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+; 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.

• Authors: R Cardin, G Saccoccio, F Masutti, S Bellentani, F Farinati, C Tiribelli
• Journal: Journal of hepatology (J Hepatol) Vol. 34 Issue 4 Pg. 587-92 (Apr 2001) ISSN: 0168-8278 [Print] Netherlands
• PMID: 11394660 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Validation Study)

Chemical References

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

Topics

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