Efficacy, Safety and Relapse of Sofosbuvir in Combination with Daclatasvir, Ledipasvir and Simeprevir for Treatment of Hepatitis C Virus in Egypt

Abstract
Background: Hepatitis C Virus infects about 185 million people equating 2.8% of worldwide population and about 500,000 people die annually from hepatitis C related liver diseases. The most common clinical presentation of the disease is the chronic hepatitis and its complications such as: Com-pensated cirrhosis, portal hypertension, decompensated cir-rhosis and Hepatocellular Carcinoma (HCC). Therapeutic management of chronic HCV patients traditionally depended on combination of peg-interferon (IFN) with ribavirin but this regimen showed many serious side effects beside its non-satisfactory efficacy. In 2013, a second generation of Direct Acting Antiviral Agents (DAAs) gave a promising efficacy and safety. Although many IFN free regimens were approved, further evaluations are needed for these regimens.
Aim: To compare sofosbuvir in combination with Da-clatasvir, Ledipasvir and Simeprevir in patients with chronic hepatitis C infection according to safety, efficacy, relapse and patient outcomes.
Patients and Methods: This is a prospective study con-ducted on 150 patients of chronic HCV who were admitted to the Viral Hepatitis Center in Al-Ahrar Educational Hospital in Zagazig {National Committee for the Control of Viral Hepatitis (NCCVH) during the first 9 months of 2017 and were selected according to the inclusion and exclusion criteria set by the (NCCVH). 58% of overall participants had cirrhosis and 2.7% were treatment-experienced. Patients were assigned into three groups: 50 patients received Sofosbuvir + Daclatasvir ± Ribavirin (SOF/DCV ± RBV) therapy, 50 patients received Sofosbuvir + Ledipasvir ± Ribavirin (SOF/LDV ± RBV) therapy and 50 patients received Sofosbuvir + Simeprevir ± Ribavirin (SOF/SIM±RBV) therapy. Three regimens were given for 12 weeks. Primary end point was the rate of achieving SVR12 by HCV RNA PCR, while secondary end point was the occurrence of virologic relapse.
Results: The SVR rate of three groups was 98%, 100% and 100% for SOF/DCV, SOF/LDV and SOF/SIM groups respectively. Only one patient had a virological failure and he was in SOF/DCV group but these results showed no statistical significance. Virological relapse occurred in only 1 patients (.67%) of the 149 patients. The patient who showed virological failure wasn't included, while the only one patient relapsed (2%) was in SOF/SIM therapy group. Results of virological relapse were statistically not significant. RVR showed a predictive value in SVR achievement and relapse occurrence was also confirmed in our study, in SVR (p=>.05) and in relapse (p=.9). Adverse events occurred in (22%) of SOF/DCV group, (26%) of SOF/LDV group and (40%) of SOF/SIM group (p=.153), thus SOF/SIM therapy showed a higher incidence of adverse events occurrence.
Conclusions: Sofosbuvir based antiviral combination therapy with (DCV, LDV and SIM) showed a highly safety, tolerability and efficacy for treatment of chronic Hepatitis C Virus.