Work

733 Increased Oxidative Dna Damage in the Livers of Chronic Hepatitis Patients: Comparison of Hepatitis C and B Virus Infections

Year: 2008

Type: article

Abstract: Background and Aims:Recently, there is an increasing evidence that oxidative stress may play a pathogenic role in chronic viral hepatitis, but little is understood about the precise mechanisms of oxidative stress formation during chronic viral infection.Methods: Hepatocytic expression of 8-hydroxydeoxyguanosine (8-OHdG), which is recognized as a promutagenic DNA legion produced by hydroxyl radicals and useful for estimating DNA damage induced by oxidative stress, was immunohistochemically investigated in patients with chronic hepatitis C (CH-C) (n = 77, median age 55.0 years) and chronic hepatitis B (CH-B) (n = 34, 54.0 years) liver biopsy samples.The relations between the damaged DNA amount and epidemiologic, biochemical and histological characteristics were evaluated in CH-C and CH-B patients.Results: 8-OHdG-positive hepatocytes were significantly more abundant in the livers of patients with CH-C compared to CH-B (median 55.0 vs. 18.8 cells/105 um2, P < 0.0001).The number of positive hepatocytes significantly increased with the elevation of serum aminotransferase levels, especially in CH-C patients [8-OHdG vs. alanine aminotransferase (ALT)/aspartate aminotrasferase (AST) were r = 0.738/0.720 in CH-C and 0.506/0.515 in CH-B].Remarkably in CH-C, 8-OHdG expression levels were strongly correlated with body and hepatic iron storage markers (8-OHdG vs. serum ferritin, r = 0.615; vs. hepatic total iron score, r = 0.520; vs. hepatic hepcidin mRNA levels, r = 0.571), although the damaged DNAs were related to serum HBV-DNA titers (r = 0.540) and age of patients (r = -0.559) in CH-B.After iron reduction therapy (phlebotomy plus iron restricted diet), hepatic 8-OHdG levels were significantly reduced from 53.4 to 21.1 cells/105 um2 (P = 0.0125) with concomitant reductions of serum transaminase and iron-related markers in five interferon-resistant CH-C patients.Conclusions: These results indicate that hepatic oxidative DNA damage is common in chronic viral hepatitis, in particular chronic HCV-infected patients, suggesting a possible link between chronic hepatic inflammation and hepatocarcinogenesis. Strong positive correlation between hepatic DNA damage and iron overload suggests that iron contents are most conceivable mediator of hepatic oxidative stress and iron reduction may be beneficial to reduce the incidence of hepatic cancer in patients with chronic HCV infection. 734

Source: Journal of Hepatology

DOI: 10.1016/s0168-8278(08)60735-7