Association between chronic hepatitis C (CHC) infection and insulin resistance (IR) is still challenging. The study assessed the impact of using direct acting antivirals (DAAs) on IR and the effect of IR on the treatment response. A total of 101 Egyptian patients with CHC who were eligible to Sofosbuvir based treatment were prospectively involved. All the patients were subjected to baseline liver function test, fasting and post prandial blood glucose, fasting insulin, quantitative HCV PCR and abdominal ultrasound. All the patients received sofosbuvir and daclatasvir with or without ribavirin for 12 weeks. HOMA-IR evaluated IR, both at baseline and at the end of treatment. The results showed that patients' mean age was 48.59±10.56 years; with female dominance (58.4%). An overall sustained response (SVR) was successfully achieved in 96 patients (95.04%). Baseline IR (defined as HOMA-IR >2) was identified in 64 patients (63.4%) with a median value
of 3.07. Patients with positive sustained virologic response (SVR) had lower median values of HOMA-IR than those with negative SVR; both at baseline and the end of treatment (p=0.004, p=0.04; respectively). By the end of treatment, ALT, AST, and FBG showed a significant decrease (p=0.0001). Fasting insulin and HOMA-IR showed a slight improvement (p>0.05).