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.