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) , Tiphaine Oudot-Mellakh (2) , Jonathan Niay (2) , Pascaline Rabiéga (3) , Vincent Pedergnana (2) , Darragh Duffy (4, 5) , Philippe Sultanik (6) , Carole Cagnot (7) , Fabrice Carrat (3) , Patrick Marcellin (8) , Fabien Zoulim (9) , Dominique Larrey (10, 11, 12) , Christophe Hézode (13, 14) , Hélène Fontaine (6) , Jean-Pierre Bronowicki (15, 16) , Stanislas Pol (4, 6) , Matthew L. Albert (5, 4) , Ioannis Theodorou (2) , Aurélie Cobat (17) , Laurent Abel (17)

1 Equipe Inserm U1163 - Human genetics of infectious diseases : Mendelian predisposition
2 CIMI - Centre d'Immunologie et de Maladies Infectieuses
3 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
4 Immunobiologie des Cellules Dendritiques
5 CIH - Centre d'Immunologie Humaine
6 Département d'hépatologie [CHU Cochin]
7 Unit for Basic and Clinical research on Viral Hepatitis
8 Service d'hépatologie
9 HCL - Hospices Civils de Lyon
10 CHRU Montpellier - Hôpital Saint Eloi
11 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
12 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
13 Service d'immunologie clinique et maladies infectieuses [Hôpitaux universitaires CHU Henri Mondor]
14 IMRB - Institut Mondor de Recherche Biomédicale
15 Service d'Hépato-gastro-entérologie [CHRU Nancy]
16 NGERE - Nutrition-Génétique et Exposition aux Risques Environnementaux
17 IMAGINE - U1163 - Imagine - Institut des maladies génétiques

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.

Mots clés: Hepatitis C virus; Induced hemolytic anemia; Genotype 1 infection; Genetic variation; Plus ribavirin; Dose reduction; Telaprevir; Variants; Boceprevir; Protect

Domaines: Maladies infectieuses

Frédégonde About, Tiphaine Oudot-Mellakh, Jonathan Niay, Pascaline Rabiéga, Vincent Pedergnana, et al.. 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. PLoS ONE, 2015, 10 (12), pp.e0145105. ⟨10.1371/journal.pone.0145105⟩. ⟨hal-01257993⟩