Efficacy of lamivudine in patients with hepatitis B e antigen-negative hepatitis B virus DNA-positive (precore mutant) chronic hepatitis B

This placebo controlled, double-blind study evaluated the efficacy and safe ty of lamivudine in patients with hepatitis B e antigen (HBeAg)-negative/he patitis B virus (HBV) DNA-positive chronic hepatitis B, Patients were rando mized to receive 100 mg lamivudine orally once daily for 52 weeks (n = 60) or placebo for 26 weeks (n = 65), Patients who were HBV DNA positive at wee k 24 were withdrawn at week 26, The primary efficacy endpoint was loss of s erum HBV DNA plus normalization of alanine transaminase (ALT) at week 24, A significantly higher proportion of patients receiving lamivudine (63%) had a complete response at week 24 compared with patients receiving placebo (6 %) (P <.001), Secondary efficacy parameters included histological response from baseline to week 52 in the lamivudine-treated patients. At week 52, 60 % of lamivudine-treated patients with liver biopsy specimens available show ed histological improvement (greater than or equal to 2-point reduction in Knodell necro-inflammatory score), 29% showed no change, and 12% worsened. In a ranked assessment of pretreatment and post-treatment biopsy pairs 11% improved, 86% showed no change, and 2% worsened in fibrosis, At week 52, 27 % of patients receiving lamivudine had YMDD (tyrosine-methionine-aspartate- aspartate amino acid motif of HBV polymerase) variant HBV. The incidence of adverse events and laboratory abnormalities was similar in both groups. In conclusion, lamivudine treatment results in a significant virological and biochemical improvement compared with placebo, induces an improvement or no change in histology in most patients, and is well tolerated. The response to lamivudine therapy in HBeAg-negative patients is similar to the response reported in previous studies of patients with HBeAg-positive chronic hepat itis B.