Even though Sofosbuvir (SOF) has revolutionized the treatment of chronicHCV infection, treatment with pegylated interferon in combination with Ribavirin isconsidered the standard of care for treatment in many countries. Aim: This study aimedto monitor the efficacy and safety of SOF/RBV with or without Peg-INF-α-2a, inEgyptian patients with chronic HCV genotype 4. Subjects: 165 patients infected withHCV-GT4 were enrolled in this prospective study. Eligible patients received therecommended doses of SOF/RBV for 24 weeks (Dual treatment) or SOF/RBV/Peg-IFN-α-2a for 12 weeks (Triple treatment). All patients were followed up for 24 weeks afterthe end of therapy. Results: The highest SVR24 rates were attained with the Triple groupcorresponding to the Dual group. Patients who failed to treatment, had higher baselinePDGF in both groups, TNF-α in the Dual group, and lower TSH in the Triple group.Adverse effects included a decrease in hemoglobin and WBCs with an increase increatinine, ferritin and TSH. The favorable effects included normalization of liverindices, correction of hypolipidemia, together with a decrease in TNF-α. Moreover, thecurrent study showed the overall frequency of IL28B genotypes was 100% for genotypeCT. Results: Results of SOF-based therapies achieved better SVR24 rates with theaddition of Peg-INF-α-2a.