Interferon-α combined with lamivudine in the treatment of chronic hepatitis

Objective To evaluate the efficacy of 1 year treatment of interferon combined with lamivudine therapy in chronic hepatitis B patients. Methods 71 patients were enrolled and randomized into two groups. 34 patients received interferon alpha and lamivudine simultaneously for 26 weeks, then lamivudine alone for another 26 weeks. 37 patients received lamivudine alone for 52 weeks. Liver biopsy was taken before therapy. The efficacy was evaluated by biochemical and virological parameters. The YMDD motif was detected by PCR, restriction fragment length polymorphism analysis (RFLP) in both groups. Results All 71 patients completed the study. Proportion of HBeAg/Anti-HBe seroconversion in combination group was higher than lamivudine group (41.2% vs 21.6%) with no significance (P= 0.08). No YMDD mutation was found during 52 weeks in combination group, and 13.5% (5/37) was found in lamivudine group. HBeAg/Anti-HBe seroconversion in combination group correlated highly with baseline ALT and HBV DNA (P= 0.04, 0.01). Categorical analysis revealed the HBeAg/Anti-HBe seroconversion rate was significantly higher in patients with serum ALT2×ULN and HBV DNA 1.0 ×10 7 copies/ml than those with lower HBV DNA levels both in combination group and lamivudine group (52.0% vs 25.8%, P= 0.04; 63.2% vs 28.6%, P= 0.03). Necro-inflammatory activity, fibrosis and the expression of HBV DNA showed no correlation with response rate in combination group. Among those who had higher levels of HBV DNA expression, seroconversion rate in combination group is higher than that in lamivudine group (46.2% vs 9.5%, P= 0.03). Conclusions The efficacy of combination therapy appeared to be better in patients with at least moderately elevated baseline ALT, high level of HBV DNA as well as HBV DNA expression in hepatocytes. Combination therapy may delay or diminish the development of YMDD mutation-related resistance to lamivudine.