2024-03-29T08:28:47Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/142012023-10-05T08:13:57Zcom_20.500.12105_15322com_20.500.12105_2051com_20.500.12105_2060com_20.500.12105_2052col_20.500.12105_16978col_20.500.12105_16963col_20.500.12105_2061
Repisalud
author
Brochado-Kith, Oscar
author
Martinez, Isidoro
author
Berenguer, Juan
author
González-García, Juan
author
Salgüero Fernandez, Sergio
author
Sepulveda-Crespo, Daniel
author
Díez, Cristina
author
Hontañón, Víctor
author
Ibañez-Samaniego, Luis
author
Pérez-Latorre, Leire
author
Fernandez-Rodriguez, Amanda
author
Jimenez-Sousa, Maria Angeles
author
Resino, Salvador
funder
Instituto de Salud Carlos III
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Plan Nacional de I+D+i (España)
funder
Fundación Seimc-Gesida
funder
Fundación ONCE
funder
Unión Europea. Fondo Social Europeo (ESF/FSE)
funder
Sistema Nacional de Salud (España)
2022-04-27T11:05:00Z
2022-04-27T11:05:00Z
2021
Front Immunol. 2021;12:723196
http://hdl.handle.net/20.500.12105/14201
34497613
10.3389/fimmu.2021.723196
1664-3224
Frontiers in Immunology
Hepatitis C virus (HCV) cure after all-oral direct-acting antiviral (DAA) therapy greatly improves the liver and immune system. We aimed to assess the impact of this HCV clearance on immune system-related markers in plasma and the gene expression profile in human immunodeficiency virus (HIV)/HCV-coinfected patients with advanced cirrhosis. We performed a prospective study on 33 HIV/HCV-coinfected patients at baseline and 36 weeks after the sustained virological response. Gene expression was evaluated by RNA-seq analysis on peripheral blood mononuclear cells (PBMCs) and plasma biomarkers by multiplex immunoassays. We found a decrease in plasma biomarkers (PD1, PDL1, CXCL10, CXCL8, IL12p70, IL10, and TGFβ) and liver disease markers (stiffness measurement (LSM), hepatic venous pressure gradient (HVPG), and transaminases, among others). Furthermore, decreased plasma levels of CXCL8, CXCL10, IL10, and PD1 were associated with reduced LSM values. We also found two upregulated (HAS1 and IRG1) and 15 downregulated (CXCL11, CCL8, CCL7, CCL2, ADARB2, RRAD, MX1, SIGLEC1, IFI44L, IFI44, IFI27, IFI6, IFIT3, IFIT1B, and IFIT1) genes at the end of follow-up, all interferon-stimulated genes (ISGs) grouped into four pathways ("cytokine-cytokine receptor interaction", "viral protein interaction with cytokine and cytokine receptor", "chemokine signaling pathway", and "hepatitis C"). Additionally, the decrease in most of these ISGs was significantly related to reduced LSM and HVPG values. In conclusion, HIV/HCV-coinfected patients with advanced-HCV-related cirrhosis who eradicated HCV following DAA therapy exhibited an improvement in liver disease markers and a significant decrease in plasma biomarkers and gene expression related to antiviral/inflammatory response, particularly in levels of several chemokines and ISGs.
eng
DAA therapy
HIV/HCV coinfection
PBMCs
Cirrhosis
Gene expression
Immune system
Plasma biomarkers
HCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients
journal article
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URL
https://repisalud.isciii.es/bitstream/20.500.12105/14201/1/HCVCureWithDirect_2021.pdf
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https://repisalud.isciii.es/bitstream/20.500.12105/14201/5/HCVCureWithDirect_2021.pdf.txt
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HCVCureWithDirect_2021.pdf.txt