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Insulin Resistance and Liver Injury in Patients with Hepatitis C Are Not Associated with Virus-Specific Changes in Adipocytokines

Adipocytokines are chemical messengers produced by adipose (fat) tissue. They include tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), leptin, and adiponectin.

As reported in the July 2007 issue of Hepatology, Australian researchers tested the hypothesis that these adipocytokines contribute to chronic HCV-associated insulin resistance and liver injury.

The investigators first compared the serum adipocytokine levels and homeostasis model assessment of insulin resistance (HOMA-IR) scores of 154 untreated, non-diabetic, HCV-infected men with stage 0-2 (absent to moderate) liver fibrosis versus those of 75 healthy HCV negative volunteers matched for age, body mass index (BMI), and waist-to-hip ratio.

Next, they examined whether adipocytokine levels were associated with the extent of hepatic steatosis, portal/periportal inflammation, and fibrosis in the total cohort of 240 HCV-infected men.


  • Significantly higher HOMA-IR scores (2.12 vs 1.63) and levels of TNF-alpha (1.28 vs 0.60 pg/mL) and IL-6 (2.42 vs 1.15 pg/mL) were noted in the HCV-infected cohort compared with HCV-uninfected control subjects.
  • However, there were no significant differences in leptin and adiponectin concentrations.
  • By multiple linear regression, independent predictors of a higher HOMA-IR score included BMI and serum leptin (positive correlation) and serum adiponectin (negative correlation), but not TNF-alpha or IL-6.
  • Only TNF-alpha levels were correlated with the extent of histological injury (portal/periportal inflammation).


"Whereas leptin and adiponectin contribute to insulin resistance, none of the adipocytokines accounted for the elevated insulin resistance in HCV-infected subjects," the authors concluded. "The adipocytokines were not associated with histological features of chronic HCV infection except for TNF-alpha which correlated with portal/periportal inflammation."

Based on these results, they suggested, "HCV-associated insulin resistance is most likely an adipocytokine-independent effect of the virus to modulate insulin sensitivity."


IH Cua, JM Hui, P Bandara, and others. Insulin resistance and liver injury in hepatitis C is not associated with virus-specific changes in adipocytokines. Hepatology 46(1): 66-73. July 2007. Hepatology is the official journal of the American Association for the Study of Liver Diseases (AASLD), published by John Wiley & Sons. Hepatology is available online via Wiley InterScience at