In vitro experiments have demonstrated not only that entecavir has stronger antiviral activity than lamivudine or adefovir against HBV wild strains, but it is also effective against lamivudine-resistant strains.[179] Entecavir has had health insurance approval in Japan since 2006, for administration of 0.5 mg per day in treatment-naïve cases. In Europe studies of entecavir therapy in patients naïve to NAs, in both HBeAg positive cases and negative patients, HBV DNA negative conversion rates and ALT normalization rates were higher for entecavir than for lamivudine.[14, 25, 180] The greatest characteristic

of entecavir is that it has a lower incidence of viral resistance than lamivudine. For this reason entecavir is currently the treatment of first choice when using NAs. Resistance to entecavir is exhibited by CHIR99021 amino acid mutation of either rtT184, rtS202 or rtM250, in addition to the lamivudine resistant amino acid mutations at rtM204V and rtL180M.[181] In the abovementioned study, increased Selleck AZD2014 HBV DNA levels were seen in 22 out of 679 patients until the 96th week of therapy. Only 1 case of entecavir-resistant HBV was confirmed at 1 year, and 1 more case at 96 weeks, in one of which lamivudine-resistant HBV had already been detected at the commencement of entecavir therapy.[180]

Long term results have been reported for entecavir administration for 5 years.[16, 182] The HBV DNA negative conversion rate was 55–81% at 1 year, 83% at 2 years, 89% at 3 years, 91% at 4 years and

94% at 5 years, and the ALT normalization rate was 65% at 1 year, 78% at 2 years, 77% at 3 years, 86% at 4 years and 80% at 5 years, while the incidence of resistant HBV was 0.2% at 1 year, 0.5% at 2 years, and 1.2% at 3–5 years. However, in these studies, entecavir 0.5 mg daily was not continuously administered Nutlin-3 in all cases. On the other hand, in a report from Hong Kong of continuous entecavir therapy for 3 years, the HBV DNA negative conversion rate was 81% at 1 year, 90% at 2 years and 92% at 3 years; the ALT normalization rate was 84% at 1 year, 88% at 2 years and 90% at 3 years; and the HBeAg seroconversion rate was 22% at 1 year, 41% at 2 years and 44% at 3 years.[19] From of these cases, 1 case of resistant HBV was confirmed at 3 years. In results from Japan concerning NAs naïve cases,[15, 18, 183] the HBV DNA negative conversion rate was 77–88% at year 1, 83–93% at year 2, 95% at year 3, and 96% at year 4. The ALT normalization rate was 83–87% at year 1, 88–89% at year 2, 92% at year 3, and 93% at year 4. The HBeAg seroconversion rate was 12–20% at year 1, 18–20% at year 2, 29% at year 3, and 38% at year 4. Histological evaluation also confirmed improvement in the Knodell necroinflammatory score and fibrosis score at 1 year and 3 years.[18] The incidence of entecavir-resistant HBV was 3.3% at 3 years.