Study on the expression of interferon alpha related genes in hepatitis C infected patients.

Abstract

HCV in Egypt is a public health problem with a prevalence rate of 14.7% and most of the patients are infected with HCV genotype 4. Nevertheless, few studies were done on Egyptian genetic factors that affect the natural course of HCV genotype 4 (Bader El Din et al., 2016). Hepatic fibrosis is a progressive disease resulting from excessive wound healing process associated with chronic liver injury (Friedman, 2008). Liver fibrosis develops from several etiologies such as viral hepatitis (hepatitis C and B), alcoholic liver disease, and non-alcoholic fatty liver disease with hepatitis C virus (HCV) being the leading cause of liver fibrosis (Takahara et al., 2008). HCV prevalence covers around 3% of the world’s population (Fischer et al., 2012). Although the therapeutic intervention of HCV has recently been improved as the consequence of discovering direct acting antiviral agents (DAAs), th e majority of patients are still at risk of fibrosis progression that is culminating in cirrhosis in 20-30% and hepatocellular carcinoma (HCC) in 4% of the case (Zeuzem et al., 2009). The immune responses to HCV are mainly responsible for viral clearance and disease pathogenesis during infection. Type I interferon (IFN) plays a crucial role in combating HCV. Following HCV sensing by host cell, type I IFN is ultimately induced by several innate pathways including Toll like receptor (TLR) 2, 3, 7, and 8 (Li and Lemon, 2013). Engagement of HCV viral single-stranded RNA (ssRNA) by TLR7 triggers downstream signaling staring with the recruitment of the adaptor molecule myeloid differentiation primary response gene 88 (MyD88) and ending with the activation of transcription factors IRF7 and NF-κB1, which induce the expression of type I IFN and inflammatory cytokines and chemokines, respectively. Upon binding to its cognate receptor, type I IFN induces IFN-stimulated genes (ISGs) that induce cell apoptosis leading to the elimination of virus-infected cells (Stetson and Medzhitov, 2006).