Objective: To evaluate the long-term effect of lamivudine on the loss of serum HBV DNA, HBeAg/antiHBe seroconversion and ALT levels in chronic hepatitis B patients and its safety profile and tolerance with multi-center, randomized, double blind and placebo controlled trial.
Method: 429 patients with chronic HBV infection as defined by positive HBsAg, HBeAg and HBV DNA were enrolled and randomized into lamivudine and placebo groups. 322 patients received lamivudine 100 mg daily and 107 patients received placebo treatment for 12 weeks. Then, all patients were offered a further 40 weeks of open label lamivudine treatment. The efficacy and safety were evaluated with clinical, biochemical, hematological and virological parameters.
Results: After 12 weeks treatment, HBV DNA response (serum HBV DNA < 1.6 ng/L) rate in lamivudine group was higher than in placebo group (92.2% VS 14.1%, P < 0.01); but at week 52, there was no difference between lamivudine and placebo/lamivudine groups (71.0% VS 77.7%, P > 0.05). Rate of HBV DNA breakthrough in lamivudine group was higher than in placebo/lamivudine group (24.4% VS 8.5%, P < 0.01). Proportion of HBeAg/anti-HBe seroconversion had no difference in two groups (7.5% VS 5.2%, P > 0.05). By week 12, ALT normalization rate in lamivudine group was higher than in placebo group (60.3% VS 27.5%, P < 0.01); but after 52 weeks treatment, there was no difference between two groups (70.9% VS 74.5%, P > 0.05). At week 48, HBV YMDD mutation rate in lamivudine group was higher than in placebo/lamivudine group (14.6% VS 5.0%, P < 0.05). The incidence of adverse events was similar for both lamivudine and placebo/lamivudine group up to week 12 and 52. There was few severe drug-related adverse event.
Conclusion: Sustained HBV replication suppression could be obtained from long-term treatment with lamivudine 100 mg daily accompanied with good tolerance and safety.