Antiviral therapy for adults with chronic hepatitis B: a systematic review for a National Institutes of Health Consensus Development Conference.
BACKGROUND
Chronic hepatitis B infection can lead to liver failure, hepatocellular carcinoma, and death.


OBJECTIVE
To evaluate the effectiveness of antiviral therapy for adults with chronic hepatitis B infection.


METHODS
Randomized, controlled trials (RCTs) of interferon (alpha2b and pegylated alpha2a), lamivudine, adefovir, entecavir, and telbivudine published from 1990 to 2008.


METHODS
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.


METHODS
Data extracted with standard protocols to calculate risk difference for clinical outcomes, viral load, HBeAg and HBsAg, ALT, histologic scores, and adverse events.


RESULTS
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.


CONCLUSIONS
Marked heterogeneity in study samples, interventions, and measured outcomes preclude definitive conclusions.


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.
Shamliyan
Tatyana A
TA
Minnesota Evidence-based Practice Center, Division of Health Policy and Management, University of Minnesota School of Public Health, 420 Delaware Street SE, Minneapolis, MN 55455, USA. shaml005@umn.edu
MacDonald
Roderick
R
Shaukat
Aasma
A
Taylor
Brent C
BC
Yuan
Jian-Min
JM
Johnson
James R
JR
Tacklind
James
J
Rutks
Indulis
I
Kane
Robert L
RL
Wilt
Timothy J
TJ
D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D035843:Biomedical Research; D006528:Carcinoma, Hepatocellular / Q000821:virology; D014943:Global Health; D006509:Hepatitis B / Q000453:epidemiology / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D008103:Liver Cirrhosis / Q000821:virology; D008113:Liver Neoplasms / Q000821:virology; D015995:Prevalence; D018570:Risk Assessment; D016896:Treatment Outcome
D000998:Antiviral Agents