Interplay between oxidative stress and hepatic steatosis in the progression of chronic hepatitis C

Background/Aims: The contribution of oxidative stress to the pathogenesis of chronic hepatitis C (CHC) is still poorly elucidated. This study investigated the relationship between oxidative stress, insulin resistance, steatosis and fibrosis in CHC. Methods: IgG against malondialdehyde-albumin adducts and HOMA-IR were measured as markers of oxidative stress and insulin resistance, respectively, in 107 consecutive CHC patients. Results: Oxidative stress was present in 61%, of the patients, irrespective of age, gender, viral load, BMI, aminotransferase level, histology activity index (HAI) and HCV genotype. Insulin resistance and steatosis were evident in 80% and 70% of the patients, respectively. In the patients infected by HCV genotype non-3, but not in those with genotype 3 infection HOMA-IR (p < 0.03), steatosis (p = 0.02) and fibrosis (p < 0.05) were higher in the subjects with oxidative stress than in those without. Multiple regression analysis revealed that, HOMA-IR (p < 0.01), fibrosis (p < 0.01) and oxidative stress (p < 0.05) were independently associated with steatosis, whereas steatosis was independently associated with oxidative stress (p < 0.03) and HOMA-IR (p < 0.02). Steatosis (p < 0.02) and HAI (p = 0.007) were also independent predictors of fibrosis. Conclusions: In patients infected by HCV genotype non-3, oxidative stress and insulin resistance contribute to steatosis, which in turn exacerbates both insulin resistance and oxidative stress and accelerates the progression of fibrosis. (C) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.