title: Hepatitis C virus infection: establishment of chronicity and liver disease progression.
abstract: Hepatitis C virus (HCV) often causes persistent infection, and is an important factor in the etiology of fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). There are no preventive or therapeutic vaccines available against HCV. Treatment strategies of HCV infection are likely to improve with recently discovered direct antiviral agents (DAAs). However, a proportion of patients still progress to liver failure and/or HCC despite having been cured of the infection. Thus, there is a need for early diagnosis and therapeutic modalities for HCV related end stage liver disease prevention. HCV genome does not integrate into its host genome, and has a predominantly cytoplasmic life cycle. Therefore, HCV mediated liver disease progression appears to involve indirect mechanisms from persistent infection of hepatocytes. Studying the underlying mechanisms of HCV mediated evasion of immune responses and liver disease progression is challenging due to the lack of a naturally susceptible small animal model. We and other investigators have used a number of experimental systems to investigate the mechanisms for establishment of chronic HCV infection and liver disease progression. HCV infection modulates immune systems. Further, HCV infection of primary human hepatocytes promotes growth, induces phenotypic changes, modulates epithelial mesenchymal transition (EMT) related genes, and generates tumor initiating stem-like cells (TISCs). HCV infection also modulates microRNAs (miRNAs), and influences growth by overriding normal death progression of primary human hepatocytes for disease pathogenesis. Understanding these ob-servations at the molecular level should aid in developing strategies for additional effective therapies against HCV mediated liver disease progression.
authors.affiliation: Department of Internal Medicine, Saint Louis University, Missouri.
authors.forename: Young-Chan
authors.initials: YC
authors.lastname: Kwon
authors.affiliation: Department of Pathology, Saint Louis University, Missouri.
authors.forename: Ratna B
authors.initials: RB
authors.lastname: Ray
authors.affiliation: Department of Molecular Microbiology & Immunology, Saint Louis University, Missouri ; Department of Internal Medicine, Saint Louis University, Missouri.
authors.forename: Ranjit
authors.initials: R
authors.lastname: Ray
keywords: DAAs; EMT; HCV; TISCs; fibrosis; miRNAs