Philippe Sultanik1,2, Vincent Mallet1,2, Sylvie Lagaye2, Armanda Casrouge3, Céline Dorival4, Yoann Barthe4, Hélène Fontaine1,2, Christophe Hézode5, Estelle Mottez6, Jean-Pierre Bronowicki7, Fabrice Carrat4,8, Ioannis Theodorou9, Laurent Abel10,11,12, Etienne Gayat13,14, Arnaud Fontanet15, Stanislas Pol1,2, Matthew L Albert3,6. 1. Department of Hepatology, Hôpital Cochin, AP-HP, Paris, France. 2. INSERM U 1016, CNRS UMR 8104, Université Paris Descartes UMR-S 1016, Paris, France. 3. The laboratory of Dendritic Cell Biology, Departement of Immunology, Institut Pasteur, INSERM U818, Paris, France. 4. UMR-S 707, Université Pierre et Marie Curie-Paris 6 & INSERM, Paris, France. 5. Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, AP-HP, Université Paris-Est, Créteil, France. 6. Centre for Human Immunology, Departement of Immunology, Institut Pasteur, INSERM S20, Paris, France. 7. Centre Hospitalier Universitaire de Nancy, Université de Lorraine, INSERM U954, Vandoeuvre-les-Nancy, France. 8. Department of Public Health, Hôpital Saint-Antoine, AP-HP, Paris, France. 9. Laboratory of Immunity and Infection, Groupe Hospitalier Pitié-Salpêtrière AP-HP, INSERM UMR-S 945, UPMC Université Paris 6, Paris, France. 10. Laboratory of Human Genetics of Infectious Diseases, Necker branch, INSERM U1163, Paris, France. 11. University Paris Descartes, Sorbonne Paris Cité, Imagine Institute, Paris, France. 12. Laboratory of Human Genetics of Infectious Diseases, Rockefeller branch, The Rockefeller University, New-York, USA. 13. Department of Anesthesiology and Critical Care Medicine - Mobile Care Unit, Hôpital Lariboisière, AP-HP, Paris, France. 14. Biomarkers and cardiac diseases, Hôpital Lariboisière, INSERM U942, Paris, France. 15. Departement of Epidemiology of Infectious Disease, Institut Pasteur, Paris, France.
Abstract
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.
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 HCVpatients and expand our understanding of how apoH may intersect with HCV infection.
Authors: Germana Grassi; Giorgia Di Caprio; Gian Maria Fimia; Giuseppe Ippolito; Marco Tripodi; Tonino Alonzi Journal: World J Gastroenterol Date: 2016-02-14 Impact factor: 5.742
Authors: Georgios Grammatikos; Julia Dietz; Nerea Ferreiros; Alexander Koch; Georg Dultz; Dimitra Bon; Ioannis Karakasiliotis; Thomas Lutz; Gaby Knecht; Peter Gute; Eva Herrmann; Stefan Zeuzem; Penelope Mavromara; Christoph Sarrazin; Josef Pfeilschifter Journal: Int J Mol Sci Date: 2016-06-13 Impact factor: 5.923