Hepatitis C and Insulin Resistance

Abstract

Chronic infection hepatitis C virus (HCV) infection affects over 200 million people worldwide. Epidemiological data suggest an association between hepatitis C and type 2 diabetes mellitus; the action of the virus C on the glucose metabolism as well as the fibrosing role of the hyperinsulinism have been studied in the last years. The increased prevalence of the type-2 diabetes in hepatitis C virus infection is not exclusively reported for cirrhotic patients. The HCV infection may promote insulin resistance (IR) due to an increased production of Tumor Necrosis Factor alpha (TNF-α), which causes over-expression of the SOCS-3 (suppressor of cytokines substrate) leading to a blockage of the transactivation of GLUT 4 transporter, thus avoiding the glucose subtraction by the cell. The TNF-α was over-expressed in hepatitis due to C virus associated to a more severe fibrosis and the non-response to treatment. Insulin resistance may be also induced by HCV core protein, leading to an increase on the TNF-α. High levels of insulin may directly stimulate the Ito cells mitogenesis and cause an over-regulation of the Connective Growth Factor. It was demonstrated that overweight, hepatic steatosis and IR influence the response to anti-viral treatment with Interferon and Ribavirin, being responsible for the therapeutic failure.