Abstract

Chronic hepatitis C virus (HCV) is a serious health problem in Egypt. Although the effectiveness of pegylated interferon (peg-IFN) and ribavirin (RBV) combined therapy, poor response rates and lamentable tolerability were recorded in the chronically HCV infected patients. Sofosbuvir (SOF) target the highly conserved active site of the HCV-specific NS5B polymerase that affect directly the viral replication and has broad genotypic coverage. In the present study we investigated the efficacy of SOF-based combination therapy and its effects on the status of immune cells from chronically infected HCV Egyptian patients. HCV Patients were treated with a combination treatment of SOF, RBV and peg-IFN-α or SOF and RBV for either 12 or 24 weeks. Then biochemical, hematological parameters, immunological phenotyping, PBMCs proliferation and apoptosis were detected pre- and post-treatment. While SOF-based combination therapy improved the liver function, anemia, leucopenia and thrombocytopenia were detected especially after treatment with SOF, RBV and peg-IFN-α-2a. We observed significant reduction in the percentage of CD3+CD4+ and CD3+CD8+ cells post-treatment with either SOF and RBV or SOF, RBV and peg-IFN-α-2a as compared to the baseline. Moreover, SOF-based combination therapy altered the percentage of CD3-CD8+, CD14+ and CD20+ cells. The proliferative capacity of PBMCs was significantly decreased in both regimens, whilst the percentage of apoptotic cells was significantly augmented. SOF-based therapy regimens are efficacious in reducing HCV load in the current study with some adverse effects that include the reduction of the mononuclear cells from the blood periphery by apoptosis.

Highlights

  • Chronic hepatitis C virus (HCV) infection affects an estimated one hundred and seventy million people around the world with an approximate prevalence 0.2–2 % in the USA and European countries (Esteban et al, 2008; Lavanchy, 2009)

  • Patient population and study design Fifty nine patients chronically infected with HCV, in addition to twenty healthy subjects were selected from Menoufia University Hospital, Menoufia Province, Egypt during the period from April 2015 to January 2016

  • sustained virological response (SVR) was achieved 89.29% of 28 patient received SOF and RBV. Both SOF-based therapy regimens are effective in reducing the HCV load in the current study

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Summary

Introduction

Chronic hepatitis C virus (HCV) infection affects an estimated one hundred and seventy million people around the world with an approximate prevalence 0.2–2 % in the USA and European countries (Esteban et al, 2008; Lavanchy, 2009). Chronic HCV infection is associated with a high risk for liver-related mortality because of a variety of Ibrahim et al / Journal of Applied Pharmaceutical Science 6 (10); 2016: 174-180. Based on these data, direct acting antiviral (DAA) therapy was performed with different drugs that directly target HCV proteins. SOF is effective in patients infected with genotype 1, 2, 3 or 4 when this treatment is combined with peg-IFN α and RBV (Lawitz et al, 2013a; 2013b). SOF plus RBV is effective in patients infected with different genotypes in the absence of treatment with peg-IFN α (Gane et al, 2013)

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