الفهرس 
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Abstract
Egypt has the largest epidemic of hepatitis C virus (HCV) in the world, estimated nationally at 14.7%. The prevalent genotype in Egypt is type 4 (73%) with a predominance of subtype 4a. The recent advent of direct-acting antivirals (DAAs) has been developed for the treatment of HCV. DAAs achieve a permanent cure in over 90% of cases and have little or no side-effects. As well as, its treatment schedules are simple and short, with little or no monitoring needed.
The Food and Drug Administration (FDA) has approved a new therapy (Sofosbuvir), to treat patients with chronic HCV infection of genotypes 1, 2, 3, and 4.The treatment regimens with the new therapy include Ribavirin and PEG-IFNα-2a.Unfortunately, there have been no field studies to prove the effectiveness of these approaches. Therefore, the present work is planned to adopt the anti-viral efficacy of PEG-IFNα-2a/Ribavirin/ Sofosbuvir combination therapy against the HCV with identification of the patients who could achieve sustained virological response (SVR) with a shorter treatment course (12 weeks) to free them of unnecessary side effects and reduce costs of previously treatment strategy.
In addition, the substitution of amino acid 70 in the core region of HCV genotype 4 especially in subtype 4d could predict the response to pegylated interferon (PEG-IFN)/Ribavirin combination therapy in Saudi population, but its effect on the triple therapy of Sofosbuvir /PEG-IFNα-2a / Ribavirin is not
Summary
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clear in Egyptian patients infected with high viral load of HCV 4a. Therefore, the pretreatment predictors of non-SVR to a 12-week regimen of the triple therapy in Egyptian patients infected with HCV 4a were investigated.
Generally, our results revealed that SVR and non-SVR were achieved by 72% and 16%, respectively butonly 12% were considered NVR following the combination therapy. Multivariate analysis identified viral- (level of viremia and substitution of aa70) and host-related factors (age, ALT and AST levels) that influenced the virological response to the combination therapy in patients with HCV 4a infection and a high viral load. In addition to, there is a significant association between core protein mutations, particularly at position 70 (Arg70Gln) and treatment outcome in HCV-4a infected patient. Subsequently, these factorsare helpful in predicting the treatment outcome.
Overall, these results concluded that Sofosbuvir with Ribavirin and PEG-IFNα-2a are highly efficient in HCV-4a Egyptian patients where SVR was achieved (72%). In addition to, there is a significant association between core protein mutations, particularly at amino acid position 70 (Arg70Gln) and treatment outcome.