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Antiviral therapy for HCV infection has been validated in randomized controlled clinical trials, but its value in the real world is less well studied. There is relatively little data on real-world responses to interferon-based therapies for patients with genotype 4 infection. We aimed to examine experience with large-scale access to antiviral therapy in chronic HCV in a real-life clinical setting in Egypt. Detailed pretreatment data of 6198 IFN-naïve chronic HCV patients who had received PEG-IFN/RBV therapy at Cairo-Fatemic Hospital, Egypt, between 2009 and 2012 were obtained from the HCV database. At week 12, 95.7% of patients had undetectable HCV RNA, and by week 24 and 48, breakthrough was 6% and 4%, respectively. However, 43.7% of patients discontinued treatment prematurely, and intent to treat end of treatment response was 44.6% (79.3% per protocol). Sustai-ned response data were available from only 1281 patients and was 84.9%. Haematological abnormalities were comparable in patients who did or did not comply with therapy. This is the first real-world, large-scale experience of antiviral therapy in chronic HCV in Egypt. Suboptimal response in HCV predominantly genotype 4 was mainly driven by noncompliance as well as gaps in the healthcare system leading to treatment discontinuation. These results need to be considered in the era of all oral antiviral regimes.