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Background  Human 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 Methods  A 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.    Results  None 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 ).    Conclusion  Our 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.

plos one

Impact of IL28B, APOH and ITPA Polymorphisms on Efficacy and Safety of TVR- or BOC-Based Triple Therapy in Treatment-Experienced HCV-1 Patients with Compensated Cirrhosis from the ANRS CO20-CUPIC Study