Insulin resistance is associated with chronic hepatitis C virus infection and fibrosis progression [corrected].
OBJECTIVE
Chronic hepatitis C virus infection is associated with an increased prevalence of type 2 diabetes. We hypothesized that virus-induced insulin resistance may be a mechanism for fibrogenesis in chronic hepatitis C virus infection.


METHODS
In 260 hepatitis C virus-infected subjects, we examined the relationship between histological findings and anthropometric and biochemical data, including insulin resistance determined by the homeostasis model assessment (HOMA-IR). We also compared fasting serum insulin, C peptide, and HOMA-IR levels between the subset of 121 hepatitis C virus patients with stage 0 or 1 hepatic fibrosis and 137 healthy volunteers matched by sex, body mass index, and waist-hip ratio.


RESULTS
Hepatitis C virus-infected subjects with stage 0 or 1 hepatic fibrosis had higher levels of insulin, C peptide, and HOMA-IR (all P < or = 0.01) compared with matched healthy controls. In the 250 hepatitis C virus patients (fibrosis stage 0 to 4), viral genotype and portal, but not lobular, inflammation were univariate predictors of HOMA-IR. By multiple linear regression analysis, independent predictors of HOMA-IR included body mass index (P < 0.001), previous failed antiviral treatment (P < 0.001), portal inflammatory grade (P < 0.001), and genotype 3 status (P = 0.01). Genotype 3 had significantly lower HOMA-IR than other genotypes (which were comparable when adjusted for effects of the remaining independent predictors). HOMA-IR was an independent predictor for the degree of fibrosis (P < 0.001) and the rate of fibrosis progression (P = 0.03).


CONCLUSIONS
Hepatitis C virus may induce insulin resistance irrespective of the severity of liver disease, and this effect seems to be genotype specific. Further, our findings support the hypothesis that insulin resistance may contribute to fibrotic progression in chronic hepatitis C virus infection.
Hui
Jason M
JM
Storr Liver Unit, Westmead Millennium Insitute, and Department of Gastroenterology and Hepatology, University of Sydney at Westmead Hospital, New South Wales, Australia.
Sud
Archana
A
Farrell
Geoffrey C
GC
Bandara
Priyanka
P
Byth
Karen
K
Kench
James G
JG
McCaughan
Geoffrey W
GW
George
Jacob
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D018450:Disease Progression; D005234:Fatty Liver / Q000209:etiology; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology*; D008297:Male; D008875:Middle Aged