Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B

Background & Aims: One-year lamivudine therapy significantly suppressed hep atitis B virus (HBV) replication, improved hepatic necroinflammatory activi ty, and prevented progression of fibrosis, However, the effects of prolonge d therapy are unknown, Methods: A total of 334 Asian patients with chronic hepatitis B from a previously reported 1-year study were randomized to rece ive either lamivudine (100 or 25 mg) or placebo for another year. The effec ts of treatment on serum HBV-DNA suppression, alanine transaminase (ALT) no rmalization, and hepatitis B e antigen (HBeAg) seroconversion were measured . The presence of YMDD variant HBV and its effect were also determined. Res ults: A significantly greater proportion of patients achieved sustained HBV -DNA suppression and ALT normalization with 100 mg lamivudine daily for 2 y ears compared with lamivudine for 1 year followed by placebo for the second year (P < 0.001). Daily lamivudine therapy for 2 years was safe and result ed in incremental HBeAg seroconversion from 17% at week 52 to 27% at week 1 04, HBeAg seroconversion during continued lamivudine therapy increased line arly with increasing pretherapy ALT levels (P < 0.001). Despite the emergen ce of YMDD mutant in 38% of the patients, they continued to clear serum HBe Ag and maintain lower median serum HBV-DNA and ALT levels than baseline val ues. In contrast, ALT levels increased 8-12 weeks after switching from lami vudine to placebo, but returned to normal once lamivudine treatment was res umed. Conclusions: Treatment with lamivudine for 2 years is both well toler ated and efficacious in patients with chronic hepatitis B.