Plasma apolipoprotein H limits HCV replication and associates with response to NS3 protease inhibitors-based therapy - Archive ouverte HAL Access content directly
Journal Articles Liver International Year : 2015

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

(1, 2) , (2, 1) , (1) , (3) , (4) , (4) , (2, 1) , (5) , (6) , (7, 8) , (9, 4) , (10) , (11, 12) , (13, 14) , (15) , (2) , (6, 3)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Vincent Mallet
Sylvie Lagaye
Ioannis Theodorou
Stanislas Pol

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

Dates and versions

pasteur-01380846 , version 1 (13-10-2016)

Identifiers

Cite

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, 2015, 35 (7), pp.1833 - 1844. ⟨10.1111/liv.12759⟩. ⟨pasteur-01380846⟩
101 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More