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Background: Oxidative stress contributes to the pathogenesis of chronic hepatitis C. The aim of this study was to assess the peroxidation of n-3 polyunsaturated fatty acids (PUFAs)- in the liver and its relation to hepatic steatosis in chronic hepatitis C. Methods: We immunohistochemically detected malondialdehyde (MDA)- , 4-hydroxy- 2- non-enal (HNE)- , and 4- hydroxy- 2- hexenal (HHE)-pro-tein adducts in liver biopsy specimens from 55 patients with chronic hepatitis C. Cells stained positively for HHE-prot-ein adducts were quantified using computer-based image analysis. Fatty-acid composition was determined, by gas chromatography, for the noncancerous portions of resected livers, with or without steatosis, obtained from two patients with hepatitis C virus-associated hepatocellular carcinoma. Results: The detection rate of HHE-protein adducts (63.6% ) was significantly higher than that of MDA protein adducts (21.8% ; P < 0.001) or HNE-protein adducts (29.1% ; P < 0.001). Areas positively stained for HHE-protein adducts (HHE-positive areas) were significantly larger in 18 patients with steatosis (6.2 ± 3.6% ) than in 17 patients without steatosis (3.4 ± 2.6% ; P = 0.01). Resected liver tissue with steatosis showed a larger HHE-positive area (18.6% ) and higher ratio of n- 6 PUFA content to n- 3 PUFA content (3∶ 1) than liver tissue without steatosis (7.2% ; 2 ∶ 3). On multivariate analysis, the HHE-positive area (odds ratio, 1.55; 95% confidence interval [CI], 1.08- 2.23; P = 0.019) was a factor associated with the presence of hepatic steatosis. Conclusions: HHE-protein adducts, which are a good marker for oxidative stress, are associated with steatosis in chronic hepatitis C.
Background: Oxidative stress contributes to the pathogenesis of chronic hepatitis C. The aim of this study was to assess the peroxidation of n-3 polyunsaturated fatty acids (PUFAs) - in the liver and its relation to hepatic steatosis in chronic hepatitis C. Methods: We immunohistochemically detected malondialdehyde (MDA) -, 4-hydroxy- 2- non-enal (HNE) -, and 4- hydroxy- 2- hexenal (HHE) -pro- tein adducts in liver biopsy specimens from 55 patients with chronic hepatitis C . Fat stained positively for HHE-prot-ein adducts were quantified using computer-based image analysis. Fatty-acid composition was determined, by gas chromatography, for the non-cancer portions of resected livers, with or without steatosis, obtained from two patients with hepatitis The detection rate of HHE-protein adducts (63.6%) was significantly higher than that of MDA protein adducts (21.8%; P <0.001) or HNE-protein adducts (29.1%; P <0.001 Areas positiv ely stained for HHE-protein adducts (HHE-positive areas) were significantly larger in 18 patients with steatosis (6.2 ± 3.6%) than in 17 patients without steatosis (3.4 ± 2.6%; P = 0.01). Resected liver tissue with steatosis showed On a multivariate analysis of the HHE-positive area (18.6%) and higher ratio of n-6 PUFA content to n-3 PUFA content (3: 1) than liver tissue without steatosis -positive area (odds ratio, 1.55; 95% confidence interval [CI], 1.08-2.23; P = 0.019) was a factor associated with the presence of hepatic steatosis. Conclusions: HHE-protein adducts, which are a good marker for oxidative stress, are associated with steatosis in chronic hepatitis C