DNA oxidative damage in leukocytes correlates with the severity of HCV-related liver disease: validation in an open population study

Abstract: Background/Aims: Oxidative DNA damage, identifiable in the formation of 8-hydroxydeoxyguanosine (8-OHdG), is relevant in the mutagenesis/carcinogenesis process. The aim of this study was to assess 8-OHdG levels in patients with hepatitis C virus (HCV) infection in relation to extent of liver damage and HCV genotype. Methods: 8-OHdG levels were measured in DNA from circulating leukocytes of 110 anti-HCV positive subjects belonging to the population of the Dionysos study, subgrouped in: 50 anti-HCV+ with persistently normal ALT, 48 with chronic hepatitis and 12 with cirrhosis, Twenty normal subjects served as Controls. 8-OHdG levels were assayed by HPLC/electrochemical detector. Results: 8-OHdG levels rose (P < 0.00001) from Controls to HCV C; chronic hepatitis and cirrhosis were associated with a further increase (P < 0.02 versus HCV+). Genotype 1 was associated with higher levels of 8-OHdG (P < 0.04). Multiple logistic regression analysis showed that, after correction for potential confoundings, 8-OHdG levels correlated (P < 0.02) with presence and extent of liver damage. Conclusions: An accumulation of 8-OHdG in circulating leukocytes is a reliable marker of the extent of liver damage in HCV + patients and is present in particular in genotype 1 infection. This genomic damage may contribute to liver carcinogenesis by causing persistent DNA changes.