1. ¹Department of Gastroenterology and Hepatology, Division of Clinical Medicine and Biomedical Science, Institute of Medical Sciences, Mie University Graduate School of Medicine, Mie, Japan
2. ²Department of Anatomy, Mie University Graduate School of Medicine, Mie, Japan
3. ³Faculty of Health Science, Suzuka University of Medical Science, Mie, Japan
4. ⁴Center for Physical and Mental Health, Mie University, Mie, Japan

Correspondence: Dr N Fujita, Department of Gastroenterology and Hepatology, Division of Clinical Medicine and Biomedical Science, Institute of Medical Sciences, Mie University Graduate School of Medicine, 2-174, Edobashi, Tsu, Mie 514-8507, Japan. E-mail: nfujita@clin.medic.mie-u.ac.jp

Received 6 November 2007; Revised 2 January 2008; Accepted 2 January 2008; Published online 29 January 2008.

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 6.73.3 years), HCC was identified in 36 patients (30.5%). Univariate analysis revealed that 16 variables, including 8-OHdG counts (65.220.2 vs 40.023.5 cells per 10⁵ m², 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.