DNA oxidative damage in leukocytes correlates with the severity of HCV-related liver disease: validation in an open population study.
OBJECTIVE
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.
Cardin
R
R
Dipartimento Scienze Chirurgiche e Gastroenterologie, Sezione di Gastroenterologia, Policlinico Universitario, Padova, Italy.
Saccoccio
G
G
Masutti
F
F
Bellentani
S
S
Farinati
F
F
Tiribelli
C
C
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000293:Adolescent; D000328:Adult; D002648:Child; D004247:DNA / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007962:Leukocytes / Q000473:pathology*; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D012016:Reference Values; D012720:Severity of Illness Index
D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine