Pre- and post-treatment predictors of the early achievement of HBeAg loss in lamivudine-resistant patients receiving adefovir therapy

Background and Aim: This study investigated the clinical variables that predict hepatitis B e antigen (HBeAg) loss in lamivudine-resistant patients receiving adefovir therapy. Methods: Fifty-six consecutive HBeAg-positive patients treated with adefovir for at least 12 months were enrolled in this study. All had serum alanine aminotransferase (ALT) levels over twice the upper limit of normal (ULN) as a result of lamivudine resistance. Predictors of HBeAg loss after switching from lamivudine to adefovir were examined. Results: During the follow-up period, 18 (32.1%) of 56 patients showed a loss of HBeAg. The estimated rates of HBeAg loss at 6, 12, and 18 months were 11.5%, 26.8%, and 42.9%, respectively. Univariate analysis revealed that pretreatment ALT levels > 10 x ULN (P = 0.029), a viral load at 3 months of therapy (P = 0.017), and viral decline by > 3 log(10) from baseline at 3 months (P < 0.001) were significantly associated with the loss of HBeAg within 12 months of therapy. With multivariate analysis using the stepwise logistic regression model, pretreatment ALT > 10 x ULN (odds ratio [OR], 4.22; 95% confidence interval [CI], 1.09-19.44; P = 0.044) and viral suppression > 3 log(10) at 3 months (OR, 10.39; 95% CI, 1.86-58.07; P = 0.008) were identified as the two independent predictors of HBeAg loss. Conclusions: Pretreatment ALT levels and the initial pattern of post-treatment viral decline are the strongest predictors of the early achievement of HBeAg loss following treatment with adefovir in lamivudine-resistant patients. These results may provide useful information for the optimal timing of adefovir rescue as well as for better monitoring after treatment.