title: Hepatic oxidative DNA damage is associated with increased risk for hepatocellular carcinoma in chronic hepatitis C.
abstract: Although the oxidative stress frequently occurs in patients with chronic hepatitis C, its role in future hepatocellular carcinoma (HCC) development is unknown. Hepatic 8-hydroxydeoxyguanosine (8-OHdG) was quantified using liver biopsy samples from 118 naïve patients who underwent liver biopsy from 1995 to 2001. The predictability of 8-OHdG for future HCC development and its relations to epidemiologic, biochemical and histological baseline characteristics were evaluated. During the follow-up period (mean was 6.7+/-3.3 years), HCC was identified in 36 patients (30.5%). Univariate analysis revealed that 16 variables, including 8-OHdG counts (65.2+/-20.2 vs 40.0+/-23.5 cells per 10(5) microm2, P<0.0001), were significantly different between patients with and without HCC. Cox proportional hazard analysis showed that the hepatic 8-OHdG (P=0.0058) and fibrosis (P=0.0181) were independent predicting factors of HCC. Remarkably, 8-OHdG levels were positively correlated with body and hepatic iron storage markers (vs ferritin, P<0.0001 vs hepatic iron score, P<0.0001). This study showed that oxidative DNA damage is associated with increased risk for HCC and hepatic 8-OHdG levels are useful as markers to identify the extreme high-risk subgroup. The strong correlation between hepatic DNA damage and iron overload suggests that the iron content may be a strong mediator of oxidative stress and iron reduction may reduce HCC incidence in patients with chronic hepatitis C.
authors.affiliation: Department of Gastroenterology and Hepatology, Division of Clinical Medicine and Biomedical Science, Institute of Medical Sciences, Mie University Graduate School of Medicine, Mie, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: N
authors.initials: N
authors.lastname: Fujita
authors.forename: R
authors.initials: R
authors.lastname: Sugimoto
authors.forename: N
authors.initials: N
authors.lastname: Urawa
authors.forename: S
authors.initials: S
authors.lastname: Horiike
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: M
authors.initials: M
authors.lastname: Iwasa
authors.forename: N
authors.initials: N
authors.lastname: Ma
authors.forename: S
authors.initials: S
authors.lastname: Kawanishi
authors.forename: S
authors.initials: S
authors.lastname: Watanabe
authors.forename: M
authors.initials: M
authors.lastname: Kaito
authors.forename: Y
authors.initials: Y
authors.lastname: Takei
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine