8-Hydroxy-2'-deoxy-guanosine is a risk factor for development of hepatocellular carcinoma in patients with chronic hepatitis C virus infection.
OBJECTIVE
Increased production of reactive oxygen species, which cause oxidative DNA damage, is considered to be related to hepatocarcinogenesis. 8-Hydroxy-2'-deoxy-guanosine (8-OHdG) is a useful marker of DNA damage induced by oxidative stress. The aim of this study was to determine whether expression of 8-OHdG is a risk factor for the development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) infection.


METHODS
The expression of 8-OHdG in liver biopsy specimens was assessed immunohistochemically. In total, 104 patients with chronic HCV infection who were diagnosed on liver biopsy between January 1987 and December 2002 were studied retrospectively. Univariate and multivariate analyses using age, gender, habitual drinking, tobacco exposure, diabetes mellitus, serum alanine aminotransferase level, HCV genotype, hepatic fibrosis, inflammation, steatosis, and 8-OHdG expression in liver biopsy specimens were conducted to identify factors related to the development of HCC.


RESULTS
On multivariate analysis, 8-OHdG and fibrosis were independent and significant risk factors for HCC development (relative risk, 2.48; P = 0.023; relative risk, 5.35; P = 0.001, respectively). Furthermore, the cumulative incidence rate of HCC in 39 patients with high 8-OHdG expression levels was significantly greater than that in 65 patients with low 8-OHdG expression levels (P = 0.043). In addition, liver 8-OHdG expression was correlated with hepatic inflammation.


CONCLUSIONS
8-OHdG is a risk factor for the development of HCC in patients with chronic HCV infection. Patients with chronic HCV who express 8-OHdG should be monitored carefully for the development of HCC.
Department of Gastroentelology and Hematology, Hokkaido University Hospital, Kitaku, Sapporo, Japan. mchuuma@med.hokudai.ac.jp
Makoto
M
Chuma
Shuhei
S
Hige
Mitsuru
M
Nakanishi
Koji
K
Ogawa
Mitsuteru
M
Natsuizaka
Yoichi
Y
Yamamoto
Masahiro
M
Asaka
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology / Q000821:virology; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015994:Incidence; D008099:Liver / Q000737:chemistry* / Q000473:pathology / Q000821:virology; D008103:Liver Cirrhosis / Q000378:metabolism / Q000821:virology; D008113:Liver Neoplasms / Q000737:chemistry* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine