Role of oxidative stress in the pathogenesis of chronic hepatitis C (CHC)

Rom J Morphol Embryol. 2009;50(3):407-12.

Abstract

Oxidative stress is an important pathophysiological mechanism in chronic hepatitis with C-virus infection (CHC). Steatosis is frequently observed in CHC and seems to have a significant impact on the natural history of the disease with respect to development of fibrosis. The aim of this study was to investigate the relationship between systemic parameters of oxidative stress, insulin resistance, steatosis degree, and fibrosis in CHC. Fifty patients with chronic hepatitis C (29 men and 21 women with the average age 45 years), with or without steatosis, were tested for: oxidative stress and antioxidant status by measuring serum malondialdehyde (MDA), total blood non-proteic thiols concentration (GSH), gamma glutamyl transpeptidase (GGT) activity, lipid parameters, and liver function tests. Our results show that the prevalence of insulin resistance (IR) in chronic hepatitis with C-virus genotype 1 was 32% and the association with hepatic steatosis was in a proportion of 48%, IR is mediated by both metabolic factors as well as viral factors. Hepatic steatosis was associated with an increase of MDA, correlated with its severity, and secondary with a decrease of GSH. The activity of serum GGT was net superior, in patients with steatosis, proportional with its degree.

Conclusions: In patients infected by HCV genotype 1, oxidative stress and insulin resistance contribute to steatosis, which in turn exacerbates both insulin resistance and oxidative stress and accelerates the progression of fibrosis. The induction of GGT is an adaptive response against oxidative damage elicited by lipid peroxidation and it may be critical in the progression of the disease.

MeSH terms

  • Fatty Liver / complications
  • Fatty Liver / pathology
  • Female
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / etiology*
  • Hepatitis C, Chronic / metabolism*
  • Humans
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / pathology
  • Male
  • Middle Aged
  • Oxidative Stress*
  • Regression Analysis