Prolonged lamivudine treatment in patients with chronic active anti-HBe-positive hepatitis.

The efficacy of lamivudine (LAM) at 100 mg/d for 1 year in normalizing serum ALT levels and suppressing HBV DNA has been demonstrated in many studies. However, frequent relapses make long-term results modest. In the present study, we evaluated the efficacy of LAM administered for 3 years in patients with chronic active anti-HBe-positive hepatitis. Thirty-four patients with chronic active anti-HBe-positive hepatitis were treated with LAM (100 mg) once daily for 3 years. Before treatment, all patients demonstrated serum ALT levels >2 times normal levels for >6 months and HBV DNA positivity >5 pg/mL as determined by the sandwich hybridization test for nucleic acid. Both ALT and HBV DNA were monitored during therapy. After 12 months of therapy, 24 of 34 patients (70.6%) showed evidence of HBV DNA clearance and normal ALT levels; 22 of 34 (64.7%) and 19 of 34 (55.8%) patients maintained a complete response after 2 and 3 years of therapy, respectively. The long-term LAM therapy (>1 year) was not associated with an increase in the response of intially nonresponder patients. The YMDD variant emerged in 17.6% of patients in the first year, in 35.2% during the second year, and 52.9% during the third year of treatment. LAM was well tolerated during the 3-year therapy in all patients. Patients with chronic active anti-HBe-positive hepatitis demonstrated that the LAM response rate tends to decrease over time due to the emergence of YMDD variants.