Plasma apolipoprotein H limits HCV replication and associates with response to NS3 protease inhibitors-based therapy

Autor:	Matthew L. Albert, Yoann Barthe, Armanda Casrouge, Arnaud Fontanet, Stanislas Pol, Sylvie Lagaye, Hélène Fontaine, Vincent Mallet, Philippe Sultanik, Christophe Hézode, Estelle Mottez, Laurent Abel, Etienne Gayat, Céline Dorival, Fabrice Carrat, Jean-Pierre Bronowicki, Ioannis Theodorou
Přispěvatelé:	Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'hépatologie, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie, systèmes d'information, modélisation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Departement d'Hépatho-Gastro-Enterologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre Hospitalier Universitaire Henri Mondor, Centre d'Immunologie Humaine (CIH), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de santé publique [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Immunité et Infection, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York]-Rockefeller Branch, Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of anesthesiology and critical care medicine, Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Département Infection et Epidémiologie - Department of Infection and Epidemiology, Institut Pasteur [Paris], The CUPIC Cohort study was sponsored and funded by The National Agency for research on Aids and Viral Hepatitis (ANRS), with support by the French Association for the Study of the Liver(AFEF). The authors also wish to acknowledge the Center for Human Immunology for its support of the research project., Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP), CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Centre Hospitalier Universitaire Henri Mondor, Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR113-Université Pierre et Marie Curie - Paris 6 (UPMC), Rockefeller Branch-rockefeller university, Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Centre Hospitalier Universitaire Henri Mondor, Centre d'Immunologie Humaine ( CIH ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR113-Université Pierre et Marie Curie - Paris 6 ( UPMC ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Biomarqueurs CArdioNeuroVASCulaires ( BioCANVAS ), Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris 13 ( UP13 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département Infection et Epidémiologie
Rok vydání:	2015
Předmět:	Male MESH : Aged MESH : Prospective Studies MESH : Viral Load MESH : Hepatitis C Chronic/blood Hepacivirus MESH : Virus Replication/drug effects Polyethylene Glycols MESH: Molecular Targeted Therapy [ SDV.IMM ] Life Sciences [q-bio]/Immunology Molecular Targeted Therapy Prospective Studies MESH: Ribavirin/therapeutic use MESH : Proline/analogs & derivatives MESH: Treatment Outcome MESH : Hepacivirus/drug effects MESH: Viral Nonstructural Proteins/metabolism MESH: Middle Aged MESH: RNA Viral/blood virus diseases MESH : beta 2-Glycoprotein I/blood Blood proteins 3. Good health beta 2-Glycoprotein I Area Under Curve MESH: Hepacivirus/genetics Drug Therapy Combination Oligopeptides Apolipoprotein H MESH : Biomarkers/blood MESH: Hepatitis C Chronic/drug therapy Proline MESH: Hepatitis C Chronic/blood virological response MESH: Proline/analogs & derivatives MESH : Antiviral Agents/therapeutic use Antiviral Agents MESH : Proline/therapeutic use Boceprevir MESH : Recombinant Proteins/therapeutic use Humans chronic hepatitis C MESH : Middle Aged Protease Inhibitors MESH: Interferon-alpha/therapeutic use MESH : Predictive Value of Tests Aged MESH: Polyethylene Glycols/therapeutic use MESH : Hepacivirus/genetics MESH: Humans Surrogate endpoint MESH : Humans MESH: beta 2-Glycoprotein I/blood MESH: ROC Curve digestive system diseases chemistry MESH: Protease Inhibitors/therapeutic use Immunology MESH: Female Biomarkers Time Factors MESH : Viral Nonstructural Proteins/antagonists & inhibitors MESH : Hepatitis C Chronic/diagnosis MESH : Protease Inhibitors/therapeutic use Viral Nonstructural Proteins Virus Replication MESH : Polyethylene Glycols/therapeutic use HCV protease inhibitor Telaprevir MESH: Virus Replication/drug effects MESH: Proline/therapeutic use chemistry.chemical_compound apolipoprotein H MESH: Hepacivirus/drug effects MESH : RNA Viral/blood MESH : Female MESH: Hepatitis C Chronic/diagnosis MESH : Viral Nonstructural Proteins/metabolism MESH: Aged Middle Aged Viral Load MESH: Hepacivirus/growth & development Recombinant Proteins MESH: Predictive Value of Tests MESH : Hepacivirus/enzymology Treatment Outcome RNA Viral biomarker [SDV.IMM]Life Sciences [q-bio]/Immunology Biomarker (medicine) Female France MESH: Viral Load MESH : Oligopeptides/therapeutic use MESH : Time Factors medicine.drug MESH : Hepatitis C Chronic/drug therapy MESH : Molecular Targeted Therapy MESH: Biomarkers/blood MESH: Hepacivirus/enzymology MESH : Male MESH : Ribavirin/therapeutic use MESH : Interferon-alpha/therapeutic use MESH : Treatment Outcome Biology Predictive Value of Tests MESH: Recombinant Proteins/therapeutic use Ribavirin medicine MESH : France NS3 MESH: Viral Nonstructural Proteins/antagonists & inhibitors Hepatology MESH : Drug Therapy Combination MESH: Time Factors Interferon-alpha Hepatitis C Chronic MESH : Hepacivirus/growth & development MESH: Male MESH: Prospective Studies MESH: France MESH: Drug Therapy Combination ROC Curve MESH: Antiviral Agents/therapeutic use MESH: Oligopeptides/therapeutic use MESH: Area Under Curve MESH : Area Under Curve MESH : ROC Curve
Zdroj:	Liver International Liver International, Wiley-Blackwell, 2015, 35 (7), pp.1833-1844. ⟨10.1111/liv.12759⟩ Liver International, 2015, 35 (7), pp.1833-1844. ⟨10.1111/liv.12759⟩ Liver International, Wiley-Blackwell, 2015, 35 (7), pp.1833-1844. 〈10.1111/liv.12759〉
ISSN:	1478-3223 1478-3231
DOI:	10.1111/liv.12759
Popis:	International audience; BACKGROUND & AIMS:Chronic infection with HCV remains a public health problem with approximately 150 million people infected worldwide. HCV intersects with lipid metabolism for replication and entry; and plasma concentrations of apolipoproteins have been identified as predictors for response to therapy. Herein, we conducted a screen of plasma proteins, including all apolipoproteins, to identify correlates of response to pegylated-interferon/ribavirin (PR) and HCV non-structural protein 3 (NS3) inhibitors (i.e., telaprevir/boceprevir) therapy in treatment-experienced cirrhotic patients from the ANRS CUPIC cohort.METHODS:We analysed 220 baseline plasma protein concentrations in 189 patients using Luminex technology and analyzed results.RESULTS:We identified baseline levels of apolipoprotein H (apoH) as a surrogate marker for sustained virological response (SVR). Notably, increased plasma concentration of apoH, used in combination with known clinical parameters, established a robust model with improved classification of patients as likely to achieve SVR (AUC = 0.77, Se = 66%, Sp = 72%, NRI = 39%). Moreover, we provide mechanistic information that indicates a previously unidentified role for apoH during viral entry. Using a human liver slices HCV infection model, we demonstrate that apoH limits replication.CONCLUSION:These data support testing of new biomarker strategies for the management of cirrhotic HCV patients and expand our understanding of how apoH may intersect with HCV infection
Databáze:	OpenAIRE
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