Viral genotype and baseline load predict the response to adefovir treatment in lamivudine-resistant chronic hepatitis B patients

Background/Aims: To determine the factors associated with virological response (VR), HBeAg loss or the emergence of adefovir (ADV)-related mutations in ADV-treated chronic hepatitis B (CHB) patients with lamivudine (LAM) resistance. Methods: Fifty-four LAM-resistant CHB patients (46% HBeAg-positive) were treated with ADV monotherapy (n = 28) or ADV plus LAM (n = 26) for a mean of 30.4 months. Results: Thirty-eight patients (70.4%) achieved VR defined as HBV-DNA levels <10(4) copies/ml within the first 12 months of treatment. Six (24%) of 25 HBeAg-positive patients exhibited HBeAg loss and 20% seroconverted to anti-HBe. Eight patients (14.8%) developed ADV-related mutations. In the multivariate analysis, female gender (HR = 0.20, 95% CI: 0.05-0.76, p = 0.018), HBeAg-negative (HR = 0.37, 95% CI: 0.14-0.96, p = 0.040) and low baseline HBV-DNA levels (HR = 0.65, 95% CI: 0.45-0.95, p = 0.027) were independent predictors of VR, whereas low HBV-DNA levels (HR = 0.36, 95% CI: 0.11-1.20, p = 0.095) and HBV-genotype D (HR = 0.06, 95% CI: 0.004-0.84, p = 0.037) independently predicted HBeAg loss. Conclusions: ADV therapy suppresses viral replication in more than 70% of LAM-R patients. Factors associated with virologic response are female gender, HBeAg-negative status and low baseline serum HBV-DNA levels. Genotype D HBV infection and low baseline HBV-DNA levels independently predict HBeAg loss. (C) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.