الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Approximately 71 million people worldwide are supposed to have chronic hepatitis C, and 10–20% of these will eventually develop cirrhosis and hepatocellular carcinoma. New direct-acting antiviral (DAA) medications have helped to succeeded complete treatment of chronic hepatitis C and achieving sustained virological response (SVR). However, after receiving the treatment, some patients may acquire HCV resistance to DAAs, which may result in treatment failure.
In the present study, we wanted to compare between the patients experiencing virologic relapse (VR) and SVR in relation to the pattern of NS5A & NS5B resistance associated substitutions (RASs) in chronic HCV genotype 4a infected Egyptian patients received Sofosbuvir (SOF) and Daclatasvir (DCV) combination therapy.
A total of 10 out of 100 serum specimens from the enrolled patients were analyzed (two and eight specimens representative for VR and SVR, respectively). They submitted to reverse transcriptase-polymerase chain reaction amplification of NS5A and NS5B genes, which were then partially sequenced by Sanger method and analyzed phylogenetically to determine genetic subtypes and RASs. Nucleotide sequences have been aligned, translated into amino acids, and compared to drug resistance mutations reported in the literature.
All patients were infected by chronic HCV-4a in the small size study, completed the treatment with SOF and DCV combination therapy and followed up after the end of treatment. SVR was gained in all but two patients who experiencing virologic relapse carry natural NS5A-RASs at position Y93H were considered as significant for DCV resistance, as well as, natural NS5B-RASs (T282S) which was considered as the main polymorphism for SOF resistance. Non responder patient’s specimens revealed S282T mutation site at NS5B gene as well as Y93H mutation site at NS5A gene and found to have abnormal level of ALT & AST.
According to our finding, the resistance to SOF as well as DCV attributable to mutations in NS5B and NS5A regions in genotype 4a, respectively. In the meanwhile, patients with detectable RASs experienced virologic relapses. Moreover, the high rates of multiple RASs in DAA treatment failures, in addition to the high cost, make it useful to encourage designing a specific treatment protocol for HCV genotype 4a- Egyptian infected patients to avoid resistance.