Background Hepatitis C virus (HCV) infection is a global health care problem, with more than 170 million people infected worldwide. With the discovery of new direct-acting antiviral drugs, a new hope to get HCV cure has arisen. This work was designed to compare the efficacy between the use of sofosbuvir (SOF)/daclatasvir (DCV) and SOF/ledipasvir (LDV) in treatment of HCV. Patients and methods A total of 430 patients were enrolled into two groups: SOF/DCV group included 340 patients and SOF/LDV group included 90 patients. Each patient received treatment for 12–24 weeks. All patients were checked at each visit (at weeks 4, 8, 12, and 24) for the potential adverse events by a check-list questions, examinations, and laboratory tests. Check-list questions include headache, gastric upset, skin rash, and sleep disturbance. Results A total of 419 (97.4%) patients achieved sustained virologic response (SVR), and only 11 (2.5%) patients failed to achieve SVR. In SOF–DCV, 97.4%, and in SOF–LDV, 97.8% achieved SVR. Minor adverse events were mainly headache, sleep distribution, gastrointestinal tract disturbance, and skin rash, which were observed in 13.8% of patients in SOF–DCV group 20% in SOF–LDV group. Conclusion The use of the two regimens SOF/DCV and SOF/LDV yielded high success ratio for viral eradication with minimal tolerable adverse effects. These regimens of therapy have a great margin of safety with high efficacy.
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