alexa TNF-{alpha}, chronic hepatitis C and diabetes: a novel triad.


Journal of Clinical & Cellular Immunology

Author(s): Knobler H, Schattner A

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Abstract Patients with chronic hepatitis C virus (HCV) infection have a significantly increased prevalence of type 2 DM compared to controls or HBV-infected patients, independent of the presence of cirrhosis. Moreover, antecedent HCV infection markedly increases the risk of developing DM in susceptible subjects. Even non-diabetic HCV patients have insulin resistance and specific defects in the insulin-signalling pathway. Activation of the tumour necrosis factor (TNF)-alpha system has a pivotal role in the inflammatory process of chronic hepatitis C, and TNF-alpha levels correlate with the degree of inflammation. TNF-alpha is known to cause insulin resistance, with similar defects in the insulin signalling pathway to those described in HCV infection. A model of mice transgenic for the HCV core protein demonstrated insulin resistance, glucose intolerance, and elevated intrahepatic TNF-alpha mRNA; all of which were ameliorated by anti-TNF-alpha antibodies. In addition, diabetic HCV patients have significantly higher levels of soluble TNF-alpha receptors, compared to non-diabetic HCV patients and controls. TNF-alpha may be the link between HCV infection and diabetes, suggesting an additional mechanism of diabetes with important implications for prognosis and therapy. This article was published in QJM and referenced in Journal of Clinical & Cellular Immunology

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