Oxidative DNA damage in circulating leukocytes occurs as an early event in chronic HCV infection.

Abstract: lChronic hepatitis C virus (HCV) infection is associated with an increased production of reactive oxygen species within the liver that are responsible for the oxidation of intracellular macromolecules. To ascertain whether the increased risk of hepatocellular carcinoma in individuals with chronic HCV infection is related to an accumulation of oxidative DNA damage, the 8-hydroxydeoxyguanosine (8-OHdG) content in the DNA of liver tissue and leukocytes of 87 individuals with HCV- or HBV-related liver disease and of 10 healthy controls was measured. Serum levels of thiobarbituric acid reactive substances (TBARS) were also assessed as an index of lipid peroxidation. Results: The 8-OHdC content in the circulating leukocytes correlated with that of liver tissue (r = 0.618, p <.0004). HCV patients had the highest median 8-OHdG levels (p <.0004). 8-OHdG leukocyte levels in HCV patients were higher than in HBV patients (p <.0004) and they significantly correlated with the clinical diagnosis (p <.025), the serum ferritin levels (p <.05), and the amount of liver steatosis (p <.001). No correlation was found with age, gender, history of drinking or smoking, ALT or GGT levels, ESR, alpha-1, or gamma-globulin level and Ishak score. TEARS levels were significantly higher in cirrhotics than in noncirrhotics (p <.01). Conclusions: The 8-OHdG level in circulating leukocytes is a reliable marker of oxidative stress occurring in the liver of individuals with chronic HCV infection. DNA oxidative damage appears to be an early and unique event in the natural history of HCV-related hepatitis. This injury increases the risk of genomic damage and may be one of the important factors involved in the carcinogenic process in eases of HCV-related chronic Liver disease.