Long-Term Histologic Improvement with Entecavir (ETV) Therapy in Patients with Chronic Hepatitis B (CHB) from Japanese and Worldwide Development Programs

Abstract

Background: ETV 0.5mg improved liver histology in global and Japanese studies in nucleoside-naïve patients with CHB. We present long-term histological results from 2 cohorts of patients who participated in Japanese and global clinical trials. Methods: In Phase II Japanese studies, the long-term histology cohort consisted of nucleoside-naïve patients from study ETV-053 and LVD-refractory patients from study ETV-052, who subsequently entered rollover study ETV-060 and received ETV 0.5mg (nucleoside-naïve) or 1mg (LVD-refractory), had ≧3 years of ETV therapy, and evaluable biopsies at baseline, Weeks 48 and 148. In the global studies, the long-term histology cohort consisted of nucleoside-naïve patients treated with ETV 0.5mg (studies -022, -027), subsequently received ETV 1mg in rollover study ETV-901, had a median of 6 years of therapy (phase III baseline to -901 biopsy), and evaluable baseline and long-term liver biopsies. We evaluated histological improvement [≧2-point decrease in Knodell necroinflammatory (KNI) score, with no worsening of fibrosis and improvement in fibrosis (≥1-point decrease). Results: In the Japanese studies, 37 naïve and 27 LVD-refractory patients had biopsies from three time points. At Week 148: 100% of naïve and 89% of LVD-refractory patients had histological improvement; 47% of naïve and 32% of LVD-refractory patients had improvement in Knodell fibrosis score. Ninety-five percent of naïve and 56% of LVD-refractory patients had HBV DNA <400 copies/mL; 95% of naïve and 93% of LVD-refractory patients normalized ALT. In the global studies, 57 patients had evaluable long term biopsies (median: 6 years; range: 3−7 years). Results for these patients are shown in the table below. Conclusions: Japanese study results demonstrated significant virological suppression and histological improvement in both naïve and LVDrefractory CHB patients treated with ETV for 3 years. A median of 6 years of ETV therapy in the global studies resulted in potent and durable virological suppression and regression of fibrosis/cirrhosis in naïve patients.