title: Apolipoprotein H expression is associated with IL28B genotype and viral clearance in hepatitis C virus infection.
abstract: OBJECTIVE
  HCV requires host lipid metabolism for replication, and apolipoproteins have been implicated in the response to treatment.
  
  
  METHODS
  We examined plasma apolipoprotein concentrations in three cohorts of patients: mono-infected patients with symptomatic acute hepatitis C (aHCV); those undergoing treatment for chronic hepatitis C (cHCV); and HIV/HCV co-infected patients being treated for their chronic hepatitis C. We also evaluated associations between apolipoproteins and IL28B polymorphisms, a defined genetic determinant of viral clearance.
  
  
  RESULTS
  Plasma apolipoprotein H (ApoH) levels were significantly higher in patients who achieved spontaneous clearance or responded to pegylated-interferon/ribavirin therapy. Strikingly, patients carrying the IL28B rs12979860 CC SNP correlated with the plasma concentration of ApoH in all three cohorts. Both ApoH and IL28B CC SNP were associated with HCV clearance in univariate analysis. Additional multivariate analysis revealed that the association between IL28B and HCV clearance was closely linked to that of Apo H and HCV clearance, suggesting that both belong to the same biological pathway to clearance. The association between IL28B CC SNP and ApoH was not observed in healthy individuals, suggesting that early post-infection events trigger differential ApoH expression in an IL28B allele dependent manner.
  
  
  CONCLUSIONS
  This relationship identifies ApoH as the first induced protein quantitative trait associated with IL28B, and characterises a novel host factor implicated in HCV clearance.
authors.affiliation: Laboratory of Dendritic Cell Immunobiology, Institut Pasteur, Paris, France; INSERM U818, Paris, France.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Laird
authors.affiliation: Community Medicine Department, National Research Center, Cairo, Egypt.
authors.forename: Amira
authors.initials: A
authors.lastname: Mohsen
authors.affiliation: Laboratory of Dendritic Cell Immunobiology, Institut Pasteur, Paris, France; INSERM U818, Paris, France.
authors.forename: Darragh
authors.initials: D
authors.lastname: Duffy
authors.affiliation: Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Rasha
authors.initials: R
authors.lastname: Mamdouh
authors.affiliation: Emerging Disease Epidemiology Unit, Institut Pasteur, Paris, France.
authors.forename: Lenaig
authors.initials: L
authors.lastname: LeFouler
authors.affiliation: Laboratory of Dendritic Cell Immunobiology, Institut Pasteur, Paris, France; INSERM U818, Paris, France.
authors.forename: Armanda
authors.initials: A
authors.lastname: Casrouge
authors.affiliation: Liver Disease Research Unit, National Hepatology & Tropical Medicine Research Institute, Cairo, Egypt.
authors.forename: Mai
authors.initials: M
authors.lastname: El-Daly
authors.affiliation: Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Mona
authors.initials: M
authors.lastname: Rafik
authors.affiliation: Liver Disease Research Unit, National Hepatology & Tropical Medicine Research Institute, Cairo, Egypt; Faculty of Medicine, Minia University, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdel-Hamid
authors.affiliation: National Reference Center for Viral Hepatitis B, C, and D, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France; INSERM U955, Créteil, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Soulier
authors.affiliation: National Reference Center for Viral Hepatitis B, C, and D, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France; INSERM U955, Créteil, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pawlotsky
authors.affiliation: INSERM U955, Créteil, France; Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Hézode
authors.affiliation: INSERM U955, Créteil, France; Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Rosa
authors.affiliation: Department of Gastroenterology and Hepatology, Hôpital Victor Dupouy, Argenteuil, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Renard
authors.affiliation: Liver Disease Research Unit, National Hepatology & Tropical Medicine Research Institute, Cairo, Egypt.
authors.forename: Mostafa K
authors.initials: MK
authors.lastname: Mohamed
authors.affiliation: Maladies Infectieuses et Tropicales, Hôpital Tenon (APHP), Paris, France; INSERM U-707, UPMC, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bonnard
authors.affiliation: Department of Virology, CHU Toulouse, Toulouse, France; INSERM U1043, IFR-BMT, Toulouse, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Izopet
authors.affiliation: Université Paris Descartes, Paris, France; Institut Cochin, INSERM (IMR-S1016), CNRS (UMR 8104), Paris, France; Assistance Publique - Hôpitaux de Paris (APHP), Groupe Hospitalier Cochin Saint-Vincent de Paul, Unité d'Hepatologie, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Mallet
authors.affiliation: Université Paris Descartes, Paris, France; Institut Cochin, INSERM (IMR-S1016), CNRS (UMR 8104), Paris, France; Assistance Publique - Hôpitaux de Paris (APHP), Groupe Hospitalier Cochin Saint-Vincent de Paul, Unité d'Hepatologie, Paris, France.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
authors.affiliation: Laboratory of Dendritic Cell Immunobiology, Institut Pasteur, Paris, France; INSERM U818, Paris, France; Assistance Publique - Hôpitaux de Paris (APHP), Groupe Hospitalier Cochin Saint-Vincent de Paul, Unité d'Hepatologie, Paris, France. Electronic address: albertm@pasteur.fr.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Albert
authors.affiliation: Emerging Disease Epidemiology Unit, Institut Pasteur, Paris, France; Conservatoire National des Arts et Métiers, Paris, France. Electronic address: fontanet@pasteur.fr.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Fontanet
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage; D060085:Coinfection; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D020641:Polymorphism, Single Nucleotide; D012254:Ribavirin / Q000008:administration & dosage*; D016896:Treatment Outcome; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects; D053482:beta 2-Glycoprotein I / Q000097:blood / Q000235:genetics; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012254:Ribavirin; D053482:beta 2-Glycoprotein I; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C571406:PEG-IFN-SA
keywords: Apolipoproteins; Hepatitis C virus; IL28B; Lipid metabolism; Quantitative trait loci