Hepatitis C and insulin resistance: Mutual interactions. A review

Worldwide approximately 200 million people are chronically infected with hepatitis C virus (HCV). Chronic HCV infection represents the leading cause of liver cirrhosis and the main iundication for liver transplantation in thte western world. In addition, chronic HCV infection is associated with numerous clinical manifestations, including type 2 diabetes. An obvious and frequently suggested explanation for the connection between HCV infection and type 2 diabetes is that cirrhosis by itself causes insulin resistence. However, the prevalance of type 2 diabetes in HCV cirrhosis is higher than in HBV cirrhosis (23.6% vs. 9.4%). This suggests that HCV infection by itself can lead to insulin resistence and predispose to the onset of type 2 diabetes. First, HCV core protein induces hepatic steatosis by inhibition of microsamal triglyceride transfer protein and hepatic steatosis causes insulin resistance. Secondly, HCV core protein inhibits, through elevation of TNF-alfa and other factors, the insulin-signalling pathways causing insulin resistence. Moreover, recent data strongly suggest that insulin resistence is an important predictor of poor response to antiviral therapy in chronic hepatitis C patients treated with peginterferon plus ribavirin.