AIM: To evaluate pegylated interferon alpha2a (PegIFN-α2a) in Egyptian patients with HCV genotype 4, and the impact of pretreatment viral load, co-existent bilharziasis and histological liver changes on response rate.METHODS: A total of 73 na(i)ve patients (61 with history of bilharziasis) with compensated chronic HCV genotype 4 were enrolled into: group A (38 patients) who received 180 mg PegIFN-alpha2a subcutaneously once weekly for a year and group B (35 patients) recved IFN alpha-2a 3 MU 3 times weekly. Ribavirin was added to each regimen at a dose of 1200 mg. Patients were followed for 72 wk and sustained response was assessed.RESULTS: Significant improvement in both end of treatment response (ETR) (P ＜ 0.002) and sustained response (SR) (P ＜ 0.05) was noted with pegylated interferon, where ETR was achieved in 29 (76.3%) and 14 patients (40%) in both groups respectively, and 25 patients in group A (65.8%) and 9 (25.7%) in group B could retain negative viraemia by the end of follow up period. Sustained virological response (SVR) showed a significant negative correlation with age and positive correlation with pretreatment inflammation in patients receiving PegIFN. Viral clearance after 3 mo of therapy was associated with high incidence of ETR and SR (P ＜0.001), but without significant difference between both forms of interferon. Significant improvement in response was achieved in patients with high grade fibrosis (grade 3 and 4) with PegIFN-α2a, where SR was seen in 5 out of 13 patients in group A, but none in group B. There was no significant difference in response between bilharzial and non-bilharzial patients in both groups. In terms of safety and tolerability, neutropenia was the predominant side effect; both drugs were comparable.CONCLUSION: PegIFN-α2a combined with ribavirin results in improvement in sustained response in HCV genotype 4, irrespective of history of bilharzial infestation.