INCREASED HEPATIC IRON CONCENTRATION IN NONALCOHOLIC STEATOHEPATITIS IS ASSOCIATED WITH INCREASED FIBROSIS

Background & Aims: Nonalcoholic steatohepatitis (NASH) is a chronic li ver disease that occasionally progresses to cirrhosis but usually has a benign course. The aim of this study was to investigate the role of the hemochromatosis mutation Cys282Tyr in development of the mild hepa tic iron overload found in some patients with NASH and its association with hepatic damage in these patients. Methods: Fifty-one patients wi th NASH were studied. The presence of the Cys282Tyr mutation was teste d in all patients, and the data were analyzed with respect to the hist ological grade of steatosis, inflammation, Perls' staining, hepatic ir on concentration (HIC), and serum iron indices. Results: Thirty-one pe rcent of patients with NASH were either homozygous or heterozygous for the Cys282Tyr mutation. This mutation was significantly associated wi th Perls' stain grade (P < 0.005), HIC (P < 0.005), and transferrin sa turation percentage (P < 0.005) but not with serum ferritin levels. Li near regression analysis showed that increased hepatic iron (Perls' st ain or HIC) had the greatest association with the severity of fibrosis (P < 0.0001). Conclusions: The Cys282Tyr mutation is responsible for most of the mild iron overload found in NASH and thus has a significan t association with hepatic damage in these patients. Heterozygosity fo r the hemochromatosis gene mutation therefore cannot always be conside red benign.