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In situ detection of oxidized n-3 polyunsaturated fatty acids in chronic hepatitis C: correlation with hepatic steatosis

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Abstract

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-nonenal (HNE)-, and 4-hydroxy-2-hexenal (HHE)-protein adducts in liver biopsy specimens from 55 patients with chronic hepatitis C. Cells stained positively for HHE-protein 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.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Yamaguchi University School of Medicine, Ube, Japan

    Akira Kitase, Takakazu Furutani, Michiari Okuda, Isao Hidaka, Yuichi Hara, Yuhki Yamaguchi & Kiwamu Okita

  2. Department of Laboratory Sciences, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, 755-8505, Japan

    Keisuke Hino

  3. Department of Surgical Pathology, Yamaguchi University Hospital, Ube, Japan

    Toshikazu Gondo

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  1. Akira Kitase
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  2. Keisuke Hino
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Kitase, A., Hino, K., Furutani, T. et al. In situ detection of oxidized n-3 polyunsaturated fatty acids in chronic hepatitis C: correlation with hepatic steatosis. J Gastroenterol 40, 617–624 (2005). https://doi.org/10.1007/s00535-005-1596-x

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  • DOI: https://doi.org/10.1007/s00535-005-1596-x

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