Time course of insulin resistance during antiviral therapy in non-diabetic, non-cirrhotic patients with genotype 1 HCV infection

Background and aims: Genotype 1 (G1) HCV is associated with insulin resistance (IR) and its clearance after antiviral therapy seems to improve insulin sensitivity. We aimed to evaluate the time-course of IR in response to antiviral therapy in non-diabetic non-cirrhotic G1 HCV patients, and to assess the impact of metabolic factors on sustained virological response (SVR). Methods: 83 consecutive naïve CHC patients with G1 HCV infection were evaluated by anthropometric and metabolic measurements, including IR, by the homeostasis model assessment (HOMA). All cases had a liver biopsy scored by a single pathologist for staging, grading and steatosis. Anthropometric parameters and HOMA were re-evaluated at the end of antiviral therapy and at follow-up. Results: SVR was achieved in 46 patients (55.4%), and, by multivariate analysis, was independently associated with male sex (OR 0.160; 95%CI 0.044-0.589), LDL cholesterol (OR 1.030; 95%CI 1.011-1.055), γ-glutamyltransferase (OR 0.980; 95%CI 0.961-1.005), and steatosis (OR 0.940; 95%CI 0.891-0.993). HOMA values significantly decreased during antiviral therapy and at follow-up, not only in patients achieving SVR (p=0.0008), but also in relapsers (p=0.04) and marginally in non-responders (p=0.08). Conclusions: In non-diabetic non-cirrhotic G1 HCV patients undergoing antiviral therapy, insulin sensitivity improves in all patients, independently of virological outcome. HCV viral clearance is only an additional factor in the improvement of insulin sensitivity. Metabolic factors and female sex are the main determinants of the low likelihood of response to antiviral therapy