Long-term use of entecavir in nucleoside-naive Japanese patients with chronic hepatitis B infection

Background & Aims: To evaluate the long-term efficacy of entecavir in nucleoside-naive chronic hepatitis B patients. Methods: One 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. Results: After 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) <= 1x the upper limit of normal (ULN) among those with abnormal baseline ALT; and 26%(32/121) achieved HBe sero-conversion 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 <= 1x 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. Conclusions: Long-term entecavir for nucleoside-naive patients resulted in high rates of virological, biochemical, and histological response, with minimal resistance. (c) 2010 Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.