Long-term entecavir therapy results in reversal of fibrosis/cirrhosis and continued histologic improvement in patients with HBeAg(+) and (-) chronic hepatitis B: results from studies ETV-022, -027 and -901

Abstract

Background: Entecavir (ETV) 0.5 mg resulted in improved liverhistology and was superior to lamivudine at 1 year in studiesETV-022 and ETV-027 (HBeAg(+) and (-) nucleoside-naïvepatients, respectively).1,2We present long term histologic resultsfor a subset of patients treated with ETV for a median of 6years. Methods: The long-term histology cohort consists of ETV-treated patients who completed study -022 or -027, subse-quently received ETV 1 mg daily in ETV-901, had an evaluablebiopsy at baseline (-022, -027) and had ≥3 years of cumulative ETV therapy (from phase III baseline to -901). Co-primary his-tology endpoints were proportions with histologic improvement(≥2-point decrease in Knodell necroinflammatory score and noworsening of Knodell fibrosis score) and improvement in Ishakfibrosis score (≥1 point decrease) compared to baseline. Keysecondary endpoints included proportions with HBV DNA <300 copies/mL, ALT normalization, and baseline HAI score ≥4that achieved a score of ≤3. Results: Sixty-three patients (47HBeAg(+);16 HBeAg(-)) met eligibility criteria for the long-termhistology cohort. Baseline characteristics of the cohort includedmean HBV DNA 9.2 log10copies/mL; mean Knodell necroin-flammatory score 7.9; and mean Ishak fibrosis score 2.4. Fifty-seven patients had evaluable long-term biopsy samples (mediantime of biopsy was 6 years; range:3−7 years). Among the fivepatients with baseline cirrhosis (Ishak fibrosis score ≥5), fourhad evaluable long term biopsies. All four demonstrated a ≥1-point improvement in Ishak fibrosis score with a median changefrom baseline of –3 (range: -1 to -4). Conclusions: Long-termtreatment with entecavir in a cohort of nucleoside-naïve chronichepatitis B patients treated for a median of 6 years resulted inprofound and durable virologic suppression, histologicimprovement, and normalization of liver histology, with regres-sion of fibrosis/cirrhosis. 1Chang TT, et al. N Engl J Med2006;354:1001-1010.2Lai CL, et al. N Engl J Med2006;354:1011-1020.