Virologic response and resistance to adefovir in patients with chronic hepatitis B

Background: The incidence and risk factors for adefovir-resistant HBV have not been clearly defined. Aims: To characterize the virologic response to adefovir, to determine the rate of adefovir resistance and to explore factors associated with initial virologic response (IVR) and adefovir resistance. Methods: All hepatitis B patients who received adefovir for >= 6 months at our center were prospectively monitored for virologic response and adefovir resistance. Results: Forty three patients were included; mean treatment duration was 18 months (range 6-45). Thirty four (79%) patients had prior lamivudine. IVR was observed in 44% patients and associated with higher pretreatment ALT (P = 0.05) and the absence of HBeAg (P = 0.02). Six (14%) patients were found to have adefovir-resistant mutations. The cumulative probability of genotypic resistance to adefovir at month 24 was 22%. Patients with adefovir resistance were more likely to have been switched from lamivudine to adefovir monotherapy (P = 0.01), to be older (P = 0.04), and to be infected with HBV genotype D (P = 0.02). Conclusions: Roughly 50% of patients failed to achieve IVR on adefovir. The cumulative probability of adefovir resistance at 2 years was 22%. Our data suggest that combination of lamivudine and adefovir may prevent emergence of adefovir resistance in patients with lamivudine-resistant HBV. (C) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.