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Abstract
BackgroundHuman genetic factors influence the outcome of pegylated interferon and ribavirin hepatitis C therapy. We explored the role of IL28B, APOH and ITPA SNPs on the outcomes of triple therapy including telaprevir or boceprevir in patients with compensated cirrhosis chronically infected with HCV-1.Patients and MethodsA total of 256 HCV-1 Caucasian treatment-experienced patients with compensated cirrhosis from the ANRS CO20-CUPIC cohort were genotyped for a total of 10 candidate SNPs in IL28B (rs12979860 and rs368234815), APOH (rs8178822, rs12944940, rs10048158, rs52797880, rs1801689 and rs1801690) and ITPA (rs1127354 and rs7270101). We tested the association of IL28B and APOH SNPs with sustained virological response and of ITPA SNPs with anemia related phenotypes by means of logistic regression assuming an additive genetic model.ResultsNone of the six APOH SNPs were associated with sustained virological response. The favorable alleles of the IL28B SNPs rs12979860 and rs368234815 were associated with sustained virological response (rs12979860: OR = 2.35[1.50–3.70], P = 2x10-4). Refined analysis showed that the effect of IL28B SNPs on sustained virological response was restricted to prior PegIFN/RBV relapse (OR = 3.80[1.82–8.92], P = 8x10-4). We also confirmed the association between ITPA low activity alleles and protection against early hemoglobin decline in triple therapy (P = 2x10-5).ConclusionOur results suggest that the screening of rs12979860 may remain interesting for decision making in prior relapse HCV-1 Caucasian patients with compensated cirrhosis eligible for a telaprevir- or boceprevir-based therapy.
Highlights
HCV infection is a major public health issue with ~80 million people chronically infected worldwide [1]
We explored the role of IL28B, APOH and inosine triphosphate (ITPA) single nucleotide polymorphism (SNP) on the outcomes of triple therapy including telaprevir or boceprevir in patients with compensated cirrhosis chronically infected with HCV genotype 1 (HCV-1)
Refined analysis showed that the effect of IL28B SNPs on sustained virological response was restricted to prior PegIFN/RBV relapse (OR = 3.80[1.82–8.92], P = 8x10-4)
Summary
HCV infection is a major public health issue with ~80 million people chronically infected worldwide [1]. Up to 2011, standard of care treatment was based on pegylated interferon and ribavirin (PegIFN/RBV) which leads to viral clearance in ~50% of the patients [2]. Rs1127354 and rs7270101, from the inosine triphosphate (ITPA) gene, encoding a protein that hydrolyses inosine triphosphate, are independent predictors of RBV-induced anemia [7]. We explored the role of IL28B, APOH and ITPA SNPs on the outcomes of triple therapy including telaprevir or boceprevir in patients with compensated cirrhosis chronically infected with HCV-1. Role of Candidate SNPs on Outcome of HCV Triple Therapy recherche.fr) under the ‟Investments for the future” program (grant n°ANR-10-IAHU-01), and in part by the Association Française pour l'Etude du Foie (AFEF, http://www.afef.asso.fr). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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