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

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 th e increased risk of hepatocellular carcinoma in individuals with chronic HC V infection is related to an accumulation of oxidative DNA damage, the 8-hy droxydeoxyguanosine (8-OHdG) content in the DNA of liver tissue and leukocy tes of 87 individuals with HCV- or HBV-related liver disease and of 10 heal thy controls was measured. Serum levels of thiobarbituric acid reactive sub stances (TBARS) were also assessed as an index of lipid peroxidation. Resul ts: The 8-OHdC content in the circulating leukocytes correlated with that o f 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 highe r than in HBV patients (p <.0004) and they significantly correlated with th e clinical diagnosis (p <.025), the serum ferritin levels (p <.05), and the amount of liver steatosis (p <.001). No correlation was found with age, ge nder, history of drinking or smoking, ALT or GGT levels, ESR, alpha-1, or g amma-globulin level and Ishak score. TEARS levels were significantly higher in cirrhotics than in noncirrhotics (p <.01). Conclusions: The 8-OHdG leve l in circulating leukocytes is a reliable marker of oxidative stress occurr ing in the liver of individuals with chronic HCV infection. DNA oxidative d amage 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 ma y be one of the important factors involved in the carcinogenic process in e ases of HCV-related chronic Liver disease. (C) 1999 Elsevier Science Inc.