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.
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.


OBJECTIVE
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.


CONCLUSIONS
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.
Tachi
Yoshihiko
Y
Department of Gastroenterology, Nagoya University School of Medicine, Nagoya, Aichi, Japan.
Katano
Yoshiaki
Y
Honda
Takashi
T
Hayashi
Kazuhiko
K
Ishigami
Masatoshi
M
Itoh
Akihiro
A
Hirooka
Yoshiki
Y
Nakano
Isao
I
Samejima
Youichi
Y
Goto
Hidemi
H
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D019943:Amino Acid Substitution / Q000187:drug effects; D000998:Antiviral Agents / Q000627:therapeutic use; D001707:Biopsy, Needle; D015331:Cohort Studies; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism; D005234:Fatty Liver / Q000453:epidemiology / Q000235:genetics / Q000473:pathology / Q000821:virology*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008111:Liver Function Tests; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D012367:RNA, Viral / Q000235:genetics; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D014758:Viral Core Proteins / Q000187:drug effects / Q000235:genetics*
D000998:Antiviral Agents; D012367:RNA, Viral; D014758:Viral Core Proteins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine