Antiviral Therapy for Adults with Chronic Hepatitis B: A Systematic Review for a National Institutes of Health Consensus Development Conference

January 14, 2009

Ann Intern Med. 2009 Jan 5. [Epub ahead of print]

Antiviral Therapy for Adults with Chronic Hepatitis B: A Systematic Review for a

National Institutes of Health Consensus Development Conference.

Shamliyan TA, Macdonald R, Shaukat A, BC, Yuan JM, JR, Tacklind

J, Rutks I, Kane RL, Wilt TJ.

the Minnesota Evidence-based Practice Center, University of Minnesota School of

Public Health, Minneapolis Veterans Affairs Center for Chronic Disease Outcomes

Research.

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 (alpha2b and pegylated

alpha2a), 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-alpha2b, pegylated interferon-alpha2a, 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-alpha2b (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-alpha2b, moderate-quality evidence suggested HBeAg loss (3 RCTs; 351

patients), seroconversion (2 RCTs; 304 patients), and ALT normalization (2 RCTs;

131 patients). Pegylated interferon-alpha2a versus lamivudine improved HBeAg

seroconversion (1 RCT; 814 patients) and ALT normalization (2 RCTs; 905

patients) off treatment. Pegylated interferon-alpha2a 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.

PMID: 19124812 [PubMed - as supplied by publisher]

January 14, 2009