Long-term continuous entecavir therapy in nucleos(t)ide-naive chronic hepatitis B patients

Background & Aims: We determined the antiviral potency and viral resistance rate after 4 years of continuous entecavir treatment in patients with chronic hepatitis B (CHB) infection. Methods: The cumulative rates of undetectable hepatitis B virus DNA (HBV DNA; <2.6 log(10) copies/ml), hepatitis B e antigen (HBeAg) seronegativity, seroconversion, alanine aminotransferase (ALT) normalization, and entecavir signature mutations were calculated in 474 nucleos(t)ide-naive CHB patients (HBeAg-positive: 47%) on continuous entecavir treatment for 4 years. Results: Median age was 47 years and follow-up period was 2.4 years, with 403, 281, 165, and 73 patients followed-up for at least 1, 2, 3, and 4 years, respectively. Incremental increases were observed in the rates of undetectable HBV DNA, HBeAg seroclearance and seroconversion, and ALT normalization, reaching 96%, 42%, 38% and 93%, respectively, by the fourth year. In all, 100% and 93% of patients negative and positive for HBeAg, respectively, had undetectable HBV DNA at year 4. Of 165 patients, HBV DNA was detectable in nine patients after 3 years. Multivariate analysis identified HBV DNA level (<= 7.6 log(10) copies/ml, OR = 15.8; 95% CI = 43.1-79.9, P = 0.001) as an independent predictor of undetectable HBV DNA at year 3. Five patients experienced virological breakthrough including two (0.4%) who developed entecavir-resistance mutations. Conclusions: Continuous treatment of nucleos(t)ide-naive CHB patients with entecavir over 4 years was associated with 96% chance of undetectable HBV DNA and only 0.4% chance of emerging entecavir-resistant mutations. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.