Genomics and HCV infection: Progression of fibrosis and treatment response

Abstract

HCV infection is a global health problem that affects 170 million people worldwide. The severity of the disease varies from asymptomatic chronic infection to cirrhosis and hepatocellular carcinoma (HCC). Recently, the standard of care for genotype 1 patients has greatly improved with the addition of protease inhibitors (telaprevir or boceprevir) to pegylated interferon (PegIFN) and ribavirin (RBV). The prediction of fibrosis progression and the response to antiviral treatment are two major issues in the management of patients with chronic hepatitis C. Differential expression of mRNAs was first analyzed for both progression of fibrosis and treatment response. Specific polymorphisms, associated with either fibrosis or viral response, were identified thanks to major improvements in genome scanning technologies. Since 2009, several independent genome wide association studies (GWAS) have reported an association between genetic polymorphisms within the IL-28B promoter and both natural and treatment-induced clearance in genotype 1 infected patients. These different studies showed the strong association and the importance of IL-28B polymorphisms in the treatment response. Combining the different genetic factors could improve their predictive value and help identify patients at a high risk of progression of fibrosis as well as those with a lower chance of responding to treatment. The aim of this review was to discuss the genomic factors (mRNAs, miRNAs, and SNPs) and HCV infection with clinical implications for either progression of fibrosis or treatment response. Recent findings on the IL-28B polymorphism and its application in clinical practice will also be discussed.

Reduction of MicroRNA 122 Expression in IFNL3 CT/TT Carriers and during Progression of Fibrosis in Patients with Chronic Hepatitis C

“…At week 12 of the treatment, 47 patients had pNR and 63 had cEVR. rs12979860 and rs8099917 are both associated with SVR and are in strong linkage disequilibrium (37,38). We selected the rs12979860 polymorphism because this polymorphism was reported to be more informative than rs8099917 in a cohort of patients with Caucasian ancestry (39).…”

Gene Expression Profiling To Predict and Assess the Consequences of Therapy-Induced Virus Eradication in Chronic Hepatitis C Virus Infection

“…Viral and host factors that influence the therapeutic response to IFN-based regimens have been described, including HCV genotype, gender, baseline viral load, early virological response, and fibrosis grade (6,7). More recently, host immunity-related predictive markers that discriminate between responders and nonresponders have been described, which include serum interferon gamma-induced protein 10 (IP-10) levels at baseline, IL-28B gene polymorphisms, as well as baseline and therapy-induced expression levels of IFNstimulated genes (ISGs) and non-ISGs in the livers of patients (8)(9)(10)(11)(12)(13)(14)(15).…”

Identification of Alpha Interferon-Induced Envelope Mutations of Hepatitis C Virus In Vitro Associated with Increased Viral Fitness and Interferon Resistance

“…Recently, certain variations near the IL28B gene were described to correlate with treatment-induced and spontaneous viral clearance (9,10). Of the viral factors, HCV genotype, viral load, and complexity of HCV quasispecies were associated with treatment outcome (8,11,12). Primarily based on analysis of HCV sequences of patients with favorable and nonfavorable treatment outcome, sequence variations in several HCV proteins, mainly Core, E2, and NS5A, were suggested as viral genetic correlates of IFN-␣ resistance (7,8).…”