Two years trial of lamivudine for the treatemnt of chronic hepatitis B

Objective To evaluate the long term efficacy and safety of lamivudine for chronic hepatitis B and the clinical influence of emergence of YMDD motif mutation of HBV. Methods This multicenter, double blind, randomized, controlled trial began in 1996. A total of 429 patients who were HBsAg, HBeAg and HBV DNA positive were enrolled. They were randomised to receive either lamivudine 100mg daily ( n =322) or placebo ( n =107) for the first 12 weeks. Thereafter all patients were offered open label lamivudine treatment and assessed every 4 weeks for a total of 104 weeks. Results After 12 weeks, 92.2% of the lamivudine recipients had undetectable serum HBV DNA(1.6pg/ml), compared with 14.1% of those in the placebo group ( P 0.01) by Abbott hybridisation method. By week 52,71.0% of the lamivudine group had a sustained serum HBV DNA response, compared with 77.7% of the placebo/lamivudine group. At the end of 2 years, HBV DNA remained below undetected level (1.6pg/ml), except in patients with the emergence of YMDD mutation whose mean HBV DNA levels increased to 10pg/ml but were much more lower than that of pre treatment baseline level. Lamivudine therapy resulted in increased HBeAg loss and HBeAg/anti HBe seroconversion, which were correlated with both baseline ALT levels and also with duration of lamivudine treatment. HBeAg loss was achieved 26.8% of patients with ALT1×ULN at 2 years, and in 35.6% and 55.6% of patients with ALT2×ULN and 5×ULN respectively. For HBeAg seroconversion, these figures were 17.4%, 22.2% and 33.3% respectively. By the end of 2 years, ALT levels were remained in normal ranges in 50.3% whose ALT were abnomal before treatment, and 83% whose ALT were normal before treatment. HBV YMDD mutation were developed in 14.6% and 49.7% patients in 52 weeks and 104 weeks. The mean HBV DNA levels were slightly increased to 10pg/ml and 15% of the patients ALT levels were exceeded baseline. 4 patients were clinically flared up needed to stop treatment. The adverse drug reactions(ADR) of lamivudine were mild to moderate, only two patients were reported as drug related severe ADR. Conclusion Sustatined HBV replication and clinical improvement could be obtained by the long term lamivudine therapy with good tolerance and safety.