Antiviral therapy for adults with chronic hepatitis B: A systematic review for a National Institutes of Health Consensus Development Conference

Tatyana A. Shamliyan, Roderick MacDonald, Aasma Shaukat, Brent C. Taylor, Jian Min Yuan, James R. Johnson, James Tacklind, Indulis Rutks, Robert L. Kane, Timothy J. Wilt

Research output: Contribution to journalArticlepeer-review

96 Scopus citations


Background: Chronic hepatitis B infection can lead to liver failure, hepatocellular carcinoma, and death. Purpose: To evaluate the effectiveness of antiviral therapy for adults with chronic hepatitis B infection. Data Sources: Randomized, controlled trials (RCTs) of interferon (α2b and pegylated α2a), lamivudine, adefovir, entecavir, and telbivudine published from 1990 to 2008. Study Selection: 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 Extraction: Data extracted with standard protocols to calculate risk difference for clinical outcomes, viral load, HBeAg and HBsAg, ALT, histologic scores, and adverse events. Data Synthesis: 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. Limitation: Marked heterogeneity in study samples, interventions, and measured outcomes preclude definitive conclusions. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)111-124
Number of pages14
JournalAnnals of internal medicine
Issue number2
StatePublished - Jan 20 2009

Bibliographical note

Funding Information:
This research was partially supported by a grant from the General Secretariat of Research and Technology, Greek Ministry of Development, through the PENED99 program.


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