Core promoter/pre-core mutations are associated with lamivudine-induced HBeAg loss in chronic hepatitis B with genotype C

Background/Aims: To clarify the factors associated with the efficacy of lamivudine. Methods: Variables including basic core promoter (BCP) and pre-core (PreC) mutations were evaluated in 60 chronic hepatitis B e antigen (HBeAg)-positive patients with genotype C. Thirty patients were treated with lamivudine and the remaining 30 patients were age- and sex-matched controls. Results: Severe fibrosis was significantly more frequent in patients with the BCP-mutant/PreC-wild (MW) and BCP-mutant/PreC-mutant (MM) patterns compared to BCP-wild/PreC-wild (WW) pattern (P=0.02). The cumulative rates of HBeAg loss at 6, 12 and 18 months were significantly higher in the lamivudine group (14.2, 36.3, and 60.9%) compared with the control group (17.6, 17.6, and 24.5%, P=0.03), and was especially pronounced in patients with the MW pattern (P=0.04). The rate of lamivudine-related HBeAg loss was significantly lower in patients with the WW pattern (P=0.03). Factors correlating with HBeAg loss were histological fibrosis and activity, hepatitis B virus-DNA levels, BCP/PreC mutation and lamivudine therapy. Multivariate analysis revealed BCP/PreC mutations and fibrosis were independent factors for HBeAg loss. Conclusions: With specific reference to the genotype C, we found earlier HBeAg loss was expected in patients carrying MM and MW patterns, while the efficacy of lamivudine was limited in patients with the WW pattern.