The hepatitis C virus (HCV) is an enveloped, single-stranded positive-sense Ribo-Nucleic Acid virus which is a major cause of chronic liver diseases, including cirrhosis and hepatocellular carcinoma (HCC), and infects approximately 3 % of the world population(150-170 million).~One of the countries most affected by HCV is Egypt. The Egyptian Demographic and Health Surveys measured antibody prevalence among the adult population aged 15-59 years at 14.7% in 2009 and at 10.0% in 2015 To attend to this challenge, Egypt developed a national strategy for Hepatitis C Virus control and established HCV prevention and treatment programs using Direct Acting-Antivirals (DAAs).~Egypt launched an ambitious national HCV treatment program aiming to treat over 250,000 chronically infected individuals per year, with the goal of achieving a national chronic infection prevalence of <2% by 2025.~Although the consequences of chronic HCV infection are generally associated with liver manifestations such as hepatic fibrosis, cirrhosis, steatosis (known as non-alcoholic fatty liver disease, NAFLD) and HCC, the liver-related mortality of 350,000 individuals annually is still underestimated due to the lack of consideration of extrahepatic effect including a growing evidence showing that HCV infection is strongly associated with the dysregulation of glucose homoeostasis such as insulin resistance (IR) and type 2 diabetes (T2D).~HCV-related type 2 diabetes mellitus may arise from a complex interaction between IR, steatosis and inflammatory processes People infected with HCV are 4 times more likely to develop Type 2 Diabetes; and HCV-infected patients with uncontrolled glucose are at higher risk to develop advanced liver fibrosis, HCC, and exhibit decreased sustained virologic response (SVR) to traditional interferon treatment.~HCV protein NS5A and the core protein directly inhibit microsomal triglyceride transfer protein (MTP) activity, thereby reducing very low-density lipoprotein (VLDL) assembly and inducing hepatic steatosis.~Over time, accumulation of hepatic triglycerides leads to hepatic IR via decreased insulin-stimulated glycogen synthesis and enhanced hepatic gluconeogenesis; such conditions further cause peripheral IR in multiple organs through increased circulating insulin and free fatty acid levels.~Regarding the molecular mechanisms of regulation of insulin signaling by HCV infection. HCV core protein has been found to increase serine rather than tyrosine phosphorylation of IRS-1 ( insulin Receptor Substrate-1) in hepatocytes, resulting in its degradation and impaired downstream signaling Protien Kinase B signalling pathway.~HCV core protein also stimulates Insulin Receptor Substrate-1 serine phosphorylation via increasing mTOR (mammalian Target Of Rapamycin)levels, resulting in decreased Protien Kinase B signaling.~Reduced surface expression of glucose transporters GLUT1 and GLUT2 with consequential reduction in glucose uptake in HCV-infected hepatocytes has also been reported.~Despite these findings of IR development via direct effects on insulin signaling pathways, the complex relationship between intrahepatic HCV infection and extrahepatic IR remains elusive.~Several miRNAs have been determined to play a key role in regulating viral replication and pathogenesis during HCV infection.~Host miRNAs can be activated by viral integration in the host genome; viral miRNAs can target host mRNAs, , or host miRNAs can target viral mRNAs.~miR-122 expression is enriched in the liver, accounting for approximately 70 % of the total miRNA population in normal adult hepatocytes with approximately 66,000 copies per cell.~miR-122 has a role in the HCV replication cycle, where it binds to two target sites (S1 and S2) in the highly conserved 5' untranslated region of the HCV genome, thus forming a complex of HCV oligomeric miR-122 that protects the HCV genome from nucleolytic degradation as well as from the host innate immune response.~Many metabolic processes are potentially targeted by miR-122, including protein metabolism, carbohydrate metabolism, lipid metabolism and phospholipid metabolism. Signaling pathway ontology revealed several IR-related pathways [eg insulin/Insulin Growth Factor/Protien Kinase B signaling, Phosphoinositide 3-Kinase signaling, apoptosis, Epidermal Growth Factor receptor signaling,G protien-coupled receptors signaling pathway.~Antagonism of miRNA-122 not only reduces viral replication but also reduces HCV propagation by decreasing the expression of enzymes involved in lipid metabolism, which can enhance HCV replication in cell culture models.~miR-122 represents an interesting therapeutic target for the treatment of liver disease including viral hepatitis, fibrosis, steatosis and HCC. Experimental studies have elegantly demonstrated that a miR-122 inhibitor efficiently reduces viral load in chronically infected HCV patients without detectable resistance.
The hepatitis C virus is a major cause of chronic liver diseases, including cirrhosis and hepatocellular carcinoma, and infects approximately 3 % of the world population (150-170 million). It is estimated that approximately 80 % of patients with acute hepatitis C fail to eliminate the virus and become chronically infected Hepatitis C virus infection is strongly associated with the dysregulation of glucose homoeostasis such as insulin resistance and type 2 diabetes. Despite these findings of insulin resistance development via direct effects on insulin signalling pathway, the complex relationship between intrahepatic Hepatitis C virus infection and extrahepatic insulin resistance remains elusive.~One of the countries most affected by Hepatitis C virus is Egypt. The Egyptian Demographic and Health Surveys measured antibody prevalence among the adult population aged 15-59 years at 10.0% in 2015-substantially higher than global levels.~Several micro ribonucleic acids have been determined to play a key role in regulating viral replication and pathogenesis during infection. micro ribonucleic acid-122 expression is enriched in the liver, accounting for approximately 70 % of the total micro ribonucleic acid population in normal adult hepatocytes. Moreover, a particularly intriguing function of micro ribonucleic acid-122 involves its role in the Hepatitis C virus replication cycle.~Antagonism of micro ribonucleic acid-122 not only reduces viral replication but also reduces Hepatitis C virus propagation by decreasing the expression of enzymes involved in lipid metabolism, which can enhance Hepatitis C virus replication in cell culture models.