OBJECTIVES: To evaluate the comparative effectiveness of antiviral drugs in adults with chronic hepatitis B monoinfection for evidence-based decision-making.
METHODS: A systematic review of randomized controlled clinical trials (RCTs) published in English. Results after interferon and nucleos(t)ides analog therapies were synthesized with random-effects meta-analyses and number needed to treat (NNT).
RESULTS: Despite sustained improvements in selected biomarkers, no one drug regimen improved all intermediate outcomes. In 16 underpowered RCTs, drug treatments did not reduce mortality, liver cancer, or cirrhosis. Sustained HBV DNA clearance was achieved in one patient when two were treated with adefovir (NNT from 1 RCT = 2 95%CI 1;2) or interferon alfa-2b (NNT from 2 RCTs = 2 95%CI 2;4), 13 with lamivudine (NNT from 1 RCT = 13 95%CI 7;1000), and 11 with peginterferon alfa-2a vs. lamivudine (NNT from 1 RCT = 11 95%CI 7;25). Sustained HBeAg seroconversion was achieved in one patient when eight were treated with interferon alfa-2b (NNT from 2 RCTs = 8 95%CI 5;33) or 10-with peginterferon alfa-2b vs. interferon alfa-2b (NNT from 1 RCT = 10 95%CI 5;1000). Greater benefits and safety after entecavir vs. lamivudine or pegylated interferon alfa-2b vs. interferon alfa-2b require future investigation of clinical outcomes. Adverse events were common and more frequent after interferon. Treatment utilization for adverse effects is unknown.
CONCLUSIONS: Individual clinical decisions should rely on comparative effectiveness and absolute rates of intermediate outcomes and adverse events. Future research should clarify the relationship of intermediate and clinical outcomes and cost-effectiveness of drugs for evidence-based policy and clinical decisions.