Impact of amino acid substitutions in the hepatitis C virus genotype 1b core region on liver steatosis and hepatic oxidative stress in patients with chronic hepatitis C

Yoshihiko Tachi, Yoshiaki Katano, Takashi Honda, Kazuhiko Hayashi, Masatoshi Ishigami, Akihiro Itoh, Yoshiki Hirooka, Isao Nakano, Youichi Samejima, Hidemi Goto
Liver International: Official Journal of the International Association for the Study of the Liver 2010, 30 (4): 554-9

BACKGROUND: Liver steatosis and hepatic oxidative stress are the histopathological features of chronic hepatitis C. Hepatitis C virus (HCV) genotype 1 core protein induces hepatic steatosis and reactive oxygen species production in transgenic mice. The amino acid substitutions in the HCV core region appear to be related to hepatocarcinogenesis.

AIMS: The aim of this study was to clarify the impact of mutations in the HCV core region on oxidative stress and lipid metabolism in patients with chronic hepatitis C.

METHODS: Sixty-seven patients (35 men, 32 women; mean age, 58.4 +/- 10.2 years) with chronic hepatitis C with high titres (>5 log IU/ml) were enrolled. Substitutions in amino acids 70, 75 and 91 of the HCV genotype 1b core region, the percentage of hepatic steatosis, and hepatic 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were investigated in all patients. Urinary 8-OHdG levels were measured in 35 patients.

RESULTS: Body mass index, alanine aminotransferase, gamma-glutamyl transferase, and triglyceride levels and substitutions of amino acid 70/Q (glutamine) were significantly associated with the presence of steatosis on univariate analysis. Multivariate analysis showed that substitution of amino acid 70 of glutamine and triglyceride levels were the independent factors related to liver steatosis. Hepatic and urinary 8-OHdG levels were significantly higher in patients with methionine at amino acid 91 of the HCV core region than in those with leucine.

CONCLUSION: Substitutions in the amino acids of the HCV genotype1b core region are associated with hepatic steatosis and oxidative stress in patients with chronic hepatitis C.

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