BACKGROUND: Hepatitis C virus (HCV) infection may induce insulin resistance (IR) irrespective of the severity of liver disease, and there is evidence of a central role for IR in failure to achieve sustained virological response (SVR) in HCV patients.OBJECTIVE: To assess IR as a predictor of the severity of hepatic fibrosis in Egyptian HCV patients, and its effect on early viral kinetics and virological response to HCV therapy.METHODS: A total of 140 chronic HCV patients were divided into two groups according to the homeostasis model assessment-IR (HOMA-IR). Group 1 consisted of 48 chronic HCV patients with HOMA-IR ≥2, and group 2 consisted of 92 chronic HVC patients without IR (HOMA IR <2). All patients were treated with combination therapy (pegylated interferon-alpha 2a plus ribavirin) for 48 weeks and studied for viral kinetics throughout the period of therapy.RESULTS: The study revealed that older age, higher body mass index and HOMA-IR≥2 were significantly associated with advanced fibrosis. Rapid virological response, complete early virological response and SVR were significantly lower in the IR-HCV group compared with the non-IR-HCV group. Univariate and multivariate analyses revealed that older age, fibrosis (F≥3), high viral load (>600,000 IU/mL) and HOMA-IR ≥2 were significantly associated with a lack of viral kinetics as well as SVR. However, HOMA-IR ≥2 was the main independent variable associated with lack of SVR. On the other hand, body mass index, plasma insulin level and HOMA-IR decreased significantly compared with starting levels in patients who achieved SVR. This suggests a cause and effect relationship between HCV infection and IR.CONCLUSION: IR in chronic HCV patients is associated with progressive fibrosis and slow viral kinetics, and could be a predictor for lack of rapid and early virological response. Therefore, HOMA-IR levels should be measured and improved before starting antiviral treatment.