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

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. (C) 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.