Research ArticleLong-term use of entecavir in nucleoside-naïve Japanese patients with chronic hepatitis B infection

Background & AimsTo evaluate the long-term efficacy of entecavir in nucleoside-naïve chronic hepatitis B patients.MethodsOne hundred and sixty-seven patients treated with entecavir 0.01 mg, 0.1 mg or 0.5 mg for 24-52 weeks in Phase II studies entered rollover study ETV-060 and received entecavir 0.5 mg daily. Responses were evaluated among patients with available samples.ResultsAfter 96 weeks in ETV-060 (120-148 weeks total entecavir treatment time), 88% (127/144) of patients had HBV-DNA <400 copies/ml; 90.1% (128/142) had alanine aminotransferase (ALT) ⩽1× the upper limit of normal (ULN) among those with abnormal baseline ALT; and 26% (32/121) achieved HBe seroconversion among those HBeAg(+) at baseline. A subset of 66 patients received entecavir 0.5 mg (approved dose) from Phase II baseline: at week 96 in ETV-060, 83% (48/58) had HBV-DNA <400 copies/ml, 88% (52/59) had ALT ⩽1× ULN, and 20% (10/49) achieved HBe seroconversion. Twenty-one out of 66 patients had paired baseline and on-treatment biopsies: 100% (21/21) and 57% (12/21) demonstrated histologic improvement, and improvement in fibrosis, respectively, over 3 years. The 3-year cumulative probability of resistance was 3.3% for all patients and 1.7% for the 0.5 mg subset.ConclusionsLong-term entecavir for nucleoside-naïve patients resulted in high rates of virological, biochemical, and histological response, with minimal resistance.