الفهرس 
REVIEW OF LITERATUREOnly 14 pages are availabe for public view
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Abstract
A round 71 million people worldwide are infected with hepatitis C virus (HCV), which continues to carry a heavy toll on liver-related morbidity and mortality (Blach et al., 2017). HCV elimination became a national health priority since Egypt has the highest global prevalence of (HCV) infection, which is linked to significant morbidity and economic burden (Blach et al., 2015).
HCV infection can have a wide range of long-term complications, including cirrhosis, advanced fibrosis, decompensated cirrhosis, and hepatocellular carcinoma (HCC) (WHO, 2015). Direct-acting antiviral medications (DAAs) taken orally are used to treat HCV infection. More than 85% of those treated with various DAA regimens across all six major genotypes had their HCV infection cleared (Zoratti et al., 2020). The main goal of therapy is to achieve a sustained virological response (SVR), defined as the absence of detectable levels of HCV RNA in the blood at the end of therapy. (Carter et al., 2016).
when patients are sent back to treatment centers and the appropriate re-treatment strategy is chosen in accordance with the existing protocol of therapy, this problem of certain patients displaying resistance to DAAs may be resolved (El Kassas et al., 2018). In individuals without cirrhosis or with compensated (Child-Pugh A) cirrhosis, SOF/VEL/VOX is suggested as a treatment for chronic (HCV) infection when a prior treatment regimen (protease inhibitor and/or NS5A inhibitor) has failed for HCV genotypes 1:6 (Bourlière et al., 2017).
The only nucleotide-based prodrug currently approved to inhibit the HCV NS5B RNA-dependent RNA polymerase is sofosbuvir, which is essential to the
introduction
current HCV treatment protocols. NS5B inhibition is thought to be caused by the 2′-C-methyl group of sofosbuvir, which encourages chain termination through steric conflict with an incoming nucleotide. The NS5B ternary complex, which consists of a binding primer, template, and active drug metabolite, has crystal structures that support this method of inhibition (Appleby et al., 2015).
The recently licensed medication Vosevi contains velpatasvir, which blocks the multifunctional, non-enzyme phosphoprotein known as HCV NS5A. This protein plays important but poorly understood roles in viral replication and virion assembly. Like other NS5A inhibitor drugs, Velpatasvir has a central aromatic scaffold surrounded by two dipeptide moieties, resulting in a roughly symmetrical structure. (Belema et al., 2014).
Eight chiral centres and one stereoisomer make up vitoxilaprevir. The design of the production process and limitations in the requirements for the raw materials control the chiral purity of voxilaprevir. It is recognized as an innovative active component. The applicant established that none of its salts or derivatives, nor it itself, have ever been active components in goods that have received European Union approval (CHMP,2017).
Success SVR at week 12 will be used to classify treatment results, whereas treatment failure (any detectable HCV RNA) at the conclusion of the 24-week treatment cycle will be used to classify results (Cheung et al., 2016).