OBJECTIVE: To investigate the effect of entecavir plus Ganshuang granule(肝爽颗粒,GSG) on advanced fibrosis and cirrhosis in patients with chronic hepatitis B virus infection.METHODS: One hundred thirty-five patients were randomly assigned to one of two cohorts: GSG cohort(n = 69) or placebo cohort(n = 66). The GSG cohort received entecavir plus GSG and the placebo cohort received entecavir plus placebo for 48 weeks. Liver biopsy was performed at baseline and between weeks 44 and 48 during this placebo-controlled trial. We assessed histological improvement(greater than a two-point decrease using the Knodell in fl ammatory score and no worsening of the Ishak fibrosis score) and fibrosis regression(a decrease of at least one point in the Ishak fibrosis score).RESULTS: There were 95.7% of patients(66/69) in the GSG cohort and 66.7%(44/66) of patients in the placebo cohort who showed necroin t. The mean reduction in flth ammation improvemene Knodell necroinflammatory score was 5.1 and 2.6, respectively. There were 89.9%(62/69) of patients in the GSG cohort and 31.8%(21/66) of patients in the placebo cohort who showed at least a one-point improvement in the Ishak fibrosis score. The mean reduction in the Ishak fibrosis score was 1.7 and 0.4,respectively.CONCLUSION: Patients with advanced fibrosis and cirrhosis caused by chronic hepatitis B showed more improvement in liver histology in a shorter time after treatment with entecavir plus GSG compared with entecavir plus placebo.