Combination of Oxidative Stress and Steatosis Is a Risk Factor for Fibrosis in Alcohol-Drinking Patients With Chronic Hepatitis C

Abstract

Alcohol and HCV have been shown to interact in stimulating hepatic oxidative damage. Thus, we investigated the contribution of oxidative mechanisms in the progression of chronic hepatitis C (CHC) in alcohol consumers. An increased IgG reactivity against lipid peroxidation-derived antigens was used as the marker for alcohol-induced oxidative damage in 125 CHC patients. Alcohol intake significantly increased the frequency of the subjects with elevated lipid peroxidation-related IgG. However, no association was evident between oxidative stress markers and the severity of steatosis, necroinflammation, or fibrosis. Multivariate analysis revealed that age (P= 0.014) and hepatic iron content (P= 0.034) were the only independent predictors of fibrosis in these patients. However, the risk of fibrosis in the subjects with both steatosis and oxidative stress-induced immune responses was 6- (OR 6.2, 95% CI 1.2-31.0) and 14-fold (OR 14.6, 95% CI 3.1-68.1) higher than in the subjects with steatosis alone or without steatosis, respectively. Multivariate analysis confirmed that the combination of steatosis and oxidative stress (P= 0.045) was, together with age (P= 0.021) and hepatic iron content (P= 0.027), an independent risk factor for fibrosis in CHC patients with alcohol intake. These results demonstrate that oxidative stress interacts with steatosis to promote the progression of CHC in alcohol-consuming patients.