In situ detection of oxidized n-3 polyunsaturated fatty acids in chronic hepatitis C: correlation with hepatic steatosis.
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.
Kitase
Akira
A
Department of Gastroenterology and Hepatology, Yamaguchi University School of Medicine, Ube, Japan.
Hino
Keisuke
K
Furutani
Takakazu
T
Okuda
Michiari
M
Gondo
Toshikazu
T
Hidaka
Isao
I
Hara
Yuichi
Y
Yamaguchi
Yuhki
Y
Okita
Kiwamu
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000447:Aldehydes / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002849:Chromatography, Gas; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008875:Middle Aged; D018384:Oxidative Stress; D012720:Severity of Illness Index; D014280:Triglycerides / Q000378:metabolism*
D000447:Aldehydes; D015415:Biomarkers; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D014280:Triglycerides; C077446:Pikasol; C045934:4-hydroxy-2-hexenal; D008315:Malondialdehyde; C027576:4-hydroxy-2-nonenal