title: 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.
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.
  
  
  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)).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Paris, France.|Paris Descartes University, Imagine Institute, Paris, France.
authors.forename: Frédégonde
authors.initials: F
authors.lastname: About
authors.affiliation: Laboratory of Immunity and Infection, Centre d'Immunologie et des Maladies Infectieuses de Paris (CIMI), INSERM U1135, Groupe Hospitalier Pitié Salpétrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.|Plateforme Génomique Inserm-ANRS, Groupe Hospitalier Pitié Salpétrière, AP-HP, UPMC Université Paris 6, Paris, France.
authors.forename: Tiphaine
authors.initials: T
authors.lastname: Oudot-Mellakh
authors.affiliation: Laboratory of Immunity and Infection, Centre d'Immunologie et des Maladies Infectieuses de Paris (CIMI), INSERM U1135, Groupe Hospitalier Pitié Salpétrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.|Plateforme Génomique Inserm-ANRS, Groupe Hospitalier Pitié Salpétrière, AP-HP, UPMC Université Paris 6, Paris, France.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Niay
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), Paris, France.
authors.forename: Pascaline
authors.initials: P
authors.lastname: Rabiéga
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Paris, France.|Paris Descartes University, Imagine Institute, Paris, France.|Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Vincent
authors.initials: V
authors.lastname: Pedergnana
authors.affiliation: Centre for Human Immunology, Department of Immunology, Institut Pasteur, Paris, France.|The Laboratory of Dendritic Cell Biology, Department of Immunology, Institut Pasteur, INSERM U818, Paris, France.
authors.forename: Darragh
authors.initials: D
authors.lastname: Duffy
authors.affiliation: Département d'Hépatologie, Hôpital Cochin, AP-HP, Université Paris Descartes, Paris, France.|INSERM UMS20, Institut Pasteur, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Sultanik
authors.affiliation: Unit for Basic and Clinical research on Viral Hepatitis, Inserm-ANRS (France REcherche Nord & sud Sida-HIV Hépatites-FRENSH), Paris, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Cagnot
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), Paris, France.|Service de Santé Publique, Hôpital Saint Antoine, AP-HP, Paris, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Carrat
authors.affiliation: Service d'Hépatologie, Hôpital Beaujon, Clichy, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.affiliation: Centre de recherche en cancérologie de Lyon (CRCL), INSERM UMR I 1052/CNRS 5286, Lyon cedex 03, France.|Université Claude-Bernard Lyon 1, Villeurbanne, France.|Hospices civils de Lyon, Hôpital de la Croix-Rousse, service d'hépatologie et de gastroentérologie, Lyon, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
authors.affiliation: CHU St Eloi Hospital, Liver Unit, Montpellier, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Larrey
authors.affiliation: Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, AP-HP, Université Paris-Est Créteil (UPEC), Créteil, France.|Institut Mondor de Recherche Biomédicale (IMRB), INSERM U955, UPEC, Créteil, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Hézode
authors.affiliation: Département d'Hépatologie, Hôpital Cochin, AP-HP, Université Paris Descartes, Paris, France.|INSERM UMS20, Institut Pasteur, Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Fontaine
authors.affiliation: Department of Hepatogastroenterology, INSERM U954, CHU de Nancy, Université de Lorraine, Vandoeuvre-Lès-Nancy, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bronowicki
authors.affiliation: Département d'Hépatologie, Hôpital Cochin, AP-HP, Université Paris Descartes, Paris, France.|INSERM UMS20, Institut Pasteur, Paris, France.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
authors.affiliation: Centre for Human Immunology, Department of Immunology, Institut Pasteur, Paris, France.|The Laboratory of Dendritic Cell Biology, Department of Immunology, Institut Pasteur, INSERM U818, Paris, France.|INSERM UMS20, Institut Pasteur, Paris, France.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Albert
authors.affiliation: Laboratory of Immunity and Infection, Centre d'Immunologie et des Maladies Infectieuses de Paris (CIMI), INSERM U1135, Groupe Hospitalier Pitié Salpétrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.|Plateforme Génomique Inserm-ANRS, Groupe Hospitalier Pitié Salpétrière, AP-HP, UPMC Université Paris 6, Paris, France.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Theodorou
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Paris, France.|Paris Descartes University, Imagine Institute, Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Cobat
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Paris, France.|Paris Descartes University, Imagine Institute, Paris, France.|St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, United States of America.
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
mesh_terms: D000740:Anemia / Q000150:complications; D004359:Drug Therapy, Combination; D006454:Hemoglobins / Q000378:metabolism; D016174:Hepacivirus / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008103:Liver Cirrhosis / Q000150:complications* / Q000188:drug therapy / Q000235:genetics / Q000821:virology; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011755:Pyrophosphatases / Q000235:genetics*; D016896:Treatment Outcome; D053482:beta 2-Glycoprotein I / Q000235:genetics*; D000095022:Interferon Lambda; D000097630:Inosine Triphosphatase
chemical_list: D006454:Hemoglobins; D007372:Interferons; D007378:Interleukins; D009842:Oligopeptides; D011392:Proline; D011755:Pyrophosphatases; D053482:beta 2-Glycoprotein I; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase