STUDY OF THE EFFECT OF SOFOSBUVIR BASED THERAPY ON ESTIMATED GLOMERULAR FILTRATION RATE IN EGYPTIAN CHRONIC HEPATITIS C PATIENTS

Abstract

Hepatitis C viral infection is endemic in Egypt with the highest prevalence rate of HCV Ab in the world (14.7%). [1] Direct-acting antiviral agents (DAAs) are molecules that target specific nonstructural proteins of virus C and result in disruption of viral replication and infection. [2] There are four classes of DAAs, which are defined by their mechanism of action and therapeutic target. They are; non-structural proteins NS 3/4A protease inhibitors (Simiprevir, paritaprevir), NS5B nucleoside polymerase inhibitors (Sofosbuvir), NS5B non-nucleoside polymerase inhibitors (Dasabuvir), and NS5A inhibitors (Daclatasvir). [3] National protocol of HCV treatment used in Egyptian patients infected with HCV (genotype 4) is a combination of daily sofosbuvir and any other DAAs. Compared to previously used treatments, sofosbuvir-based regimens provide a higher cure rate (>90%), fewer side effects, and a twoto fourfold reduction in duration of therapy.[4, 5]It allows most people to be treated successfully without the use of peglated interferon.[6,7]. Sofosbuvir is only administered orally. The peak concentration after oral administration is 0.5–2 hours post-dose, regardless of initial dose.[8&9] It is a prodrug. It is metabolized to the active metabolite antiviral agent GS-461203 (2'-deoxy-2'α-fluoro-β-C-methyluridine-5'triphosphate) in the liver. GS-461203 serves as a defective substrate for the NS5B protein, which is the viral RNA polymerase, thus acts as an inhibitor of viral RNA synthesis.[10] It appears to have a high barrier to develop resistance .Following a single 400mg oral dose of sofosbuvir 80٪ is excreted in urine; 14٪ is excreted in faeces, and 2.5٪ in expired air.[11] Sofosbuvir in patients with HCV infection and mild to moderate renal impairment (eGFR ≥30 ml/ min/1.73 m2) should be given according to the general recommendations. No dose Journal of the Medical Research Institute