Aims: To compare interferon monotherapy with its combination with lamivudine for hepatitis B e antigen (HBeAg)-positive hepatitis B treatment.

Methods: Two independent researchers identified pertinent randomized controlled trials. The trials were evaluated for methodological quality and heterogeneity. Rates of sustained virological and biochemical responses, and HBeAg clearance and seroconversion were used as primary efficacy measures. Quantitative meta-analyses were conducted to assess differences between groups for conventional and pegylated interferon, and overall.

Results: Greater sustained virological, biochemical and seroconversion rates were observed with addition of lamivudine to conventional [odds ratio (OR)=3.1, 95% confidence intervals (CI) (1.7-5.5), P<0.0001, OR=1.8, 95% CI (1.2-2.7), P=0.007 and OR=1.8, 95% CI (1.1-2.8), P=0.01 respectively], although not pegylated [OR=1.1, 95% CI (0.5-2.3), P=0.8, OR=1.0, 95% CI (0.7-1.3), P=0.94, and OR=0.9, 95% CI (0.6-1.2), P=0.34 respectively] interferon-alpha, with no significant affect on HBeAg clearance rates [OR=1.6, 95% CI (0.9-2.7), P=0.09, and OR=0.8, 95% CI (0.6-1.1), P=0.26 respectively]. Excluding virological response (P<0.001), pegylated interferon monotherapy and conventional interferon and lamivudine combination therapy were similarly efficacious (P>0.05), with the former studied in harder to treat patients, as evidenced by the superior virological response observed with conventional as compared with pegylated interferon monotherapy (P<0.0001).

Conclusion: In comparable populations, pegylated interferon monotherapy is likely to be equally or more efficacious than conventional interferon and lamivudine combination therapy, thus constituting the treatment of choice, with no added benefit with lamivudine addition. However, when conventional interferon is used, its combination with lamivudine should be considered.