin 034.html
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Isis, Elan venture launches phase II trial for HCV drug Source: Reuters Industry Breifing Date: March 21, 2002 http://www.reuters.gov/archive/2002/03/21/business/links/20020321 drgd008.html
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Teens in detention may be at risk for hepatitis C Source: Reuters Health eLine Date: March 11, 2002 http://www.reuters.gov/archive/2002/03/11/eline/links/20020311elin 014.html
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Pegylated interferon improves hepatitis C outcome in HIV+ patients Source: Reuters Industry Breifing Date: February 28, 2002 http://www.reuters.gov/archive/2002/02/28/business/links/20020228 clin013.html
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FDA approves Chiron's hepatitis C, HIV assay Source: Reuters Industry Breifing Date: February 28, 2002 http://www.reuters.gov/archive/2002/02/28/business/links/20020228 rglt012.html
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Maternal injection drug use increases risk of vertical hepatitis C transmission Source: Reuters Medical News Date: February 22, 2002 http://www.reuters.gov/archive/2002/02/22/professional/links/20020 222epid006.html
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Hepatitis C apparently transmitted from an anesthesiologist to a patient Source: Reuters Industry Breifing Date: February 20, 2002 http://www.reuters.gov/archive/2002/02/20/business/links/20020220 clin006.html
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Rheumatologic symptoms often associated with hepatitis C infection Source: Reuters Medical News Date: February 18, 2002 http://www.reuters.gov/archive/2002/02/18/professional/links/20020 218clin013.html
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Phlebotomy may delay progression of liver fibrosis in chronic hepatitis C patients Source: Reuters Medical News Date: February 06, 2002 http://www.reuters.gov/archive/2002/02/06/professional/links/20020 206clin010.html
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Hemochromatosis gene mutations do not affect progression of chronic hepatitis C Source: Reuters Medical News Date: January 30, 2002 http://www.reuters.gov/archive/2002/01/30/professional/links/20020 130epid003.html
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Hungarian court rules for hepatitis C patient infected by transfusion Source: Reuters Medical News Date: January 25, 2002 http://www.reuters.gov/archive/2002/01/25/professional/links/20020 125legl001.html
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Hepatitis C patient wins lawsuit against Hungary Source: Reuters Health eLine Date: January 25, 2002 http://www.reuters.gov/archive/2002/01/25/eline/links/20020125elin 036.html
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Roche says no problem with Brazil on hepatitis C drug pricing Source: Reuters Industry Breifing Date: January 15, 2002 http://www.reuters.gov/archive/2002/01/15/business/links/20020115 inds009.html
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XTL hepatitis C therapy effective in phase Ia trial Source: Reuters Industry Breifing Date: January 14, 2002 http://www.reuters.gov/archive/2002/01/14/business/links/20020114 drgd003.html
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Polymorphonuclear neutrophils are elevated in the lungs of hepatitis C patients Source: Reuters Medical News Date: January 02, 2002 http://www.reuters.gov/archive/2002/01/02/professional/links/20020 102clin006.html
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HIV may enhance sexual transmission of hepatitis C Source: Reuters Medical News Date: December 28, 2001 http://www.reuters.gov/archive/2001/12/28/professional/links/20011 228epid002.html
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Maxim begins phase II trial of Ceplene with Rebetol, Peg-Intron for hepatitis C Source: Reuters Industry Breifing Date: December 18, 2001 http://www.reuters.gov/archive/2001/12/18/business/links/20011218 drgd001.html
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Bristol-Myers licenses Chiron's HCV technology Source: Reuters Industry Breifing Date: November 27, 2001 http://www.reuters.gov/archive/2001/11/27/business/links/20011127 inds009.html
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High-dose interferon therapy shows promise in treating HBV/HCV hepatitis Source: Reuters Industry Breifing Date: November 22, 2001 http://www.reuters.gov/archive/2001/11/22/business/links/20011122 clin008.html
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Cytokine levels explain poor IFN response in HCV-infected African Americans Source: Reuters Industry Breifing Date: November 22, 2001 http://www.reuters.gov/archive/2001/11/22/business/links/20011122 clin004.html
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HCV treatment in HIV-infected patients best before immunosuppression occurs Source: Reuters Industry Breifing Date: November 19, 2001 http://www.reuters.gov/archive/2001/11/19/business/links/20011119 clin003.html
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High-dose interferon alpha-2b prevents chronic hepatitis C infection Source: Reuters Industry Breifing Date: November 14, 2001 http://www.reuters.gov/archive/2001/11/14/business/links/20011114 clin013.html
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Early interferon treatment may curb hepatitis C Source: Reuters Health eLine Date: November 14, 2001 http://www.reuters.gov/archive/2001/11/14/eline/links/20011114elin 002.html
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ViroPharma, Wyeth-Ayerst hepatitis C candidate fails in phase IIa Source: Reuters Industry Breifing Date: November 12, 2001 http://www.reuters.gov/archive/2001/11/12/business/links/20011112 drgd003.html
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Daily injection more effective than thrice-weekly interferon alpha-2b for HCV/HIV Source: Reuters Industry Breifing Date: October 29, 2001 http://www.reuters.gov/archive/2001/10/29/business/links/20011029 clin020.html
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
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allows you to browse across an alphabetical index. Or you can search by date at http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within their 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.
Internet Wire Internet Wire is more focused on technology than the other wires. To access this site, go to http://www.internetwire.com and use the “Search Archive” option. Type in “hepatitis C” (or synonyms). As this service is oriented to technology, you may wish to search for press releases covering diagnostic procedures or tests that you may have read about. Search Engines Free-to-view news can also be found in the news section of your favorite search engines (see the health news page at Yahoo: http://dir.yahoo.com/Health/News_and_Media/, or use this Web site’s general news search page http://news.yahoo.com/. Type in “hepatitis C” (or synonyms). If you know the name of a company that is relevant to hepatitis C, you can go to any stock trading Web site (such as www.etrade.com) and search for the company name there. News items across various news sources are reported on indicated hyperlinks.
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 C” (or synonyms).
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Newsletter Articles If you choose not to subscribe to a newsletter, you can nevertheless find references to newsletter articles. We recommend that you use the Combined Health Information Database, while limiting 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.” By making these selections, and typing in “hepatitis C” (or synonyms) into the “For these words:” box, you will only receive results on newsletter articles. You should check back periodically with this database as it is updated every 3 months. The following is a typical result when searching for newsletter articles on hepatitis C: ·
Assault on Your Liver: Inside the ABCs (and DEFGs) of Viral Hepatitis Source: Mayo Clinic Women's Healthsource. 3(7): 4, 5. July 1999. Contact: Available from Mayo Foundation for Medical Education and Research. 200 First Street SW, Rochester, MN 55905. Summary: This health newsletter article describes the different strains of viral hepatitis and their impact on the liver. The liver is a noncomplaining organ, which functions to filter out harmful chemicals, fight infection, and convert energy for the body's use. When hepatitis hits, however, illnesses can range from mild to potentially life threatening. The author describes how to tell the difference between each type of hepatitis, whether risk factors are present or not, and what happens after infection. Blood tests are used to diagnose hepatitis. Some tests detect specific antibodies the body produces in response to infection with a particular hepatitis virus; others measure how well the liver is functioning; others actually test for the virus itself. The author lists the epidemiology and incubation of each type (hepatitis A through E), then reminds readers of the transmission of each type. Treatment, vaccination options, risk factors, and preventive measures are then noted. Hepatitis A is spread through the fecal oral route (not washing hands properly after contact with infected feces), ingestion of contaminated food and water, or close personal contact with an infected person (anal or oral). Hepatitis B is transmitted through contact with body fluids containing HBV, sexual contact, or sharing contaminated needles. Hepatitis E is associated with contaminated water. Vaccinations are available for hepatitis A, B, and D (hepatitis B vaccine prevents hepatitis D infection); no vaccine is available
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for hepatitis C or E. One sidebar reviews strategies for optimum liver care, with or without the presence of hepatitis. ·
Research Agenda for Viral Hepatitis (editorial) Source: Liver Update. 9(2): 1-2. Fall 1995. Contact: Available from American Liver Foundation. 1425 Pompton Avenue, Cedar Grove, NJ 07009. (800) 233-0179 or (201) 857-2626 or (201) 256-2550. Summary: In this editorial, the authors call for an escalated research agenda for viral hepatitis. They stress that research efforts should be directed toward understanding the natural history of disease, defining the pathogenetic mechanisms of these viral infections, and developing effective preventive and therapeutic means to control the infections. They discuss the hepatitis B virus, the hepatitis C virus, other hepatotropic viruses, prevention with vaccination, and treatment options, including liver transplantation.
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Hepatitis C: Shedding Light on the Shadow Epidemic Source: Harvard Health Letter. 24(9): 1-3. July 1999. Contact: Available from Harvard Medical School Health Publications Group. Harvard Health Letter, P.O. Box 420300, Palm Coast, FL 321420300. (800) 829-9045. E-mail:
[email protected]. Summary: When people learn they have hepatitis C, their initial reaction is often disbelief and confusion. Many of those carrying this silent and sometimes deadly bloodborne virus feel perfectly healthy and learn of their infection only after donating blood or having routine blood tests. This newsletter article reports on a recent effort by the Centers for Disease Control and Prevention (CDC) to improve people's awareness by launching a hepatitis C public information campaign. People who are not now infected with HCV are not likely to get it unless they use IV drugs. Improved blood screening has made the risk of contracting HCV from a transfusion exceedingly low. However, most people who have HCV don't realize they're carrying the virus, which can lurk in the liver for decades before symptoms appear. It is important for people to know they have HCV so they can avoid alcohol (which accelerates liver damage), undergo frequent blood tests to monitor their liver function, and consider treatments with antiviral drugs that can reduce or eliminate the virus in some people. The majority of carriers remain fairly healthy, but at least 20 to 30 percent eventually develop cirrhosis (scarring of the liver caused by prolonged inflammation). Several blood tests can determine if a person has been infected with HCV. The author describes these tests and then
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briefly outlines the treatment options for HCV. One sidebar offers the contact information (telephone numbers and websites) for three resource organizations. 2 references.
Academic Periodicals covering Hepatitis C Academic periodicals can be a highly technical yet valuable source of information on hepatitis C. We have compiled the following list of periodicals known to publish articles relating to hepatitis C and which are currently indexed within the National Library of Medicine’s PubMed database (follow hyperlinks to view more information, summaries, etc., for each). In addition to these sources, to keep current on articles written on hepatitis C published by any of the periodicals listed below, you can simply follow the hyperlink indicated or go to the following Web site: www.ncbi.nlm.nih.gov/pubmed. Type the periodical’s name into the search box to find the latest studies published. If you want complete details about the historical contents of a periodical, you can also visit 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.” The following is a sample of periodicals which publish articles on hepatitis C: ·
Acta Haematologica. (Acta Haematol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ac ta+Haematologica&dispmax=20&dispstart=0
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Antimicrobial Agents and Chemotherapy. (Antimicrob Agents Chemother) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=An timicrobial+Agents+and+Chemotherapy&dispmax=20&dispstart=0
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Clinical Chemistry. (Clin Chem) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Cli nical+Chemistry&dispmax=20&dispstart=0
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Hepatology (Baltimore, Md. . (Hepatology) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=He patology+(Baltimore,+Md.+&dispmax=20&dispstart=0
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Journal of Alternative and Complementary Medicine (New York, N. . . (J Altern Complement Med) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Jo urnal+of+Alternative+and+Complementary+Medicine+(New+York,+N. +.+&dispmax=20&dispstart=0
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Journal of Biochemistry. (J Biochem (Tokyo)) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Jo urnal+of+Biochemistry&dispmax=20&dispstart=0
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Journal of Clinical Microbiology. (J Clin Microbiol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Jo urnal+of+Clinical+Microbiology&dispmax=20&dispstart=0
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Journal of Gastroenterology and Hepatology. (J Gastroenterol Hepatol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Jo urnal+of+Gastroenterology+and+Hepatology&dispmax=20&dispstart=0
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Journal of Gastroenterology. (J Gastroenterol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Jo urnal+of+Gastroenterology&dispmax=20&dispstart=0
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Journal of Hepatology. (J Hepatol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Jo urnal+of+Hepatology&dispmax=20&dispstart=0
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Journal of Virology. (J Virol) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Jo urnal+of+Virology&dispmax=20&dispstart=0
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Radiation Research. (Radiat Res) http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi?field=0®exp=Ra diation+Research&dispmax=20&dispstart=0
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CHAPTER 9. PHYSICIAN GUIDELINES AND DATABASES Overview Doctors and medical researchers rely on a number of information sources to help patients with their conditions. Many will subscribe to journals or newsletters published by their professional associations or refer to specialized textbooks or clinical guides published for the medical profession. In this chapter, we focus on databases and Internet-based guidelines created or written for this professional audience.
NIH Guidelines For the more common diseases, The National Institutes of Health publish guidelines that are frequently consulted by physicians. Publications are typically written by one or more of the various NIH Institutes. For physician guidelines, commonly referred to as “clinical” or “professional” guidelines, you can visit the following Institutes: ·
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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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.29 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:30 ·
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
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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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
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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/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to caner-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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). 30 See http://www.nlm.nih.gov/databases/databases.html. 29
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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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
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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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
While all of the above references may be of interest to physicians who study and treat hepatitis C, the following are particularly noteworthy.
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 “Brochure/Pamphlet,” “Fact Sheet,” or “Information Package” and hepatitis C 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.” By making these selections and typing “hepatitis C” (or synonyms) into the “For these words:” box above, you will only receive results on fact sheets dealing with hepatitis C. The following is a sample result:
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·
NIH Consensus Statement: Management of Hepatitis C Source: Bethesda, MD: National Institutes of Health Office of Medical Applications of Research. 1997. 41 p. Contact: Available from NIH Consensus Program Information Center. P.O. Box 2577, Kensington, MD 20891. (888) 644-2667. Also available on the Internet at http://consensus.nih.gov. Price: Single copy free. Summary: This NIH Consensus Statement was derived from the March 1997 Consensus Development Conference on the management of hepatitis C. The conference brought together experts in relevant fields, including internal medicine, hepatology, gastroenterology, infectious diseases, medical ethics, transfusion medicine, epidemiology, and biostatistics. This group and representatives of the public addressed six questions: What is the natural history of hepatitis C? What is the most appropriate approach to diagnose and monitor patients? What is the most effective therapy for hepatitis C? Which patients with hepatitis C should be treated? What recommendations to patients can be made to prevent transmission of hepatitis C? What are the most important areas for future research? Hepatitis C is a common infection with a variable course that can lead to chronic hepatitis, cirrhosis (scarring of the liver), and hepatocellular carcinoma (liver cancer). The course of illness may be adversely affected by various factors, especially alcohol consumption. Therefore, more than one drink per day is strongly discouraged in patients with hepatitis C, and abstinence from alcohol is recommended. Initial therapy with interferon alfa (or equivalent) should be 3 million units three times per week for 12 months. Patients not responding to therapy after 3 months should not receive further treatment with interferon alone, but should be considered for combination therapy of interferon and ribavirin or for enrollment in investigational studies. Individuals infected with the hepatitis C virus should not donate blood, organs, tissues, or semen. Safe sexual practices, including the use of latex condoms, is strongly encouraged for individuals with multiple sexual partners. Expansion of needle exchange programs should be considered in an effort to reduce the rate of transmission of hepatitis C among injection drug users. The brochure lists the names and affiliations of the consensus panel members.
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Hepatitis C and Incarcerated Populations: The Next Wave for Correctional Health Initiatives Source: Washington, DC: Association of State and Territorial Health Officials. 2000. 28 p.
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Contact: Available from Association of State and Territorial Health Officials (ASTHO). 1275 K Street, NW, Suite 800, Washington, DC 200054006. (202) 371-9090. Fax (202) 371-9797. Price: Single copy free. Also available for free in PDF format at www.astho.org/infectious/documents/hivaids/HepC-Incarcerated.pdf. Summary: This report, Hepatitis C and Incarcerated Populations, was prepared as part of the Association of State and Territorial Health Officials (ASTHO) Prison Project with support from the National Center for Infectious Diseases of the Centers for Disease Control and Prevention (CDC). The mission of the Prison Project is to help focus and stimulate disease prevention activities in correctional settings. An estimated 20 to 40 percent of inmates are infected with the hepatitis C virus (HCV). The rates are higher among injection drug users and inmates infected with HIV. This report discusses the realities of responding to HCV within the incarceration setting, reviews the challenges to intervention, and illustrates how a number of states are responding to this issue. The report makes eleven recommendations: the CDC should develop specific guidelines for the prevention and control of HCV in incarcerated populations; funding should be made available for community interventions to address HCV prevention, screening, diagnosis, and treatment of at risk populations prior to incarceration; states should consider integrating viral hepatitis into existing HIV and AIDS programs; public health officials should acknowledge corrections' role in community health; intervention strategies should involved collaboration between corrections and public health and other involved groups such as community-based organizations; states should be enlisted to help outline guidelines that address HCV infection among incarcerated patients; states should assume a high HCV infection rate among incarcerated patients; the Federal Government should lift the restriction on the use of federal funds for needle exchange services; states should explore the removal of legal barriers such as drug paraphernalia and prescription laws; injection drug users should be referred to the most appropriate source for counseling and treatment; and strategies that address HCV and incarcerated populations must recognize and address factors that can modify the approach to care (i.e., overcrowded, overstressed correctional health care systems, questionable quality of care, lack of continuity care, and comorbid conditions). 32 references. ·
Health Emergency 2001: The Spread of Drug-Related AIDS and Hepatitis C Among African Americans and Latinos Contact: Dogwood Center, PO Box 187, Princeton, NJ, 08542, (609) 9244797.
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Summary: This report examines the spread of the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and hepatitis C virus (HCV) among African Americans and Hispanics, resulting from the use of injection drugs. The report provides information about the epidemiology of HIV/AIDS among black and Hispanic injection drug users (IDUs) in the United States (US). It examines the failure of drug treatment programs to seize upon the opportunity to reinforce HIV prevention messages within the context of the programs' structures. It examines issues related to the legality of needle exchange programs and what can be done to speed up the legalization of such services in many cities, counties, and states. The report discusses HIV/AIDS among black and Hispanic drug users, and examines the cost of treating HIV/AIDS versus the cost of HIV prevention through needle exchange programs. It explains the special challenges for African-American and Hispanic women and children and the prevention of the spread of HIV/AIDS and HCV through needle exchange and safer sex intervention programs. The report cites studies that show that not only can needle exchange programs reduce IDUs' chances of contracting HIV/AIDS, but also HCV thereby saving the US healthcare system even more money. It examines ways that African Americans and Hispanics with HIV/AIDS are still disadvantaged in the US healthcare system. It makes recommendations for improving needle exchange programs and HIV/AIDS healthcare aimed at black and Hispanics in the US. ·
Hepatitis C & Incarcerated Populations : The Next Wave for Correctional Health Initiatives Contact: Association of State and Territorial Health Officials, 1275 K St NW Ste 800, Washington, DC, 20005-4006, (202) 371-9090, http://www.astho.org. Summary: This report, for health care professionals and correctional facility personnel, discusses the impact of the hepatitis C virus (HCV) on incarcerated populations. It identifies factors that prevent HCV-infected incarcerated individuals from seeking treatment such as: (1) the fear that health problems could prolong incarceration, (2) the possibility that available treatment for HCV may have worse side effects than the symptoms of the disease itself, and (3) factors that may preclude an HCVinfected patient from treatment eligibility or dissuade individuals from treatment. The report provides preventative strategies such as surveillance, counseling, education, and provision of discharge referrals. Samples of state's collaboration initiatives for addressing the issue of
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HCV in correctional facilities, conclusions, and recommendations are provided. ·
Hagase la Prueba de la Hepatitis C: Debe hacerse la prueba de la Hepatitis C si se le ha notificado que ha recibido sangre posiblemente infectada por el virus hepatitis C (VHC) o si usted ha Contact: CDC National Prevention Information Network, PO Box 6003, Rockville, MD, 20849-6003, (800) 458-5231, http://cdcnpin.org. Summary: This brochure for the general public discusses who should be tested for hepatitis C and the effects, treatment, transmission, and prevention of hepatitis C. Persons should be tested if they were notified that they received blood that possibly contained hepatitis C virus (HCV) or if they received blood before July 1992. Persons may have received this blood before tests to identify blood donors with hepatitis C were available or when tests were less precise than they are now. Hepatitis C is a liver disease caused by infection with HCV, which is found in the blood of persons who have this disease. If persons test positive for hepatitis C, they will need to see a doctor to determine if they have liver disease and how severe it is, to determine if they should be treated for the liver disease, to learn how they can protect their livers from further harm, and to learn how they can prevent spreading HCV to others. Persons should not donate blood as a means of being tested. Whether persons feel sick or not, they should have a blood test for hepatitis C. To take care of their livers, persons with HCV should see their doctors regularly, not drink alcohol, tell their doctor about all medicines they are taking, and be vaccinated against hepatitis A if there is liver damage. Antiviral medicines are approved for the treatment of persons with chronic hepatitis C. Treatment is effective in about 2-3 out of every 10 persons treated. Others at risk of getting hepatitis C are persons who have ever injected street drugs, healthcare workers exposed to blood in the workplace, and babies born to infected mothers. HCV also can be spread by sex, but this does not occur very often. To prevent the spread of HCV, persons with hepatitis C should not donate blood, body organs, other tissue, or sperm; should not share personal care articles that might have blood on them; should cover cuts and open sores; and may consider using barrier precautions during sex. Sexual practices involving one steady partner do not need to change, and persons with HCV do not need to avoid pregnancy or breast feeding. HCV is not spread by breast feeding, casual contact, food or water, sneezing, coughing, or sharing eating utensils or drinking glasses. Injection drug users should seek treatment, use clean drug works, and get vaccinated against hepatitis A and B. Persons having sex with more than one partner can get other
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diseases, should use latex condoms, should be vaccinated against hepatitis B, and may want to consider abstinence from sex. ·
Hepatitis C: What Science Knows About a Serious Viral Disease Source: Costa Mesa, CA: ICN Pharmaceuticals, Inc. 1993. 26 p. Contact: Available from ICN Pharmatceuticals, Inc. ICN Plaza, 3300 Hyland Avenue, Costa Mesa, CA 92626. (800) 548-5100. Fax (714) 6417205. Price: Single copy free. Summary: The objective of this publication is to provide the most current information about hepatitis C to health care professionals, whose patients may have the disease or be at risk for it, and to lay out the current issues and controversies for medical journalists, who play a key role in introducing these issues to the public. After an introductory section, the publication addresses eleven topics in three chapters: the epidemiology of hepatitis C; the natural history of hepatitis C; and issues in the diagnosis and management of hepatitis C. Specific topics include discovery of the hepatitis C virus (HCV); risk factors; acute infection and beyond; the public health outlook; the molecular biology of HCV; clinical signs and symptoms; chronic hepatitis C; complications and long-term prognosis; diagnostic tests; and treatment options. 52 references. (AA-M).
·
Hepatitis C and Incarcerated Populations: The Next Wave for Correctional Health Initiatives Source: Washington, DC: Association of State and Territorial Health Officials. 2000. 28 p. Contact: Available from Association of State and Territorial Health Officials (ASTHO). 1275 K Street, NW, Suite 800, Washington, DC 200054006. (202) 371-9090. Fax (202) 371-9797. Price: Single copy free. Also available for free in PDF format at www.astho.org/infectious/documents/hivaids/HepC-Incarcerated.pdf. Summary: This report, Hepatitis C and Incarcerated Populations, was prepared as part of the Association of State and Territorial Health Officials (ASTHO) Prison Project with support from the National Center for Infectious Diseases of the Centers for Disease Control and Prevention (CDC). The mission of the Prison Project is to help focus and stimulate disease prevention activities in correctional settings. An estimated 20 to 40 percent of inmates are infected with the hepatitis C virus (HCV). The rates are higher among injection drug users and inmates infected with HIV. This report discusses the realities of responding to HCV within the incarceration setting, reviews the challenges to intervention, and illustrates how a number of states are responding to this issue. The report
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makes eleven recommendations: the CDC should develop specific guidelines for the prevention and control of HCV in incarcerated populations; funding should be made available for community interventions to address HCV prevention, screening, diagnosis, and treatment of at risk populations prior to incarceration; states should consider integrating viral hepatitis into existing HIV and AIDS programs; public health officials should acknowledge corrections' role in community health; intervention strategies should involved collaboration between corrections and public health and other involved groups such as community-based organizations; states should be enlisted to help outline guidelines that address HCV infection among incarcerated patients; states should assume a high HCV infection rate among incarcerated patients; the Federal Government should lift the restriction on the use of federal funds for needle exchange services; states should explore the removal of legal barriers such as drug paraphernalia and prescription laws; injection drug users should be referred to the most appropriate source for counseling and treatment; and strategies that address HCV and incarcerated populations must recognize and address factors that can modify the approach to care (i.e., overcrowded, overstressed correctional health care systems, questionable quality of care, lack of continuity care, and comorbid conditions). 32 references. ·
Hepatitis Report: A Critical Review of the Research and Treatment of Hepatitis C Virus (HCV) and Hepatitis and HIV Coinfection Source: New York, NY: Treatment Action Group. 2000. 134 p. Contact: Treatment Action Group. 350 Seventh Avenue, Suite 1603, New York, NY 10036. (212) 972-9022. Fax (212) 971-9019. Website: www.treatmentactiongroup.org. Price: Single copy free. Summary: This report is designed to bring clinicians, allied health care workers, and patients up to date on hepatitis C virus (HCV), including epidemiology, natural history, diagnosis, pathogenesis, and treatment. After an analysis of peer reviewed articles, over 40 researchers, clinicians, primary care physicians, government health administrators, industry representatives, and patients with viral hepatitis were interviewed for this report. Eleven chapters cover epidemiology, modes of transmission, and risk factors; pathogenesis, viral dynamics, and immunologic response; natural history, clinical manifestations, and prognostic indicators of disease progression and survival of HCV infection; diagnostic considerations; the use of interferon to treat HCV infection; the mechanism of HCV resistance to interferon; experimental treatments and new areas of research; hepatitis and HIV coinfection; current opinions and controversies in HCV infection; research and policy
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recommendations; and clinician's response. The natural history chapter reminds readers that not all patients with HCV inexorably deteriorate to end stage liver disease, liver transplantation, or death. The diagnosis of HCV is often complex with multiple tests and the confusion of liver biopsy evaluation. The role of HCV in response to HIV therapy is largely unknown. Approximately only half of HCV patients respond to current therapies, but the report considers whether perhaps only half may actually need therapy in the long term. Unfortunately, clinicians cannot determine which patients will progress to fibrosis and end stage liver disease and so most patients are treated, especially if they have some scarring without cirrhosis. Interferon remains the mainstay of therapy, with pegylated IFNs providing new advances. Each chapter includes illustrations and a list of references. ·
Hepatitis C Update: Recommendations from the NIH and CDC Source: JAAPA. Journal of the American Academy of Physician Assistants. 11(12): 35-37. December 1998. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Fax (201) 573-4956. Summary: In March 1997, the National Institutes of Health (NIH) conducted a consensus development conference on the management of hepatitis C virus (HCV) infection. In July 1998, the Centers for Disease Control and Prevention (CDC) held a consultants meeting on HCV, from which it developed recommendations for the prevention and control of HCV infection and related chronic disease. This article reviews these two sets of recommendations, summarizing and comparing the guidelines in the areas of screening, counseling, monitoring, and treatment. The CDC recommends screening persons at low risk of HCV infection with the enzyme immunoassay (EIA) HCV antibody test, which has a sensitivity of greater than 97 percent. If indicated, the recombinant immunoblot assay is used as a confirmation test. The NIH, on the other hand, recommends measurement of HCV RNA with the polymerase chain reaction, if indicated, as a confirmatory test of a positive EIA. The CDC recommends that people who test positive for HCV should be counseled about being evaluated for their disease and possibly being treated. They should be instructed about reducing the risk of transmitting the virus to another person and refraining from donating blood or other body tissues. The CDC recommends vaccination against hepatitis A in a person who has chronic HCV infection; the NIH recommends vaccination against hepatitis A and B. Liver biopsy remains the gold standard for assessing disease activity, including progression to fibrosis and cirrhosis. Treatment is recommended when findings on liver biopsy include
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periportal or bridging fibrosis and a moderate degree of inflammation and necrosis. Patients who have had one or more episodes of decompensated cirrhosis (ascites, variceal bleedings, or encephalopathy) should be referred to a center that performs liver transplantation. 1 figure. 3 references. ·
Recommendations for Prevention and Control of Hepatitis C Virus (HCV) Infection and HCV-Related Chronic Disease Source: MMWR. Recommendations and Reports. 47(RR-19): 1-39. October 16, 1998. Contact: Available from Superintendent of Documents. United States Government Printing Office, Washington, DC 20402. (202) 512-1800. Also available for free at www.cdc.gov or from the Center for Disease Control and Prevention's file transfer protocol server at ftp.cdc.gov. Summary: These recommendations expand on previous (1991) recommendations by the Centers for Disease Control (CDC) for preventing hepatitis C virus (HCV) infection; these earlier guidelines focused on screening and followup of blood, plasma, organ, tissue, and semen donors. The recommendations in this report provide broader guidelines for preventing transmission; identifying, counseling, and testing persons at risk for HCV infection; and providing appropriate medical evaluation and management of HCV infected persons. The background section covers epidemiology, screening and diagnostic tests, clinical features and natural history, clinical management and treatment, and postexposure prophylaxis and followup. The section on primary prevention recommendations covers blood, plasma derivatives, organs, tissues, and semen; high risk drug and sexual practices; and percutaneous exposures to blood in health care and other settings. The secondary prevention recommendations discuss persons for whom routine HCV testing is and is not recommended, testing for HCV infection, and prevention messages and medical evaluation. The section on public health surveillance covers surveillance for acute HCV, laboratory reports of anti-HCV-positive tests, serologic surveys, and surveillance for chronic liver disease. This report is intended to serve as a resource for health care professionals, public health officials, and organizations involved in the development, delivery, and evaluation of prevention and clinical services. The document includes a posttest and response form readers can use to qualify for continuing medical education credit. 3 figures. 9 tables. 158 references. (AA-M).
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The NLM Gateway31 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.32 One target audience for the Gateway is the Internet user who is new to NLM’s online resources and does not know what information is available or how best to search for it. This audience may include physicians and other healthcare providers, researchers, librarians, students, and, increasingly, patients, their families, and the public.33 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “hepatitis C” (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 Items Found Journal Articles 27446 Books / Periodicals / Audio Visual 289 Consumer Health 209 Meeting Abstracts 719 Other Collections 14 Total 28677
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x. 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). 33 Other users may find the Gateway useful for an overall search of NLM’s information resources. Some searchers may locate what they need immediately, while others will utilize the Gateway as an adjunct tool to other NLM search services such as PubMed® and MEDLINEplus®. The Gateway connects users with multiple NLM retrieval systems while also providing a search interface for its own collections. These collections include various types of information that do not logically belong in PubMed, LOCATORplus, or other established NLM retrieval systems (e.g., meeting announcements and pre-1966 journal citations). The Gateway will provide access to the information found in an increasing number of NLM retrieval systems in several phases. 31 32
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HSTAT34 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.35 HSTAT’s audience includes healthcare providers, health service researchers, policy makers, insurance companies, consumers, and the information professionals who serve these groups. HSTAT provides access to a wide variety of publications, including clinical practice guidelines, quick-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.36 Simply search by “hepatitis C” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
Coffee Break: Tutorials for Biologists37 Some patients may wish to have access to 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. To this end, we recommend “Coffee Break,” 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.38 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.39 This site has new Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. The HSTAT URL is http://hstat.nlm.nih.gov/. 36 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. 37 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 38 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. 39 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. 34 35
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articles every few weeks, so it can be considered an online magazine of sorts, and intended for general background information. You can access the Coffee Break Web site at 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 a few examples that may interest you: ·
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
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Image Engine: Multimedia electronic medical record system that integrates a wide range of digitized clinical images with textual data stored in the University of Pittsburgh Medical Center’s MARS electronic medical record system; see the following Web site: http://www.cml.upmc.edu/cml/imageengine/imageEngine.html.
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Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
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MedWeaver: Prototype system that allows users to search differential diagnoses for any list of signs and symptoms, to search medical literature, and to explore relevant Web sites; see http://www.med.virginia.edu/~wmd4n/medweaver.html.
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Metaphrase: Middleware component intended for use by both caregivers and medical records personnel. It converts the informal language generally used by caregivers into terms from formal, controlled vocabularies; see the following Web site: http://www.lexical.com/Metaphrase.html.
The Genome Project and Hepatitis C With all the discussion in the press about the Human Genome Project, it is only natural that physicians, researchers, and patients want to know about how human genes relate to hepatitis C. In the following section, we will discuss databases and references used by physicians and scientists who work in this area.
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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).40 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. Go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html to search the database. Type “hepatitis C” (or synonyms) in 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. By following these links, especially the link titled “Database Links,” you will be exposed to numerous specialized databases that are largely used by the scientific community. These databases are overly technical and seldom used by the general public, but offer an abundance of information. The following is an example of the results you can obtain from the OMIM for hepatitis C: ·
Adenomatous Polyposis of the Colon Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?175100
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Adenosine Deaminase Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?102700
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Angioedema, Hereditary Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?106100
·
Aryl Hydrocarbon Receptor-interacting Protein Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?605555
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.
40
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·
Asthma Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?600807
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Atpase, Cu(2+)-transporting, Beta Polypeptide Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?606882
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Atp-binding Cassette, Subfamily A, Member 1 Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?600046
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Autoimmune Diseases Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?109100
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Autoimmune Polyendocrinopathy Syndrome, Type I Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?240300
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Bare Lymphocyte Syndrome, Type Ii Web site: http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?209920 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 the system of the body associated with it. 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 re-visit it from time to time. The following systems and associated disorders are addressed: ·
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 disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.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-
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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, Baldness, Cockayne syndrome, Glaucoma, 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: ·
PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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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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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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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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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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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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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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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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3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” In the box next to “for,” enter “hepatitis C” (or synonyms) and click “Go.”
Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database41 This online resource can be quite useful. It 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 also search across syndromes using an alphabetical index. You can also search at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database42 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 42 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html#mission. 41
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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. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “hepatitis C” (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). This database is extremely technical as it was created for specialists. The articles are the results which are the most accessible to non-professionals and often listed under the heading “Citations.” The contact names are also accessible to non-professionals.
Specialized References The following books are specialized references written for professionals interested in hepatitis C (sorted alphabetically by title, hyperlinks provide rankings, information, and reviews at Amazon.com): · American Psychiatric Press Textbook of Substance Abuse Treatment by Marc Galanter (Editor), Herbert D. Kleber (Editor); Hardcover - 595 pages, 2nd edition (May 15, 1999), American Psychiatric Press; ISBN: 0880488204; http://www.amazon.com/exec/obidos/ASIN/0880488204/icongroupinterna · Combining Medication and Psychosocial Treatments for Addictions: The BRENDA Approach by Joseph Volpicelli (Editor), et al; Hardcover 208 pages, 1st edition (February 15, 2001), Guilford Press; ISBN: 1572306181; http://www.amazon.com/exec/obidos/ASIN/1572306181/icongroupinterna · Drink, Drugs and Dependence: From Science to Clinical Practice by Woody Caan (Editor); Paperback - 272 pages (June 1, 2002), Routledge;
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ISBN: 0415279011; http://www.amazon.com/exec/obidos/ASIN/0415279011/icongroupinterna · Neurobiology of Addictions: Implications for Clinical Practice by Richard T. Spence (Editor), et al; Hardcover (February 2002); ISBN: 0789016664; http://www.amazon.com/exec/obidos/ASIN/0789016664/icongroupinterna · Solutions for the ‘Treatment-Resistant’ Addicted Client : Therapeutic Techniques for Engaging Challenging Clients by Nicholas A. Roes; Textbook Binding (January 2002), Haworth Press; ISBN: 0789011204; http://www.amazon.com/exec/obidos/ASIN/0789011204/icongroupinterna · Substance Abuse: A Guide for Health Professionals by American Academy of Pediatrics, et al; Paperback - 379 pages, 2nd edition (November 15, 2001), American Nurses Association; ISBN: 1581100728; http://www.amazon.com/exec/obidos/ASIN/1581100728/icongroupinterna
Vocabulary Builder Angioedema: A vascular reaction involving the deep dermis or subcutaneous or submucal tissues, representing localized edema caused by dilatation and increased permeability of the capillaries, and characterized by development of giant wheals. [EU] 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]
Dissertations 243
CHAPTER 10. DISSERTATIONS ON HEPATITIS C Overview University researchers are active in studying almost all known diseases. The result of research is often published in the form of Doctoral or Master’s dissertations. You should understand, therefore, that applied diagnostic procedures and/or therapies can take many years to develop after the thesis that proposed the new technique or approach was written. In this chapter, we will give you a bibliography on recent dissertations relating to hepatitis C. You can read about these in more detail using the Internet or your local medical library. We will also provide you with information on how to use the Internet to stay current on dissertations.
Dissertations on Hepatitis C ProQuest Digital Dissertations is the largest archive of academic dissertations available. From this archive, we have compiled the following list covering dissertations devoted to hepatitis C. You will see that the information provided includes the dissertation’s title, its author, and the author’s institution. To read more about the following, simply use the Internet address indicated. The following covers recent dissertations dealing with hepatitis C:
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·
Communicating about Emerging Infectious Diseases: the Development and Dissemination of Recommendations on Hepatitis C to Primary Care Physicians by Barden, Louise Schuchardt; Phd from University of Georgia, 2001, 204 pages http://wwwlib.umi.com/dissertations/fullcit/3025243
·
Couples Coping with Chronic Hepatitis C by Bergmann, Catherine Melanie; Phd from University of Maryland College Park, 2001, 206 pages http://wwwlib.umi.com/dissertations/fullcit/3008992
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Empirical Approaches to Modeling Hiv and Hepatitis C (immune Deficiency) by Salomon, Joshua Asher; Phd from Harvard University, 2001, 163 pages http://wwwlib.umi.com/dissertations/fullcit/3011472
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Genetic Analysis of the Internal Ribosomal Entry Site of Hepatitis C Virus by Zhao, Weidong; Phd from State University of New York at Stony Brook, 2001, 97 pages http://wwwlib.umi.com/dissertations/fullcit/3024899
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Hepatitis C Virus among Young Drug Users by Hahn, Judith Alissa; Phd from University of California, Berkeley, 2001, 99 pages http://wwwlib.umi.com/dissertations/fullcit/3019664
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Modulation of Hepatitis C Virus Internal Ribosome Entry Sitemediated Translation by Rna Sequence Encoding the Viral Core Protein by Wang, Ting-hsien; Phd from The University of North Carolina at Chapel Hill, 2001, 114 pages http://wwwlib.umi.com/dissertations/fullcit/3031927
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Molecular Studies of Poliovirus: Inhibition of Picornavirus and Hepatitis C Virus Ires-mediated Translation and a Molecular Dissection of Polioviral 2a(pro) Proteinase by Li, Xiaoyu; Phd from State University of New York at Stony Brook, 2001, 164 pages http://wwwlib.umi.com/dissertations/fullcit/3024856
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Prevalence of Hepatitis C Infection in a Texas Prison by Chao, Grace C.; Mph from The University of Texas Graduate Sch. of Biomedical Sci. at Galveston, 2001, 35 pages http://wwwlib.umi.com/dissertations/fullcit/1406867
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The Pathogenesis of Human Immunodeficiency Virus in a Cohort of Patients Co-infected with Hepatitis C Virus (immune Deficiency) by Bowker, Samantha L.; Msc from University of Alberta (canada), 2001, 143 pages http://wwwlib.umi.com/dissertations/fullcit/MQ60415
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·
Using Administrative Data to Assemble a Cohort of Women Infected with Hepatitis C by Yeung, Latifa Tse Fung; Msc from University of Toronto (canada), 2001, 111 pages http://wwwlib.umi.com/dissertations/fullcit/MQ63070
Keeping Current As previously mentioned, an effective way to stay current on dissertations dedicated to hepatitis C is to use the database called ProQuest Digital Dissertations via the Internet, located at the following Web address: http://wwwlib.umi.com/dissertations. The site allows you to freely access the last two years of citations and abstracts. Ask your medical librarian if the library has full and unlimited access to this database. From the library, you should be able to do more complete searches than with the limited 2-year access available to the general public.
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PART III. APPENDICES
ABOUT PART III Part III is a collection of appendices on general medical topics which may be of interest to patients with hepatitis C and related conditions.
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APPENDIX A. RESEARCHING YOUR MEDICATIONS Overview There are a number of sources available on new or existing medications which could be prescribed to patients with hepatitis C. While a number of hard copy or CD-Rom resources are available to patients and physicians for research purposes, a more flexible method is to use Internet-based databases. In this chapter, we will begin with a general overview of medications. We will then proceed to outline official recommendations on how you should view your medications. You may also want to research medications that you are currently taking for other conditions as they may interact with medications for hepatitis C. Research can give you information on the side effects, interactions, and limitations of prescription drugs used in the treatment of hepatitis C. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
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Your Medications: The Basics43 The Agency for Health Care Research and Quality has published extremely useful guidelines on how you can best participate in the medication aspects of hepatitis C. Taking medicines is not always as simple as swallowing a pill. It can involve many steps and decisions each day. The AHCRQ recommends that patients with hepatitis C take part in treatment decisions. Do not be afraid to ask questions and talk about your concerns. By taking a moment to ask questions early, you may avoid problems later. Here are some points to cover each time a new medicine is prescribed: ·
Ask about all parts of your treatment, including diet changes, exercise, and medicines.
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Ask about the risks and benefits of each medicine or other treatment you might receive.
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Ask how often you or your doctor will check for side effects from a given medication.
Do not hesitate to ask what is important to you about your medicines. You may want a medicine with the fewest side effects, or the fewest doses to take each day. You may care most about cost, or how the medicine might affect how you live or work. Or, you may want the medicine your doctor believes will work the best. Telling your doctor will help him or her select the best treatment for you. Do not be afraid to “bother” your doctor with your concerns and questions about medications for hepatitis C. You can also talk to a nurse or a pharmacist. They can help you better understand your treatment plan. Feel free to bring a friend or family member with you when you visit your doctor. Talking over your options with someone you trust can help you make better choices, especially if you are not feeling well. Specifically, ask your doctor the following: ·
The name of the medicine and what it is supposed to do.
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How and when to take the medicine, how much to take, and for how long.
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What food, drinks, other medicines, or activities you should avoid while taking the medicine.
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What side effects the medicine may have, and what to do if they occur.
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If you can get a refill, and how often.
43
This section is adapted from AHCRQ: http://www.ahcpr.gov/consumer/ncpiebro.htm.
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·
About any terms or directions you do not understand.
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What to do if you miss a dose.
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If there is written information you can take home (most pharmacies have information sheets on your prescription medicines; some even offer large-print or Spanish versions).
Do not forget to tell your doctor about all the medicines you are currently taking (not just those for hepatitis C). This includes prescription medicines and the medicines that you buy over the counter. Then your doctor can avoid giving you a new medicine that may not work well with the medications you take now. When talking to your doctor, you may wish to prepare a list of medicines you currently take, the reason you take them, and how you take them. Be sure to include the following information for each: ·
Name of medicine
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Reason taken
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Dosage
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Time(s) of day
Also include any over-the-counter medicines, such as: ·
Laxatives
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Diet pills
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Vitamins
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Cold medicine
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Aspirin or other pain, headache, or fever medicine
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Cough medicine
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Allergy relief medicine
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Antacids
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Sleeping pills
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Others (include names)
Learning More about Your Medications Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications your doctor has recommended for hepatitis C. One such source
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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 non-profit 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 www.usp.org. The USP currently provides standards for over 3,700 medications. The resulting USP DIÒ Advice for the PatientÒ can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database.44 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 Pharmacopoeia (USP). It is important to read the disclaimer by the USP (http://www.nlm.nih.gov/medlineplus/drugdisclaimer.html) before using the information provided. Of course, we as editors cannot be certain as to what medications you are taking. Therefore, we have compiled a list of medications associated with the treatment of hepatitis C. Once again, due to space limitations, we only list a sample of medications and provide hyperlinks to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to hepatitis C: 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/antihemophilicf actorsystemic202671.html
Though cumbersome, the FDA database can be freely browsed at the following site: www.fda.gov/cder/da/da.htm.
44
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Factor Ix ·
Systemic - U.S. Brands: BeneFix; Mononine http://www.nlm.nih.gov/medlineplus/druginfo/factorixsystemic 202674.html
Interferon Alfacon-1 ·
Systemic - U.S. Brands: Infergen http://www.nlm.nih.gov/medlineplus/druginfo/interferonalfaco n1systemic203504.html
Peginterferon Alfa-2B ·
Systemic - U.S. Brands: PEG-Intron http://www.nlm.nih.gov/medlineplus/druginfo/peginterferonalf a2bsystemic500287.html
Ribavirin ·
Systemic - U.S. Brands: Virazole http://www.nlm.nih.gov/medlineplus/druginfo/ribavirinsystemi c202509.html
Ribavirin and Interferon Alfa-2B, Recombinant ·
Systemic - U.S. Brands: Rebetron http://www.nlm.nih.gov/medlineplus/druginfo/ribavirinandinte rferonalfa2bre500032.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. You may be able to access these sources from your local medical library or your doctor’s office.
Reuters Health Drug Database The Reuters Health Drug Database can be searched by keyword at the hyperlink: http://www.reutershealth.com/frame2/drug.html. The following medications are listed in the Reuters’ database as associated with hepatitis C (including those with contraindications):45 45
Adapted from A to Z Drug Facts by Facts and Comparisons.
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·
Hepatitis B Vaccine http://www.reutershealth.com/atoz/html/Hepatitis_B_Vaccine.htm
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Interferon Alfacon-I http://www.reutershealth.com/atoz/html/Interferon_Alfacon-I.htm
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Interferon beta-1a http://www.reutershealth.com/atoz/html/Interferon_beta-1a.htm
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Interferon Beta-1b (rIFN-B) http://www.reutershealth.com/atoz/html/Interferon_Beta-1b_(rIFNB).htm
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Interferon Beta-1b(rIFN-B) http://www.reutershealth.com/atoz/html/Interferon_Beta-1b(rIFNB).htm
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Peginterferon Alfa-2B http://www.reutershealth.com/atoz/html/Peginterferon_Alfa-2B.htm
Mosby’s GenRx Mosby’s GenRx 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. Information can be obtained at the following hyperlink: http://www.genrx.com/Mosby/PhyGenRx/group.html.
Physicians Desk Reference The Physicians Desk Reference database (also available in CD-Rom and book format) is a full-text drug database. The database is searchable by brand name, generic name or by indication. It features multiple drug interactions reports. Information can be obtained at the following hyperlink: http://physician.pdr.net/physician/templates/en/acl/psuser_t.htm. Other Web Sites A number of additional Web sites discuss drug information. As an example, you may like to look at www.drugs.com which 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. which allows users to
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download articles on various drugs and therapeutics for a nominal fee: http://www.medletter.com/.
Contraindications and Interactions (Hidden Dangers) Some of the medications mentioned in the previous discussions can be problematic for patients with hepatitis C--not because they are used in the treatment process, but because of contraindications, or side effects. Medications with contraindications are those that could react with drugs used to treat hepatitis C or potentially create deleterious side effects in patients with hepatitis C. You should ask your physician about any contraindications, especially as these might apply to other medications that you may be taking for common ailments. Drug-drug interactions occur when two or more drugs react with each other. This drug-drug interaction may cause you to experience an unexpected side effect. Drug interactions may make your medications less effective, cause unexpected side effects, or increase the action of a particular drug. Some drug interactions can even be harmful to you. Be sure to read the label every time you use a nonprescription or prescription drug, and take the time to learn about drug interactions. These precautions may be critical to your health. You can reduce the risk of potentially harmful drug interactions and side effects with a little bit of knowledge and common sense. Drug labels contain important information about ingredients, uses, warnings, and directions which you should take the time to read and understand. Labels also include warnings about possible drug interactions. Further, drug labels may change as new information becomes available. This is why it’s especially important to read the label every time you use a medication. When your doctor prescribes a new drug, discuss all over-thecounter and prescription medications, dietary supplements, vitamins, botanicals, minerals and herbals you take as well as the foods you eat. Ask your pharmacist for the package insert for each prescription drug you take. The package insert provides more information about potential drug interactions.
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A Final Warning At some point, you may hear of alternative medications from friends, relatives, or in the news media. Advertisements may suggest that certain alternative drugs can produce positive results for patients with hepatitis C. Exercise caution--some of these drugs may have fraudulent claims, and others may actually hurt you. The Food and Drug Administration (FDA) is the official U.S. agency charged with discovering which medications are likely to improve the health of patients with hepatitis C. The FDA warns patients to watch out for46: ·
Secret formulas (real scientists share what they know)
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Amazing breakthroughs or miracle cures (real breakthroughs don’t happen very often; when they do, real scientists do not call them amazing or miracles)
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Quick, painless, or guaranteed cures
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If it sounds too good to be true, it probably isn’t true.
If you have any questions about any kind of 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, 1888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
General References In addition to the resources provided earlier in this chapter, the following general references describe medications (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·
Complete Guide to Prescription and Nonprescription Drugs 2001 (Complete Guide to Prescription and Nonprescription Drugs, 2001) by H. Winter Griffith, Paperback 16th edition (2001), Medical Surveillance; ISBN: 0942447417; http://www.amazon.com/exec/obidos/ASIN/039952634X/icongroupinterna
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The Essential Guide to Prescription Drugs, 2001 by James J. Rybacki, James W. Long; Paperback - 1274 pages (2001), Harper Resource; ISBN: 0060958162; http://www.amazon.com/exec/obidos/ASIN/0060958162/icongroupinterna
46
This section has been adapted from http://www.fda.gov/opacom/lowlit/medfraud.html.
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·
Handbook of Commonly Prescribed Drugs by G. John Digregorio, Edward J. Barbieri; Paperback 16th edition (2001), Medical Surveillance; ISBN: 0942447417; http://www.amazon.com/exec/obidos/ASIN/0942447417/icongroupinterna
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Johns Hopkins Complete Home Encyclopedia of Drugs 2nd ed. by Simeon Margolis (Ed.), Johns Hopkins; Hardcover - 835 pages (2000), Rebus; ISBN: 0929661583; http://www.amazon.com/exec/obidos/ASIN/0929661583/icongroupinterna
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Medical Pocket Reference: Drugs 2002 by Springhouse Paperback 1st edition (2001), Lippincott Williams & Wilkins Publishers; ISBN: 1582550964; http://www.amazon.com/exec/obidos/ASIN/1582550964/icongroupinterna
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PDR by Medical Economics Staff, Medical Economics Staff Hardcover 3506 pages 55th edition (2000), Medical Economics Company; ISBN: 1563633752; http://www.amazon.com/exec/obidos/ASIN/1563633752/icongroupinterna
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Pharmacy Simplified: A Glossary of Terms by James Grogan; Paperback 432 pages, 1st edition (2001), Delmar Publishers; ISBN: 0766828581; http://www.amazon.com/exec/obidos/ASIN/0766828581/icongroupinterna
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Physician Federal Desk Reference by Christine B. Fraizer; Paperback 2nd edition (2001), Medicode Inc; ISBN: 1563373971; http://www.amazon.com/exec/obidos/ASIN/1563373971/icongroupinterna
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Physician’s Desk Reference Supplements Paperback - 300 pages, 53 edition (1999), ISBN: 1563632950; http://www.amazon.com/exec/obidos/ASIN/1563632950/icongroupinterna
Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH]
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APPENDIX B. RESEARCHING ALTERNATIVE MEDICINE Overview Complementary and alternative medicine (CAM) is one of the most contentious aspects of modern medical practice. You may have heard of these treatments on the radio or on television. Maybe you have seen articles written about these treatments in magazines, newspapers, or books. Perhaps your friends or doctor have mentioned alternatives. In this chapter, we will begin by giving you a broad perspective on complementary and alternative therapies. Next, we will introduce you to official information sources on CAM relating to hepatitis C. Finally, at the conclusion of this chapter, we will provide a list of readings on hepatitis C from various authors. We will begin, however, with the National Center for Complementary and Alternative Medicine’s (NCCAM) overview of complementary and alternative medicine.
What Is CAM?47 Complementary and alternative medicine (CAM) covers a broad range of healing philosophies, approaches, and therapies. Generally, it is defined as those treatments and healthcare practices which are not taught in medical schools, used in hospitals, or reimbursed by medical insurance companies. Many CAM therapies are termed “holistic,” which generally means that the healthcare practitioner considers the whole person, including physical, mental, emotional, and spiritual health. Some of these therapies are also known as “preventive,” which means that the practitioner educates and 47
Adapted from the NCCAM: http://nccam.nih.gov/nccam/fcp/faq/index.html#what-is.
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treats the person to prevent health problems from arising, rather than treating symptoms after problems have occurred. People use CAM treatments and therapies in a variety of ways. Therapies are used alone (often referred to as alternative), in combination with other alternative therapies, or in addition to conventional treatment (sometimes referred to as complementary). Complementary and alternative medicine, or “integrative medicine,” includes a broad range of healing philosophies, approaches, and therapies. Some approaches are consistent with physiological principles of Western medicine, while others constitute healing systems with non-Western origins. While some therapies are far outside the realm of accepted Western medical theory and practice, others are becoming established in mainstream medicine. Complementary and alternative therapies are used in an effort to prevent illness, reduce stress, prevent or reduce side effects and symptoms, or control or cure disease. Some commonly used methods of complementary or alternative therapy include mind/body control interventions such as visualization and relaxation, manual healing including acupressure and massage, homeopathy, vitamins or herbal products, and acupuncture.
What Are the Domains of Alternative Medicine?48 The list of CAM practices changes continually. The reason being is that these new practices and therapies are often proved to be safe and effective, and therefore become generally accepted as “mainstream” healthcare practices. Today, CAM practices may be grouped within five major domains: (1) alternative medical systems, (2) mind-body interventions, (3) biologicallybased treatments, (4) manipulative and body-based methods, and (5) energy therapies. The individual systems and treatments comprising these categories are too numerous to list in this sourcebook. Thus, only limited examples are provided within each. Alternative Medical Systems Alternative medical systems involve complete systems of theory and practice that have evolved independent of, and often prior to, conventional biomedical approaches. Many are traditional systems of medicine that are
48
Adapted from the NCCAM: http://nccam.nih.gov/nccam/fcp/classify/index.html.
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practiced by individual cultures throughout the world, including a number of venerable Asian approaches. Traditional oriental medicine emphasizes the balance or disturbances of qi (pronounced chi) or vital energy in health and disease, respectively. Traditional oriental medicine consists of a group of techniques and methods including acupuncture, herbal medicine, oriental massage, and qi gong (a form of energy therapy). Acupuncture involves stimulating specific anatomic points in the body for therapeutic purposes, usually by puncturing the skin with a thin needle. Ayurveda is India’s traditional system of medicine. Ayurvedic medicine (meaning “science of life”) is a comprehensive system of medicine that places equal emphasis on body, mind, and spirit. Ayurveda strives to restore the innate harmony of the individual. Some of the primary Ayurvedic treatments include diet, exercise, meditation, herbs, massage, exposure to sunlight, and controlled breathing. Other traditional healing systems have been developed by the world’s indigenous populations. These populations include Native American, Aboriginal, African, Middle Eastern, Tibetan, and Central and South American cultures. Homeopathy and naturopathy are also examples of complete alternative medicine systems. Homeopathic medicine is an unconventional Western system that is based on the principle that “like cures like,” i.e., that the same substance that in large doses produces the symptoms of an illness, in very minute doses cures it. Homeopathic health practitioners believe that the more dilute the remedy, the greater its potency. Therefore, they use small doses of specially prepared plant extracts and minerals to stimulate the body’s defense mechanisms and healing processes in order to treat illness. Naturopathic medicine is based on the theory that disease is a manifestation of alterations in the processes by which the body naturally heals itself and emphasizes health restoration rather than disease treatment. Naturopathic physicians employ an array of healing practices, including the following: diet and clinical nutrition, homeopathy, acupuncture, herbal medicine, hydrotherapy (the use of water in a range of temperatures and methods of applications), spinal and soft-tissue manipulation, physical therapies (such as those involving electrical currents, ultrasound, and light), therapeutic counseling, and pharmacology.
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Mind-Body Interventions Mind-body interventions employ a variety of techniques designed to facilitate the mind’s capacity to affect bodily function and symptoms. Only a select group of mind-body interventions having well-documented theoretical foundations are considered CAM. For example, patient education and cognitive-behavioral approaches are now considered “mainstream.” On the other hand, complementary and alternative medicine includes meditation, certain uses of hypnosis, dance, music, and art therapy, as well as prayer and mental healing.
Biological-Based Therapies This category of CAM includes natural and biological-based practices, interventions, and products, many of which overlap with conventional medicine’s use of dietary supplements. This category includes herbal, special dietary, orthomolecular, and individual biological therapies. Herbal therapy employs an individual herb or a mixture of herbs for healing purposes. An herb is a plant or plant part that produces and contains chemical substances that act upon the body. Special diet therapies, such as those proposed by Drs. Atkins, Ornish, Pritikin, and Weil, are believed to prevent and/or control illness as well as promote health. Orthomolecular therapies aim to treat disease with varying concentrations of chemicals such as magnesium, melatonin, and mega-doses of vitamins. Biological therapies include, for example, the use of laetrile and shark cartilage to treat cancer and the use of bee pollen to treat autoimmune and inflammatory diseases.
Manipulative and Body-Based Methods This category includes methods that are based on manipulation and/or movement of the body. For example, chiropractors focus on the relationship between structure and function, primarily pertaining to the spine, and how that relationship affects the preservation and restoration of health. Chiropractors use manipulative therapy as an integral treatment tool. In contrast, osteopaths place particular emphasis on the musculoskeletal system and practice osteopathic manipulation. Osteopaths believe that all of the body’s systems work together and that disturbances in one system may have an impact upon function elsewhere in the body. Massage therapists manipulate the soft tissues of the body to normalize those tissues.
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Energy Therapies Energy therapies focus on energy fields originating within the body (biofields) or those from other sources (electromagnetic fields). Biofield therapies are intended to affect energy fields (the existence of which is not yet experimentally proven) that surround and penetrate the human body. Some forms of energy therapy manipulate biofields by applying pressure and/or manipulating the body by placing the hands in or through these fields. Examples include Qi gong, Reiki and Therapeutic Touch. Qi gong is a component of traditional oriental medicine that combines movement, meditation, and regulation of breathing to enhance the flow of vital energy (qi) in the body, improve blood circulation, and enhance immune function. Reiki, the Japanese word representing Universal Life Energy, is based on the belief that, by channeling spiritual energy through the practitioner, the spirit is healed and, in turn, heals the physical body. Therapeutic Touch is derived from the ancient technique of “laying-on of hands.” It is based on the premises that the therapist’s healing force affects the patient’s recovery and that healing is promoted when the body’s energies are in balance. By passing their hands over the patient, these healers identify energy imbalances. Bioelectromagnetic-based therapies involve the unconventional use of electromagnetic fields to treat illnesses or manage pain. These therapies are often used to treat asthma, cancer, and migraine headaches. Types of electromagnetic fields which are manipulated in these therapies include pulsed fields, magnetic fields, and alternating current or direct current fields.
Can Alternatives Affect My Treatment? A critical issue in pursuing complementary alternatives mentioned thus far is the risk that these might have undesirable interactions with your medical treatment. It becomes all the more important to speak with your doctor who can offer advice on the use of alternatives. Official sources confirm this view. Though written for women, we find that the National Women’s Health Information Center’s advice on pursuing alternative medicine is appropriate for patients of both genders and all ages.49
49
Adapted from http://www.4woman.gov/faq/alternative.htm.
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Is It Okay to Want Both Traditional and Alternative Medicine? Should you wish to explore non-traditional types of treatment, be sure to discuss all issues concerning treatments and therapies with your healthcare provider, whether a physician or practitioner of complementary and alternative medicine. Competent healthcare management requires knowledge of both conventional and alternative therapies you are taking for the practitioner to have a complete picture of your treatment plan. The decision to use complementary and alternative treatments is an important one. Consider before selecting an alternative therapy, the safety and effectiveness of the therapy or treatment, the expertise and qualifications of the healthcare practitioner, and the quality of delivery. These topics should be considered when selecting any practitioner or therapy.
Finding CAM References on Hepatitis C Having read the previous discussion, you may be wondering which complementary or alternative treatments might be appropriate for hepatitis C. For the remainder of this chapter, we will direct you to a number of official sources which can assist you in researching studies and publications. Some of these articles are rather technical, so some patience may be required.
The Combined Health Information Database For a targeted search, The Combined Health Information Database is a bibliographic database produced by health-related agencies of the Federal Government (mostly from the National Institutes of Health). This database is updated four times a year at the end of January, April, July, and October. Check the titles, summaries, and availability of CAM-related information by using the “Simple Search” option at the following Web site: http://chid.nih.gov/simple/simple.html. In the drop box at the top, select “Complementary and Alternative Medicine.” Then type “hepatitis C” (or synonyms) in the second search box. We recommend that you select 100 “documents per page” and to check the “whole records” options. The following was extracted using this technique: ·
Hepatitis C: A Retrospective Study, Literature Review, and Naturopathic Protocol Source: Alternative Medicine Review. 5(4): 355-370. August 2000.
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Summary: This journal article presents a retrospective study, literature review, and naturopathic protocol for hepatitis C. The authors performed a retrospective review of 41 consecutive hepatitis C patients. Of 14 patients with baseline and follow-up data who had not undergone interferon therapy, 7 had a greater than 25 percent reduction in serum alanine aminotransferase (ALT) levels after at least 1 month on a naturopathic protocol that included colchicine, ursodeoxycholic acid (UDCA), silymarin, and antioxidants. This finding suggests that a conservative approach using diet and lifestyle modification together with safe and indicated natural therapies may be effective in the treatment of hepatitis C. Primary interventions (supported by human research) include colchicine, UDCA, silymarin, vitamin E, glycyrrhiza glabra, and sho-saiko-to (a Japanese herbal medicine). Secondary interventions (supported by animal and/or in vitro research are of limited benefit) include selenium, cod liver oil, n-acetyl-L-cysteine, thymus extract, Liv52, and lipoic acid. Tertiary interventions (whose benefit is largely theoretical) include folic acid, vitamin B-12, vitamin C, DHEA, and melatonin. The article has 4 tables and 95 references. ·
Hepatitis C: Epidemiology and Review of Complementary/Alternative Medicine Treatments Source: Alternative Medicine Review. 4(4): 220-238. 1999. Summary: This journal article reviews the epidemiology of hepatitis C and the complementary and alternative therapies used for its treatment. The first part discusses the prevalence, history, virus genotypes, transmission, and clinical course of hepatitis C. It also addresses coinfection with human immunodeficiency virus, the risk of hepatocellular carcinoma, liver biopsy and the assessment of disease progression, and mechanisms of action of ribavirin. The second part reviews the efficacy of various antioxidants and immunomodulatory and antiviral botanicals and plant extracts that have been used to treat hepatitis. These botanicals include phytosterols, vitamin E, N-acetylcysteine, glycyrrhizin, catechins, and silymarin. Although some of these botanicals have been evaluated only in hepatitis B, evidence suggests that they may have applicability in hepatitis C. The article has 5 figures, 1 table, and 120 references.
·
Treatment of Hepatitis C: Emerging Evidence of the Need for Change Source: Alternative Medicine Review. 4(4): 219. 1999. Summary: This editorial discusses the need to consider alternative therapies for hepatitis C. The author argues that current treatments are costly and associated with serious side effects that exclude their use in certain patient populations, including pregnant women and patients with
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human immunodeficiency virus infection. On the other hand, there is evidence of lowered viral loads and improved liver histology with botanical extracts such as glycyrrhizin, catechin, and silymarin. In the author's opinion, there is an urgent need to consider the benefits and, in some cases, necessities of alternative therapies for hepatitis C. ·
Review Article: Glycyrrhizin As a Potential Treatment for Chronic Hepatitis C Source: Alimentary Pharmacology and Therapeutics. 12(3): 199-205. March 1998. Summary: This journal article reviews the literature on glycyrrhizin as a potential treatment for chronic hepatitis C, including its metabolism and pharmacokinetics, side effects, and anti-viral and hepatoprotective effects. Glycyrrhizin is a natural compound extracted from the roots of 'Glycyrrhiza glabra.' In Japan, glycyrrhizin has been used for more than 20 years as a treatment for chronic hepatitis. In randomized controlled trials, it induced a significant reduction of serum aminotransferases and an improvement in liver histology compared with placebo. In addition, recent results from a retrospective study suggest that long-term use of glycyrrhizin may be effective in preventing the development of hepatocellular carcinoma in patients with chronic hepatitis C. The mechanism by which glycyrrhizin improves liver biochemistry and histology is unknown, however, and the optimal treatment schedule has yet to be defined. Still, in the author's opinion, glycyrrhizin appears to have potential for reducing the long-term complications of chronic viral hepatitis in patients who do not respond with viral clearance to interferon therapy. The article has 3 figures, 1 table, and 43 references.
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Two Cases of Hepatitis C Treated With Herbs and Supplements Source: Journal of Alternative and Complementary Medicine: Research on Paradigm, Practice and Policy. 3(1): 77-82. 1997. Summary: This journal article describes two cases of hepatitis C treated with herbs and nutritional supplements. In both cases, the diagnosis and treatment were based on biomedical findings and traditional Chinese medicine (TCM) analysis. The first case was a man, age 53 years, with hepatitis C and severe fatigue. His TCM diagnosis was excess heat in the liver and blood, liver and kidney yin deficiency, and qi and blood deficiency. He was treated with two Chinese herbal formulas (Granule formula and eclipta tablets), supplemented with Mycoferon and Silymarin. The patient reported an immediate increase in energy, and serum liver enzyme levels showed improvement within 4 months. The second case was a woman, aged 61 years, with an 8-year history of
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hepatitis C. She had extreme fatigue and depression, mild hypertension, frequent kidney and bladder infections, and edema in both legs. Her TCM diagnosis was kidney and liver yin deficiency, kidney yang deficiency, excess heat in the liver and blood with some blood stasis, and qi and blood deficiency. She was prescribed the same Granule formula and eclipta tablets, Mycoferon, Silymarin, and vitamin B12 with folic acid. The treatment decreased serum liver enzymes, increased energy, and greatly reduced the frequency and severity of kidney and bladder infections. The article has 1 table and 8 references. ·
Hepatitis C: Treatment Alternatives Source: Gaithersburg, MD: National Center for Complementary and Alternative Medicine Clearinghouse. 2000. 8 p. Contact: Available from National Center for Complementary and Alternative Medicine Clearinghouse. P.O. Box 7923, Gaithersburg, MD 20898. (888) 644-6226; INTERNATIONAL PHONE: (301) 519-3153; TTY: (866) 464-3615; FAX: (866) 464-3616; E-MAIL:
[email protected]. Price: Free. Publication Number: D004. Summary: This monograph discusses alternative treatments for hepatitis C. The most promising alternative treatment appears to be the herb commonly called milk thistle. Available evidence suggests that milk thistle does not cure liver disease, but it may improve the way the liver works in patients with cirrhosis. However, there is no evidence indicating that milk thistle directly affects hepatitis C virus (HCV). Licorice root and ginseng also may help reduce the damage to liver tissue caused by hepatitis. Ginger and St. John's wort have been used to treat some of the side effects of conventional treatment with interferon. This article provides the following information: (1) overview of hepatitis C; (2) a summary of evidence for the potential benefits of milk thistle and other herbs; (3) a glossary of terms; (4) practical suggestions for people with HCV infection; (5) a list of organizations for additional information; and (6) 21 references.
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Oral Thymic Extract To Treat Hepatitis C (letters to the editor) Source: Annals of Internal Medicine. 131(4): 312. August 17, 1999. Summary: These letters to the editor discuss Raymond and colleagues' recent report of negative results in a trial of oral thymic extract for the treatment of hepatitis C virus (HCV) infection (see AMJA02251 for the report). The letter by R.D. Blank questions the authors' reported use of a 'qualitative' multicycle reverse transcription polymerase chain (PCR) reaction assay, which would render the reported HCV quantitation data
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meaningless. In a separate letter, J.L. Frossard suggests that thymic extract alone had no effect in chronic hepatitis C because the authors tested it in patients who did not respond to previous monotherapy with interferon. In response to these letters, G.A. Abrams (one of Raymond's coauthors) points out that the PCR assay was misidentified as qualitative when, in fact, it was quantitative. He agrees with J.L. Frossard that combination therapy is more effective than monotherapy in naive patients, but challenges his statement that patients in whom interferon monotherapy fails will probably not respond to a new monotherapy. ·
Oral Thymic Extract for Chronic Hepatitis C in Patients Previously Treated With Interferon Source: Annals of Internal Medicine. 129(10): 797-800. 1998. Summary: This journal article describes a randomized, double-blind, controlled trial of an oral thymic extract for chronic hepatitis C in patients previously treated with interferon. Thirty-eight patients who did not respond to or were intolerant of interferon therapy were randomly assigned to receive either Complete Thymic Formula (an over-thecounter herbal dietary Supplement) or placebo for 12 weeks. All participants then received active treatment for another 6 months in an open-label phase. Titers of hepatitis C virus (HCV) RNA were measured before enrollment, 3 months after randomization, and after 6 months of active therapy. At 3 months, there were no differences between the treatment and placebo groups in mean HCV RNA titers. The 19 patients who completed 6 months of treatment with Complete Thymic Formula remained positive for HCV, and their mean HCV RNA titers were not significantly changed at 6 months compared with baseline. One patient developed severe thrombocytopenia that may have been associated with use of the thymic formula. The authors conclude that HCV patients should be advised of the apparent lack of efficacy and potential risks of Complete Thymic Formula. The article has 2 tables and 16 references. (See AMJA02244 for commentaries on this article.).
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 allow patients to search for articles that specifically relate to hepatitis C and complementary medicine. To search the database, go to the following Web site: www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on
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PubMed.” Enter “hepatitis C” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine (CAM) that are related to hepatitis C: ·
A case-control study of risk factors for sporadic hepatitis C virus infection in the southwestern United States. Author(s): Balasekaran R, Bulterys M, Jamal MM, Quinn PG, Johnston DE, Skipper B, Chaturvedi S, Arora S. Source: The American Journal of Gastroenterology. 1999 May; 94(5): 1341-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10235216&dopt=Abstract
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A case-control study on the risk factors of hepatitis C virus infection among Koreans. Author(s): Kim YS, Ahn YO, Kim DW. Source: Journal of Korean Medical Science. 1996 February; 11(1): 38-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8703369&dopt=Abstract
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A clinical study on bing gan ling oral liquid for treatment of hepatitis C. Author(s): You S, Zhou M, Xue B, Fang T, Jiang W, Li C, Xu H, Jiang J, Wang Y, Xu S. Source: J Tradit Chin Med. 1998 September; 18(3): 209-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10453617&dopt=Abstract
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A conservative triple antioxidant approach to the treatment of hepatitis C. Combination of alpha lipoic acid (thioctic acid), silymarin, and selenium: three case histories. Author(s): Berkson BM. Source: Medizinische Klinik (Munich, Germany : 1983). 1999 October 15; 94 Suppl 3: 84-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10554539&dopt=Abstract
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A pilot study of iron depletion as adjuvant therapy in chronic hepatitis C patients not responding to interferon. Author(s): Guyader D, Boucher E, Andre P, Even C, Cottereau J, Bianchi A, Gasser P, Mendler MH, Deugnier Y, Brissot P.
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Source: The American Journal of Gastroenterology. 1999 June; 94(6): 16968. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10364051&dopt=Abstract ·
A survey of antibodies to hepatitis C virus in Ethiopia. Author(s): Frommel D, Tekle-Haimanot R, Berhe N, Aussel L, Verdier M, Preux PM, Denis F. Source: Am J Trop Med Hyg. 1993 October; 49(4): 435-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7692753&dopt=Abstract
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Analyzing the mechanisms of interferon-induced apoptosis using CrmA and hepatitis C virus NS5A. Author(s): Ezelle HJ, Balachandran S, Sicheri F, Polyak SJ, Barber GN. Source: Virology. 2001 March 1; 281(1): 124-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11222103&dopt=Abstract
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Antioxidant drugs combined with alpha-interferon in chronic hepatitis C not responsive to alpha-interferon alone: a randomized, multicentre study. Author(s): Ideo G, Bellobuono A, Tempini S, Mondazzi L, Airoldi A, Benetti G, Bissoli F, Cestari C, Colombo E, Del Poggio P, Fracassetti O, Lazzaroni S, Marelli A, Paris B, Prada A, Rainer E, Roffi L. Source: European Journal of Gastroenterology & Hepatology. 1999 November; 11(11): 1203-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10563527&dopt=Abstract
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Approach to the patient with chronic hepatitis C virus infection. Author(s): Herrine SK. Source: Annals of Internal Medicine. 2002 May 21; 136(10): 747-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12020143&dopt=Abstract
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Changes of liver fibrosis in chronic hepatitis C patients with no response to interferon-alpha therapy: including quantitative assessment by a morphometric method. Author(s): Yagura M, Murai S, Kojima H, Tokita H, Kamitsukasa H, Harada H.
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Source: Journal of Gastroenterology. 2000; 35(2): 105-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10680665&dopt=Abstract ·
Chronic hepatitis C in children: a clinical and immunohistochemical comparative study with adult patients. Author(s): Garcia-Monzon C, Jara P, Fernandez-Bermejo M, Hierro L, Frauca E, Camarena C, Diaz C, De la Vega A, Larrauri J, Garcia-Iglesias C, Borque MJ, Sanz P, Garcia-Buey L, Moreno-Monteagudo JA, MorenoOtero R. Source: Hepatology (Baltimore, Md.). 1998 December; 28(6): 1696-701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9828237&dopt=Abstract
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Cleavage activity of hepatitis C virus serine proteinase. Author(s): Kakiuchi N, Komoda Y, Hijikata M, Shimotohno K. Source: Journal of Biochemistry. 1997 October; 122(4): 749-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9399578&dopt=Abstract
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Combination therapy with interferon alpha and ribavirin for chronic hepatitis C virus infection in thalassaemic patients. Author(s): Telfer PT, Garson JA, Whitby K, Grant PR, Yardumian A, Hoffbrand AV, Wonke B. Source: British Journal of Haematology. 1997 September; 98(4): 850-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9326177&dopt=Abstract
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Commercial tattooing as a potentially important source of hepatitis C infection. Clinical epidemiology of 626 consecutive patients unaware of their hepatitis C serologic status. Author(s): Haley RW, Fischer RP. Source: Medicine; Analytical Reviews of General Medicine, Neurology, Psychiatry, Dermatology, and Pediatries. 2001 March; 80(2): 134-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11307589&dopt=Abstract
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Could chelation therapy with deferoxamine enhance the percentage of responders to interferon therapy in chronic hepatitis C? Author(s): Leonardi S, Musumeci S.
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Source: Acta Haematologica. 1993; 90(4): 211-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8140864&dopt=Abstract ·
Does the control of alanine aminotransferase levels lead to a regression of liver fibrosis in chronic hepatitis C patients? Author(s): Yagura M, Murai S, Kojima H, Tokita H, Kamitsukasa H, Harada H. Source: Hepatology Research : the Official Journal of the Japan Society of Hepatology. 2001 February; 19(2): 144-157. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11164739&dopt=Abstract
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Effects of a mistletoe preparation with defined lectin content on chronic hepatitis C: an individually controlled cohort study. Author(s): Huber R, Ludtke R, Klassen M, Muller-Buscher G, WolffVorbeck G, Scheer R. Source: European Journal of Medical Research. 2001 September 28; 6(9): 399-405. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11669085&dopt=Abstract
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Effects of handling and storage of blood on the stability of hepatitis C virus RNA: implications for NAT testing in transfusion practice. Author(s): Grant PR, Kitchen A, Barbara JA, Hewitt P, Sims CM, Garson JA, Tedder RS. Source: Vox Sanguinis. 2000; 78(3): 137-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10838513&dopt=Abstract
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Effects of storage and type of blood collection tubes on hepatitis C virus level in whole blood samples. Author(s): Kessler HH, Stelzl E, Raggam RB, Haas J, Kirchmeir F, Hegenbarth K, Daghofer E, Santner BI, Marth E, Stauber RE. Source: Journal of Clinical Microbiology. 2001 May; 39(5): 1788-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11325991&dopt=Abstract
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Effects of the Japanese herbal medicine "Sho-saiko-to" (TJ-9) on in vitro interleukin-10 production by peripheral blood mononuclear cells of patients with chronic hepatitis C. Author(s): Yamashiki M, Nishimura A, Suzuki H, Sakaguchi S, Kosaka Y.
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Source: Hepatology (Baltimore, Md.). 1997 June; 25(6): 1390-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9185758&dopt=Abstract ·
Epidemiology of hepatitis C virus infection in chronic haemodialysis. Author(s): Chauveau P. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1996; 11 Suppl 4: 39-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8918751&dopt=Abstract
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Evaluation of molecular parameters for routine assessment of viremia in patients with chronic hepatitis C who are undergoing antiviral therapy. Author(s): Kessler HH, Pierer K, Santner BI, Vellimedu SK, Stelzl E, Marth E, Fickert P, Stauber RE. Source: Journal of Human Virology. 1998 July-August; 1(5): 314-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10195258&dopt=Abstract
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Genetic heterogeneity of the hepatitis C virus. Author(s): Bukh J, Miller RH, Purcell RH. Source: Princess Takamatsu Symp. 1995; 25: 75-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=8875612&dopt=Abstract
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Hepatitis C and human immunodeficiency virus RNA degradation by methylene blue/light treatment of human plasma. Author(s): Muller-Breitkreutz K, Mohr H. Source: Journal of Medical Virology. 1998 November; 56(3): 239-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9783692&dopt=Abstract
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Hepatitis C in Peru: risk factors for infection, potential iatrogenic transmission, and genotype distribution. Author(s): Sanchez JL, Sjogren MH, Callahan JD, Watts DM, Lucas C, Abdel-Hamid M, Constantine NT, Hyams KC, Hinostroza S, FigueroaBarrios R, Cuthie JC.
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Source: Am J Trop Med Hyg. 2000 November-December; 63(5-6): 242-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11421371&dopt=Abstract ·
Hepatitis C practice routines among Connecticut's naturopathic physicians. Author(s): Jacoby D, St Louis T, Navarro V. Source: The American Journal of Gastroenterology. 2001 September; 96(9): 2801-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11570394&dopt=Abstract
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Hepatitis C virus (HCV)-induced IgG-IgM rheumatoid factor (RF) complex may be the main causal factor for cold-dependent activation of complement in patients with rheumatic disease. Author(s): Wei G, Yano S, Kuroiwa T, Hiromura K, Maezawa A. Source: Clinical and Experimental Immunology. 1997 January; 107(1): 838. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9010261&dopt=Abstract
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Hepatitis C virus acute exacerbation during chemotherapy and radiotherapy for oesophageal carcinoma. Author(s): de Pree C, Giostra E, Galetto A, Perrin L, Zulian GB. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 1994 November; 5(9): 861-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7848891&dopt=Abstract
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Hepatitis C virus infection and liver disease in children with thalassemia. Author(s): Locasciulli A, Monguzzi W, Tornotti G, Bianco P, Masera G. Source: Bone Marrow Transplantation. 1993; 12 Suppl 1: 18-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7690633&dopt=Abstract
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Hepatitis c virus infection in employees of a large university hospital in Israel. Author(s): Sermoneta-Gertel S, Donchin M, Adler R, Baras M, Perlstein T, Manny N, Shouval D, Galun E.
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Source: Infect Control Hosp Epidemiol. 2001 December; 22(12): 754-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11876453&dopt=Abstract ·
Hepatitis C virus infection in the United States. Author(s): Alter MJ. Source: Journal of Hepatology. 1999; 31 Suppl 1: 88-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10622567&dopt=Abstract
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Hepatitis C virus-induced leuko-thrombocytopenia and haemolysis. Author(s): Emilia G, Luppi M, Ferrari MG, Barozzi P, Marasca R, Torelli G. Source: Journal of Medical Virology. 1997 October; 53(2): 182-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9334931&dopt=Abstract
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Hepatitis C. Author(s): Lavanchy D, Gavinio P. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2000 July-August; 14 Suppl B: 67B-76B. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10938509&dopt=Abstract
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Hepatitis C. Author(s): Jadoul M. Source: Lancet. 1998 April 18; 351(9110): 1209. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9643723&dopt=Abstract
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Hepatitis C: epidemiology and review of complementary/alternative medicine treatments. Author(s): Patrick L. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 1999 August; 4(4): 220-38. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10468647&dopt=Abstract
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Hepatitis C: public health strategies. Author(s): Lavanchy D.
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Source: Journal of Hepatology. 1999; 31 Suppl 1: 146-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10622578&dopt=Abstract ·
Hepatitis C; a retrospective study, literature review, and naturopathic protocol. Author(s): Milliman WB, Lamson DW, Brignall MS. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 2000 August; 5(4): 355-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10956381&dopt=Abstract
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Hepatocellular carcinoma associated with hepatitis C virus infection in Japan: projection to other countries in the foreseeable future. Author(s): Yoshizawa H. Source: Oncology. 2002; 62 Suppl 1: 8-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11868791&dopt=Abstract
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Herbal and complementary and alternative medicine therapies for liver disease. A focus on Chinese traditional medicine in hepatitis C virus. Author(s): Cohen MR. Source: Clin Liver Dis. 2001 May; 5(2): 461-78, Vii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11385972&dopt=Abstract
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High dosage alpha-interferon for treatment of children and young adults with chronic hepatitis C disease. Author(s): Marcellini M, Kondili LA, Comparcola D, Spada E, Sartorelli MR, Palumbo M, Rapicetta M. Source: The Pediatric Infectious Disease Journal. 1997 November; 16(11): 1049-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9384338&dopt=Abstract
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Impaired response to high-dose interferon treatment in AfricanAmericans with chronic hepatitis C. Author(s): De Maria N, Colantoni A, Idilman R, Friedlander L, Harig J, Van Thiel DH.
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Source: Hepatogastroenterology. 2002 May-June; 49(45): 788-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=12063991&dopt=Abstract ·
In vitro cold activation of complement shown by an overestimation of total complement 4: a study in patients with hepatitis C virus infection. Author(s): Maguire OC, Curry MP, O'Gorman P, Parfrey N, Hegarty J, Cunningham SK. Source: Annals of Clinical Biochemistry. 2001 November; 38(Pt 6): 687-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11732652&dopt=Abstract
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In vitro effects of sho-saiko-to on production of granulocyte colonystimulating factor by mononuclear cells from patients with chronic hepatitis C. Author(s): Yamashiki M, Nishimura A, Nobori T, Nakabayashi S, Takagi T, Inoue K, Ito M, Matsushita K, Ohtaki H, Kosaka Y. Source: International Journal of Immunopharmacology. 1997 July; 19(7): 381-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9568542&dopt=Abstract
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In vitro study of the NS2-3 protease of hepatitis C virus. Author(s): Pieroni L, Santolini E, Fipaldini C, Pacini L, Migliaccio G, La Monica N. Source: Journal of Virology. 1997 September; 71(9): 6373-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=9261354&dopt=Abstract
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Inhibitory effects of sudanese medicinal plant extracts on hepatitis C virus (HCV) protease. Author(s): Hussein G, Miyashiro H, Nakamura N, Hattori M, Kakiuchi N, Shimotohno K. Source: Phytotherapy Research : Ptr. 2000 November; 14(7): 510-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11054840&dopt=Abstract
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Injection with nondisposable needles as an important route for transmission of acute community-acquired hepatitis C virus infection in Taiwan. Author(s): Chen TZ, Wu JC, Yen FS, Sheng WY, Hwang SJ, Huo TI, Lee SD.
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Source: Journal of Medical Virology. 1995 July; 46(3): 247-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7561798&dopt=Abstract ·
Intrafamilial transmission of hepatitis C virus in hemodialysis patients. Author(s): Hou CH, Chen WY, Kao JH, Chen DS, Yang Y, Chen JJ, Lee SH, Wu DJ, Yang SC. Source: Journal of Medical Virology. 1995 April; 45(4): 381-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=7545208&dopt=Abstract
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Intraspousal transmission of GB virus C/hepatitis G virus in an hepatitis C virus hyperendemic area in Japan. Author(s): Akiyoshi F, Sata M, Noguchi S, Suzuki H, Ide T, Uchimura Y, Sasaki M, Tanaka K, Miyajima I, Mizokami M, Tanikawa K. Source: The American Journal of Gastroenterology. 1999 June; 94(6): 162731. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10364035&dopt=Abstract
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Iron reduction as an adjuvant to interferon therapy in patients with chronic hepatitis C who have previously not responded to interferon: a multicenter, prospective, randomized, controlled trial. Author(s): Di Bisceglie AM, Bonkovsky HL, Chopra S, Flamm S, Reddy RK, Grace N, Killenberg P, Hunt C, Tamburro C, Tavill AS, Ferguson R, Krawitt E, Banner B, Bacon BR. Source: Hepatology (Baltimore, Md.). 2000 July; 32(1): 135-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=10869301&dopt=Abstract
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Iscador Qu for chronic hepatitis C: an exploratory study. Author(s): Tusenius KJ, Spoek JM, Kramers CW. Source: Complementary Therapies in Medicine. 2001 March; 9(1): 12-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db= PubMed&list_uids=11264964&dopt=Abstract
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Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: ·
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.comÒ: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.thedacare.org/healthnotes/
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Open Directory Project: http://dmoz.org/Health/Alternative/
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TPN.com: http://www.tnp.com/
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
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WebMDÒHealth: http://my.webmd.com/drugs_and_herbs
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WellNet: http://www.wellnet.ca/herbsa-c.htm
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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 C; 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: ·
Chinese Medicine Gonglaomu Alternative names: Chinese Mahonia Stem; Caulis Mahoniae Source: Chinese Materia Medica Hyperlink: http://www.newcenturynutrition.com/
·
Herbs and Supplements Bupleurum
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Alternative names: Bupleurum chinense, Bupleurum falcatum Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Herb/Bupleurum.htm Glycyrrhiza glabra Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/Licoricech.h tml Glycyrrhiza1 Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hyperlink: http://www.herbmed.org/ Interferon Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Drug/Interferon.htm Licorice Alternative names: Glycyrrhiza glabra, Spanish Licorice Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/Licoricech.h tml Spanish Licorice Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsHerbs/Licoricech.h tml Taurine Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000196.html ·
Related Conditions Erythema Source: Integrative Medicine Communications; www.onemedicine.com
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Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/SkinDi sordersErythemacc.html Hepatitis Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Concern/Hepatitis.htm Hepatitis, Viral Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/Hepati tisViralcc.html Skin Disorders, Erythema Source: Integrative Medicine Communications; www.onemedicine.com Hyperlink: http://www.drkoop.com/interactivemedicine/ConsConditions/SkinDi sordersErythemacc.html Viral Hepatitis Source: Prima Communications, Inc. Hyperlink: http://www.personalhealthzone.com/pg000255.html
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: 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. The following additional references describe, in broad terms, alternative and complementary medicine (sorted alphabetically by title; hyperlinks provide rankings, information, and reviews at Amazon.com): · Clear Body, Clear Mind : The Effective Purification Program by L. Ron Hubbard; Paperback - 312 pages (June 2002), Bridge Publications; ISBN: 1573182249; http://www.amazon.com/exec/obidos/ASIN/1573182249/icongroupinterna
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· End Your Addiction Now: The Proven Nutritional Supplement Program That Can Set You Free by Charles Gant, Greg Lewis; Hardcover - 320 pages (January 2002), Warner Books; ISBN: 0446527238; http://www.amazon.com/exec/obidos/ASIN/0446527238/icongroupinterna · Reaching New Highs: Alternative Therapies for Drug Addicts by H. K. Heggenhougen; Hardcover (June 1997), Jason Aronson; ISBN: 0765700360; http://www.amazon.com/exec/obidos/ASIN/0765700360/icongroupinterna · The Tao of Sobriety : Helping You to Recover from Alcohol and Drug Addiction by David Gregson, et al; Paperback - 176 pages, 1st edition (January 2002), St. Martin’s Press; ISBN: 0312242506; http://www.amazon.com/exec/obidos/ASIN/0312242506/icongroupinterna For additional information on complementary and alternative medicine, ask your doctor or write to: National Institutes of Health National Center for Complementary and Alternative Medicine Clearinghouse P. O. Box 8218 Silver Spring, MD 20907-8218
Vocabulary Builder The following vocabulary builder gives definitions of words used in this chapter that have not been defined in previous chapters: Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH]
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APPENDIX C. RESEARCHING NUTRITION Overview Since the time of Hippocrates, doctors have understood the importance of diet and nutrition to patients’ health and well-being. Since then, they have accumulated an impressive archive of studies and knowledge dedicated to this subject. Based on their experience, doctors and healthcare providers may recommend particular dietary supplements to patients with hepatitis C. Any dietary recommendation is based on a patient’s age, body mass, gender, lifestyle, eating habits, food preferences, and health condition. It is therefore likely that different patients with hepatitis C may be given different recommendations. Some recommendations may be directly related to hepatitis C, while others may be more related to the patient’s general health. These recommendations, themselves, may differ from what official sources recommend for the average person. In this chapter we will begin by briefly reviewing the essentials of diet and nutrition that will broadly frame more detailed discussions of hepatitis C. We will then show you how to find studies dedicated specifically to nutrition and hepatitis C.
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Food and Nutrition: General Principles What Are Essential Foods? Food is generally viewed by official sources as consisting of six basic elements: (1) fluids, (2) carbohydrates, (3) protein, (4) fats, (5) vitamins, and (6) minerals. Consuming a combination of these elements is considered to be a healthy diet: ·
Fluids are essential to human life as 80-percent of the body is composed of water. Water is lost via urination, sweating, diarrhea, vomiting, diuretics (drugs that increase urination), caffeine, and physical exertion.
·
Carbohydrates are the main source for human energy (thermoregulation) and the bulk of typical diets. They are mostly classified as being either simple or complex. Simple carbohydrates include sugars which are often consumed in the form of cookies, candies, or cakes. Complex carbohydrates consist of starches and dietary fibers. Starches are consumed in the form of pastas, breads, potatoes, rice, and other foods. Soluble fibers can be eaten in the form of certain vegetables, fruits, oats, and legumes. Insoluble fibers include brown rice, whole grains, certain fruits, wheat bran and legumes.
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Proteins are eaten to build and repair human tissues. Some foods that are high in protein are also high in fat and calories. Food sources for protein include nuts, meat, fish, cheese, and other dairy products.
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Fats are consumed for both energy and the absorption of certain vitamins. There are many types of fats, with many general publications recommending the intake of unsaturated fats or those low in cholesterol.
Vitamins and minerals are fundamental to human health, growth, and, in some cases, disease prevention. Most are consumed in your diet (exceptions being vitamins K and D which are produced by intestinal bacteria and sunlight on the skin, respectively). Each vitamin and mineral plays a different role in health. The following outlines essential vitamins: ·
Vitamin A is important to the health of your eyes, hair, bones, and skin; sources of vitamin A include foods such as eggs, carrots, and cantaloupe.
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Vitamin B1, also known as thiamine, is important for your nervous system and energy production; food sources for thiamine include meat, peas, fortified cereals, bread, and whole grains.
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Vitamin B2, also known as riboflavin, is important for your nervous system and muscles, but is also involved in the release of proteins from
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nutrients; food sources for riboflavin include dairy products, leafy vegetables, meat, and eggs. ·
Vitamin B3, also known as niacin, is important for healthy skin and helps the body use energy; food sources for niacin include peas, peanuts, fish, and whole grains
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Vitamin B6, also known as pyridoxine, is important for the regulation of cells in the nervous system and is vital for blood formation; food sources for pyridoxine include bananas, whole grains, meat, and fish.
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Vitamin B12 is vital for a healthy nervous system and for the growth of red blood cells in bone marrow; food sources for vitamin B12 include yeast, milk, fish, eggs, and meat.
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Vitamin C allows the body’s immune system to fight various diseases, strengthens body tissue, and improves the body’s use of iron; food sources for vitamin C include a wide variety of fruits and vegetables.
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Vitamin D helps the body absorb calcium which strengthens bones and teeth; food sources for vitamin D include oily fish and dairy products.
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Vitamin E can help protect certain organs and tissues from various degenerative diseases; food sources for vitamin E include margarine, vegetables, eggs, and fish.
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Vitamin K is essential for bone formation and blood clotting; common food sources for vitamin K include leafy green vegetables.
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Folic Acid maintains healthy cells and blood and, when taken by a pregnant woman, can prevent her fetus from developing neural tube defects; food sources for folic acid include nuts, fortified breads, leafy green vegetables, and whole grains.
It should be noted that one can overdose on certain vitamins which become toxic if consumed in excess (e.g. vitamin A, D, E and K). Like vitamins, minerals are chemicals that are required by the body to remain in good health. Because the human body does not manufacture these chemicals internally, we obtain them from food and other dietary sources. The more important minerals include: ·
Calcium is needed for healthy bones, teeth, and muscles, but also helps the nervous system function; food sources for calcium include dry beans, peas, eggs, and dairy products.
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Chromium is helpful in regulating sugar levels in blood; food sources for chromium include egg yolks, raw sugar, cheese, nuts, beets, whole grains, and meat.
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·
Fluoride is used by the body to help prevent tooth decay and to reinforce bone strength; sources of fluoride include drinking water and certain brands of toothpaste.
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Iodine helps regulate the body’s use of energy by synthesizing into the hormone thyroxine; food sources include leafy green vegetables, nuts, egg yolks, and red meat.
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Iron helps maintain muscles and the formation of red blood cells and certain proteins; food sources for iron include meat, dairy products, eggs, and leafy green vegetables.
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Magnesium is important for the production of DNA, as well as for healthy teeth, bones, muscles, and nerves; food sources for magnesium include dried fruit, dark green vegetables, nuts, and seafood.
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Phosphorous is used by the body to work with calcium to form bones and teeth; food sources for phosphorous include eggs, meat, cereals, and dairy products.
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Selenium primarily helps maintain normal heart and liver functions; food sources for selenium include wholegrain cereals, fish, meat, and dairy products.
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Zinc helps wounds heal, the formation of sperm, and encourage rapid growth and energy; food sources include dried beans, shellfish, eggs, and nuts.
The United States government periodically publishes recommended diets and consumption levels of the various elements of food. Again, your doctor may encourage deviations from the average official recommendation based on your specific condition. To learn more about basic dietary guidelines, visit the Web site: http://www.health.gov/dietaryguidelines/. Based on these guidelines, many foods are required to list the nutrition levels on the food’s packaging. Labeling Requirements are listed at the following site maintained by the Food and Drug Administration: http://www.cfsan.fda.gov/~dms/labcons.html. When interpreting these requirements, the government recommends that consumers become familiar with the following abbreviations before reading FDA literature:50 ·
DVs (Daily Values): A new dietary reference term that will appear on the food label. It is made up of two sets of references, DRVs and RDIs.
·
DRVs (Daily Reference Values): A set of dietary references that applies to fat, saturated fat, cholesterol, carbohydrate, protein, fiber, sodium, and potassium.
50
Adapted from the FDA: http://www.fda.gov/fdac/special/foodlabel/dvs.html.
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·
RDIs (Reference Daily Intakes): A set of dietary references based on the Recommended Dietary Allowances for essential vitamins and minerals and, in selected groups, protein. The name “RDI” replaces the term “U.S. RDA.”
·
RDAs (Recommended Dietary Allowances): A set of estimated nutrient allowances established by the National Academy of Sciences. It is updated periodically to reflect current scientific knowledge. What Are Dietary Supplements?51
Dietary supplements are widely available through many commercial sources, including health food stores, grocery stores, pharmacies, and by mail. Dietary supplements are provided in many forms including tablets, capsules, powders, gel-tabs, extracts, and liquids. Historically in the United States, the most prevalent type of dietary supplement was a multivitamin/mineral tablet or capsule that was available in pharmacies, either by prescription or “over the counter.” Supplements containing strictly herbal preparations were less widely available. Currently in the United States, a wide array of supplement products are available, including vitamin, mineral, other nutrients, and botanical supplements as well as ingredients and extracts of animal and plant origin. The Office of Dietary Supplements (ODS) of the National Institutes of Health is the official agency of the United States which has the expressed goal of acquiring “new knowledge to help prevent, detect, diagnose, and treat disease and disability, from the rarest genetic disorder to the common cold.”52 According to the ODS, dietary supplements can have an important impact on the prevention and management of disease and on the maintenance of health.53 The ODS notes that considerable research on the effects of dietary supplements has been conducted in Asia and Europe where This discussion has been adapted from the NIH: http://ods.od.nih.gov/whatare/whatare.html. 52 Contact: The Office of 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]. 53 Adapted from http://ods.od.nih.gov/about/about.html. The Dietary Supplement Health and Education Act defines dietary supplements as “a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients: a vitamin, mineral, amino acid, herb or other botanical; or a dietary substance for use to supplement the diet by increasing the total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of any ingredient described above; and intended for ingestion in the form of a capsule, powder, softgel, or gelcap, and not represented as a conventional food or as a sole item of a meal or the diet.” 51
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the use of plant products, in particular, has a long tradition. However, the overwhelming majority of supplements have not been studied scientifically. To explore the role of dietary supplements in the improvement of health care, the ODS plans, organizes, and supports conferences, workshops, and symposia on scientific topics related to dietary supplements. The ODS often works in conjunction with other NIH Institutes and Centers, other government agencies, professional organizations, and public advocacy groups. To learn more about official information on dietary supplements, visit the ODS site at http://ods.od.nih.gov/whatare/whatare.html. Or contact: The Office of 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]
Finding Studies on Hepatitis C The NIH maintains an office dedicated to patient nutrition and diet. 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). 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.54 IBIDS is available to the public free of charge through the ODS Internet page: 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. We recommend that you start with the Consumer Database. While you may not find references for the topics that are of most interest to you, check back 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.
54
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periodically as this database is frequently updated. More studies can be found by searching the Full IBIDS Database. Healthcare professionals and researchers generally use the third option, which lists peer-reviewed citations. In all cases, we suggest that you take advantage of the “Advanced Search” option that allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “hepatitis C” (or synonyms) into the search box. To narrow the search, you can also select the “Title” field. The following is a typical result when searching for recently indexed consumer information on hepatitis C: ·
Determinants of the quality of life of patients with diabetes under intensified insulin therapy. Author(s): Department of Psychosomatic Medicine and Psychotherapy, Medical Clinic and Policlinic, Charite Campus-Virchow, Humboldt University, Berlin, Germany.
[email protected] Source: Rose, M Burkert, U Scholler, G Schirop, T Danzer, G Klapp, B F Diabetes-Care. 1998 November; 21(11): 1876-85 0149-5992
The following information is typical of that found when using the “Full IBIDS Database” when searching using “hepatitis C” (or a synonym): ·
A case of chronic hepatitis C developing insulin-dependent diabetes mellitus associated with various autoantibodies during interferon therapy. Author(s): Department of Internal Medicine II, Miyazaki Medical College, Kiyotake 5200, 889-1601, Miyazaki, Japan. Source: Uto, H Matsuoka, H Murata, M Okamoto, T Miyata, Y Hori, T Ido, A Hirono, S Hayashi, K Tsubouchi, H Diabetes-Res-Clin-Pract. 2000 August; 49(2-3): 101-6 0168-8227
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A clinical study on bing gan ling oral liquid for treatment of hepatitis C. Author(s): Nanjing University of Traditional Chinese Medicine and Pharmacy and Materia Medica. Source: You, S Zhou, M Xue, B Fang, T Jiang, W Li, C Xu, H Jiang, J Wang, Y Xu, S J-Tradit-Chin-Med. 1998 September; 18(3): 209-14 02546272
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A conservative triple antioxidant approach to the treatment of hepatitis C. Combination of alpha lipoic acid (thioctic acid), silymarin, and selenium: three case histories. Author(s): Integrative Medical Center of New Mexico, New Mexico State University, Las Cruces, USA.
[email protected] Source: Berkson, B M Med-Klin. 1999 October 15; 94 Suppl 384-9 07235003
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·
A synthetic peptide derived from the non-structural protein 3 of hepatitis C virus serves as a specific substrate for PKC. Author(s): Bernhard-Nocht-Institut fur Tropenmedizin, Hamburg, Germany. Source: Borowski, P Resch, K Schmitz, H Heiland, M Biol-Chem. 2000 January; 381(1): 19-27 1431-6730
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Adding interventions to interferon in chronic HCV infections. Author(s): Department of Medicine, Imperial College School of Medicine, St Mary's Hospital, London. Source: Main, J Gut. 1996 November; 39(5): 769 0017-5749
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Analysis of HLA alleles in Japanese patients with cirrhosis due to chronic hepatitis C. Author(s): Department of Gastroenterology, Saiseikai Kumamoto Hospital, Japan. Source: Higashi, Y Kamikawaji, N Suko, H Ando, M J-GastroenterolHepatol. 1996 March; 11(3): 241-6 0815-9319
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Characterization and mutational analysis of the helicase and NTPase activities of hepatitis C virus full-length NS3 protein. Author(s): Department of Medicine, Imperial College School of Medicine, London, UK. Source: Wardell, A D Errington, W Ciaramella, G Merson, J McGarvey, M J J-Gen-Virol. 1999 March; 80 ( Pt 3)701-9 0022-1317
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Characterization of antiviral activity of lactoferrin against hepatitis C virus infection in human cultured cells. Author(s): Virology and Glycobiology Division, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo, Japan. Source: Ikeda, M Nozaki, A Sugiyama, K Tanaka, T Naganuma, A Tanaka, K Sekihara, H Shimotohno, K Saito, M Kato, N Virus-Res. 2000 January; 66(1): 51-63 0168-1702
·
Chronic hepatitis C is mild in menstruating women. Author(s): Institute of Medicine, Amedeo Avogadro University and Maggiore della Carita Hospital, Novara, Italy.
[email protected] Source: Sartori, M Andorno, S Rigamonti, C Grossini, E Nicosia, G Boldorini, R J-Gastroenterol-Hepatol. 2000 December; 15(12): 1411-7 08159319
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Combination therapy with interferon-alpha plus N-acetyl cysteine for chronic hepatitis C: a placebo controlled double-blind multicentre study. Author(s): Department of Virology, Royal Free and University College Medical School, London, United Kingdom.
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Source: Grant, P R Black, A Garcia, N Prieto, J Garson, J A J-Med-Virol. 2000 August; 61(4): 439-42 0146-6615 ·
Cryofiltration and oral corticosteroids provide successful treatment for an elderly patient with cryoglobulinemic glomerulonephritis associated with hepatitis C virus infection. Author(s): Second Department of Internal Medicine, Kansai Medical University, Osaka. Source: Mori, Y Kishimoto, N Imai, Y Tanaka, Y Fujiyama, A Shibasaki, Y Nagata, T Masaki, H Umeda, Y Matsubara, H Iwasaka, T Intern-Med. 2000 July; 39(7): 564-9 0918-2918
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DNA helicase activity of the hepatitis C virus nonstructural protein 3. Author(s): Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon. Source: Gwack, Y Kim, D W Han, J H Choe, J Eur-J-Biochem. 1997 November 15; 250(1): 47-54 0014-2956
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Doppler sonography measurement of portal blood flow velocity after glucagon injection in patients with chronic HCV infection. Author(s): Department of Infectious and Tropical Diseases, University La Sapienza, Rome, Italy. Source: Sereno, S Toccaceli, F Russo, V Iacomi, F Zardi, E M Laghi, V Ultrasound-Med-Biol. 2001 May; 27(5): 723-6 0301-5629
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Ectopic expression of hepatitis C virus core protein differentially regulates nuclear transcription factors. Author(s): Cytokine Research Laboratory, Department of Molecular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. Source: Shrivastava, A Manna, S K Ray, R Aggarwal, B B J-Virol. 1998 December; 72(12): 9722-8 0022-538X
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Effects of iron loading on pathogenicity in hepatitis C virus-infected chimpanzees. Author(s): Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX, USA. Source: Bassett, S E Di Bisceglie, A M Bacon, B R Sharp, R M GovindaraJanuary, S Hubbard, G B Brasky, K M Lanford, R E Hepatology. 1999 June; 29(6): 1884-92 0270-9139
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Feasibility of autologous stem cell transplantation in chronic carriers of hepatitis B and hepatitis C virus. Author(s): Department of Medical and Morphological Research, University Hospital, Udine, Italy.
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Source: Sperotto, A Silvestri, F Fanin, R Damiani, D Geromin, A Cerno, M Stocchi, R Patriarca, F Baccarani, M Leuk-Lymphoma. 2000 January; 36(34): 323-30 1042-8194 ·
Hepatic fibrogenesis and hepatitis C. Author(s): Liver Center and Department of Medicine and Cell Biology, Duke University Medical Center, Durham, NC 27710, USA. Source: Rockey, D C Semin-Gastrointest-Dis. 2000 April; 11(2): 69-83 1049-5118
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Hepatitis B associated with an alternative therapy centre: look back is extended to include hepatitis C. Source: Anonymous Commun-Dis-Rep-CDR-Wkly. 1998 June 5; 8(23): 201 1350-9357
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Hepatitis C and alcohol. Author(s): Service d'hepatologie, Hopital Beaujon, Clichy, France.
[email protected] Source: Degos, F J-Hepatol. 1999; 31 Suppl 1113-8 0168-8278
·
Hepatitis C. Author(s): World Health Organization, Communicable Diseases Surveillance and Response, Geneva, Switzerland.
[email protected] Source: Lavanchy, D Gavinio, P Can-J-Gastroenterol. 2000 Jul-August; 14 Suppl B67B-76B 0835-7900
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/
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.thedacare.org/healthnotes/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDÒHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,,00.html
The following is a specific Web site relating to hepatitis C; please note that the particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: ·
Minerals Iron Source: Healthnotes, Inc.; www.healthnotes.com Hyperlink: http://www.thedacare.org/healthnotes/Supp/Iron.htm
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Vocabulary Builder The following vocabulary builder defines words used in the references in this chapter that have not been defined in previous chapters: 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] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Hormone: A chemical substance formed in glands in the body and carried in the blood to organs and tissues, where it influences function, structure, and behavior. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulindependent diabetes mellitus. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH]
Neural: 1. pertaining to a nerve or to the nerves. 2. situated in the region of the spinal axis, as the neutral arch. [EU] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Overdose: 1. to administer an excessive dose. 2. an excessive dose. [EU] 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] Psychosomatic: Pertaining to the mind-body relationship; having bodily symptoms of psychic, emotional, or mental origin; called also psychophysiologic. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication.
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[NIH]
Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH]
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APPENDIX D. FINDING MEDICAL LIBRARIES Overview At a medical library you can find medical texts and reference books, consumer health publications, specialty newspapers and magazines, as well as medical journals. In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Before going to the library, highlight the references mentioned in this sourcebook that you find interesting. Focus on those items that are not available via the Internet, and ask the reference librarian for help with your search. He or she may know of additional resources that could be helpful to you. Most importantly, 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. NLM’s interlibrary loan services are only available to libraries. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.55
55
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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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 Open to the Public In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries that are generally open to the public and have reference facilities. The following is the NLM’s list plus hyperlinks to each library Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of 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):56 ·
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute), http://www.asmi.org/LIBRARY.HTM
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos (Community Health Library of Los Gatos), http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://www-med.stanford.edu/healthlibrary/
56
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries 299
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: San José PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation), http://go.sutterhealth.org/comm/resc-library/sac-resources.html
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California: University of California, Davis. Health Sciences Libraries
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System), http://www.valleycare.com/library.html
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California: Washington Community Health Resource Library (Washington Community Health Resource Library), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.exempla.org/conslib.htm
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
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Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute), http://www.christianacare.org/health_guide/health_guide_pmri_health _info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library), http://hml.org/CHIS/
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·
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Northwestern Memorial Hospital, Health Learning Center), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital), http://www.centralbap.com/education/community/library.htm
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Kentucky: University of Kentucky - Health Information Library (University of Kentucky, Chandler Medical Center, Health Information Library), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical Library-Shreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center), http://www.mmc.org/library/
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Maine: Parkview Hospital, http://www.parkviewhospital.org/communit.htm#Library
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital Health Information Library (Western Maine Health), http://www.wmhcc.com/hil_frame.html
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre), http://www.deerlodge.mb.ca/library/libraryservices.shtml
Finding Medical Libraries 301
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Md., Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://medlibwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources Consumer Health Information, http://www.sladen.hfhs.org/library/consumer/index.html
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center), http://www.saintpatrick.org/chi/librarydetail.php3?ID=41
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·
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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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/
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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), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: Saint Francis Health System Patient/Family Resource Center (Saint Francis Health System), http://www.sfhtulsa.com/patientfamilycenter/default.asp
Finding Medical Libraries 303
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System), http://www.hsls.pitt.edu/chi/hhrcinfo.html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://ww2.mcgill.ca/mghlib/
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South Dakota: Rapid City Regional Hospital - Health Information Center (Rapid City Regional Hospital, Health Information Center), http://www.rcrh.org/education/LibraryResourcesConsumers.htm
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Texas: Matustik Family Resource Center (Cook Children’s Health Care System), http://www.cookchildrens.com/Matustik_Library.html
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center), http://www.swmedctr.com/Home/
Principles of Drug Addiction Treatment 305
APPENDIX E. TREATMENT
PRINCIPLES
OF
DRUG
ADDICTION
Overview57 No single treatment is appropriate for all individuals. Matching treatment settings, interventions, and services to each individual’s particular problems and needs is critical to his or her ultimate success in returning to productive functioning in the family, workplace, and society. This appendix reproduces information created by the National Institute for Drug Abuse (NIDA) concerning drug abuse treatment entitled “Principles of Drug Addiction Treatment: A Research-Based Guide”.
Principles of Effective Treatment Treatment needs to be readily available. Because individuals who are addicted to drugs may be uncertain about entering treatment, taking advantage of opportunities when they are ready for treatment is crucial. Potential treatment applicants can be lost if treatment is not immediately available or is not readily accessible. Effective treatment attends to multiple needs of the individual, not just his or her drug use. To be effective, treatment must address the individual’s drug use and any associated medical, psychological, social, vocational, and legal problems.
Adapted from the National Institute on Drug Abuse: http://165.112.78.61/PODAT/PODATIndex.html.
57
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An individual’s treatment and services plan must be assessed continually and modified as necessary to ensure that the plan meets the person’s changing needs. A patient may require varying combinations of services and treatment components during the course of treatment and recovery. In addition to counseling or psychotherapy, a patient at times may require medication, other medical services, family therapy, parenting instruction, vocational rehabilitation, and social and legal services. It is critical that the treatment approach be appropriate to the individual’s age, gender, ethnicity, and culture. Remaining in treatment for an adequate period of time is critical for treatment effectiveness. The appropriate duration for an individual depends on his or her problems and needs. Research indicates that for most patients, the threshold of significant improvement is reached at about 3 months in treatment. After this threshold is reached, additional treatment can produce further progress toward recovery. Because people often leave treatment prematurely, programs should include strategies to engage and keep patients in treatment.
Counseling and Other Behavioral Therapies Counseling (individual and/or group) and other behavioral therapies are critical components of effective treatment for addiction. In therapy, patients address issues of motivation, build skills to resist drug use, replace drugusing activities with constructive and rewarding non-drug-using activities, and improve problem-solving abilities. Behavioral therapy also facilitates interpersonal relationships and the individual’s ability to function in the family and community. Medications Medications are an important element of treatment for many patients, especially when combined with counseling and other behavioral therapies. Methadone and levo-alpha-acetylmethadol (LAAM) are very effective in helping individuals addicted to heroin or other opiates stabilize their lives and reduce their illicit drug use. Naltrexone is also an effective medication for some opiate addicts and some patients with co-occurring alcohol dependence. For persons addicted to nicotine, a nicotine replacement product (such as patches or gum) or an oral medication (such as bupropion) can be an effective component of treatment. For patients with mental disorders, both behavioral treatments and medications can be critically important.
Principles of Drug Addiction Treatment 307
Patients with Mental Disorders Addicted or drug-abusing individuals with coexisting mental disorders should have both disorders treated in an integrated way. Because addictive disorders and mental disorders often occur in the same individual, patients presenting for either condition should be assessed and treated for the cooccurrence of the other type of disorder.
Medical Detoxification Medical detoxification is only the first stage of addiction treatment and by itself does little to change long-term drug use. Medical detoxification safely manages the acute physical symptoms of withdrawal associated with stopping drug use. While detoxification alone is rarely sufficient to help addicts achieve long-term abstinence, for some individuals it is a strongly indicated precursor to effective drug addiction treatment.
Patient Cooperation Treatment does not need to be voluntary to be effective. Strong motivation can facilitate the treatment process. Sanctions or enticements in the family, employment setting, or criminal justice system can increase significantly both treatment entry and retention rates and the success of drug treatment interventions. Possible drug use during treatment must be monitored continuously. Lapses to drug use can occur during treatment. The objective monitoring of a patient’s drug and alcohol use during treatment, such as through urinalysis or other tests, can help the patient withstand urges to use drugs. Such monitoring also can provide early evidence of drug use so that the individual’s treatment plan can be adjusted. Feedback to patients who test positive for illicit drug use is an important element of monitoring. Treatment programs should provide assessment for HIV/AIDS, hepatitis B and C, tuberculosis and other infectious diseases, and counseling to help patients modify or change behaviors that place themselves or others at risk of infection. Counseling can help patients avoid high-risk behavior. Counseling also can help people who are already infected manage their illness.
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Recovery Recovery from drug addiction can be a long-term process and frequently requires multiple episodes of treatment. As with other chronic illnesses, relapses to drug use can occur during or after successful treatment episodes. Addicted individuals may require prolonged treatment and multiple episodes of treatment to achieve long-term abstinence and fully restored functioning. Participation in self-help support programs during and following treatment often is helpful in maintaining abstinence.
What Is Drug Addiction? Drug addiction is a complex illness. It is characterized by compulsive, at times uncontrollable, drug craving, seeking, and use that persist even in the face of extremely negative consequences. For many people, drug addiction becomes chronic, with relapses possible even after long periods of abstinence. The path to drug addiction begins with the act of taking drugs. Over time, a person’s ability to choose not to take drugs can be compromised. Drug seeking becomes compulsive, in large part as a result of the effects of prolonged drug use on brain functioning and, thus, on behavior. The compulsion to use drugs can take over the individual’s life. Addiction often involves not only compulsive drug taking but also a wide range of dysfunctional behaviors that can interfere with normal functioning in the family, the workplace, and the broader community. Addiction also can place people at increased risk for a wide variety of other illnesses. These illnesses can be brought on by behaviors, such as poor living and health habits, that often accompany life as an addict, or because of toxic effects of the drugs themselves. Because addiction has so many dimensions and disrupts so many aspects of an individual’s life, treatment for this illness is never simple. Drug treatment must help the individual stop using drugs and maintain a drug-free lifestyle, while achieving productive functioning in the family, at work, and in society. Effective drug abuse and addiction treatment programs typically incorporate many components, each directed to a particular aspect of the illness and its consequences. Three decades of scientific research and clinical practice have yielded a variety of effective approaches to drug addiction treatment. Extensive data
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document that drug addiction treatment is as effective as are treatments for most other similarly chronic medical conditions. In spite of scientific evidence that establishes the effectiveness of drug abuse treatment, many people believe that treatment is ineffective. In part, this is because of unrealistic expectations. Many people equate addiction with simply using drugs and therefore expect that addiction should be cured quickly, and if it is not, treatment is a failure. In reality, because addiction is a chronic disorder, the ultimate goal of long-term abstinence often requires sustained and repeated treatment episodes. Of course, not all drug abuse treatment is equally effective. Research also has revealed a set of overarching principles that characterize the most effective drug abuse and addiction treatments and their implementation. Treatment varies depending on the type of drug and the characteristics of the patient. The best programs provide a combination of therapies and other services.
Frequently Asked Questions What Is Drug Addiction Treatment? ·
There are many addictive drugs, and treatments for specific drugs can differ. Treatment also varies depending on the characteristics of the patient.
·
Problems associated with an individual’s drug addiction can vary significantly. People who are addicted to drugs come from all walks of life. Many suffer from mental health, occupational, health, or social problems that make their addictive disorders much more difficult to treat. Even if there are few associated problems, the severity of addiction itself ranges widely among people.
·
A variety of scientifically based approaches to drug addiction treatment exist. Drug addiction treatment can include behavioral therapy (such as counseling, cognitive therapy, or psychotherapy), medications, or their combination. Behavioral therapies offer people strategies for coping with their drug cravings, teach them ways to avoid drugs and prevent relapse, and help them deal with relapse if it occurs. When a person’s drugrelated behavior places him or her at higher risk for AIDS or other infectious diseases, behavioral therapies can help to reduce the risk of disease transmission. Case management and referral to other medical, psychological, and social services are crucial components of treatment for
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many patients. The best programs provide a combination of therapies and other services to meet the needs of the individual patient, which are shaped by such issues as age, race, culture, sexual orientation, gender, pregnancy, parenting, housing, and employment, as well as physical and sexual abuse. ·
Treatment medications, such as methadone, LAAM, and naltrexone, are available for individuals addicted to opiates. Nicotine preparations (patches, gum, nasal spray) and bupropion are available for individuals addicted to nicotine.
·
The best treatment programs provide a combination of therapies and other services to meet the needs of the individual patient. CHILD CARE SERVICES FAMILY SERVICES
P ROCESSING / A SSESSEMENT
HOUSING/ TRANSPORTATION SERVICES
FINANCIAL SERVICES
VOCATIONAL SERVICES
INTAKE
B EHAVIORAL T HERAPY AND C OUNSELING
T REATMENT P LAN
S UBSTANCE U SE MONITORING
C LINICAL AND C ASE MANAGEMENT
P HARMACOTHERAPY
S ELF -H ELP /P EER S UPPORT G ROUPS
MENTAL HEALTH SERVICES
MEDI CAL SERVICES
C ONTINUING C ARE LEGAL SERVICES
EDUCATIONAL SERVICES AIDS/HIV SERVICES
Components of Comprehensive Drug Abuse Treatment ·
Medications, such as antidepressants, mood stabilizers, or neuroleptics, may be critical for treatment success when patients have co-occurring mental disorders, such as depression, anxiety disorder, bipolar disorder, or psychosis.
·
Treatment can occur in a variety of settings, in many different forms, and for different lengths of time. Because drug addiction is typically a chronic disorder characterized by occasional relapses, a short-term, one-time treatment often is not sufficient. For many, treatment is a long-term process that involves multiple interventions and attempts at abstinence.
Why Can’t Drug Addicts Quit on Their Own? Nearly all addicted individuals believe in the beginning that they can stop using drugs on their own, and most try to stop without treatment. However,
Principles of Drug Addiction Treatment 311
most of these attempts result in failure to achieve long-term abstinence. Research has shown that long-term drug use results in significant changes in brain function that persist long after the individual stops using drugs. These drug-induced changes in brain function may have many behavioral consequences, including the compulsion to use drugs despite adverse consequences. This is the defining characteristic of addiction. Understanding that addiction has such an important biological component may help explain an individual’s difficulty in achieving and maintaining abstinence without treatment. Psychological stress from work or family problems, social cues (such as meeting individuals from one’s drug-using past), or the environment (such as encountering streets, objects, or even smells associated with drug use) can interact with biological factors to hinder attainment of sustained abstinence and make relapse more likely. Research studies indicate that even the most severely addicted individuals can participate actively in treatment and that active participation is essential to good outcomes.
How Effective Is Drug Addiction Treatment? In addition to stopping drug use, the goal of treatment is to return the individual to productive functioning in the family, workplace, and community. Measures of effectiveness typically include levels of criminal behavior, family functioning, employability, and medical condition. Overall, treatment of addiction is as successful as treatment of other chronic diseases, such as diabetes, hypertension, and asthma. Treatment of addiction is as successful as treatment of other chronic diseases such as diabetes, hypertension, and asthma. According to several studies, drug treatment reduces drug use by 40 to 60 percent and significantly decreases criminal activity during and after treatment. For example, a study of therapeutic community treatment for drug offenders demonstrated that arrests for violent and nonviolent criminal acts were reduced by 40 percent or more. Methadone treatment has been shown to decrease criminal behavior by as much as 50 percent. Research shows that drug addiction treatment reduces the risk of HIV infection and that interventions to prevent HIV are much less costly than treating HIV-related illnesses. Treatment can improve the prospects for employment, with gains of up to 40 percent after treatment. Although these effectiveness rates hold in general, individual treatment outcomes depend on the extent and nature of the patient’s presenting
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problems, the appropriateness of the treatment components and related services used to address those problems, and the degree of active engagement of the patient in the treatment process. How Long Does Drug Addiction Treatment Usually Last? Individuals progress through drug addiction treatment at various speeds, so there is no predetermined length of treatment. However, research has shown unequivocally that good outcomes are contingent on adequate lengths of treatment. Generally, for residential or outpatient treatment, participation for less than 90 days is of limited or no effectiveness, and treatments lasting significantly longer often are indicated. For methadone maintenance, 12 months of treatment is the minimum, and some opiate-addicted individuals will continue to benefit from methadone maintenance treatment over a period of years. Good outcomes are contingent on adequate lengths of treatment. Many people who enter treatment drop out before receiving all the benefits that treatment can provide. Successful outcomes may require more than one treatment experience. Many addicted individuals have multiple episodes of treatment, often with a cumulative impact.
What Helps People Stay in Treatment? Since successful outcomes often depend upon retaining the person long enough to gain the full benefits of treatment, strategies for keeping an individual in the program are critical. Whether a patient stays in treatment depends on factors associated with both the individual and the program. Individual factors related to engagement and retention include motivation to change drug-using behavior, degree of support from family and friends, and whether there is pressure to stay in treatment from the criminal justice system, child protection services, employers, or the family. Within the program, successful counselors are able to establish a positive, therapeutic relationship with the patient. The counselor should ensure that a treatment plan is established and followed so that the individual knows what to expect during treatment. Medical, psychiatric, and social services should be available. Whether a patient stays in treatment depends on factors associated with both the individual and the program. Since some individual problems (such as serious mental illness, severe cocaine or crack use, and criminal
Principles of Drug Addiction Treatment 313
involvement) increase the likelihood of a patient dropping out, intensive treatment with a range of components may be required to retain patients who have these problems. The provider then should ensure a transition to continuing care or “aftercare” following the patient’s completion of formal treatment.
Is the Use of Medications Like Methadone Simply Replacing One Drug Addiction with Another? No. As used in maintenance treatment, methadone and LAAM are not heroin substitutes. They are safe and effective medications for opiate addiction that are administered by mouth in regular, fixed doses. Their pharmacological effects are markedly different from those of heroin. Injected, snorted, or smoked heroin causes an almost immediate “rush” or brief period of euphoria that wears off very quickly, terminating in a “crash.” The individual then experiences an intense craving to use more heroin to stop the crash and reinstate the euphoria. The cycle of euphoria, crash, and craving is repeated several times a day which leads to a cycle of addiction and behavioral disruption. These characteristics of heroin use result from the drug’s rapid onset of action and its short duration of action in the brain. An individual who uses heroin multiple times per day subjects his or her brain and body to marked, rapid fluctuations as the opiate effects come and go. These fluctuations can disrupt a number of important bodily functions. Because heroin is illegal, addicted persons often become part of a volatile drug-using street culture characterized by hustling and crimes for profit. Methadone and LAAM have far more gradual onsets of action than heroin, and as a result, patients stabilized on these medications do not experience any rush. In addition, both medications wear off much more slowly than heroin, so there is no sudden crash, and the brain and body are not exposed to the marked fluctuations seen with heroin use. Maintenance treatment with methadone or LAAM markedly reduces the desire for heroin. If an individual maintained on adequate, regular doses of methadone (once a day) or LAAM (several times per week) tries to take heroin, the euphoric effects of heroin will be significantly blocked. According to research, patients undergoing maintenance treatment do not suffer the medical abnormalities and behavioral destabilization that rapid fluctuations in drug levels cause in heroin addicts.
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What Role Can the Criminal Justice System Play in the Treatment of Drug Addiction? Increasingly, research is demonstrating that treatment for drug-addicted offenders during and after incarceration can have a significant beneficial effect upon future drug use, criminal behavior, and social functioning. The case for integrating drug addiction treatment approaches with the criminal justice system is compelling. Combining prison- and community-based treatment for drug-addicted offenders reduces the risk of both recidivism to drug-related criminal behavior and relapse to drug use. For example, a recent study found that prisoners who participated in a therapeutic treatment program in the Delaware State Prison and continued to receive treatment in a work-release program after prison were 70 percent less likely than non-participants to return to drug use and incur rearrest. Individuals who enter treatment under legal pressure have outcomes as favorable as those who enter treatment voluntarily. The majority of offenders involved with the criminal justice system are not in prison but are under community supervision. For those with known drug problems, drug addiction treatment may be recommended or mandated as a condition of probation. Research has demonstrated that individuals who enter treatment under legal pressure have outcomes as favorable as those who enter treatment voluntarily. The criminal justice system refers drug offenders into treatment through a variety of mechanisms, such as diverting nonviolent offenders to treatment, stipulating treatment as a condition of probation or pretrial release, and convening specialized courts that handle cases for offenses involving drugs. Drug courts, another model, are dedicated to drug offender cases. They mandate and arrange for treatment as an alternative to incarceration, actively monitor progress in treatment, and arrange for other services to drug-involved offenders. The most effective models integrate criminal justice and drug treatment systems and services. Treatment and criminal justice personnel work together on plans and implementation of screening, placement, testing, monitoring, and supervision, as well as on the systematic use of sanctions and rewards for drug abusers in the criminal justice system. Treatment for incarcerated drug abusers must include continuing care, monitoring, and supervision after release and during parole.
Principles of Drug Addiction Treatment 315
How Does Drug Addiction Treatment Help Reduce the Spread of HIV/AIDS and Other Infectious Diseases? Many drug addicts, such as heroin or cocaine addicts and particularly injection drug users, are at increased risk for HIV/AIDS as well as other infectious diseases like hepatitis, tuberculosis, and sexually transmitted infections. For these individuals and the community at large, drug addiction treatment is disease prevention. Drug injectors who do not enter treatment are up to six times more likely to become infected with HIV than injectors who enter and remain in treatment. Drug users who enter and continue in treatment reduce activities that can spread disease, such as sharing injection equipment and engaging in unprotected sexual activity. Participation in treatment also presents opportunities for screening, counseling, and referral for additional services. The best drug abuse treatment programs provide HIV counseling and offer HIV testing to their patients.
Where Do 12-Step or Self-Help Programs Fit into Drug Treatment? Self-help groups can complement and extend the effects of professional treatment. The most prominent self-help groups are those affiliated with Alcoholics Anonymous (AA), Narcotics Anonymous (NA), and Cocaine Anonymous (CA), all of which are based on the 12-step model, and Smart Recovery®. Most drug addiction treatment programs encourage patients to participate in a self-help group during and after formal treatment.
How Can Families and Friends Make a Difference in the Life of Someone Needing Treatment? Family and friends can play critical roles in motivating individuals with drug problems to enter and stay in treatment. Family therapy is important, especially for adolescents. Involvement of a family member in an individual’s treatment program can strengthen and extend the benefits of the program.
Is Drug Addiction Treatment Worth Its Cost? Drug addiction treatment is cost-effective in reducing drug use and its associated health and social costs. Treatment is less expensive than
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alternatives, such as not treating addicts or simply incarcerating addicts. For example, the average cost for 1 full year of methadone maintenance treatment is approximately $4,700 per patient, whereas 1 full year of imprisonment costs approximately $18,400 per person. According to several conservative estimates, every $1 invested in addiction treatment programs yields a return of between $4 and $7 in reduced drugrelated crime, criminal justice costs, and theft alone. When savings related to health care are included, total savings can exceed costs by a ratio of 12 to 1. Major savings to the individual and society also come from significant drops in interpersonal conflicts, improvements in workplace productivity, and reductions in drug-related accidents.
Drug Addiction Treatment in the United States Drug addiction is a complex disorder that can involve virtually every aspect of an individual’s function in the family, at work, and in the community. Because of addiction’s complexity and pervasive consequences, drug addiction treatment typically must involve many components. Some of those components focus directly on the individual’s drug use. Others, like employment training, focus on restoring the addicted individual to productive membership in the family and society. Treatment for drug abuse and addiction is delivered in many different settings, using a variety of behavioral and pharmacological approaches. In the United States, more than 11,000 specialized drug treatment facilities provide rehabilitation, counseling, behavioral therapy, medication, case management, and other types of services to persons with drug use disorders. Because drug abuse and addiction are major public health problems, a large portion of drug treatment is funded by local, State, and Federal governments. Private and employer-subsidized health plans also may provide coverage for treatment of drug addiction and its medical consequences. Drug abuse and addiction are treated in specialized treatment facilities and mental health clinics by a variety of providers, including certified drug abuse counselors, physicians, psychologists, nurses, and social workers. Treatment is delivered in outpatient, inpatient, and residential settings. Although specific treatment approaches often are associated with particular treatment
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settings, a variety of therapeutic interventions or services can be included in any given setting.
General Categories of Treatment Programs Research studies on drug addiction treatment have typically classified treatment programs into several general types or modalities, which are described in the following text. Treatment approaches and individual programs continue to evolve, and many programs in existence today do not fit neatly into traditional drug addiction treatment classifications.
Agonist Maintenance Treatment Agonist maintenance treatment for opiate addicts usually is conducted in outpatient settings, often called methadone treatment programs. These programs use a long-acting synthetic opiate medication, usually methadone or LAAM, administered orally for a sustained period at a dosage sufficient to prevent opiate withdrawal, block the effects of illicit opiate use, and decrease opiate craving. Patients stabilized on adequate, sustained dosages of methadone or LAAM can function normally. They can hold jobs, avoid the crime and violence of the street culture, and reduce their exposure to HIV by stopping or decreasing injection drug use and drug-related high-risk sexual behavior. Patients stabilized on opiate agonists can engage more readily in counseling and other behavioral interventions essential to recovery and rehabilitation. The best, most effective opiate agonist maintenance programs include individual and/or group counseling, as well as provision of, or referral to, other needed medical, psychological, and social services.
Narcotic Antagonist Treatment Using Naltrexone Narcotic antagonist treatment using Naltrexone for opiate addicts usually is conducted in outpatient settings although initiation of the medication often begins after medical detoxification in a residential setting. Naltrexone is a long-acting synthetic opiate antagonist with few side effects that is taken orally either daily or three times a week for a sustained period of time. Individuals must be medically detoxified and opiate-free for several days before Naltrexone can be taken to prevent precipitating an opiate abstinence syndrome. When used this way, all the effects of self-administered opiates, including euphoria, are completely blocked. The theory behind this
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treatment is that the repeated lack of the desired opiate effects, as well as the perceived futility of using the opiate, will gradually over time result in breaking the habit of opiate addiction. Naltrexone itself has no subjective effects or potential for abuse and is not addicting. Patient noncompliance is a common problem. Therefore, a favorable treatment outcome requires that there also be a positive therapeutic relationship, effective counseling or therapy, and careful monitoring of medication compliance. Patients stabilized on Naltrexone can hold jobs, avoid crime and violence, and reduce their exposure to HIV. Many experienced clinicians have found Naltrexone most useful for highly motivated, recently detoxified patients who desire total abstinence because of external circumstances, including impaired professionals, parolees, probationers, and prisoners in workrelease status. Patients stabilized on Naltrexone can function normally. They can hold jobs, avoid the crime and violence of the street culture, and reduce their exposure to HIV by stopping injection drug use and drug-related highrisk sexual behavior.
Outpatient Drug-Free Treatment Outpatient drug-free treatment in the types and intensity of services offered. Such treatment costs less than residential or inpatient treatment and often is more suitable for individuals who are employed or who have extensive social supports. Low-intensity programs may offer little more than drug education and admonition. Other outpatient models, such as intensive day treatment, can be comparable to residential programs in services and effectiveness, depending on the individual patient’s characteristics and needs. In many outpatient programs, group counseling is emphasized. Some outpatient programs are designed to treat patients who have medical or mental health problems in addition to their drug disorder.
Long-Term Residential Treatment Long-term residential treatment provides care 24 hours per day, generally in non-hospital settings. The best-known residential treatment model is the therapeutic community (TC), but residential treatment may also employ other models, such as cognitive-behavioral therapy. TCs are residential programs with planned lengths of stay of 6 to 12 months. TCs focus on the “resocialization” of the individual and use the program’s entire “community,” including other residents, staff, and the social context,
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as active components of treatment. Addiction is viewed in the context of an individual’s social and psychological deficits, and treatment focuses on developing personal accountability and responsibility and socially productive lives. Treatment is highly structured and can at times be confrontational, with activities designed to help residents examine damaging beliefs, self-concepts, and patterns of behavior and to adopt new, more harmonious and constructive ways to interact with others. Many TCs are quite comprehensive and can include employment training and other support services on site. Compared with patients in other forms of drug treatment, the typical TC resident has more severe problems, with more co-occurring mental health problems and more criminal involvement. Research shows that TCs can be modified to treat individuals with special needs, including adolescents, women, those with severe mental disorders, and individuals in the criminal justice system.
Short-Term Residential Programs Short-term residential programs provide intensive but relatively brief residential treatment based on a modified 12-step approach. These programs were originally designed to treat alcohol problems, but during the cocaine epidemic of the mid-1980’s, many began to treat illicit drug abuse and addiction. The original residential treatment model consisted of a 3 to 6 week hospital-based inpatient treatment phase followed by extended outpatient therapy and participation in a self-help group, such as Alcoholics Anonymous. Reduced health care coverage for substance abuse treatment has resulted in a diminished number of these programs, and the average length of stay under managed care review is much shorter than in early programs.
Medical Detoxification Medical Detoxification is a process whereby individuals are systematically withdrawn from addicting drugs in an inpatient or outpatient setting, typically under the care of a physician. Detoxification is sometimes called a distinct treatment modality but is more appropriately considered a precursor of treatment, because it is designed to treat the acute physiological effects of stopping drug use. Medications are available for detoxification from opiates, nicotine, benzodiazepines, alcohol, barbiturates, and other sedatives. In some cases, particularly for the last three types of drugs, detoxification may be a
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medical necessity, and untreated withdrawal may be medically dangerous or even fatal. Detoxification is not designed to address the psychological, social, and behavioral problems associated with addiction and therefore does not typically produce lasting behavioral changes necessary for recovery. Detoxification is most useful when it incorporates formal processes of assessment and referral to subsequent drug addiction treatment.
Treating Criminal Justice-Involved Drug Abusers and Addicts Research has shown that combining criminal justice sanctions with drug treatment can be effective in decreasing drug use and related crime. Individuals under legal coercion tend to stay in treatment for a longer period of time and do as well as or better than others not under legal pressure. Often, drug abusers come into contact with the criminal justice system earlier than other health or social systems, and intervention by the criminal justice system to engage the individual in treatment may help interrupt and shorten a career of drug use. Treatment for the criminal justice-involved drug abuser or drug addict may be delivered prior to, during, after, or in lieu of incarceration. Combining criminal justice sanctions with drug treatment can be effective in decreasing drug use and related crime.
Prison-Based Treatment Programs Offenders with drug disorders may encounter a number of treatment options while incarcerated, including didactic drug education classes, selfhelp programs, and treatment based on therapeutic community or residential milieu therapy models. The TC model has been studied extensively and can be quite effective in reducing drug use and recidivism to criminal behavior. Those in treatment should be segregated from the general prison population, so that the “prison culture” does not overwhelm progress toward recovery. As might be expected, treatment gains can be lost if inmates are returned to the general prison population after treatment. Research shows that relapse to drug use and recidivism to crime are significantly lower if the drug offender continues treatment after returning to the community.
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Community-Based Treatment for Criminal Justice Populations A number of criminal justice alternatives to incarceration have been tried with offenders who have drug disorders, including limited diversion programs, pretrial release conditional on entry into treatment, and conditional probation with sanctions. The drug court is a promising approach. Drug courts mandate and arrange for drug addiction treatment, actively monitor progress in treatment, and arrange for other services to drug-involved offenders. Federal support for planning, implementation, and enhancement of drug courts is provided under the U.S. Department of Justice Drug Courts Program Office. As a well-studied example, the Treatment Accountability and Safer Communities (TASC) program provides an alternative to incarceration by addressing the multiple needs of drug-addicted offenders in a communitybased setting. TASC programs typically include counseling, medical care, parenting instruction, family counseling, school and job training, and legal and employment services. The key features of TASC include: ·
Coordination of criminal justice and drug treatment;
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Early identification, assessment, and referral of drug-involved offenders;
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Monitoring offenders through drug testing; and
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Use of legal sanctions as inducements to remain in treatment.
Scientifically-Based Approaches to Drug Addiction Treatment This section presents several examples of treatment approaches and components that have been developed and tested for efficacy through research supported by the National Institute on Drug Abuse (NIDA). Each approach is designed to address certain aspects of drug addiction and its consequences for the individual, family, and society. The approaches are to be used to supplement or enhance (not replace) existing treatment programs. This section is not a complete list of efficacious, scientifically-based treatment approaches. Additional approaches are under development as part of NIDA’s continuing support of treatment research.
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Relapse Prevention Relapse prevention, a cognitive-behavioral therapy, was developed for the treatment of problem drinking and adapted later for cocaine addicts. Cognitive-behavioral strategies are based on the theory that learning processes play a critical role in the development of maladaptive behavioral patterns. Individuals learn to identify and correct problematic behaviors. Relapse prevention encompasses several cognitive-behavioral strategies that facilitate abstinence as well as provide help for people who experience relapse. The relapse prevention approach to the treatment of cocaine addiction consists of a collection of strategies intended to enhance self-control. Specific techniques include exploring the positive and negative consequences of continued use, self-monitoring to recognize drug cravings early on and to identify high-risk situations for use, and developing strategies for coping with and avoiding high-risk situations and the desire to use. A central element of this treatment is anticipating the problems patients are likely to meet and helping them develop effective coping strategies. Research indicates that the skills individuals learn through relapse prevention therapy remain after the completion of treatment. In one study, most people receiving this cognitive-behavioral approach maintained the gains they made in treatment throughout the year following treatment.
The Matrix Model The Matrix model provides a framework for engaging stimulant abusers in treatment and helping them achieve abstinence. Patients learn about issues critical to addiction and relapse, receive direction and support from a trained therapist, become familiar with self-help programs, and are monitored for drug use by urine testing. The program includes education for family members affected by the addiction. The therapist functions simultaneously as teacher and coach, fostering a positive, encouraging relationship with the patient and using that relationship to reinforce positive behavior change. The interaction between the therapist and the patient is realistic and direct but not confrontational or parental. Therapists are trained to conduct treatment sessions in a way that promotes the patient’s self-esteem, dignity, and self-worth. A positive relationship between patient and therapist is a critical element for patient retention.
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Treatment materials draw heavily on other tested treatment approaches. Thus, this approach includes elements pertaining to the areas of relapse prevention, family and group therapies, drug education, and self-help participation. Detailed treatment manuals contain work sheets for individual sessions; other components include family educational groups, early recovery skills groups, relapse prevention groups, conjoint sessions, urine tests, 12-step programs, relapse analysis, and social support groups. A number of projects have demonstrated that participants treated with the Matrix model demonstrate statistically significant reductions in drug and alcohol use, improvements in psychological indicators, and reduced risky sexual behaviors associated with HIV transmission. These reports, along with evidence suggesting comparable treatment response for methamphetamine users and cocaine users and demonstrated efficacy in enhancing naltrexone treatment of opiate addicts, provide a body of empirical support for the use of the model.
Supportive-Expressive Psychotherapy Supportive-expressive psychotherapy is a time-limited, focused psychotherapy that has been adapted for heroin- and cocaine-addicted individuals. The therapy has two main components: ·
Supportive techniques to help patients feel comfortable in discussing their personal experiences.
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Expressive techniques to help patients identify and work through interpersonal relationship issues.
Special attention is paid to the role of drugs in relation to problem feelings and behaviors, and how problems may be solved without recourse to drugs. The efficacy of individual supportive-expressive psychotherapy has been tested with patients in methadone maintenance treatment who had psychiatric problems. In a comparison with patients receiving only drug counseling, both groups fared similarly with regard to opiate use, but the supportive-expressive psychotherapy group had lower cocaine use and required less methadone. Also, the patients who received supportiveexpressive psychotherapy maintained many of the gains they had made. In an earlier study, supportive-expressive psychotherapy, when added to drug counseling, improved outcomes for opiate addicts in methadone treatment with moderately severe psychiatric problems.
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Individualized Drug Counseling Individualized drug counseling focuses directly on reducing or stopping the addict’s illicit drug use. It also addresses related areas of impaired functioning such as employment status, illegal activity, family/social relations as well as the content and structure of the patient’s recovery program. Through its emphasis on short-term behavioral goals, individualized drug counseling helps the patient develop coping strategies and tools for abstaining from drug use and then maintaining abstinence. The addiction counselor encourages 12-step participation and makes referrals for needed supplemental medical, psychiatric, employment, and other services. Individuals are encouraged to attend sessions one or two times per week. In a study that compared opiate addicts receiving only methadone to those receiving methadone coupled with counseling, individuals who received only methadone showed minimal improvement in reducing opiate use. The addition of counseling produced significantly more improvement. The addition of onsite medical/psychiatric, employment, and family services further improved outcomes. In another study with cocaine addicts, individualized drug counseling, together with group drug counseling, was quite effective in reducing cocaine use. Thus, it appears that this approach has great utility with both heroin and cocaine addicts in outpatient treatment.
Motivational Enhancement Therapy Motivational enhancement therapy is a client-centered counseling approach for initiating behavior change by helping clients to resolve ambivalence about engaging in treatment and stopping drug use. This approach employs strategies to evoke rapid and internally motivated change in the client, rather than guiding the client stepwise through the recovery process. This therapy consists of an initial assessment battery session, followed by two to four individual treatment sessions with a therapist. The first treatment session focuses on providing feedback generated from the initial assessment battery to stimulate discussion regarding personal substance use and to elicit self-motivational statements. Motivational interviewing principles are used to strengthen motivation and build a plan for change. Coping strategies for high-risk situations are suggested and discussed with the client. In subsequent sessions, the therapist monitors change, reviews cessation strategies being used, and continues to encourage
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commitment to change or sustained abstinence. Clients are sometimes encouraged to bring a significant other to sessions. This approach has been used successfully with alcoholics and with marijuana-dependent individuals.
Behavioral Therapy Behavioral therapy for Adolescents incorporates the principle that unwanted behavior can be changed by clear demonstration of the desired behavior and consistent reward of incremental steps toward achieving it. Therapeutic activities include fulfilling specific assignments, rehearsing desired behaviors, and recording and reviewing progress, with praise and privileges given for meeting assigned goals. Urine samples are collected regularly to monitor drug use. The therapy aims to equip the patient to gain three types of control: ·
Stimulus Control helps patients avoid situations associated with drug use and learn to spend more time in activities incompatible with drug use.
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Urge Control helps patients recognize and change thoughts, feelings, and plans that lead to drug use.
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Social Control involves family members and other people important in helping patients avoid drugs. A parent or significant other attends treatment sessions when possible and assists with therapy assignments and reinforcing desired behavior.
According to research studies, this therapy helps adolescents become drug free and increases their ability to remain drug free after treatment ends. Adolescents also show improvement in several other areas such as employment/school attendance, family relationships, depression, institutionalization, and alcohol use. Such favorable results are attributed largely to including family members in therapy and rewarding drug abstinence as verified by urinalysis.
Multidimensional Family Therapy (MDFT) for Adolescents Multidimensional family therapy (MDFT) for adolescents is an outpatient family-based drug abuse treatment for teenagers. MDFT views adolescent drug use in terms of a network of influences (that is, individual, family, peer, community) and suggests that reducing unwanted behavior and increasing desirable behavior occur in multiple ways in different settings. Treatment includes individual and family sessions held in the clinic, in the home, or
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with family members at the family court, school, or other community locations. During individual sessions, the therapist and adolescent work on important developmental tasks, such as developing decision-making, negotiation, and problem-solving skills. Teenagers acquire skills in communicating their thoughts and feelings to deal better with life stressors, and vocational skills. Parallel sessions are held with family members. Parents examine their particular parenting style, learning to distinguish influence from control and to have a positive and developmentally appropriate influence on their child.
Multisystemic Therapy (MST) Multisystemic therapy (MST) addresses the factors associated with serious antisocial behavior in children and adolescents who abuse drugs. These factors include characteristics of the adolescent (for example, favorable attitudes toward drug use), the family (poor discipline, family conflict, parental drug abuse), peers (positive attitudes toward drug use), school (dropout, poor performance), and neighborhood (criminal subculture). By participating in intense treatment in natural environments (homes, schools, and neighborhood settings) most youths and families complete a full course of treatment. MST significantly reduces adolescent drug use during treatment and for at least 6 months after treatment. Reduced numbers of incarcerations and out-of-home placements of juveniles offset the cost of providing this intensive service and maintaining the clinicians’ low caseloads.
Combined Behavioral and Nicotine Replacement Therapy for Nicotine Addiction Combined behavioral and nicotine replacement therapy for nicotine addiction consists of two main components: ·
The transdermal nicotine patch or nicotine gum reduces symptoms of withdrawal, producing better initial abstinence.
·
The behavioral component concurrently provides support reinforcement of coping skills, yielding better long-term outcomes.
and
Through behavioral skills training, patients learn to avoid high-risk situations for smoking relapse early on and later to plan strategies to cope with such situations. Patients practice skills in treatment, social, and work
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settings. They learn other coping techniques, such as cigarette refusal skills, assertiveness, and time management. The combined treatment is based on the rationale that behavioral and pharmacological treatments operate by different yet complementary mechanisms that produce potentially additive effects.
Community Reinforcement Approach (CRA) Community reinforcement approach (CRA) plus vouchers is an intensive 24week outpatient therapy for treatment of cocaine addiction. The treatment goals are twofold: ·
To achieve cocaine abstinence long enough for patients to learn new life skills that will help sustain abstinence.
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To reduce alcohol consumption for patients whose drinking is associated with cocaine use.
Patients attend one or two individual counseling sessions per week, where they focus on improving family relations, learning a variety of skills to minimize drug use, receiving vocational counseling, and developing new recreational activities and social networks. Those who also abuse alcohol receive clinic-monitored disulfiram (Antabuse) therapy. Patients submit urine samples two or three times each week and receive vouchers for cocaine-negative samples. The value of the vouchers increases with consecutive clean samples. Patients may exchange vouchers for retail goods that are consistent with a cocaine-free lifestyle. This approach facilitates patients’ engagement in treatment and systematically aids them in gaining substantial periods of cocaine abstinence. The approach has been tested in urban and rural areas and used successfully in outpatient detoxification of opiate-addicted adults and with inner-city methadone maintenance patients who have high rates of intravenous cocaine abuse.
Voucher-Based Reinforcement Therapy in Methadone Treatment Voucher-based reinforcement therapy in Methadone maintenance treatment helps patients achieve and maintain abstinence from illegal drugs by providing them with a voucher each time they provide a drug-free urine sample. The voucher has monetary value and can be exchanged for goods and services consistent with the goals of treatment. Initially, the voucher
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values are low, but their value increases with the number of consecutive drug-free urine specimens the individual provides. Cocaine- or heroinpositive urine specimens reset the value of the vouchers to the initial low value. The contingency of escalating incentives is designed specifically to reinforce periods of sustained drug abstinence. Studies show that patients receiving vouchers for drug-free urine samples achieved significantly more weeks of abstinence and significantly more weeks of sustained abstinence than patients who were given vouchers independent of urinalysis results. In another study, urinalyses positive for heroin decreased significantly when the voucher program was started and increased significantly when the program was stopped.
Day Treatment with Abstinence Contingencies and Vouchers Day treatment with abstinence contingencies and vouchers was developed to treat homeless crack addicts. For the first 2 months, participants must spend 5.5 hours daily in the program, which provides lunch and transportation to and from shelters. Interventions include individual assessment and goal setting, individual and group counseling, multiple psycho-educational groups (for example, didactic groups on community resources, housing, cocaine, and HIV/AIDS prevention; establishing and reviewing personal rehabilitation goals; relapse prevention; weekend planning), and patientgoverned community meetings during which patients review contract goals and provide support and encouragement to each other. Individual counseling occurs once a week, and group therapy sessions are held three times a week. After 2 months of day treatment and at least 2 weeks of abstinence, participants graduate to a 4-month work component that pays wages that can be used to rent inexpensive, drug-free housing. A voucher system also rewards drug-free related social and recreational activities. This innovative day treatment was compared with treatment consisting of twice-weekly individual counseling and 12-step groups, medical examinations and treatment, and referral to community resources for housing and vocational services. Innovative day treatment followed by work and housing dependent upon drug abstinence had a more positive effect on alcohol use, cocaine use, and days homeless.
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Resources The National Institute on Drug Abuse58 General inquiries: ·
NIDA Public Information Office, Telephone: 301-443-1124.
Inquiries about NIDA’s treatment research activities: ·
Division of Treatment Research and Development (301) 443-6173 (for questions regarding behavioral therapies and medications);
·
Division of Epidemiology, Services and Prevention Research (301) 4434060 (for questions regarding access to treatment, organization, management, financing, effectiveness and cost-effectiveness).
Center for Substance Abuse Treatment (CSAT) CSAT, a part of the Substance Abuse and Mental Health Services Administration, is responsible for supporting treatment services through block grants and developing knowledge about effective drug treatment, disseminating the findings to the field, and promoting their adoption. CSAT also operates the National Treatment Referral 24-hour Hotline (1-800-662HELP) which offers information and referral to people seeking treatment programs and other assistance. CSAT publications are available through the National Clearinghouse on Alcohol and Drug Information (1-800-729-6686). Additional information can be found at CSAT’s Web Site: http://www.samhsa.gov/csat.
Selected NIDA Educational Resources on Drug Addiction Treatment The following are available from the National Clearinghouse on Alcohol and Drug Information (NCADI), the National Technical Information Service (NTIS), or the Government Printing Office (GPO). To order, refer to the NCADI (1-800-729-6686), NTIS (1-800-553-6847), or GPO (202-512-1800) number provided with the resource description.
58
The NIDA: http://www.nida.nih.gov.
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Manuals and Clinical Reports ·
Measuring and Improving Cost, Cost-Effectiveness, and Cost-Benefit for Substance Abuse Treatment Programs (1999). Offers substance abuse treatment program managers tools with which to calculate the costs of their programs and investigate the relationship between those costs and treatment outcomes. NCADI # BKD340. Available online at http://www.nida.nih.gov/IMPCOST/IMPCOSTIndex.html.
·
A Cognitive-Behavioral Approach: Treating Cocaine Addiction (1998). This is the first in NIDA’s “Therapy Manuals for Drug Addiction” series. Describes cognitive-behavioral therapy, a short-term focused approach to helping cocaine-addicted individuals become abstinent from cocaine and other drugs. NCADI # BKD254. Available online at http://www.nida.nih.gov/TXManuals/CBT/CBT1.html.
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A Community Reinforcement Plus Vouchers Approach: Treating Cocaine Addiction (1998). This is the second in NIDA’s “Therapy Manuals for Drug Addiction” series. This treatment integrates a community reinforcement approach with an incentive program that uses vouchers. NCADI # BKD255. Available online at http://www.nida.nih.gov/TXManuals/CRA/CRA1.html.
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An Individual Drug Counseling Approach to Treat Cocaine Addiction: The Collaborative Cocaine Treatment Study Model (1999). This is the third in NIDA’s “Therapy Manuals for Drug Addiction” series. Describes specific cognitive-behavioral models that can be implemented in a wide range of differing drug abuse treatment settings. NCADI # BKD337. Available online at http://www.nida.nih.gov/TXManuals/IDCA/IDCA1.html.
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Mental Health Assessment and Diagnosis of Substance Abusers: Clinical Report Series (1994). Provides detailed descriptions of psychiatric disorders that can occur among drug-abusing clients. NCADI # BKD148.
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Relapse Prevention: Clinical Report Series (1994). Discusses several major issues to relapse prevention. Provides an overview of factors and experiences that can lead to relapse. Reviews general strategies for preventing relapses, and describes four specific approaches in detail. Outlines administrative issues related to implementing a relapse prevention program. NCADI # BKD147.
·
Addiction Severity Index Package (1993). Provides a structured clinical interview designed to collect information about substance use and functioning in life areas from adult clients seeking drug abuse treatment. Includes a handbook for program administrators, a resource manual, two
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videotapes, and a training AVA19615VNB2KUS. $150.
facilitator’s
manual.
NTIS
#
Research Monographs ·
Beyond the Therapeutic Alliance: Keeping the Drug-Dependent Individual in Treatment (Research Monograph 165) (1997). Reviews current treatment research on the best ways to retain patients in drug abuse treatment. NTIS # 97-181606. $47; GPO # 017-024-01608-0. $17. http://www.nida.nih.gov/pdf/monographs/monograph165/download16 5.html.
·
Treatment of Drug-Exposed Women and Children: Advances in Research Methodology (Research Monograph 166) (1997). Presents experiences, products, and procedures of NIDA-supported Treatment Research Demonstration Program projects. NCADI # M166; NTIS # 96179106. $75; GPO # 017-01592-0. $13. Available online at http://www.nida.nih.gov/pdf/monographs/monograph166/download.ht ml.
·
Treatment of Drug-Dependent Individuals With Comorbid Mental Disorders (Research Monograph 172) (1997). Promotes effective treatment by reporting state-of-the-art treatment research on individuals with comorbid mental and addictive disorders and research on HIVrelated issues among people with comorbid conditions. NCADI # M172; NTIS # 97-181580. $41; GPO # 017-024-01605. $10. Available online at http://www.nida.nih.gov/pdf/monographs/monograph172/download17 2.html
·
Medications Development for the Treatment of Cocaine Dependence: Issues in Clinical Efficacy Trials (Research Monograph 175) (1998). A state-of-the-art handbook for clinical investigators, pharmaceutical scientists, and treatment researchers. NCADI # M175. http://www.nida.nih.gov/pdf/monographs/monograph175/download17 5.html Videos
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Adolescent Treatment Approaches (1991). Emphasizes the importance of pinpointing and addressing individual problem areas, such as sexual abuse, peer pressure, and family involvement in treatment. Running time: 25 min. NCADI # VHS40. $12.50.
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·
NIDA Technology Transfer Series: Assessment (1991). Shows how to use a number of diagnostic instruments as well as how to assess the implementation and effectiveness of the plan during various phases of the patient’s treatment. Running time: 22 min. NCADI # VHS38. $12.50.
·
Drug Abuse Treatment in Prison: A New Way Out (1995). Portrays two comprehensive drug abuse treatment approaches that have been effective with men and women in State and Federal Prisons. Running time: 23 min. NCADI # VHS72. $12.50.
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Dual Diagnosis (1993). Focuses on the problem of mental illness in drugabusing and drug-addicted populations, and examines various approaches useful for treating dual-diagnosed clients. Running time: 27 min. NCADI # VHS58. $12.50.
·
LAAM: Another Option for Maintenance Treatment of Opiate Addiction (1995). Shows how LAAM can be used to meet the opiate treatment needs of individual clients from the provider and patient perspectives. Running time: 16 min. NCADI # VHS73. $12.50.
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Methadone: Where We Are (1993). Examines issues such as the use and effectiveness of methadone as a treatment, biological effects of methadone, the role of the counselor in treatment, and societal attitudes toward methadone treatment and patients. Running time: 24 min. NCADI # VHS59. $12.50.
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Relapse Prevention (1991). Helps practitioners understand the common phenomenon of relapse to drug use among patients in treatment. Running time: 24 min. NCADI # VHS37. $12.50.
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Treatment Issues for Women (1991). Assists treatment counselors help female patients to explore relationships with their children, with men, and with other women. Running time: 22 min. NCADI # VHS39. $12.50.
·
Treatment Solutions (1999). Describes the latest developments in treatment research and emphasizes the benefits of drug abuse treatment, not only to the patient, but also to the greater community. Running time: 19 min. NCADI # DD110. $12.50.
·
Program Evaluation Package (1993). A practical resource for treatment program administrators and key staff. Includes an overview and case study manual, a guide for evaluation, a resource guide, and a pamphlet. NTIS # 95-167268/BDL. $86.50.
·
Relapse Prevention Package (1993). Examines two effective relapse prevention models, the Recovery Training and Self-Help (RTSH) program and the Cue Extinction model. NTIS # 95-167250. $189; GPO # 017-024-01555-5. $57. (Sold by GPO as a set of 7 books)
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Other Federal Resources ·
The National Clearinghouse for Alcohol and Drug Information (NCADI). NIDA publications and treatment materials along with publications from other Federal agencies are available from this information source. Staff provide assistance in English and Spanish, and have TDD capability. Phone: 1-800-729-6686. Website: http://www.health.org.
·
The National Institute of Justice (NIJ). As the research agency of the Department of Justice, NIJ supports research, evaluation, and demonstration programs relating to drug abuse in the contexts of crime and the criminal justice system. For information, including a wealth of publications, contact the National Criminal Justice Reference Service by telephone (1-800-851-3420 or 1-301-519-5500) or on the World Wide Web (http://www.ojp.usdoj.gov/nij).
Vocabulary Builder Agonist: A chemical compound that mimics the action of a natural neurotransmitter. [NIH] Antidepressants: A group of drugs used in treating depressive disorders. [NIH]
Barbiturate: A type of central nervous system (CNS) depressant often prescribed to promote sleep. [NIH] Benzodiazepine: A type of CNS depressant prescribed to relieve anxiety; among the most widely prescribed medications, including Valium and Librium. [NIH] Bupropion: A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment. [NIH] Crack: Short term for a smokable form of cocaine. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Detoxification: A process of allowing the body to rid itself of a drug while managing the symptoms of withdrawal; often the first step in a drug treatment program. [NIH] Euphoria: An exaggerated feeling of physical and mental well-being, especially when not justified by external reality. Euphoria may be induced
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by drugs such as opioids, amphetamines, and alcohol and is also a feature of mania. [EU] Institutionalization: The caring for individuals in institutions and their adaptation to routines characteristic of the institutional environment, and/or their loss of adaptation to life outside the institution. [NIH] LAAM: An approved medication for the treatment of opioid addiction, taken 3 to 4 times a week. [NIH] Methamphetamine: A central nervous system stimulant and sympathomimetic with actions and uses similar to dextroamphetamine. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed. [NIH] Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Nicotine: An alkaloid derived from the tobacco plant that is responsible for smoking's psychoactive and addictive effects; is toxic at high doses but can be safe and effective as medicine at lower doses. [NIH] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [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] 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] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Withdrawal: A variety of symptoms that occur after chronic use of some drugs is reduced or stopped. [NIH]
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APPENDIX F. MORE ON HEPATITIS C Overview59 Hepatitis C is a liver disease. Hepatitis (HEP-ah-TY-tis) makes your liver swell and stops it from working right. You need a healthy liver. The liver does many things to keep you alive. The liver fights infections and stops bleeding. It removes drugs and other poisons from your blood. The liver also stores energy for when you need it.
Adapted from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): http://www.niddk.nih.gov/health/digest/pubs/hep/hepc/hepc.htm. 59
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What Causes Hepatitis C? Hepatitis C is caused by a virus. A virus is a germ that causes sickness. (For example, the flu is caused by a virus.) People can pass viruses to each other. The virus that causes hepatitis C is called the hepatitis C virus.
How Could I Get Hepatitis C? You could get hepatitis C by: ·
Sharing drug needles.
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Getting pricked with a needle that has infected blood on it (hospital workers can get hepatitis C this way).
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Being born to a mother with hepatitis C.
In rare cases, you could get hepatitis C by: ·
Getting a tattoo or body piercing with unsterilized, dirty tools.
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Having sex with an infected person, especially if you or your partner has other sexually transmitted diseases.
You cannot get hepatitis C by: ·
Shaking hands with an infected person.
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Hugging an infected person.
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Kissing an infected person.
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Sitting next to an infected person.
Could I Get Hepatitis C from a Blood Transfusion? If you had a blood transfusion or organ transplant before 1992, you might have hepatitis C. Before 1992, doctors could not check blood for hepatitis C, and some people received infected blood. If you had a blood transfusion or organ transplant before 1992, ask a doctor to test you for hepatitis C.
More on Hepatitis C 337
What Are the Symptoms? Many people with hepatitis C don’t have symptoms. However, some people with hepatitis C feel like they have the flu. So, you might: ·
Feel tired.
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Feel sick to your stomach.
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Have a fever.
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Not want to eat.
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Have stomach pain.
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Have diarrhea.
Some people have: ·
Dark yellow urine.
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Light-colored stools.
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Yellowish eyes and skin.
If you have symptoms, or think you might have hepatitis C, go to a doctor.
What Are the Tests for Hepatitis C? The doctor will take some blood to check for hepatitis C. To check for hepatitis C, the doctor will test your blood. These tests show if you have hepatitis C and how serious it is. The doctor may also do a liver biopsy. Biopsy (BYE-op-see) is a simple test. The doctor removes a tiny piece of your liver through a needle. The doctor checks the piece of liver for signs of hepatitis C and liver damage.
How Is Hepatitis C Treated? ·
Hepatitis C is treated through shots of medicine.
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Hepatitis C is treated with a drug called interferon alone or in combination with the drug ribavirin.
You may need surgery if you have hepatitis C for many years. Over time, hepatitis C can cause your liver to stop working. If that happens, you will
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need a new liver. The surgery is called a liver transplant. It involves taking out the old, damaged liver and putting in a new, healthy one from a donor.
How Can I Protect Myself? You can protect yourself and others from hepatitis C: ·
Don’t share drug needles with anyone.
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Wear gloves if you have to touch anyone’s blood.
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Don’t use an infected person’s toothbrush, razor, or anything else that could have blood on it.
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If you get a tattoo or body piercing, make sure it is done with clean tools.
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If you have several sex partners, you should use a condom during sex.
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If you have hepatitis C, don’t give your blood or plasma. The person who receives it could become infected with the virus.
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If you inject drugs, use your own needles.
For More Information You can also get information about hepatitis C from these groups: American Liver Foundation 1425 Pompton Avenue Cedar Grove, NJ 07009-1000 Tel: (800) 223-0179 (This is a free call.) Hepatitis Foundation International 30 Sunrise Terrace Cedar Grove, NJ 07009-1423 Tel: (800) 891-0707 (This is a free call.)
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APPENDIX
G.
NIH CONSENSUS STATEMENT MANAGEMENT OF HEPATITIS C
ON
Overview NIH Consensus Development Conferences are convened to evaluate available scientific information and resolve safety and efficacy issues related to biomedical technology. The resultant NIH Consensus Statements are intended to advance understanding of the technology or issue in question and to be useful to health professionals and the public.60 Each NIH consensus statement is the product of an independent, non-Federal panel of experts and is based on the panel’s assessment of medical knowledge available at the time the statement was written. Therefore, a consensus statement provides a “snapshot in time” of the state of knowledge of the conference topic. The NIH makes the following caveat: “When reading or downloading NIH consensus statements, keep in mind that new knowledge is inevitably accumulating through medical research. Nevertheless, each NIH consensus statement is retained on this website in its original form as a record of the NIH Consensus Development Program.”61 The following concensus statement was posted on the NIH site and not indicated as “out of date” in March 2002. It was originally published, however, in March 1997.62
This paragraph has been adapted from the NIH: http://odp.od.nih.gov/consensus/cons/cons.htm. 61 Adapted from the NIH: http://odp.od.nih.gov/consensus/cons/consdate.htm. 62 Management of Hepatitis C. NIH Consensus Statement Online, 1997 Mar 24-26 [cited 2002, February, 15]; 15(3): 1-41. http://consensus.nih.gov/cons/105/105_statement.htm. 60
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Abstract Objective To provide health care providers, patients, and the general public with a responsible assessment of current available methods to diagnose, treat, and manage hepatitis C. Participants A non-Federal, nonadvocate, 12-member panel representing the fields of general internal medicine, hepatology, gastroenterology, infectious diseases, medical ethics, transfusion medicine, epidemiology, biostatistics, and the public. In addition, 25 experts from these same fields presented data to the panel and a conference audience of 1,600.
Evidence The literature was searched through Medline and an extensive bibliography of references was provided to the panel and the conference audience. Experts prepared abstracts with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. Consensus Process The panel, answering predefined questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature. The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after conference
Conclusions Hepatitis C is a common infection with variable course that can lead to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The course of illness may be adversely affected by various factors, especially alcohol consumption. Therefore, more than one drink per day is strongly discouraged in patients with hepatitis C, and abstinence from alcohol is recommended. Initial therapy with interferon alfa (or equivalent) should be
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3 million units three times per week for 12 months. Patients not responding to therapy after 3 months should not receive further treatment with interferon alone, but should be considered for combination therapy of interferon and ribavirin or for enrollment in investigational studies. Individuals infected with the hepatitis C virus should not donate blood, organs, tissues, or semen. Safe sexual practices, including the use of latex condoms, is strongly encouraged for individuals with multiple sexual partners. Expansion of needle exchange programs should be considered in an effort to reduce the rate of transmission of hepatitis C among injection drug users.
What Is Hepatitis C? The hepatitis C virus (HCV) is one of six viruses (A, B, C, D, E, and G) that together account for the majority of cases of viral hepatitis. According to the National Health and Nutrition Examination Survey of 1988-94 and other population-based surveys, estimates of the incidence and prevalence of HCV infection have been made. Nearly 4 million Americans are infected with hepatitis C. The infection is more common in minority populations (3.2 percent of African-Americans and 2.1 percent of Mexican-Americans) than in non-Hispanic whites (1.5 percent). The incidence of hepatitis C infection appears to be declining since its peak in 1989. Currently, approximately 30,000 acute new infections are estimated to occur each year, about 25-30 percent of which are diagnosed. Hepatitis C accounts for 20 percent of all cases of acute hepatitis. Currently, hepatitis C is responsible for an estimated 8,000-10,000 deaths annually, and without effective intervention that number is postulated to triple in the next 10-20 years. Hepatitis C is now the leading reason for liver transplantation in the United States. The switch from commercial to volunteer blood donors and the development of a diagnostic blood test for hepatitis B in the early 1970s led to screening of blood donors and reduced from 30 to 10 percent the incidence of hepatitis following multiple transfusions. The remainder of these transfusionassociated cases were termed “non-A, non-B” hepatitis. In 1989, Michael Houghton and his colleagues ushered in a new era for the discovery of infectious agents when they used molecular biologic techniques to clone hepatitis C, the agent responsible for 80-90 percent of non-A, non-B hepatitis. This was a scientific tour de force because the technique was successful in identifying an agent that had not been visualized, grown in culture, or immunologically defined. Following the introduction of sensitive and
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effective blood tests for the detection of hepatitis C, the risk of transfusionrelated hepatitis is now in the range of 1 in 100,000 units transfused. Hepatitis C is transmitted primarily by the parenteral route, and sources of infection include injection drug use, needle-stick accidents, and transfusions of blood or blood products. Since 1990 and the introduction of tests for antiHCV, new cases of posttransfusion hepatitis C have virtually disappeared. Hepatitis C virus is not easily cleared by the host’s immunologic defenses. Thus, a persistent infection develops in perhaps as many as 85 percent of patients with acute hepatitis C. This inability to clear the virus by the infected host sets the stage for the development of chronic liver disease. The range of disease states following hepatitis C infection is broad. Lastly, in contrast to hepatitis A and B, there is no effective vaccine to prevent acquisition of hepatitis C infection. For the reasons listed above, the National Institute of Diabetes and Digestive and Kidney Diseases and the Office of Medical Applications of Research of the National Institutes of Health, along with cosponsors the National Institute of Allergy and Infectious Diseases, National Heart, Lung, and Blood Institute, National Institute on Drug Abuse, and Centers for Disease Control and Prevention, sponsored a Consensus Development Conference on March 24-26, 1997. Following 1-1/2 days of testimony by experts in the relevant fields and discussion from the audience, a consensus panel representing general internal medicine, hepatology, gastroenterology, infectious diseases, medical ethics, transfusion medicine, epidemiology, biostatistics, and the public considered the evidence and formulated a consensus statement to address the following six predefined questions: ·
What is the natural history of hepatitis C?
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What is the most appropriate approach to diagnose and monitor patients?
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What is the most effective therapy for hepatitis C?
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Which patients with hepatitis C should be treated?
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What recommendations to patients can be made to prevent transmission of hepatitis C?
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What are the most important areas for future research?
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What Is the Natural History of Hepatitis C? The Virus The hepatitis C virus is an RNA virus of the Flaviviridae family. Individual isolates consist of closely related yet heterogeneous populations of viral genomes (quasispecies). Probably as a consequence of this genetic diversity, HCV has the ability to escape the host’s immune surveillance, leading to a high rate of chronic infection. Comparing the genomic nucleotide sequences from different HCV isolates enables classification of viruses into several genotypes and many more subtypes. The extensive genetic heterogeneity of HCV has important diagnostic and clinical implications, perhaps explaining variations in clinical course, difficulties in vaccine development, and lack of response to therapy.
Clinical Course Data on the natural history of hepatitis C are limited, because the onset of infection is often unrecognized and the early course of the disease is indolent and protracted in many individuals. Prospective cohort studies are few, are typically small, include relatively few subjects whose date of infection can be well documented (e.g., blood transfusion recipients and victims of accidental needle sticks), and have relatively short followup. The natural history of this disease appears to differ according to geography, alcohol use, virus characteristics (e.g., genotype, viral load), coinfection with other viruses, and other unexplained factors.
Acute Infection After initial exposure, HCV RNA can be detected in blood in 1-3 weeks. Within an average of 50 days (range: 15-150 days), virtually all patients develop liver cell injury, as shown by elevation of serum alanine aminotransferase (ALT). The majority of patients are asymptomatic and anicteric. Only 25-35 percent develop malaise, weakness, or anorexia, and some become icteric. Fulminant liver failure following HCV infection has been reported but is a rare occurrence. Antibodies to HCV (anti-HCV) almost invariably become detectable during the course of illness. Anti-HCV can be detected in 50-70 percent of patients at the onset of symptoms and in approximately 90 percent of patients 3 months after onset of infection. HCV infection is self-limited in only 15 percent of cases. Recovery is characterized
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by disappearance of HCV RNA from blood and return of liver enzymes to normal.
Chronic Infection About 85 percent of HCV-infected individuals fail to clear the virus by 6 months and develop chronic hepatitis with persistent, although sometimes intermittent, viremia. This capacity to produce chronic hepatitis is one of the most striking features of HCV infection. The majority of patients with chronic infection have abnormalities in ALT levels that can fluctuate widely. About one-third of patients have persistently normal serum ALT levels. Antibodies to HCV or circulating viral RNA can be demonstrated in virtually all patients. Chronic hepatitis C is typically an insidious process, progressing, if at all, at a slow rate without symptoms or physical signs in the majority of patients during the first two decades after infection. A small proportion of patients with chronic hepatitis C -- perhaps less than 20 percent -- develop nonspecific symptoms, including mild intermittent fatigue and malaise. Symptoms first appear in many patients with chronic hepatitis C at the time of development of advanced liver disease. In chronic hepatitis, inflammatory cells infiltrate the portal tracts and may also collect in small clusters in the parenchyma. The latter instance is usually accompanied by focal liver cell necrosis. The margin of the parenchyma and portal tracts may become inflamed, with liver cell necrosis at this site (interface hepatitis). If and when the disease progresses, the inflammation and liver cell death may lead to fibrosis. Mild fibrosis is confined to the portal tracts and immediately adjacent parenchyma. More severe fibrosis leads to bridging between portal tracts and between portal tracts and hepatic veins. Such fibrosis can progress to cirrhosis, defined as a state of diffuse fibrosis in which fibrous septae separate clusters of liver cells into nodules. The extent of fibrosis determines the stage of disease and can be reliably assessed. Severe fibrosis and necroinflammatory changes predict progression to cirrhosis. Once cirrhosis is established, complications can ensue that are secondary to liver failure and/or to portal hypertension, such as jaundice, ascites, variceal hemorrhage, and encephalopathy. The development of any of these complications marks the transition from a compensated to a decompensated cirrhosis. The rate of progression is highly variable. Long-term studies suggest that most patients with progressive liver disease who develop cirrhosis have
NIH Consensus Statement on Management of Hepatitis C 345
detectable ALT elevations; these can, however, be intermittent. The relationship is inconsistent between ALT levels and disease severity as judged histologically. Although patients with HCV infection and normal ALT levels have been referred to as “healthy” HCV carriers, liver biopsies can show histological evidence of chronic hepatitis in many of these patients.
Cirrhosis of the Liver Chronic hepatitis C infection leads to cirrhosis in at least 20 percent of patients within 2 decades of the onset of infection. Cirrhosis and end-stage liver disease may occasionally develop rapidly, especially among patients with concomitant alcohol use. Hepatocellular Carcinoma (HCC) Chronic infection by HCV is associated with an increased risk of liver cancer. The prevailing concept is that hepatocellular carcinoma (HCC) occurs against a background of inflammation and regeneration associated with chronic hepatitis over the course of approximately 3 or more decades. Most cases of HCV-related HCC occur in the presence of cirrhosis. The risk that a person with chronic hepatitis C will develop HCC appears to be 1-5 percent after 20 years, with striking variations in rates in different geographic areas of the world. Once cirrhosis is established, the rate of development of HCC increases to 1-4 percent per year. Among patients with cirrhosis due to hepatitis C, HCC develops more commonly in men than in women and in older than in younger patients.
Extrahepatic Manifestations of HCV Patients with chronic hepatitis C occasionally present with extrahepatic manifestations or syndromes considered to be of immunologic origin, including arthritis, keratoconjunctivitis sicca, lichen planus, glomerulonephritis, and essential mixed cryoglobulinemia. Cryoglobulins may be detected in the serum of about one-third of patients with HCV, but the clinical features of essential mixed cryoglobulinemia develop in only about 1-2 percent of patients. Chronic hepatitis C may be a major underlying cause of porphyria cutanea tarda.
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Mortality After an average followup of 18 years, a prospective study of patients who received blood transfusions showed no difference in overall mortality between HCV-infected cases and noninfected controls. Liver-related mortality, although rare, was twice as high in the cases (3.2 percent vs. 1.5 percent). A recent European study showed that survival among hepatitis C patients with compensated cirrhosis was 91 percent after 5 years and 79 percent after 10 years. Among patients developing decompensated cirrhosis, however, 5-year survival was only 50 percent.
Diagnosing and Monitoring Hepatitis C A variety of tests are available for hepatitis C diagnosis. Tests that detect antibody against the virus include the enzyme immunoassays (EIAs), which contain HCV antigens from the core and nonstructural genes, and the recombinant immunoblot assays (RIBAs), which contain the same HCV antigens as EIA in an immunoblot format. In addition, several polymerase chain reaction (PCR)-based assays for HCV RNA have been developed to detect the RNA virus directly. Liver biopsy can determine the extent of liver injury due to HCV. Although some histologic findings are characteristic of HCV infection, such as portal lymphoid aggregates, steatosis, and bile duct injury, these alone are not sufficiently specific to establish a diagnosis of hepatitis C. There are currently no reliable, readily available tests for detection of HCV antigens in the liver. The EIA tests are reproducible and inexpensive and have been automated. They are suitable for screening low- and high-prevalence populations and as an initial test for patients with clinical liver disease. The RIBA test is most frequently used as a supplemental assay. Qualitative HCV RNA detection by reverse transcription (RT)-PCR is generally accepted as the most sensitive test, and a standardized assay has been developed. However, significant variability of results among laboratories has been reported in proficiency surveys. Clinicians should be aware of the proficiency record of laboratories performing HCV RNA testing to ensure test accuracy for their patients. Using carefully standardized research PCR tests for HCV RNA as a reference standard, the sensitivity of the second-generation enzyme immunoassay, EIA-2, is 92-95 percent. Its specificity has not been precisely established. Studies performed to date indicate that 25-60 percent of blood donors with no risk factors for hepatitis C who are positive by the EIA-2 test are also positive by the PCR test for HCV RNA. Of low-risk donors who are both
NIH Consensus Statement on Management of Hepatitis C 347
EIA-2 and RIBA-positive, 70-75 percent are positive for HCV RNA. Positive predictive values are much higher in patients with hepatitis C risk factors, elevated ALT levels, or clinical liver disease. Practitioners frequently encounter patients suspected of having HCV infection. In low-risk populations, such as blood donors who report no risk factors for HCV (e.g., parenteral drug use, history of transfusion, multiple sexual partners), a negative EIA test is sufficient to rule out infection. However, low-risk individuals with positive EIA tests should undergo supplementary RIBA testing. If the RIBA is negative, the anti-HCV EIA result is likely to have been a false positive, and the patient is unlikely to have hepatitis C. If the RIBA is positive, the patient can be assumed to have or to have had hepatitis C. These patients can benefit by testing for HCV RNA by PCR, the result of which will indicate whether the patient has ongoing viremia or not. A single positive assay for HCV RNA by PCR confirms HCV infection; unfortunately, a single negative assay does not prove that the patient is not viremic or has recovered from hepatitis C. Followup testing for ALT levels and perhaps repeating the HCV RNA in the future may be needed. If the results of the RIBA are “indeterminate,” followup testing is indicated to demonstrate whether HCV RNA is present. It is hoped that further advances in anti-HCV testing will eventually decrease the percentage of false-positive EIA and indeterminate RIBA results. Individuals with even mildly elevated ALT levels, with or without risk factors for hepatitis C, should be tested for anti-HCV by EIA and, if positive, the results confirmed by either supplemental RIBA or qualitative HCV RNA by PCR. Obviously anti-HCV testing is very helpful in all patients with clinical liver disease. In patients presenting with biochemical or clinical evidence of liver disease (e.g., repeatedly elevated ALT levels), a positive EIA test is sufficient to diagnose hepatitis C infection, especially if risk factors are present. A qualitative HCV RNA test can be used for confirmation. If the patient is being considered for antiviral therapy, liver biopsy is of value to assess disease severity. Testing for serum ALT levels is the most inexpensive and noninvasive means of assessing disease activity. However, a single determination of ALT levels is not always accurate in reflecting the severity of the underlying liver disease. In most studies, there is only a weak association between ALT levels and severity of the histopathological findings on liver biopsy. Serial determinations of ALT levels over time may provide a better means of assessing liver injury, but the accuracy of this approach has not really been
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shown. Nevertheless, the resolution of elevated ALT levels with antiviral therapy does appear to be an important indicator of disease response, and serial determinations of ALT levels can be recommended as the general means of monitoring patients with this disease. Testing for HCV RNA by PCR can be very helpful in initial diagnosis, but repeat testing over time is generally not helpful in management of untreated patients; almost all remain viremic, and a negative result may merely reflect a transient fall of viral titer below the level of detection rather than permanent clearance. On the other hand, repeat testing for HCV RNA during antiviral therapy can be helpful, because loss of HCV RNA with treatment is a strong predictor of a sustained beneficial response. Testing for HCV RNA level (or viral load) by a quantitative assay, either quantitative PCR (qPCR) or the branched DNA signal amplification assay (bDNA), can provide accurate information on viral titer. In many studies, the likelihood of a response to interferon alfa has correlated with a low level of HCV RNA present before treatment. However, there is no level of HCV RNA that absolutely precludes the possibility of a response and there is little or no correlation between disease severity or disease progression and level or titer of HCV RNA. Furthermore, current assays are not as sensitive as the standard, qualitative PCR test and suffer from lack of standardization. Thus, sequential testing for HCV RNA levels is not clinically helpful in management of patients. At least 6 genotypes and more than 30 subtypes of HCV RNA have been identified. HCV genotype may be an independent predictor of response to interferon alfa therapy. In many studies, patients with genotypes 2 and 3 are more likely to have a sustained treatment response than those with genotypes 1a or 1b. Methods of genotyping include PCR-based techniques and, more recently, less expensive serotyping (antibody) assays. However, both genotyping and serotyping should be considered research tools and not part of a diagnostic or therapeutic algorithm in clinical practice. Liver biopsy is considered the gold standard for assessment of patients with chronic hepatitis. When combined with serial determinations of ALT levels, liver biopsy is very helpful in judging the severity or activity of the liver disease and the stage or degree of fibrosis. Liver biopsy is recommended before treatment to assess the grade and stage of disease and to exclude other forms of liver disease or complications (such as concurrent alcoholic liver disease, medication-induced liver injury, and iron overload). However, liver biopsy is expensive and is associated with some morbidity. Therefore,
NIH Consensus Statement on Management of Hepatitis C 349
serial ALT and qualitative HCV RNA testing are recommended for monitoring patients under treatment.
What Is the Most Effective Therapy for Hepatitis C? Although several different forms of interferon have been evaluated in the treatment of patients with chronic hepatitis C, the bulk of available evidence pertains to the alpha interferons (interferon alfa). The efficacy of interferon alfa therapy currently is defined biochemically as normalization of serum ALT and virologically as loss of serum HCV RNA. Serum ALT and HCV RNA are measured at two time points: at the end of treatment (End-ofTreatment Response [ETR]) and 6 months posttreatment (Sustained Response [SR]). Based on these markers, randomized clinical trials have demonstrated that treatment with interferon alfa benefits some patients with chronic hepatitis C. In terms of biochemical response, treatment with interferon alfa at a dosage of 3 million units administered subcutaneously three times weekly for 6 months has produced a biochemical ETR of 40-50 percent and a biochemical SR of 15-20 percent. In terms of virological response, the 6-month course of treatment has produced an ETR of 30-40 percent and an SR of 10-20 percent. The biochemical and virological improvement has been accompanied by histological improvement. Increasing the duration of treatment to 12 months is not associated with higher biochemical or virological ETR, but the biochemical SR is increased to 20-30 percent. For patients who do not achieve a biochemical or virological ETR (nonresponders), retreatment with a standard dose of interferon alfa is rarely effective. Further therapy with newer interferons and/or higher dosages may achieve a virological SR of only 10 percent. For patients who achieve a biochemical ETR with 6 months of treatment, but who relapse during followup, retreatment for 12 months has been associated with a biochemical ETR rate of 75-85 percent and an SR rate of 30-40 percent. The benefit of treatment of longer duration is still being evaluated. It should be recognized that although interferon treatment may be associated with favorable effects on biochemical and virological markers, its effects on important clinical outcomes such as quality of life and disease progression remain undetermined. Three months after beginning an initial course of therapy, patients who are unlikely to respond to that dosage and frequency can be identified by persistent elevation of serum ALT levels and presence of HCV RNA in the serum.In this situation, therapy should be discontinued because the
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likelihood of future response is extremely low. If either HCV RNA is negative or ALT levels are normal (or both), therapy should be continued for 12 months. Nonresponders should be encouraged to participate in clinical trials directed toward this difficult-to-treat group. Most of the clinical trials in chronic hepatitis C have evaluated interferon alfa-2b. Other trials have used interferon alfa-2a, interferon alfa-n1, consensus interferon, interferon beta, and interferon alfa-n3. All forms of interferon appear to have similar efficacy in chronic hepatitis C. Because most patients do not experience sustained response, attempts have been made to identify individuals who are more likely to respond to therapy. The important factors associated with a favorable response to treatment include HCV genotype 2 or 3, low serum HCV RNA level (less than 1,000,000 copies/ml), and absence of cirrhosis. Flulike symptoms (fever, chills, malaise, headache, arthralgia, myalgia, tachycardia) occur early in the majority of patients who receive interferon, but generally diminish with continued therapy. Later side effects include fatigue, alopecia, bone marrow suppression, and neuropsychiatric effects such as apathy, cognitive changes, irritability, and depression. Relapse of drug and/or alcohol abuse may occur. Nocturnal administration of interferon reduces the frequency of side effects, and the flu-like syndrome is ameliorated by pretreatment with acetaminophen. A reduction in interferon dosage is required in 10-40 percent of patients because of side effects, and treatment must be discontinued in 5-10 percent. Higher dosages tend to be associated with higher rates of side effects. Severe side effects are observed in less than 2 percent of patients. These include autoimmune disease (thyroid disease being most common), depression with suicidal risk, seizure disorder, acute cardiac and renal failure, retinopathy, interstitial pulmonary fibrosis, hearing impairment, and sepsis. Rare deaths have occurred due to liver failure or sepsis, principally in patients with cirrhosis. An important side effect of interferon in hepatitis C is a paradoxical worsening of liver disease with therapy. This exacerbation of hepatitis is probably an autoimmune reaction, and it can be severe. Indeed, fatal occurrences have been reported. Thus, patients with hepatitis C whose serum ALT levels increase on therapy should be followed more carefully, and if levels rise to greater than twice the baseline, interferon should be promptly discontinued.
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It is appropriate that a percutaneous liver biopsy be obtained before initiating therapy with interferon in order to assess the degree of necroinflammatory activity, the extent of fibrosis, and the presence of any other cause of liver injury.Laboratory tests that should be obtained before starting therapy include liver chemistries (serum ALT, bilirubin, albumin, prothrombin time), complete blood count (CBC) with differential and platelet count, antinuclear antibodies, thyroid stimulating hormone, serum HCV RNA, and glucose. Monitoring during therapy should be done at 2- to 4-week intervals with serum ALT and CBC. Both serum ALT and serum HCV RNA testing should be done after 3 months to assess whether the patient is responding to therapy. This should be repeated at the end of therapy to document end-of-treatment response. Followup testing, with serum ALT and serum HCV RNA, should be done 6 months after therapy is stopped to determine whether there has been a sustained response. Followup liver biopsy is not necessary. Disappointing results with interferon have prompted interest in new treatment approaches to chronic hepatitis C. Early work with corticosteroids, ursodiol, and thymosin has produced scant or no evidence of sustained benefit. High concentrations of iron in liver tissue may blunt the response to interferon. This has sparked interest in iron reduction therapy, through phlebotomy or chelation, in an attempt to enhance the response to interferon. Thus far, studies of iron reduction have been inconclusive. The adjunctive drug of most promise, at present, is ribavirin, an oral antiviral agent that, when used alone, reduces serum ALT levels in approximately 50 percent of patients. However, ribavirin by itself does not lower serum HCV RNA levels, and relapses occur in virtually all patients when therapy is stopped. Of greater promise are recent reports that the combination of interferon alfa and ribavirin leads to higher sustained virological response rates (40-50 percent) than interferon alfa alone in 6month clinical trials. Ribavirin has not been licensed or approved for use in hepatitis C by the Food and Drug Administration. Large-scale trials of the combination in hepatitis C are now under way. Combination therapy with ribavirin and interferon has also shown promise in the retreatment of those who relapse. Hemolytic anemia has been the major side effect of ribavirin, necessitating a dosage reduction in more than 10 percent of patients.
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Which Patients With Hepatitis C Should Be Treated? All patients with chronic hepatitis C are potential candidates for specific therapy. However, given the current status of therapies for hepatitis C, treatment is clearly recommended only in a selected group of patients. In others, treatment decisions are less clear and should be made on an individual basis or in the context of clinical trials. Treatment is recommended for the group of patients with chronic hepatitis C who are at the greatest risk for progression to cirrhosis. These patients are characterized by persistently elevated ALT, positive HCV RNA, and a liver biopsy with either portal or bridging fibrosis and at least moderate degrees of inflammation and necrosis. Indication for therapy is less obvious in other groups of patients. One such group consists of patients with persistent ALT elevations, but with less severe histological changes -- that is, no fibrosis and minimal necroinflammatory changes. In these patients, progression to cirrhosis is likely to be slow, if at all; therefore, observation and serial measurements of ALT and liver biopsy every 3-5 years is an acceptable alternative to treatment with interferon. Another such group consists of patients with compensated cirrhosis (without jaundice, ascites, variceal hemorrhage, or encephalopathy), in whom current data do not definitively show that interferon therapy will prolong survival or delay development of hepatocellular carcinoma. Similarly, firm recommendations on treatment with interferon cannot be made for patients below age 18 or over age 60 because of incomplete data. In all these groups of patients, treatment decisions should be made jointly between patient and physician, after full discussion of risks and benefits. However, where possible, treatment in these instances should be undertaken in the context of clinical trials, so that data become available for future decision making. Patients with decompensated cirrhosis should not be treated with currently available therapy for hepatitis C and should be considered for liver transplantation. Therapeutic trials for hepatitis C in these patients should be performed only in the setting of clinical trials carried out in collaboration with liver transplant centers. Data suggest a benefit from interferon treatment with higher clearance of HCV RNA in patients with acute hepatitis C. In light of these findings, interferon treatment of patients with acute hepatitis C could be recommended.
NIH Consensus Statement on Management of Hepatitis C 353
Current studies suggest that treatment of patients with persistently normal ALT is not beneficial and may actually induce liver enzyme abnormalities. Therefore, these patients should not receive therapy outside of placebocontrolled clinical trials. Nonspecific symptoms such as fatigue are difficult to interpret and should not influence treatment decisions. However, patients with clinical evidence of essential mixed cryoglobulinemia could benefit from long-term therapy with interferon. Because severity of disease or progression to cirrhosis has not been conclusively related to the mode of acquisition of hepatitis C or to particular risk groups, therapy should not be denied on the basis of these factors. However, treatment of patients who are drinking significant amounts of alcohol or who are actively using illicit drugs should be delayed until these habits are discontinued for at least 6 months. Such patients are at risk for the potential toxic effects of alcohol and other drugs and also present problems with compliance. Treatment for addiction should be provided prior to treatment for hepatitis C. Patients with chronic hepatitis C and concurrent HIV infection may have an accelerated course of disease. Therefore, patients who have stable HIV infection with good clinical and functional status should be considered for treatment, according to guidelines outlined in this statement. Even though high HCV RNA levels or genotype 1 predict a less favorable response to therapy, treatment should not be withheld on the basis of these parameters. Contraindications to treatment with interferon that must be carefully considered are history of major depressive illness, cytopenias, hyperthyroidism, renal transplant, and convincing evidence of autoimmune disease.
Prevent Transmission of Hepatitis C The large reservoir of individuals infected with HCV globally provides a source of transmission to others at risk. Prior to the identification of HCV, the majority of non-A, non-B hepatitis cases were associated with blood transfusion, injection drug use, health care, employment, or sexual or household exposure to a contact with hepatitis. HCV is now rarely
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transmitted by transfusion because of screening tests that exclude infectious donors. Direct percutaneous exposure is the most efficient method for transmitting HCV. In drug users, HCV infection is acquired rapidly after beginning injection drug use, with 50-80 percent of new users becoming positive for antibody to HCV within 6-12 months. Injection drug use accounts for half of all new infections annually and perhaps greater than 50 percent of chronic infections. In addition, it is thought that the majority of the rest of the cases can be explained by transfusion prior to 1990, occupational exposures to blood, hemodialysis, high-risk sexual activity (multiple partners, history of sexually transmitted diseases), and noninjection illegal drug use (intranasal cocaine). Percutaneous exposures such as body piercing and tattooing are potential sources of transmission if contaminated equipment or supplies are used, although their role in transmission of HCV in the United States has not been confirmed. It is now considered that the route of transmission is unknown in less than 10 percent of newly acquired cases of hepatitis C. Data regarding transmissibility by sexual contact have been conflicting. Based on studies in sexually transmitted disease clinics, sexual transmission appears to occur; however, even with multiple sexual partners the risk is low. The risk appears to be increased by coinfection with HIV or other sexually transmitted diseases. Although transmission in long-term monogamous relationships may occur, the risk is thought to be minimal. There is some evidence for occupational and nosocomial transmission of HCV infection. Health care workers have a higher prevalence than the general population, although many may have acquired it from other sources. However, inadvertent needle stick injuries and lack of application of universal precautions may be contributing factors. The risk of infection from needle sticks in hepatitis C is intermediate between that of HIV and hepatitis B. HCV transmission between patients in dialysis centers may be related to poor infection control practices. Although transmission from health care workers to patients has been documented, such transmission is thought to be rare. Perinatal transmission between mother and baby has been documented, although the risk is estimated at no more than 6 percent. The risk is increased if the mother is coinfected with HIV. Although data are limited, there is no evidence that breast-feeding transmits HCV from mother to baby.
NIH Consensus Statement on Management of Hepatitis C 355
Areas for Future Research ·
Continued monitoring of the epidemiology of acute and chronic hepatitis C is necessary. Additional studies of the specific mode of transmission in minority groups, low socioeconomic groups, institutionalized individuals, and injection and intranasal drug users are needed, as well as more information on sexual, household, occupational, nosocomial, and perinatal transmission.
·
Large-scale, long-term studies are needed to better define the natural history of hepatitis C and especially to identify factors associated with disease progression to cirrhosis. Studies of the natural history are needed in special groups, such as minorities, children, those over 60, HCVinfected patients with normal ALT, HCV-infected patients coinfected with HIV, and injection drug users. Information is also needed about the role of ultrasound and alpha fetoprotein monitoring for early detection of hepatocellular carcinoma in patients with chronic hepatitis C.
·
Studies are needed on the recovery from and persistence of viral infection as well as the pathogenesis and mechanism of liver cell injury by HCV. Is damage due to cytopathic effects of the virus on the liver cell, or is it immunologically mediated? What is the mechanism of hepatic fibrosis? Can fibrosis be separated from inflammation/necrosis of the liver? Such studies would be greatly facilitated by development of suitable animal and cell culture models. The mechanism of development of hepatocellular carcinoma in patients with hepatitis C needs elucidation.
·
Given the large number of persons who are already infected with HCV, there is an urgent need for effective antiviral therapeutics capable of inhibiting virus replication and stopping or delaying the progression of liver disease. A major bottleneck to the drug discovery process is the absence of a readily available cell culture system that is fully permissive for viral replication. Thus, development of such systems should be a high priority. An improved understanding of the molecular virology of HCV is also critically important to antiviral drug development. These studies should include the development of infectious molecular clones, which would allow analyses of structure-function relations among HCV nonstructural proteins that participate in the viral replication cycle.
·
Alcohol ingestion clearly worsens the course of hepatitis C, but the reasons for this interaction are unknown. Studies of the interaction between HCV and obesity, diabetes mellitus, iron, and medications are also needed.
·
Unresolved questions remain regarding the diagnostic tests for hepatitis C. What is the prevalence of significant liver disease among RIBA-
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positive, HCV RNA-negative individuals? What should be the gold standard for HCV RNA assays? What is the frequency of intermittent viremia in untreated patients? What are the criteria for selecting patients for, or withdrawing patients from, treatment? How can the reliability of HCV RNA tests be improved? How can the dynamic range and intraassay variability of the HCV RNA test be improved? ·
Future clinical trials should expand the range of outcomes studied to include quality of life from the patient’s point of view, as well as costs and survival. In addition, those trials should include minorities, patients over age 60, patients under age 18, HIV-coinfected patients, and liver transplant patients. We need to identify effective, nontoxic therapeutic agents. Clinical trials are also needed to identify optimal treatment regimens for those who do not respond to interferon therapy, or who relapse following interferon therapy. Prospective studies are needed to identify and test prospectively the factors that predict response to therapy. In addition, studies are needed of possible drug interactions, especially between the antiretroviral drugs used to treat HIV infection and those drugs used to treat hepatitis C.
·
Although continued education of risk groups and screening of blood, organs, tissue, and semen remain vitally important, the key to prevention is development of an effective and safe vaccine for hepatitis C. This will require a better understanding of the molecular determinants of both cellular and humoral immunity to HCV, the nature of antigenic variation as related to viral quasispecies diversity, and the mechanism(s) by which HCV regularly eludes the host immune system and establishes persistent infection.
·
Strategies should be developed to educate at-risk groups concerning transmission of disease, as well as provide access to diagnosis and treatment. It would be helpful also to evaluate the role of intranasal cocaine use as a possible route of infection.
Conclusions and Recommendations ·
Individuals who have a history of transfusions of blood or blood products prior to 1990, who are on chronic hemodialysis, who have a history of injection drug use, who have had multiple sexual partners, who are the spouses or close household contacts of hepatitis C patients, and who share instruments for intranasal cocaine use should be tested for hepatitis C.
NIH Consensus Statement on Management of Hepatitis C 357
·
Hepatitis C is a common infection with variable course that can lead to chronic hepatitis, cirrhosis, liver failure, and hepatocellular carcinoma. The course of illness may be adversely affected by various factors, especially alcohol consumption. Therefore, more than one drink per day is strongly discouraged in patients with hepatitis C, and abstinence from alcohol is recommended. Those addicted to alcohol or drugs should be helped to obtain treatment for their addiction so that they might qualify for anti-HCV therapy.
·
An EIA test for anti-HCV should be the initial test for diagnosis of hepatitis C.In low-risk populations, a supplemental RIBA test and/or a qualitative PCR test for HCV RNA should be performed in those whose EIA test is positive. In patients with clinical findings of liver disease, HCV RNA by PCR can be used for confirmation.
·
Because of assay variability, qualitative and quantitative PCR testing for HCV RNA must be interpreted cautiously. Rigorous proficiency testing is recommended for clinical laboratories performing this assay. The branched DNA signal amplification assay for viral level has been standardized, but may fail to detect low titers of HCV RNA. Sequential measurement of HCV RNA levels (viral load) has not, to date, proven useful in managing patients with hepatitis C.
·
Liver biopsy is indicated when histologic findings will assist decision making regarding patient management. In patients who are not treated with antiviral therapy initially, liver biopsy can be considered to assess disease progression.
·
HCV genotyping and tests for HCV RNA levels (viral load) may provide useful prognostic information, especially regarding response to therapy, but at present must be considered research tools.
·
Currently available therapy for chronic hepatitis C is indicated for patients who have persistently abnormal ALT (greater than 6 months),a positive HCV RNA, and liver biopsy demonstrating either portal or bridging fibrosis and at least moderate degrees of inflammation and necrosis. Patients with milder histological disease, compensated cirrhosis, or who are under age 18 or over 60 should be managed on an individual basis or in the context of clinical trials. Patients with decompensated cirrhosis should not be treated with interferon but should be considered for liver transplantation. Patients with persistently normal ALT and minimal histologic abnormalities should not be treated outside clinical trials. Contraindications to treatment of patients with interferon that must be considered are a history of major depressive illness, cytopenia, active alcohol use or illicit drug use, hyperthyroidism, renal transplantation, or autoimmune disease. Therapy should not be limited
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by mode of acquisition, risk group, HIV status, HCV RNA level, or genotype. ·
Because 12-month regimens with interferon are more successful in achieving sustained responses, initial therapy with interferon alfa (or its equivalent) should be 3 million units three times weekly subcutaneously for 12 months.
·
Nonresponders to interferon therapy can be identified early by assessing the serum ALT level and presence of serum HCV RNA after 3 months of therapy. If the ALT level remains abnormal and the serum HCV RNA remains detectable, interferon therapy should be stopped, because further treatment is unlikely to produce a response. Nonresponders should not be retreated with the same regimen, but should be considered for combination therapy or enrollment in investigational protocols using different dosages or agents.
·
Patients who have an end-of-treatment response to a 6-month course of interferon alfa, but then relapse, should receive retreatment with a 12month course of interferon alfa or be considered for combination therapy with interferon plus ribavirin or other regimens, preferably in a clinical trial.
·
Hepatitis A and B vaccination is recommended for all HCV-positive patients.
·
Patient support groups should be encouraged, especially for those undergoing therapy, those who fail therapy, and also those recovering from addiction.
The following recommendations are made to avoid transmission of hepatitis C: ·
In health care settings, adherence to universal (standard) precautions for the protection of medical personnel and patients is essential.
·
HCV-positive individuals should refrain from donating blood, organs, tissues, or semen. In some situations, the use of organs and tissues from HCV-positive individuals may be considered. For example, in emergency situations the use of a donor organ in which the HCV status is either positive or unknown may be considered in a HCV-negative recipient after full disclosure and informed consent. Strategies should be developed to identify prospective blood donors with any prior history of injection drug use. Such individuals must be deferred from donating blood.
NIH Consensus Statement on Management of Hepatitis C 359
·
Safer sexual practices should be strongly encouraged in persons with multiple sexual partners, including the use of latex condoms. In monogamous long-term relationships, transmission is rare. Although HCV-positive individuals and their partners should be informed of the potential for transmission, there are insufficient data to recommend changes in current sexual practice in persons with a steady partner. It is recommended that sexual partners of infected patients should be tested for antibody to HCV.
·
In households with an HCV-positive member, sharing razors and toothbrushes should be avoided. Covering open wounds is recommended. Injection needles should be carefully disposed of using universal precaution techniques. It is not necessary to avoid close contact with family members or to avoid sharing meals or utensils. There is no evidence to justify exclusion of HCV-positive children or adults from participation in social, educational, and employment activities.
·
Pregnancy is not contraindicated in HCV-infected individuals. Perinatal transmission from mother to baby occurs in less than 6 percent of instances. There is no evidence that breast-feeding transmits HCV from mother to baby; therefore, it is considered safe. Babies born to HCVpositive mothers should be tested for anti-HCV at 1 year.
·
Needle exchange and other safer injection drug use programs may be of benefit in reducing parenterally transmitted diseases. Expansion of such programs should be considered in an effort to reduce the rate of transmission of hepatitis C.
·
It is important that clear and evidenced-based information be provided to both patients and physicians regarding the natural history, means of prevention, management, and therapy of hepatitis C.
Vocabulary Builder Alopecia: Baldness; absence of the hair from skin areas where it normally is present. [EU] Apathy: Lack of feeling or emotion; indifference. [EU] Arthralgia: Pain in a joint. [EU] Cryoglobulinemia: A condition characterized by the presence of abnormal or abnormal quantities of cryoglobulins in the blood. They are precipitated into the microvasculature on exposure to cold and cause restricted blood flow in exposed areas. [NIH]
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Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatomegaly: Enlargement of the liver. [EU] Humoral: Of, relating to, proceeding from, or involving a bodily humour now often used of endocrine factors as opposed to neural or somatic. [EU] Hyperthyroidism: 1. excessive functional activity of the thyroid gland. 2. the abnormal condition resulting from hyperthyroidism marked by increased metabolic rate, enlargement of the thyroid gland, rapid heart rate, high blood pressure, and various secondary symptoms. [EU] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Keratoconjunctivitis: Inflammation of the cornea and conjunctiva. [EU] Myalgia: Pain in a muscle or muscles. [EU] Paradoxical: Occurring at variance with the normal rule. [EU] Parenchyma: The essential elements of an organ; used in anatomical nomenclature as a general term to designate the functional elements of an organ, as distinguished from its framework, or stroma. [EU] Prothrombin: Factor II. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU]
Retinopathy: 1. retinitis (= inflammation of the retina). 2. retinosis (= degenerative, noninflammatory condition of the retina). [EU] Splenomegaly: Enlargement of the spleen. [EU] Tachycardia: Excessive rapidity in the action of the heart; the term is usually applied to a heart rate above 100 per minute and may be qualified as atrial, junctional (nodal), or ventricular, and as paroxysmal. [EU] Veins: The vessels carrying blood toward the heart. [NIH]
Online Glossaries 361
ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries and glossaries. 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://www.graylab.ac.uk/omd/
·
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
·
Terms and Definitions (Office of Rare Diseases): http://rarediseases.info.nih.gov/ord/glossary_a-e.html
Beyond these, MEDLINEplus contains a very user-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia Web site address is http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a) and drkoop.com (http://www.drkoop.com/). Topics of interest can be researched by using keywords before continuing elsewhere, as these basic definitions and concepts will be useful in more advanced areas of research. You may choose to print various pages specifically relating to hepatitis C and keep them on file. The NIH, in particular, suggests that patients with hepatitis C visit the following Web sites in the ADAM Medical Encyclopedia:
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·
Basic Guidelines for Hepatitis C Hepatitis C Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000284.htm HSV Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001368.htm
·
Signs & Symptoms for Hepatitis C Clay colored stools Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003129.htm Dark urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003138.htm Fatigue Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Hepatomegaly Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003275.htm Itching Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003217.htm Jaundice Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003243.htm
Online Glossaries 363
Loss of appetite Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003121.htm Nausea and vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Splenomegaly Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003276.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm ·
Diagnostics and Tests for Hepatitis C Albumin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003480.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 ELISA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003332.htm ESR Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003638.htm Hepatitis virus serology 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 ·
Background Topics for Hepatitis C Acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002215.htm
Online Glossaries 365
Antibody Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002223.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Immunity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000821.htm 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 Safer sex behaviors Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001949.htm Support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002150.htm
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries and glossaries: ·
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
·
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
·
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
Glossary 367
HEPATITIS C GLOSSARY The following is a complete glossary of terms used in this sourcebook. The definitions are derived from official public sources including the National Institutes of Health [NIH] and the European Union [EU]. After this glossary, we list a number of additional hardbound and electronic glossaries and dictionaries that you may wish to consult. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Pertaining to the abdomen. [EU] Abortion: 1. the premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. premature stoppage of a natural or a pathological process. [EU] Abscess: A localized collection of pus caused by suppuration buried in tissues, organs, or confined spaces. [EU] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] 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] Aggressiveness:
The quality of being aggressive (= characterized by
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aggression; militant; enterprising; spreading with vigour; chemically active; variable and adaptable). [EU] Agonist: A chemical compound that mimics the action of a natural neurotransmitter. [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] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Alopecia: Baldness; absence of the hair from skin areas where it normally is present. [EU] Amantadine: An antiviral that is used in the prophylactic or symptomatic treatment of influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake. [NIH] Anal: Pertaining to the anus. [EU] Analog: A chemical compound that is similar to another drug in its effects but differs slightly in its chemical structure. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthetic: An agent that causes insensitivity to pain. [NIH] Angioedema: A vascular reaction involving the deep dermis or subcutaneous or submucal tissues, representing localized edema caused by dilatation and increased permeability of the capillaries, and characterized by development of giant wheals. [EU] Anorexia: Lack or loss of the appetite for food. [EU] Antibiotic: A chemical substance produced by a microorganism which has the capacity, in dilute solutions, to inhibit the growth of or to kill other microorganisms. Antibiotics that are sufficiently nontoxic to the host are used as chemotherapeutic agents in the treatment of infectious diseases of man, animals and plants. [EU] Antidepressants: A group of drugs used in treating depressive disorders. [NIH]
Glossary 369
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 Tlymphocytes, 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] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antioxidant: One of many widely used synthetic or natural substances added to a product to prevent or delay its deterioration by action of oxygen in the air. Rubber, paints, vegetable oils, and prepared foods commonly contain antioxidants. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anxiety: The unpleasant emotional state consisting of psychophysiological responses to anticipation of unreal or imagined danger, ostensibly resulting from unrecognized intrapsychic conflict. Physiological concomitants include increased heart rate, altered respiration rate, sweating, trembling, weakness, and fatigue; psychological concomitants include feelings of impending danger, powerlessness, apprehension, and tension. [EU] Apathy: Lack of feeling or emotion; indifference. [EU] Arthralgia: Pain in a joint. [EU] Ascites: Effusion and accumulation of serous fluid in the abdominal cavity; called also abdominal or peritoneal dropsy, hydroperitonia, and hydrops abdominis. [EU] Asialoglycoproteins: Endogenous glycoproteins from which sialic acid has been removed by the action of sialidases. They bind tightly to their cell surface receptor which is located on hepatocyte plasma membranes. After internalization by adsorptive endocytosis they are delivered to lysosomes for degradation. Therefore receptor-mediated clearance of asialoglycoproteins is an important aspect of the turnover of plasma glycoproteins. They are elevated in serum of patients with hepatic cirrhosis or hepatitis. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Showing or causing no symptoms. [EU] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by
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autoimmune diseases. [NIH] Barbiturate: A type of central nervous system (CNS) depressant often prescribed to promote sleep. [NIH] Benzodiazepine: A type of CNS depressant prescribed to relieve anxiety; among the most widely prescribed medications, including Valium and Librium. [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] Biliary: Pertaining to the bile, to the bile ducts, or to the gallbladder. [EU] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biopsy: The removal and examination, usually microscopic, of tissue from the living body, performed to establish precise diagnosis. [EU] Bromovirus: A genus of tripartite plant viruses in the family bromoviridae. Transmission is by beetles. [NIH] Bupropion: A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment. [NIH] Calibration: Determination, by measurement or comparison with a standard, of the correct value of each scale reading on a meter or other measuring instrument; or determination of the settings of a control device that correspond to particular values of voltage, current, frequency or other output. [NIH] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, poly- and heterosaccharides. [EU] Carcinoma: A malignant new growth made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. [EU] Cardiac: Pertaining to the heart. [EU]
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Catechin: Extracted from Uncaria gambier, Acacia catechu and other plants; it stabilizes collagen and is therefore used in tanning and dyeing; it prevents capillary fragility and abnormal permeability, but was formerly used as an antidiarrheal. [NIH] Catheterization: The employment or passage of a catheter. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Chelation: Combination with a metal in complexes in which the metal is part of a ring. [EU] Chemotherapy: The treatment of disease by means of chemicals that have a specific toxic effect upon the disease - producing microorganisms or that selectively destroy cancerous tissue. [EU] Chimera: An individual that contains cell populations derived from different zygotes. [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] Chloroquine: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Chronic: Persisting over a long period of time. [EU] Circumcision: Excision of the prepuce or part of it. [NIH] Cirrhosis: Liver disease characterized pathologically by loss of the normal microscopic lobular architecture, with fibrosis and nodular regeneration. The term is sometimes used to refer to chronic interstitial inflammation of any organ. [EU] 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] 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: Disturbed orientation in regard to time, place, or person, sometimes accompanied by disordered consciousness. [EU]
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Conjugated: Acting or operating as if joined; simultaneous. [EU] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Counterimmunoelectrophoresis: Immunoelectrophoresis in which immunoprecipitation occurs when antigen at the cathode is caused to migrate in an electric field through a suitable medium of diffusion against a stream of antibody migrating from the anode as a result of endosmotic flow. [NIH]
Crack: Short term for a smokable form of cocaine. [NIH] Craving: A powerful, often uncontrollable desire for drugs. [NIH] Cryoglobulinemia: A condition characterized by the presence of abnormal or abnormal quantities of cryoglobulins in the blood. They are precipitated into the microvasculature on exposure to cold and cause restricted blood flow in exposed areas. [NIH] Cucumovirus: A genus of plant viruses of the family bromoviridae, which infect cucurbits and solanaceous plants. Transmission occurs via aphids in a non-persistent manner, and also via seeds. The type species cucumber mosaic virus, a cucumovirus, should not be confused with cucumber green mottle mosaic virus, a tobamovirus. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Pertaining to the skin; dermal; dermic. [EU] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form CYSTINE. [NIH] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. [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] Decompensation: Failure of compensation; cardiac decompensation is marked by dyspnea, venous engorgement, and edema. [EU] Deferoxamine: Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the form of its mesylate. [NIH]
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Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] Detoxification: A process of allowing the body to rid itself of a drug while managing the symptoms of withdrawal; often the first step in a drug treatment program. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diffusion: The process of becoming diffused, or widely spread; the spontaneous movement of molecules or other particles in solution, owing to their random thermal motion, to reach a uniform concentration throughout the solvent, a process requiring no addition of energy to the system. [EU] Ectopic: Pertaining to or characterized by ectopia. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effusion: The escape of fluid into a part or tissue, as an exudation or a transudation. [EU] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH] Encephalopathy: Any degenerative disease of the brain. [EU] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endogenous: Developing or originating within the organisms or arising from causes within the organism. [EU] Endoscopy: Visual inspection of any cavity of the body by means of an endoscope. [EU] Enzyme: A protein molecule that catalyses chemical reactions of other substances without itself being destroyed or altered upon completion of the reactions. Enzymes are classified according to the recommendations of the Nomenclature Committee of the International Union of Biochemistry. Each enzyme is assigned a recommended name and an Enzyme Commission (EC) number. They are divided into six main groups; oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. [EU] 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 health-related event occurring in such outbreaks. [EU] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH]
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Escherichia: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria whose organisms occur in the lower part of the intestine of warmblooded animals. The species are either nonpathogenic or opportunistic pathogens. [NIH] Euphoria: An exaggerated feeling of physical and mental well-being, especially when not justified by external reality. Euphoria may be induced by drugs such as opioids, amphetamines, and alcohol and is also a feature of mania. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extraction: The process or act of pulling or drawing out. [EU] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Fatal: Causing death, deadly; mortal; lethal. [EU] 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] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fibrosis: The formation of fibrous tissue; fibroid or fibrous degeneration [EU] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Flaviviridae: A family of RNA viruses, some formerly classified under Togoviridae, many of which cause disease in humans and domestic animals. The three genera are flavivirus, pestivirus, and hepatitis c-like viruses. [NIH] 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] Gastrointestinal: Pertaining to or communicating with the stomach and intestine, as a gastrointestinal fistula. [EU] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Glomerulonephritis: A variety of nephritis characterized by inflammation
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of the capillary loops in the glomeruli of the kidney. It occurs in acute, subacute, and chronic forms and may be secondary to haemolytic streptococcal infection. Evidence also supports possible immune or autoimmune mechanisms. [EU] Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. [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] Glycyrrhiza: A genus of leguminous herbs or shrubs whose roots yield glycyrrhetinic acid and its derivatives, carbenoxolone for example. Licorice toxicity is manifested as hypokalemia, low blood potassium. Licorice is used as flavoring and aromatic in pharmaceuticals and as candy. [NIH] Granule: A small pill made from sucrose. [EU] Haemodialysis: The removal of certain elements from the blood by virtue of the difference in the rates of their diffusion through a semipermeable membrane, e.g., by means of a haemodialyzer. [EU] Haemolysis: Disruption of the integrity of the red cell membrane causing release of haemoglobin. Haemolysis may be caused by bacterial haemolysins, by antibodies that cause complement-dependent lysis, by placing red cells in a hyptonic solution, or by defects in the red cell membrane. [EU] Helicobacter: A genus of gram-negative, spiral-shaped bacteria that is pathogenic and has been isolated from the intestinal tract of mammals, including humans. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH]
Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatic: Pertaining to the liver. [EU] Hepatitis: Inflammation of the liver. [EU] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatomegaly: Enlargement of the liver. [EU] Hepatotoxic: Toxic to liver cells. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used
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alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpesviridae: A family of enveloped, linear, double-stranded DNA viruses infecting a wide variety of animals. There are three subfamilies based on biological characteristics: alphaherpesvirinae, betaherpesvirinae, and gammaherpesvirinae. [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] Hormone: A chemical substance formed in glands in the body and carried in the blood to organs and tissues, where it influences function, structure, and behavior. [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] 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] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hypertension: Persistently high arterial blood pressure. Various criteria for its threshold have been suggested, ranging from 140 mm. Hg systolic and 90 mm. Hg diastolic to as high as 200 mm. Hg systolic and 110 mm. Hg diastolic. Hypertension may have no known cause (essential or idiopathic h.) or be associated with other primary diseases (secondary h.). [EU] Hyperthermia: Abnormally high body temperature, especially that induced for therapeutic purposes. [EU] Hyperthyroidism: 1. excessive functional activity of the thyroid gland. 2. the abnormal condition resulting from hyperthyroidism marked by increased metabolic rate, enlargement of the thyroid gland, rapid heart rate, high blood pressure, and various secondary symptoms. [EU] Iatrogenic: Resulting from the activity of physicians. Originally applied to disorders induced in the patient by autosuggestion based on the physician's examination, manner, or discussion, the term is now applied to any adverse condition in a patient occurring as the result of treatment by a physician or surgeon, especially to infections acquired by the patient during the course of treatment. [EU] Idiopathic: Of the nature of an idiopathy; self-originated; of unknown causation. [EU] Ilarvirus: A genus of the family bromoviridae which infects mainly woody plants. Species are divided into ten subgroups. Tobacco streak virus is the
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type species. [NIH] Incarceration: Abnormal retention or confinement of a body part; specifically : a constriction of the neck of a hernial sac so that the hernial contents become irreducible. [EU] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] 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] 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] Infusion: The therapeutic introduction of a fluid other than blood, as saline solution, solution, into a vein. [EU] Ingestion: The act of taking food, medicines, etc., into the body, by mouth. [EU]
Institutionalization: The caring for individuals in institutions and their adaptation to routines characteristic of the institutional environment, and/or their loss of adaptation to life outside the institution. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulindependent diabetes mellitus. [NIH] Interferons: Proteins secreted by vertebrate cells in response to a wide variety of inducers. They confer resistance against many different viruses, inhibit proliferation of normal and malignant cells, impede multiplication of intracellular parasites, enhance macrophage and granulocyte phagocytosis, augment natural killer cell activity, and show several other immunomodulatory functions. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Interstitial: Pertaining to or situated between parts or in the interspaces of a
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tissue. [EU] Intravenous: Within a vein or veins. [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] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH]
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] Keratoconjunctivitis: Inflammation of the cornea and conjunctiva. [EU] LAAM: An approved medication for the treatment of opioid addiction, taken 3 to 4 times a week. [NIH] 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] Lesion: Any pathological or traumatic discontinuity of tissue or loss of function of a part. [EU] Lethal: Deadly, fatal. [EU] 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] Localization: 1. the determination of the site or place of any process or lesion. 2. restriction to a circumscribed or limited area. 3. prelocalization. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH]
Lymphocytic: Pertaining to, characterized by, or of the nature of lymphocytes. [EU] Lymphoma: Any neoplastic disorder of the lymphoid tissue, the term lymphoma often is used alone to denote malignant lymphoma. [EU] Malaise: A vague feeling of bodily discomfort. [EU] Membrane: A thin layer of tissue which covers a surface, lines a cavity or
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divides a space or organ. [EU] Metabolite: process. [EU]
Any substance produced by metabolism or by a metabolic
Methadone: A long-acting synthetic medication shown to be effective in treating heroin addiction. [NIH] Methamphetamine: A central nervous system stimulant and sympathomimetic with actions and uses similar to dextroamphetamine. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microgram: A unit of mass (weight) of the metric system, being onemillionth of a gram (10-6 gm.) or one one-thousandth of a milligram (10-3 mg.). [EU] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU]
Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Monotherapy: A therapy which uses only one drug. [EU] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Mycobacterium: An organism of the genus Mycobacterium. [EU] Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. [NIH] Nausea: An unpleasant sensation, vaguely referred to the epigastrium and abdomen, and often culminating in vomiting. [EU] Necrosis: The sum of the morphological changes indicative of cell death and caused by the progressive degradative action of enzymes; it may affect groups of cells or part of a structure or an organ. [EU] Neonatal: Pertaining to the first four weeks after birth. [EU]
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Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [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] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuropathy: A general term denoting functional disturbances and/or pathological changes in the peripheral nervous system. The etiology may be known e.g. arsenical n., diabetic n., ischemic n., traumatic n.) or unknown. Encephalopathy and myelopathy are corresponding terms relating to involvement of the brain and spinal cord, respectively. The term is also used to designate noninflammatory lesions in the peripheral nervous system, in contrast to inflammatory lesions (neuritis). [EU] Neutrophil: Having an affinity for neutral dyes. [EU] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nicotine: An alkaloid derived from the tobacco plant that is responsible for smoking's psychoactive and addictive effects; is toxic at high doses but can be safe and effective as medicine at lower doses. [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] 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] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] 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
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the passage of solute molecules, but is permeable to the solvent). [EU] Overdose: 1. to administer an excessive dose. 2. an excessive dose. [EU] Palliative: 1. affording relief, but not cure. 2. an alleviating medicine. [EU] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Paradoxical: Occurring at variance with the normal rule. [EU] Parenchyma: The essential elements of an organ; used in anatomical nomenclature as a general term to designate the functional elements of an organ, as distinguished from its framework, or stroma. [EU] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Particle: A tiny mass of material. [EU] Pathogen: Any disease-producing microorganism. [EU] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [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] Pharmacokinetics: The pattern of absorption, distribution, and excretion of a drug over time. [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] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]
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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] Polyproteins: Proteins which are synthesized as a single polymer and then cleaved into several distinct proteins. [NIH] Porphyria: A pathological state in man and some lower animals that is often due to genetic factors, is characterized by abnormalities of porphyrin metabolism, and results in the excretion of large quantities of porphyrins in the urine and in extreme sensitivity to light. [EU] 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] Potexvirus: A genus of plant viruses that cause mosaic and ringspot symptoms. Transmission occurs mechanically. [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] Preoperative: Preceding an operation. [EU] 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] Prisons: Penal institutions, or places of confinement for war prisoners. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Prophylaxis: The prevention of disease; preventive treatment. [EU] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH]
Prothrombin: Factor II. [EU] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH]
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Psychosomatic: Pertaining to the mind-body relationship; having bodily symptoms of psychic, emotional, or mental origin; called also psychophysiologic. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH]
Pulmonary: Pertaining to the lungs. [EU] Radiotherapy: The treatment of disease by ionizing radiation. [EU] Receptor: 1. a molecular structure within a cell or on the surface characterized by (1) selective binding of a specific substance and (2) a specific physiologic effect that accompanies the binding, e.g., cell-surface receptors for peptide hormones, neurotransmitters, antigens, complement fragments, and immunoglobulins and cytoplasmic receptors for steroid hormones. 2. a sensory nerve terminal that responds to stimuli of various kinds. [EU] Recombinant: 1. a cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU]
Remission: A diminution or abatement of the symptoms of a disease; also the period during which such diminution occurs. [EU] Resection: Excision of a portion or all of an organ or other structure. [EU] Retinopathy: 1. retinitis (= inflammation of the retina). 2. retinosis (= degenerative, noninflammatory condition of the retina). [EU] 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] Rheumatoid: Resembling rheumatism. [EU] 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] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous
384 Hepatitis C
glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Sarcoma: A tumour made up of a substance like the embryonic connective tissue; tissue composed of closely packed cells embedded in a fibrillar or homogeneous substance. Sarcomas are often highly malignant. [EU] Sarin: An organophosphorous ester compound that produces potent and irreversible inhibition of cholinesterase. It is toxic to the nervous system and is a chemical warfare agent. [NIH] Schistosoma: A genus of trematode flukes belonging to the family Schistosomatidae. There are over a dozen species. These parasites are found in man and other mammals. Snails are the intermediate hosts. [NIH] Schizophrenia: A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, hallucinations, emotional disharmony, and regressive behavior. [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] Sedative: 1. allaying activity and excitement. 2. an agent that allays excitement. [EU] 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] Serine: A non-essential amino acid occurring in natural form as the Lisomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Seroconversion: The change of a serologic test from negative to positive, indicating the development of antibodies in response to infection or immunization. [EU] Serology: The study of serum, especially of antigen-antibody reactions in vitro. [NIH] Serum: The clear portion of any body fluid; the clear fluid moistening serous membranes. 2. blood serum; the clear liquid that separates from blood on clotting. 3. immune serum; blood serum from an immunized animal used for passive immunization; an antiserum; antitoxin, or antivenin. [EU]
Glossary 385
Silymarin: A mixture of flavonoids extracted from seeds of the milk thistle, Silybum marianum. It consists primarily of three isomers: silicristin, silidianin, and silybin, its major component. Silymarin displays antioxidant and membrane stabilizing activity. It protects various tissues and organs against chemical injury, and shows potential as an antihepatoxic agent. [NIH] 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] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Splenomegaly: Enlargement of the spleen. [EU] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] Stavudine: A dideoxynucleoside analog that inhibits reverse transcriptase and has in vitro activity against HIV. [NIH] Steatosis: Fatty degeneration. [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] Substrate: A substance upon which an enzyme acts. [EU] Surgical: Of, pertaining to, or correctable by surgery. [EU] Symptomatic: 1. pertaining to or of the nature of a symptom. 2. indicative (of a particular disease or disorder). 3. exhibiting the symptoms of a particular disease but having a different cause. 4. directed at the allying of symptoms, as symptomatic treatment. [EU] Systemic: Pertaining to or affecting the body as a whole. [EU] Tachycardia: Excessive rapidity in the action of the heart; the term is usually applied to a heart rate above 100 per minute and may be qualified as atrial, junctional (nodal), or ventricular, and as paroxysmal. [EU]
386 Hepatitis C
Telecommunications: electronic means. [NIH]
Transmission of information over distances via
Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Thermoregulation: Heat regulation. [EU] Thrombocytopenia: Decrease in the number of blood platelets. [EU] Thrombosis: The formation, development, or presence of a thrombus. [EU] Thymosin: 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] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tolerance: A condition in which higher doses of a drug are required to produce the same effect as during initial use; often is associated with physical dependence. [NIH] Tomography: The recording of internal body images at a predetermined plane by means of the tomograph; called also body section roentgenography. [EU]
Toxic: Causing temporary or permanent effects that are detrimental to the functioning of a body organ or group of organs. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transfusion: The introduction of whole blood or blood component directly into the blood stream. [EU] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH] Transplantation: The grafting of tissues taken from the patient's own body or from another. [EU] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of mycobacterium. [NIH] Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH]
Glossary 387
Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU]
Vaccination: The introduction of vaccine into the body for the purpose of inducing immunity. Coined originally to apply to the injection of smallpox vaccine, the term has come to mean any immunizing procedure in which vaccine is injected. [EU] Vaccine: A suspension of attenuated or killed microorganisms (bacteria, viruses, or rickettsiae), administered for the prevention, amelioration or treatment of infectious diseases. [EU] Vaccinia: The cutaneous and sometimes systemic reactions associated with vaccination with smallpox vaccine. [EU] Vaginal: 1. of the nature of a sheath; ensheathing. 2. pertaining to the vagina. 3. pertaining to the tunica vaginalis testis. [EU] Vasculitis: Inflammation of a vessel, angiitis. [EU] Veins: The vessels carrying blood toward the heart. [NIH] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [NIH] Viruses: Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. [NIH] Withdrawal: A variety of symptoms that occur after chronic use of some drugs is reduced or stopped. [NIH] World Health Organization: A specialized agency of the United Nations designed as a coordinating authority on international health work; its aim is to promote the attainment of the highest possible level of health by all peoples. [NIH]
General Dictionaries and Glossaries While the above glossary is essentially complete, the dictionaries listed here cover virtually all aspects of medicine, from basic words and phrases to more advanced terms (sorted alphabetically by title; hyperlinks provide rankings, information and reviews at Amazon.com): ·
Dictionary of Medical Acronymns & Abbreviations by Stanley Jablonski (Editor), Paperback, 4th edition (2001), Lippincott Williams & Wilkins Publishers, ISBN: 1560534605, http://www.amazon.com/exec/obidos/ASIN/1560534605/icongroupinterna
388 Hepatitis C
·
Dictionary of Medical Terms : For the Nonmedical Person (Dictionary of Medical Terms for the Nonmedical Person, Ed 4) by Mikel A. Rothenberg, M.D, et al, Paperback - 544 pages, 4th edition (2000), Barrons Educational Series, ISBN: 0764112015, http://www.amazon.com/exec/obidos/ASIN/0764112015/icongroupinterna
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A Dictionary of the History of Medicine by A. Sebastian, CD-Rom edition (2001), CRC Press-Parthenon Publishers, ISBN: 185070368X, http://www.amazon.com/exec/obidos/ASIN/185070368X/icongroupinterna
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Dorland’s Illustrated Medical Dictionary (Standard Version) by Dorland, et al, Hardcover - 2088 pages, 29th edition (2000), W B Saunders Co, ISBN: 0721662544, http://www.amazon.com/exec/obidos/ASIN/0721662544/icongroupinterna
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Dorland’s Electronic Medical Dictionary by Dorland, et al, Software, 29th Book & CD-Rom edition (2000), Harcourt Health Sciences, ISBN: 0721694934, http://www.amazon.com/exec/obidos/ASIN/0721694934/icongroupinterna
·
Dorland’s Pocket Medical Dictionary (Dorland’s Pocket Medical Dictionary, 26th Ed) Hardcover - 912 pages, 26th edition (2001), W B Saunders Co, ISBN: 0721682812, http://www.amazon.com/exec/obidos/ASIN/0721682812/icongroupinterna /103-4193558-7304618
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Melloni’s Illustrated Medical Dictionary (Melloni’s Illustrated Medical Dictionary, 4th Ed) by Melloni, Hardcover, 4th edition (2001), CRC PressParthenon Publishers, ISBN: 85070094X, http://www.amazon.com/exec/obidos/ASIN/85070094X/icongroupinterna
·
Stedman’s Electronic Medical Dictionary Version 5.0 (CD-ROM for Windows and Macintosh, Individual) by Stedmans, CD-ROM edition (2000), Lippincott Williams & Wilkins Publishers, ISBN: 0781726328, http://www.amazon.com/exec/obidos/ASIN/0781726328/icongroupinterna
·
Stedman’s Medical Dictionary by Thomas Lathrop Stedman, Hardcover 2098 pages, 27th edition (2000), Lippincott, Williams & Wilkins, ISBN: 068340007X, http://www.amazon.com/exec/obidos/ASIN/068340007X/icongroupinterna
·
Tabers Cyclopedic Medical Dictionary (Thumb Index) by Donald Venes (Editor), et al, Hardcover - 2439 pages, 19th edition (2001), F A Davis Co, ISBN: 0803606540, http://www.amazon.com/exec/obidos/ASIN/0803606540/icongroupinterna
Index 389
INDEX A Abdomen ...................18, 33, 35, 367, 379 Abdominal...14, 18, 21, 41, 43, 58, 64, 68, 71, 139, 208, 369, 381 Abortion .................................94, 138, 367 Abscess .................................................94 Acetaminophen....................................350 Acetylcysteine..............................135, 265 Adenosine............................101, 139, 367 Adjuvant.......................................269, 278 Agar .....................................................162 Aggressiveness .....................................97 Agonist.................................................317 Alanine.......23, 62, 77, 107, 265, 272, 343 Alimentary......................................86, 381 Alleles ............................................99, 290 Alopecia...............................................350 Amantadine .............................27, 28, 107 Anal ...............................................21, 219 Analog .......................78, 86, 87, 378, 385 Anemia ........145, 165, 181, 239, 351, 386 Anesthetic ..................34, 64, 70, 175, 371 Anorexia ..................................14, 21, 343 Antibiotic ......................................145, 385 Antidepressants...................................310 Antigen ...93, 98, 100, 127, 138, 141, 162, 170, 172, 175, 176, 193, 208, 372, 373, 376, 384 Antioxidant.....................87, 269, 289, 385 Anxiety.................................310, 333, 370 Apathy .................................334, 350, 380 Arthralgia .............................................350 Ascites .........103, 149, 203, 233, 344, 352 Asialoglycoproteins..............173, 175, 369 Assay....92, 134, 137, 138, 172, 193, 214, 232, 267, 346, 347, 348, 356, 357 Asymptomatic .......78, 138, 154, 168, 200, 208, 343, 381 B Bile...........34, 50, 175, 182, 346, 370, 378 Biliary.................40, 41, 59, 203, 208, 381 Bilirubin ................................149, 194, 351 Biochemical .......100, 101, 103, 108, 139, 176, 192, 347, 349, 368, 375 Bupropion ....................................306, 310 C Capsid .........................................177, 387 Capsules........................................66, 287 Carbohydrate...............176, 203, 286, 375 Cardiac ..........................77, 140, 350, 372 Catechin ..............................................266
Catheterization...................................... 94 Causal........................... 93, 176, 274, 375 Chelation..................................... 271, 351 Chemotherapy .................................... 274 Chloroform .......................................... 151 Cholesterol.................. 142, 284, 286, 378 Circumcision ......................................... 94 Cocaine...... 13, 14, 46, 97, 312, 315, 319, 322, 323, 324, 327, 328, 330, 333, 354, 356, 372 Condoms... 15, 19, 21, 226, 230, 341, 359 Confusion.................... 220, 232, 334, 380 Conjugated.......................................... 162 Contamination..................................... 200 Counterimmunoelectrophoresis.......... 162 Crack........................................... 312, 328 Craving.......................... 11, 308, 313, 317 Cues.................................................... 311 Curative....................................... 294, 380 Cutaneous............. 57, 143, 145, 378, 387 Cysteine .............................. 135, 265, 290 Cytokines ............................................ 101 Cytomegalovirus ................................. 173 Cytotoxic ..................................... 100, 125 D Decompensation ................... 99, 140, 372 Deferoxamine ..................................... 271 Degenerative ...... 141, 285, 360, 373, 383 Detoxification .............. 307, 317, 319, 327 Diarrhea ...... 18, 119, 155, 157, 159, 203, 284, 337 Diffusion .............. 141, 162, 176, 372, 375 E Edema................. 140, 242, 267, 368, 372 Electrophoresis ................................... 131 Encephalopathy .... 95, 103, 233, 344, 352 Endemic .............................. 131, 145, 385 Endogenous........................................ 153 Endoscopy ............................................ 94 Enzyme .. 56, 62, 85, 92, 93, 97, 102, 110, 118, 144, 145, 162, 211, 232, 266, 346, 353, 373, 382, 385 Epidemic .... 145, 173, 188, 201, 206, 319, 385 Epitopes .............................................. 100 Euphoria...................................... 313, 317 Exogenous .......................... 153, 176, 374 Extraction ............................................ 134 Extravasation ........................................ 96 F Fatal .............. 62, 145, 320, 350, 378, 386
390 Hepatitis C
Fatigue....18, 21, 41, 42, 68, 84, 171, 191, 200, 266, 344, 350, 353, 369 Feces ...................................................219 Fibrosis .14, 34, 65, 97, 99, 101, 108, 215, 232, 270, 272, 344, 348, 350, 351, 352, 355, 357, 371 Fluorescence ...............................141, 374 G Gastrointestinal...195, 196, 203, 208, 374, 385 Genital ...................................26, 177, 387 Genotype ......57, 66, 76, 93, 99, 102, 106, 144, 183, 273, 343, 348, 350, 353, 358, 381 Ginseng ...............................................267 Glomerulonephritis ................93, 291, 345 Glycoproteins......151, 173, 175, 176, 369, 375 Glycosylation .......................................173 Glycyrrhiza...........................................265 H Haemodialysis .....................................273 Haemolysis ..........................................275 Hemolysis ............................................165 Hemorrhage.................................344, 352 Hepatic ...4, 103, 106, 108, 133, 175, 344, 355, 369 Hepatotoxic..........................................110 Herpes .....................................26, 34, 376 Homologous ........139, 155, 166, 170, 368 Hormone.....208, 286, 294, 351, 377, 378, 385 Humoral ...............................................356 Hydrophobic ........142, 158, 176, 376, 378 Hypertension ...............103, 267, 311, 344 Hyperthermia .......................................168 Hyperthyroidism...........353, 357, 360, 376 I Iatrogenic .............................................273 Idiopathic .............................108, 142, 376 Incarceration....... 97, 227, 228, 230, 314, 320, 321 Incubation ................................14, 92, 219 Indicative .......87, 143, 149, 172, 379, 385 Induction ..............103, 107, 125, 163, 173 Influenza ................................33, 164, 368 Infusion ............................................69, 97 Ingestion ..............................219, 287, 355 Institutionalization ................................325 Insulin ..................................289, 294, 377 Interferons .............................75, 102, 349 Intermittent...........................344, 345, 356 Interstitial ...............................34, 350, 371 Intravenous.......61, 75, 86, 101, 109, 170, 181, 195, 327, 381 Invasive .................................................94
J Jaundice....... 14, 18, 21, 24, 42, 43, 202, 344, 352 K Keratoconjunctivitis ............................. 345 L Lesion ......................................... 143, 378 Lethal .................................... 85, 103, 374 Lipoprotein .......... 117, 142, 177, 378, 387 Localization ......................................... 117 Lupus .................................... 93, 140, 371 Lymphocytic ........................................ 172 Lymphoma ...................... 69, 86, 133, 378 M Malaise.......................... 14, 343, 344, 350 Membrane...... 87, 96, 104, 141, 142, 155, 164, 208, 375, 380, 385 Metabolite ........................................... 287 Methadone ... 22, 310, 312, 313, 316, 317, 323, 324, 327, 332 Methamphetamine .............................. 323 Microbiology.................................. 85, 369 Microsomal.......................................... 120 Molecular ..... 98, 102, 104, 107, 118, 144, 153, 161, 193, 224, 230, 235, 237, 273, 341, 355, 356, 383 Monotherapy .. 65, 92, 152, 165, 191, 201, 268 Morphogenesis ................................... 102 Mutagenesis ....................................... 111 Myalgia................................ 177, 350, 377 N Naltrexone................... 310, 323, 334, 379 Nausea........................ 18, 21, 41, 42, 171 Necrosis ..... 100, 101, 233, 344, 352, 355, 357 Neonatal........................................ 41, 109 Neural ................................. 285, 360, 376 Neuropathy ........................................... 93 Niacin .................................................. 285 Nicotine ....................... 306, 310, 319, 326 Nosocomial ........... 92, 143, 354, 355, 380 Nucleocapsid ...................... 150, 177, 380 O Opiate ..... 306, 312, 313, 317, 323, 324, 327, 332 Osmotic............................................... 203 Overdose ............................................ 285 P Pancreatitis ......................................... 203 Paradoxical ......................................... 350 Parenchyma........................................ 344 Parenteral ................... 155, 196, 342, 347 Particle ................................................ 151 Pathogen....................................... 34, 377 Percutaneous...................... 233, 351, 354
Index 391
Perinatal ......................................181, 355 Pharmacokinetics ................................266 Phenotype ...................................144, 381 Polyethylene ............................64, 86, 381 Polypeptide...87, 142, 145, 208, 376, 385, 386 Polyproteins.........................................158 Porphyria .......................................40, 345 Potassium............................141, 286, 375 Preclinical ............................................106 Precursor .....................................307, 319 Preoperative ..........................................97 Prisons.........................................124, 189 Progressive........67, 75, 93, 143, 344, 379 Prophylaxis ....................29, 173, 201, 233 Protease ...... 96, 102, 149, 154, 157, 166, 277 Prothrombin .........................................351 Psychiatric .......58, 68, 312, 323, 324, 330 Psychiatry ......................................87, 382 Psychotherapy.....................306, 309, 323 Pulmonary ...................................108, 350 R Radiotherapy .......................................274 Receptor .....101, 105, 117, 123, 139, 148, 175, 369 Recombinant ..75, 92, 125, 149, 150, 155, 159, 162, 170, 173, 232, 346 Recurrence ..................................148, 149 Regeneration .........................34, 345, 371 Remission................................75, 87, 383 Retinopathy .........................................350 Retreatment.................181, 349, 351, 358 Rheumatoid ...................93, 140, 274, 371 Riboflavin.............................................284 S Saliva .....................................................56 Schizophrenia........................................78 Secretion .......35, 119, 144, 155, 203, 384 Sedative.................................................64 Selenium......................265, 269, 286, 289 Semen .....24, 56, 226, 233, 341, 356, 358 Serine ............................96, 135, 158, 271 Seroconversion............................120, 186 Serology ......................................204, 364 Serum .103, 108, 124, 145, 149, 167, 175, 182, 195, 208, 265, 266, 343, 344, 345, 347, 349, 350, 351, 358, 369, 384
Silymarin ............... 75, 265, 266, 269, 289 Sneezing ............................................. 229 Somatostatin ....................................... 203 Spectrum............................. 100, 119, 181 Sporadic.............. 154, 161, 167, 196, 269 Stasis .................................................. 267 Stavudine .............................................. 55 Steatosis ..................................... 106, 346 Stimulant ............................. 322, 334, 379 Substrate............................................. 290 Symptomatic .... 33, 76, 87, 208, 368, 381, 385 Systemic ............... 93, 140, 145, 371, 387 T Tachycardia ........................................ 350 Telecommunications............................. 20 Thalassemia........................................ 274 Thermoregulation................................ 284 Thrombocytopenia .............. 171, 268, 275 Thrombosis ........................................... 93 Thymosin ...................................... 71, 351 Thyroxine ............................................ 286 Tolerance ............................................ 108 Transdermal........................................ 326 Transgenes ......................................... 107 Transplantation .... 23, 38, 40, 61, 95, 101, 105, 148, 180, 192, 195, 200, 202, 203, 210, 220, 232, 233, 291, 341, 352, 357 Tuberculosis.......... 27, 143, 307, 315, 378 U Urinalysis ........ 68, 88, 307, 325, 328, 386 Urinary ........................................ 177, 387 Urogenital............................................ 170 V Vaccination .. 20, 145, 160, 200, 219, 220, 232, 358, 387 Vaccine ...... 15, 35, 59, 98, 125, 139, 145, 150, 200, 219, 342, 343, 356, 367, 387 Vaccinia ...................................... 100, 125 Vaginal ............................................ 21, 24 Vasculitis......................... 68, 93, 208, 381 Veins ........................................... 344, 378 Virion................................... 151, 177, 380 W Withdrawal .. 307, 317, 320, 326, 333, 373
392 Hepatitis C
Index 393
394 Hepatitis C
