Hepatitis C virus-associated insulin resistance: pathogenic mechanisms and clinical implications

It is now widely recognized that chronic hepatitis C is a metabolic disease, strongly associated with Type 2 diabetic mellitus and insulin resistance (IR). Chronic hepatitis C virus (HCV) infection promotes IR mainly through interfering with the insulin signaling pathway in hepatocytes, increasing the inflammatory response with production of cytokines such as TNF-alpha and IL-6, and increasing oxidative stress. Accumulated evidence indicates that HCV-associated IR may lead to fibrosis progression, resistance to antiviral therapy, hepatocarcinogenesis and extrahepatic manifestations. Thus, HCV-associated IR is a therapeutic target at any stage of HCV infection. However, specific pharmaceutical treatments of IR are still being evaluated in clinical trials, but available data do not warrant their use in all chronic hepatitis C patients with IR.