title: Insulin resistance and liver injury in hepatitis C is not associated with virus-specific changes in adipocytokines.
abstract: The role of tumor necrosis factor alpha, interleukin 6, leptin, and adiponectin in the pathogenesis of hepatitis C virus (HCV)-associated insulin resistance (IR) remains controversial. We tested the hypothesis that these adipocytokines contribute to chronic HCV-associated IR and liver injury by first comparing their serum levels and homeostasis model assessment of insulin resistance (HOMA-IR) in 154 untreated, non-diabetic, HCV-infected male subjects with fibrosis stage 0-2, to that in 75 healthy volunteers matched for age, body mass index (BMI), and waist-hip ratio (WHR). We next examined whether the adipocytokine levels were associated with the extent of hepatic steatosis, portal/periportal inflammation and fibrosis in our total cohort of 240 HCV-infected male subjects. Significantly higher levels of HOMA-IR (2.12 versus 1.63, P = 0.01), TNFalpha (1.28 versus 0.60 pg/ml, P < 0.001) and IL6 (2.42 versus 1.15 pg/ml, P = 0.001) were noted in the HCV cohort compared with healthy controls respectively, but there were no significant differences in leptin and adiponectin concentrations. By multiple linear regression, independent predictors of HOMA-IR included the body mass index, and the serum levels of leptin (positive correlation) and adiponectin (negative correlation), but not that of TNFalpha and IL6. Only TNFalpha levels were correlated with the extent of histological injury (portal/periportal inflammation, P = 0.02).
  
  
  CONCLUSIONS
  Whereas leptin and adiponectin contribute to IR, none of the adipocytokines accounted for the elevated IR in HCV-infected subjects. The adipocytokines were not associated with histological features of chronic HCV infection except for TNFalpha which correlated with portal/periportal inflammation. HCV-associated IR is most likely an adipocytokine-independent effect of the virus to modulate insulin sensitivity.
authors.affiliation: Storr Liver Unit, Westmead Millennium Institute and Department of Gastroenterology and Hepatology, University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia.
authors.forename: Ian Homer Y
authors.initials: IH
authors.lastname: Cua
authors.forename: Jason M
authors.initials: JM
authors.lastname: Hui
authors.forename: Priyanka
authors.initials: P
authors.lastname: Bandara
authors.forename: James G
authors.initials: JG
authors.lastname: Kench
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Farrell
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: McCaughan
authors.forename: Jacob
authors.initials: J
authors.lastname: George
mesh_terms: D052242:Adiponectin / Q000502:physiology*; D000328:Adult; D001706:Biopsy; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000502:physiology*; D020738:Leptin / Q000502:physiology*; D008099:Liver / Q000473:pathology* / Q000821:virology; D008103:Liver Cirrhosis / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D019562:Viral Load
chemical_list: D052242:Adiponectin; D015850:Interleukin-6; D020738:Leptin; D014409:Tumor Necrosis Factor-alpha