Incidence and risk factors for non-alcoholic steatohepatitis: Prospective study of 5408 women enrolled in Italian tamoxifen chemoprevention trial

Objective: To assess the incidence, cofactors, and excess risk of development of non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis, attributable to tamoxifen in women. Design: Prospective, randomised, double blind, placebo controlled trial. Setting and participants: 5408 healthy women who had had hysterectomies recruited into the Italian tamoxifen chemoprevention trial from 58 centres in Italy. Intervention: Women were randomly assigned to receive tamoxifen (20 mg daily) or placebo for five years. Main outcome measure: Development of non-alcoholic fatty liver disease in all women with normal baseline liver function who showed at least two elevations of alanine aminotransferase (≥ 1.5 times upper limit of normal) over a six month period. Results: During follow up, 64 women met the predefined criteria: 12 tested positive for hepatitis C virus, and the remaining 52 were suspected of having developed non-alcoholic fatty liver disease (34 tamoxifen, 18 placebo) - hazard ratio = 2.0 (95% confidence interval 1.1 to 3.5; P=0.04). In all 52 women ultrasonography confirmed the presence of fatty liver. Other factors associated with the development of non-alcoholic fatty liver disease.