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. 2015 Dec 15;10(12):e0145105.
doi: 10.1371/journal.pone.0145105. eCollection 2015.

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

Frédégonde About  1   2 , Tiphaine Oudot-Mellakh  3   4 , Jonathan Niay  3   4 , Pascaline Rabiéga  5 , Vincent Pedergnana  1   2   6 , Darragh Duffy  7   8 , Philippe Sultanik  9   10 , Carole Cagnot  11 , Fabrice Carrat  5   12 , Patrick Marcellin  13 , Fabien Zoulim  14   15   16 , Dominique Larrey  17 , Christophe Hézode  18   19 , Hélène Fontaine  9   10 , Jean-Pierre Bronowicki  20 , Stanislas Pol  9   10 , Matthew L Albert  7   8   10 , Ioannis Theodorou  3   4 , Aurélie Cobat  1   2 , Laurent Abel  1   2   21 ; ANRS CO20-CUPIC study group
Collaborators, Affiliations

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

Frédégonde About et al. PLoS One. .

Abstract

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Rate of SVR by genotypes for IL28B SNPs.
(A) SVR rates by genotypes for rs12979860 (left panel) and rs368234815 (right panel). (B) SVR rates by genotypes for rs12979860 according to prior treatment response.
Fig 2
Fig 2. Rate of early hemoglobin decline by genotypes for rs1127354 and rs7270101 (A) and by predicted ITPA activity (B).
Severity of ITPA deficiency was defined as in Fellay et al [7] considering rs1127354 C and rs7270101 A equivalent low activity variants.
See this image and copyright information in PMC

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