A randomized double-blind placebo-controlled study of lamivudine in the treatment of patients with chronic hepatitis B virus infection

Objective To evaluate the effect of lamivudine on the loss of serum hepatit is B virus (HBV) DNA, HBeAg/antiHBe seroconversion and ALT levels in chroni c hepatitis B patients and its safety profile and tolerance compared with p lacebo. Methods Four hundred and twenty-nine patients with chronic HBV infection as defined by positive HBsAg, HBeAg and HBV DNA were enrolled and randomized into lamivudine and placebo groups. Three hundred and twenty-two patients r eceived lamivudine 100 mg daily and 107 patients received placebo treatment for 12 weeks. Then, all patients were offered a further 9-month open label lamivudine treatment. The efficacy and safety were evaluated with clinical , biochemical, hematological and virological parameters. Results During the 12-week treatment period, 92.2% of lamivudine treated pa tients became HBV DNA negative (below 1.6 pg/ml) compared with only 14.1% o f those receiving placebo (P < 0.01). At the end of 12 week, the sustained negative rate for HBV DNA in the lamivudine treated group was 78. 5% compar ed with the placebo group (11. 1%; P < 0.01). There was a trend to a high p roportion of patients treated with lamivudine to lose HBeAg (8.1%) and deve lop antiHBe (10.2%) than treated with placebo (5.3% and 6.4% respectively), but this difference was not statistically significant. Patients with eleva ted ALT levels at baseline became normal in 60. 3% of the lamivudine treate d group compared with the placebo group where only 27.5% were normal (P < 0 .01). Lamivudine was well tolerated in a dose of (100 mg daily) and the ove rall incidence of adverse events was similar to that of the placebo. Conclusions Lamivudine (100 mg daily) is very effective in the inhibition o f HBV replication, indicated by the rapid loss of serum HBV DNA, and often accompanied by a decrease of serum ALT levels. Lamivudine is well tolerated without severe adverse events during treatment.