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

BACKGROUND: Genotype 1 (G1) hepatitis C virus (HCV) is associated with insulin resistance (IR) and its clearance 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 effect of metabolic factors on sustained virological response (SVR). METHODS: A total of 83 consecutive treatment-naive G1 chronic hepatitis C (CHC) patients were evaluated by anthropometric and metabolic measurements, including IR using the homeostasis model assessment (HOMA). Patients were considered to have IR if HOMA was >2.7. All cases had a liver biopsy scored 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 (55.4%) patients. By logistic regression, female gender (odds ratio [OR] 0.132, 95% confidence interval [CI] 0.33-0.529), gamma-glutamyltransferase >50 IU (OR 0.217, 95% CI 0.066-0.720) and presence of steatosis (OR 0.134, 95% CI 0.028-0.654) were independent negative predictors of SVR, whereas low-density lipoprotein cholesterol >107 IU (OR 6.671, 95% CI 1.164-11.577) was a positive predictor of SVR. The proportion of patients with IR significantly decreased (P=0.02) during antiviral therapy and at follow-up in patients achieving SVR. A similar trend, even if not significant, was observed in relapsers and non-responders. CONCLUSIONS: In non-diabetic G1 HCV patients undergoing antiviral therapy, IR improved in all patients, independently of virological outcome. HCV viral clearance was an additional factor in IR improvement. Female gender, hepatic steatosis and other metabolic parameters, but not IR, were identified as negative predictors of SVR in this study