Background: hepatitis C virus (HCV) infection in one of worldwide chief causes chronic liver illness. The extended effect of it is highly inconstant, ranging from least histological changes to broad fibrosis and cirrhosis with possibility of hepatocellular carcinoma (HCC). The morbidity and mortality of this global infection are growing. The estimated worldwide prevalence of HCV is a by the World Health Organization (WHO) affecting >170 million people worldwide. There is a varied distribution of HCV infection with about 23 million people likely to have it in the countries of Eastern Mediterranean Region. This is nearly number of infected people in both Americas and Europe. Egypt is considered to have highest prevalence worldwide with an expected 14.7% of total population seropositive for HCV. Aim of the Work: to compare the different new lines of antiviral combination therapies against hepatitis C virus genotype 4 in Egyptian patients as regards efficacy and safety. Material and Methods: an open label, single-center, parallel-groups, randomized controlled clinical study, comparing the different lines of antiviral combination therapies against hepatitis C virus in Egyptian patients as regards efficacy reflected by the sustained virological response and safety through reporting adverse effects occur with each drug combination. This study was conducted on confirmed HCV chronically infected patients with diagnosis based on HCV-RNA PCR. The cases were collected from viral hepatitis treatment unit in Electricity hospital, one of the centers of National Committee for Control of Viral Hepatitis (NCCVH). All cases in this study were assessed and managed according to updated guidelines by NCCVH in parallel with the European Association for Study of Liver (EASL) and the American European Association for Study of Liver (AASLD). Results: this study was conducted on 1000 patients with confirmed diagnosis of chronic HCV with positive serum HCV RNA by PCR technique. The cases were collected for this study had chronic hepatitis either without cirrhosis or with compensated cirrhosis differentiated by using the FIB-4 score. They could be INF-naïve or INF-experienced. The antiviral regimens used were SOF/SIM, SOF/LDV±RBV, SOF/DCV±RBV, PAR/OMB/RBV, and IFN/SOF/RBV. Out of 1737 patients who underwent initial evaluation, 531 patients were not eligible for therapy due to the presence of one or more exclusion criteria. The main causes for treatment exclusion were advanced liver decompensation, inadequately controlled diabetes and HBV co-infection. The total number of patients enrolled and eligible for antiviral treatment was 1206, 1000 of them started the treatment course, while 206 patients did not start it due to receiving treatment in other centres or died before starting the treatment. Conclusion: 1000 patients started antiviral therapy for HCV, they showed good adherence to treatment and high SVR rates compared to other recently published real-life studies. We used seven different treatment regimens, all of which proved to be efficacious and safe with no clear preference for each over others.