HCV infection causes cirrhosis in human by step-wise regulation of host genes involved in cellular functioning and defense during fibrosis: Identification of bio-markers

Abstract

Chronic Hepatitis C Viral (HCV) infection is a leading health problem worldwide and resulted in fibrotic scar formation, and finally liver-cirrhosis. Although contemporary therapies can partially reverse this destructive process, the rehabilitation is too slow and unsuitable for all chronic infections. The current study elucidates the mechanism of disease progression from early (F1) to moderate (F2, F3), and to severe fibrosis (F4)/cirrhosis in HCV genotype 3a infected patients to find out new candidates as potential disease progression markers and antiviral therapeutic agents. A total of 550 genes were found differentially regulated in the four fibrosis stages and grouped in 22 classes according to their biological functions. Gene set enrichment (GSEA) and Ingenuity pathway analysis (IPA) were used to identify the regulation of crucial biological functions and pathways involved in HCV progression. HCV differentially regulated the expression of genes involved in apoptosis, cell structure, signal transduction, proliferation, metabolism, cytokine signaling, immune response, cell adhesion and maintenance, and post translational modifications by pathway analysis. There was an increasing trend of proliferative and cell growth related genes and shutting down of immune response as the disease progress mild to moderate to advanced stage cirrhosis. The myriad of changes in gene expression showed more chances of developing liver cancer in patients infected with HCV genotype 3a in a systematic manner. The identified gene set can act as disease markers for prediction, whether the fibrosis lead to cirrhosis and its association with end stage liver disease development.