Insulin resistance and liver injury in hepatitis C is not associated with virus-specific changes in adipocytokines

Authors

  • Ian Homer Y. Cua,

    1. Storr Liver Unit, Westmead Millennium Institute and Department of Gastroenterology and Hepatology, University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia
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  • Jason M. Hui,

    1. Faculty of Medicine, University of New South Wales, New South Wales, Australia
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  • Priyanka Bandara,

    1. Storr Liver Unit, Westmead Millennium Institute and Department of Gastroenterology and Hepatology, University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia
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  • James G. Kench,

    1. Department of Tissue Pathology, Institute of Clinical Pathology and Medical Research, University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia
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  • Geoffrey C. Farrell,

    1. Gastroenterology and Hepatology Unit and Australian National University Medical School, The Canberra Hospital, ACT, Australia
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  • Geoffrey W. McCaughan,

    1. A.W. Morrow Gastroenterology and Liver Center, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
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  • Jacob George

    Corresponding author
    1. Storr Liver Unit, Westmead Millennium Institute and Department of Gastroenterology and Hepatology, University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia
    • Storr Liver Unit, Westmead Hospital, Westmead, NSW 2145, Australia
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    • fax: (612) 96357582


  • Potential conflict of interest: Nothing to report.

Abstract

The role of tumor necrosis factor α, 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), TNFα (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 TNFα and IL6. Only TNFα levels were correlated with the extent of histological injury (portal/periportal inflammation, P = 0.02). Conclusion: 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 TNFα which correlated with portal/periportal inflammation. HCV-associated IR is most likely an adipocytokine-independent effect of the virus to modulate insulin sensitivity. (HEPATOLOGY 2007;46:66–73.)

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