[Comparison of peg-interferon monotherapy to peg-interferon and nucleoside analogue combination therapy for hepatitis...

To evaluate the efficacy and safety of pegylated-interferon (Peg-IFN) treatment as monotherapy or in combination with nucleoside analogues (NAs) for treating chronic hepatis B (CHB) infection.Searches of PubMed, OVID, EMBASE, and the Chinese Medical (WanFang, CNKI, and VIP) databases were conducted to identify all relevant randomized controlled trials published since January 1990. Twelve studies comparing Peg-IFN monotherapy to NA combination therapy (lamivudine (LAM), n =8); adefovir (ADV), n = 4) met the inclusion criteria (treatment duration, range: 48-52 weeks; follow-up, range: 24 weeks to three years). Meta-analysis was performed with RevMan 5.0 using the fixed-effects and random-effects models. Patients who had received combination therapy had a higher biochemical response rate at the end of treatment than those who had received monotherapy (51.1% vs. 38.9%, odds ratio (OR) = 1.63, 95% confidence interval (CI): 1.33-2.01, P less than 0.01). Subgroup analysis of Peg-IFN combination therapies with LAM or ADV indicated that neither NA type significantly enhanced the increased efficacy of combination therapy compared to monotherapy. The combination therapy subgroups also had higher virologic response rates at the end of treatment than the monotherapy subgroups (LAM: 65.9% vs. 34.9%, OR = 3.57, 95% CI: 1.83-6.95, P less than 0.01; ADV: 74.6% vs. 46.2%, OR = 3.66, 95% CI: 2.13-6.30, P less than 0.01). Moreover, the combination therapy group had a higher sustained biochemical response rate at the end of follow-up than the monotherapy group (47.6% vs. 42.1%, OR = 1.28, 95% CI: 1.05-1.55, P less than 0.05). The LAM combination therapy subgroup had a significantly higher biochemical response rate than the monotherapy subgroup, but there was no significant difference between the LAM and ADV combination therapy subgroups. At the end of follow-up, the ADV combination therapy subgroup had a significantly lower rate of hepatitis B e antigen (HBeAg) than the monotherapy subgroup, but there was no significant difference between the ADV and LAM combination therapy subgroups for HbeAg reduction. The combination therapy group and monotherapy group showed no statistically significant differences in HBsAg reduction or occurrence of severe adverse events. Peg-IFN/NA combination therapy produces a higher biochemical response rate in CHB patients than PEG-IFN monotherapy. Moreover, Peg-IFN/ADV combination therapy produces a greater reduction in HBeAg than Peg-IFN monotherapy.