Antiviral effect of entecavir in chronic hepatitis B: Influence of prior exposure to nucleos(t)ide analogues

Background & Aims: Entecavir is a potent inhibitor of viral replication in nucleos(t)ide analogue (NA)-naive chronic hepatitis B patients, but data on the efficacy in NA-experienced subjects are limited. Methods: In a multi-center cohort study we investigated 161 chronic hepatitis B patients (34% NA-experienced) treated with entecavir monotherapy. Results: During a median follow-up of 11 (3-23) months, 82 (79%) of 104 NA-naive patients achieved virologic response (VR), defined as HBV DNA < 80 IU/ml, and none of the patients (0%) developed genotypic entecavir-resistance. VR was demonstrated in 31 (54%) of 57 NA-experienced patients during a median follow-up of 12 (3-31) months. Patients with lamivudine-resistant mutations at the start of entecavir monotherapy had a reduced probability of achieving VR compared to lamivudine-naive patients (HR 0.14; 95% CI 0.04-0.58; p = 0.007). Antiviral efficacy was not decreased by prior treatment with lamivudine when lamivudine-resistance had never developed (HR 0.81; 95% CI 0.43-1.52; p = 0.52). Prior adefovir therapy without development of adefovir-resistance (HR 0.84; 95% CI 0.43-1.64; p = 0.61) and presence of adefovir-resistance (HR 0.86; 95% CI 0.27-2.71; p = 0.80) did not influence antiviral response to entecavir. Switching to a tenofovir-containing treatment regimen resulted in viral load decline in patients with entecavir-resistance associated mutations. Conclusions: Entecavir proved to be efficacious in NA-naive patients. The antiviral efficacy of entecavir was not influenced by prior treatment with adefovir or presence of adefovir-resistance. Entecavir should not be used in patients with previous lamivudine-resistance, yet it may still be an option in lamivudine-experienced patients in case lamivudine-resistance never developed. (c) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.