Tatyana A. Shamliyan, MD, MS; Roderick MacDonald, MS; Aasma Shaukat, MD, MPH; Brent C. Taylor, PhD, MPH; Jian-Min Yuan, MD, PhD; James R. Johnson, MD; James Tacklind, BS; Indulis Rutks, BS; Robert L. Kane, MD; Timothy J. Wilt, MD, MPH
Disclaimer: The authors of this report are responsible for its content. Statements in the paper should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
Acknowledgment: The authors thank the technical expert panel members Dr. Miriam Alter, Dr. Gary Davis, Dr. Daryl Lau, Dr. Michael Sorrell, and Dr. Myron Tong for their scientific and clinical input throughout this project; Shilpa Amin, MD, MBSC, AHRQ Task Order Officer, for her guidance throughout the project; and Dr. John Ward for reviewing and commenting on the draft. They also thank the librarians Judith Stanke and Dr. Del Reed for their contributions to the literature search; Maureen Carlyle and Marilyn Eells for their excellent technical assistance in preparation of the full evidence report and this manuscript; and Rebecca Schultz and Nancy Russell for their assistance with formatting the tables.
Grant Support: By Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services contract number 290-02-0009.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Tatyana A. Shamliyan, MD, MS, Division of Health Policy and Management, University of Minnesota School of Public Health, D351 Mayo (MMC 197), 420 Delaware Street SE, Minneapolis, MN 55455; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Shamliyan and Kane: Division of Health Policy and Management, University of Minnesota School of Public Health, D351 Mayo (MMC 197), 420 Delaware Street SE, Minneapolis, MN.
Mr. MacDonald, Drs. Taylor and Wilt, and Mr. Rutks: Center for Chronic Disease Outcomes Research, Minneapolis Veterans Affairs Medical Center, 1 Veterans Drive, Minneapolis, MN 55417.
Dr. Shaukat: Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota Medical School, 420 Delaware Street SE (MMC 36), Minneapolis, MN 55455.
Dr. Yuan: Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Room 300, West Bank Office Building, 1300 South Second Street, Minneapolis, MN 55454.
Dr. Johnson: Department of Infectious Diseases, Minneapolis Veterans Affairs Medical Center (111-F), 1 Veterans Drive, Minneapolis, MN 55417.
Mr. Tacklind: Agency for Healthcare Research and Quality Center for Chronic Disease Outcomes Research and the Cochrane Prostatic Diseases and Urologic Cancers Group, Minneapolis Veterans Affairs Medical Center, 1 Veterans Drive, Minneapolis, MN 55417.
Author Contributions: Conception and design: T.A. Shamliyan, R.L. Kane, T.J. Wilt.
Analysis and interpretation of the data: T.A. Shamliyan, R. MacDonald, A. Shaukat, B.C. Taylor, J.R. Johnson, T.J. Wilt.
Drafting of the article: T.A. Shamliyan, R. MacDonald, A. Shaukat.
Critical revision of the article for important intellectual content: T.A. Shamliyan, A. Shaukat, B.C. Taylor, J.-M. Yuan, J.R. Johnson, R.L. Kane, T.J. Wilt.
Final approval of the article: T.A. Shamliyan, A. Shaukat, B.C. Taylor, J.-M. Yuan, J.R. Johnson, R.L. Kane, T.J. Wilt.
Provision of study materials or patients: I. Rutks.
Statistical expertise: R. MacDonald.
Obtaining of funding: R.L. Kane, T.J. Wilt.
Administrative, technical, or logistic support: R. MacDonald, J. Tacklind, I. Rutks, R.L. Kane, T.J. Wilt.
Collection and assembly of data: T.A. Shamliyan, R. MacDonald, A. Shaukat, J. Tacklind, I. Rutks.
Chronic hepatitis B infection can lead to liver failure, hepatocellular carcinoma, and death.
To evaluate the effectiveness of antiviral therapy for adults with chronic hepatitis B infection.
Randomized, controlled trials (RCTs) of interferon (α2b and pegylated α2a), lamivudine, adefovir, entecavir, and telbivudine published from 1990 to 2008.
Randomized, controlled clinical trials of adults with chronic hepatitis B published in English after 1989 that reported death; incidence of hepatocellular carcinoma or liver failure; prevalence and incidence of cirrhosis; presence or seroconversion of hepatitis B e antigen (HBeAg) or surface antigen (HBsAg), viral load of hepatitis B virus DNA; aspartate aminotransferase and alanine aminotransferase (ALT) levels; or fibrosis scores after therapy with interferon-α2b, pegylated interferon-α2a, lamivudine, adefovir, entecavir, and telbivudine.
Data extracted with standard protocols to calculate risk difference for clinical outcomes, viral load, HBeAg and HBsAg, ALT, histologic scores, and adverse events.
In 16 RCTs (4431 patients), drug treatment did not improve clinical outcomes of chronic hepatitis B infection, but the trials were underpowered. In 60 RCTs that examined intermediate outcomes, no single treatment improved all intermediate outcomes. Low-quality evidence suggested HBsAg clearance after interferon-α2b (2 RCTs; 211 patients). Moderate-quality evidence suggested ALT normalization at follow-up after treatment with adefovir (2 RCTs; 600 patients) and HBeAg loss with lamivudine (2 RCTs; 318 patients). With interferon-α2b, moderate-quality evidence suggested HBeAg loss (3 RCTs; 351 patients), seroconversion (2 RCTs; 304 patients), and ALT normalization (2 RCTs; 131 patients). Pegylated interferon-α2a versus lamivudine improved HBeAg seroconversion (1 RCT; 814 patients) and ALT normalization (2 RCTs; 905 patients) off treatment. Pegylated interferon-α2a combined with lamivudine versus lamivudine improved HBeAg loss (1 RCT; 543 patients) and ALT normalization (2 RCTs; 905 patients). Adverse events during antiretroviral therapy occurred in more than 50% of patients but were not associated with increased treatment discontinuation. However, most studies excluded patients with hepatic or renal insufficiency or other serious comorbid conditions.
Marked heterogeneity in study samples, interventions, and measured outcomes preclude definitive conclusions.
Evidence was insufficient to assess treatment effect on clinical outcomes or determine whether inconsistent improvements in selected intermediate measures are reliable surrogates. Future research is needed to provide evidence-based recommendations about optimal antiviral therapy in adults with chronic hepatitis B infection.
Table. Effects of Drug Therapies for Chronic Hepatitis B on Clinical Outcomes
Absolute rates of the frequent (>40%) adverse effects after interferon therapy, by baseline HBeAg status.
HBeAg = hepatitis B e antigen.
The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.
Shamliyan TA, MacDonald R, Shaukat A, Taylor BC, Yuan J, Johnson JR, et al. Antiviral Therapy for Adults With Chronic Hepatitis B: A Systematic Review for a National Institutes of Health Consensus Development Conference. Ann Intern Med. 2009;150:111-124. doi: 10.7326/0003-4819-150-2-200901200-00101
Download citation file:
Published: Ann Intern Med. 2009;150(2):111-124.
Copyright © 2017 American College of Physicians. All Rights Reserved.
Print ISSN: 0003-4819 | Online ISSN: 1539-3704
Conditions of Use
This PDF is available to Subscribers Only