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

J Hepatol. 2001 Apr;34(4):587-92. doi: 10.1016/s0168-8278(00)00098-2.

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+; 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Adolescent
  • Adult
  • Child
  • DNA / metabolism*
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / blood
  • Female
  • Genotype
  • Hepacivirus / genetics
  • Hepatitis C / pathology
  • Hepatitis C / physiopathology*
  • Humans
  • Leukocytes / pathology*
  • Liver / pathology
  • Male
  • Middle Aged
  • Oxidative Stress*
  • Reference Values
  • Severity of Illness Index*

Substances

  • 8-Hydroxy-2'-Deoxyguanosine
  • DNA
  • Deoxyguanosine