Clinical Implication of Insulin Resistance in Chronic Hepatitis C Patients

Chronic hepatitis C virus (HCV) infection is the leading cause for the development of liver cirrhosis and hepatocellular carcinoma, however, it also causes metabolic disorders. Insulin resistance is representative of these metabolic disorders, and not only leads to the development of diabetes but also affects the outcome of antiviral treatment with interferon. Historically, the standard of care for chronic HCV infection was pegylated interferon and ribavirin, but only 40-50% of HCV genotype 1 patients achieve a sustained virological response (SVR). We successfully established a pretreatment prediction model for the treatment outcome using a homeostasis model assessment of insulin resistance (HOMA-IR) and the interleukin 28B genotype (rs 8099917). In recent years, antiviral agents targeting viral proteins critical for HCV replication have become available. Of these, telaprevir, an HCV NS3/4A serine protease inhibitor, has been available in Japan since 2011. As a result, about 80% of patients with HCV genotype 1 can achieve SVR. Nonetheless, insulin resistance is associated with treatment failure, especially for difficult-to-treat patients. In the near future, almost all patients with chronic HCV infection will achieve virological clearance with combined direct antiviral agents, however, insulin resistance will remain a risk for hepatocellular carcinoma. Therefore, the prevention of obesity and avoidance of excessive alcohol intake are very important after achieving SVR.