Impact of amino acid substitutions in hepatitis C virus genotype 1b core region on liver steatosis and glucose tolerance in non-cirrhotic patients without overt diabetes.
OBJECTIVE
The hepatitis C virus (HCV) core protein induces hepatic steatosis and glucose intolerance in transgenic mice. The aim of this study was to clarify the impact of mutations in the HCV core region on hepatic steatosis and glucose tolerance in patients with chronic hepatitis C.


METHODS
Seventy-four Japanese patients (27 men, 47 women; mean age, 61.9 years) infected with HCV 1b with high viral load (>5 log IU/ml), without cirrhosis and overt diabetes, were enrolled. Substitutions in amino acids 70 and 91 of the HCV genotype 1b core region, the percentage of hepatic steatosis by liver histology, and glucose tolerance evaluated by the oral glucose tolerance test were investigated in all patients.


RESULTS
Steatosis was observed in 40 patients (54%). Transaminase activities, γ-glutamyl-transpeptidase, serum ferritin levels, homeostasis model assessment of insulin resistance index, and substitutions of amino acid 70 were significantly associated with the presence of steatosis, upon univariate analysis. Glucose intolerance was more prevalent in patients with steatosis (63%) than in those without steatosis (32%, P = 0.012). Multivariate analysis showed that substitution of amino acid 70 (odds ratio: 4.924; 95% confidence interval: 1.442-16.815; P = 0.014) and glucose intolerance (odds ratio: 3.369; 95% confidence interval: 1.076-10.544; P = 0.040) were independent factors related to liver steatosis. Levels of plasma glucose and serum insulin after glucose load were similar between patients with and without substitutions of amino acids 70 and 91.


CONCLUSIONS
Amino acid substitutions in the HCV genotype 1b core region are associated with hepatic steatosis in patients with chronic hepatitis C, independent of glucose intolerance.
Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan. sumida@nara-jadecom.jp
Yoshio
Y
Sumida
Kazuyuki
K
Kanemasa
Tasuku
T
Hara
Yutaka
Y
Inada
Kyoko
K
Sakai
Shunsuke
S
Imai
Naohisa
N
Yoshida
Kohichiroh
K
Yasui
Yoshito
Y
Itoh
Takeshi
T
Okanoue
Toshikazu
T
Yoshikawa
D000368:Aged; D019943:Amino Acid Substitution; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D001786:Blood Glucose / Q000032:analysis; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D005234:Fatty Liver / Q000175:diagnosis / Q000821:virology*; D005260:Female; D005838:Genotype; D018149:Glucose Intolerance / Q000175:diagnosis / Q000821:virology*; D005951:Glucose Tolerance Test; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000175:diagnosis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007564:Japan; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase
D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase