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

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
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Contributor : Marie-Christine Vougny Connect in order to contact the contributor
Submitted on : Thursday, October 13, 2016 - 3:28:35 PM
Last modification on : Friday, September 23, 2022 - 4:42:24 PM

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Philippe Sultanik, Vincent Mallet, Sylvie Lagaye, Armanda Casrouge, Céline Dorival, et al.. Plasma apolipoprotein H limits HCV replication and associates with response to NS3 protease inhibitors-based therapy. Liver International, Wiley-Blackwell, 2015, 35 (7), pp.1833 - 1844. ⟨10.1111/liv.12759⟩. ⟨pasteur-01380846⟩



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