الفهرس 
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Abstract
Hepatitis C virus (HCV) causes both acute and chronic infections and represents a global problem for public healthcare systems worldwide because of its high prevalence, high rates of transfer and severe health-related complications. chronic HCV infection is the major reason of liver transplantation in developed countries. In Egypt, HCV infection is a major public health problem, where it has the highest prevalence rate in the world. HCV prevalence in Egypt was 14.7% in 2009 and 10% in 2015. HCV genotype 4 (G4) is the common genotype in the Middle East, Northern Africa, and Sub-Saharan Africa. In Egypt 93% of HCV patients are infected with G4.
The standard treatment for chronic HCV infection was pegylated interferon/ ribavirin (Peg IFN/RBV). Sustained virologic response (SVR) rates were 60% only for those infected with HCV genotype 4 (G4), whereas over 80% for HCV patients with genotype 2 (G2) or genotype 3 (G3).
In the last decade, direct acting antivirals (DAAs) had emerged and proved efficacy in lowering viral loads besides high safety in HCV patients of different genotypes. Sofosbuvir and daclatasvir combination had shown safety and efficacy in HCV G4 patients with attenuation of liver fibrosis despite combination’s higher costs when compared with PEG IFN-RBV regimen.
Another combination of DAAs is ombitasvir, paritaprevir, and ritonavir combination plus RBV which is administered for 12 weeks. It has shown high SVR12 rates in Egyptian HCV G4 patients with or without cirrhosis.
The prediction of treatment failure was critical due to prolonged and costly pegylated interferon and ribavirin (Peg IFN/RBV) treatment and dose-limiting side effects. Many host and viral factors were taken into consideration for achieving Peg IFN/RBV treatment success. One of the host factors that helps in predicting HCV treatment success is single nucleotide polymorphism (SNPs) in rs12979860 on chromosome 19q13 near interferon Lambda 3 (IFNL3) or interleukin 28B (IL28B) gene. These SNPs had shown a strong association with both spontaneous HCV clear¬ance and response to Peg IFN/RBV treatment by sever¬al genome-wide-association studies (GWAS).
IL28B variants cause different host response to the antiviral therapy due to the expression of endogenous IFNL3 with different levels of activity that might alter the host response to the antiviral therapy. SVR rates in HCV patients receiving PEG IFN/RBV were highly detected in CC genotype when compared to CT and TT. The CC genotype frequency has shown to decline sharply from healthy to chronic HCV subjects.
Liver biopsies were frequently used for determination of liver tissue consistency, but they are invasive and costly, as well as potential errors that had occurred during sampling. Moreover, observers’ discrepancies in assessing hepatic fibrosis were noticed. Consequently, many noninvasive parameters had been used instead. Fibrosis 4 (FIB-4) index and Aspartate to platelet ratio index (APRI) are applicable and proven calculated parameters that has been used to detect degree of liver fibrosis. DAAs had shown to improve both indices.
IFN-free regimens have shown to give better FIB-4 results. Sofosbuvir and daclatasvir combination had shown safety and efficacy in HCV G4 patients with attenuation of liver fibrosis. Studies on the effect of gene polymorphism on safety and efficacy of DAAs in chronic HCV Egyptian patients are still deficient.
The burden of chronic HCV infection on the Egyptian economy usually includes direct and indirect costs. Direct costs are costs for diagnosis and care, indirect costs are due to disability and premature death.