Chronic hepatitis C virus (HCV) infection is associated with an increased risk for the development of type 2 diabetes and HCV infection itself may promote insulin resistance, irrespective of the severity of liver disease.~In patients with HCV infection, an increase in fasting insulin levels is associated with the presence of serum HCV core, the severity of hepatic fibrosis and a decrease in expression of insulin receptor substrate (IRS) 1 and IRS2, central molecules of the insulin-signaling cascade. Down-regulation of IRS1 and IRS2 has also been observed in HCV core-transgenic mice livers and HCV core-transfected human hepatoma cells.~High levels of tumor necrosis factor-alpha, which acts by disturbing tyrosine phosphorylation of insulin receptor substrate-1, may be associated with insulin resistance both in animal models and in HCV patients.~Insulin resistance seems to be genotype specific and may play a role in fibrogenesis in chronic hepatitis C.~In patients infected with genotype non-3, insulin resistance is associated with the degree of fibrosis, the rate of fibrosis progression and previous failed antiviral treatment.~Insulin resistance, fibrosis, and genotype are independent predictors of the response to antiviral therapy in chronic hepatitis C patients treated with peginterferon plus ribavirin. A sustained virological response is achieved in 33% of patients with genotype 1 and insulin resistance compared with 60% of genotype 1 patients without insulin resistance.~Insulin resistance is associated with a 3-fold risk of failure to antiviral treatment in patients with genotype 1 In an in vitro model, increased levels of insulin may promote increased HCV replication.~RATIONALE Decreased insulin resistance and reduced hyperinsulinemia may facilitate the efficacy of anti-viral drugs on HCV replication.~INDICATION Genotype 1 Chronic HCV hepatitis (CHC) associated with insulin resistance (IR).~OBJECTIVES To compare the efficacy and safety of Pegylated-Interferon and Ribavirin plus metformin to Pegylated-Interferon and Ribavirin for treatment of naïve patients with Genotype 1 Chronic HCV infection and insulin resistance.
Chronic hepatitis C virus (HCV) infection is associated with an increased risk for the development of type 2 diabetes and HCV infection itself may promote insulin resistance, irrespective of the severity of liver disease.~Insulin resistance seems to be genotype specific and may play a role in fibrogenesis in chronic hepatitis C.~In an in vitro model, increased levels of insulin may promote increased HCV replication.~RATIONALE Decreased insulin resistance and reduced hyperinsulinemia may facilitate the efficacy of anti-viral drugs on HCV replication.