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HCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients
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-coi...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419228/ https://www.ncbi.nlm.nih.gov/pubmed/34497613 http://dx.doi.org/10.3389/fimmu.2021.723196 |
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author | Brochado-Kith, Óscar Martínez, Isidoro Berenguer, Juan González-García, Juan Salgüero, Sergio Sepúlveda-Crespo, Daniel Díez, Cristina Hontañón, Víctor Ibañez-Samaniego, Luis Pérez-Latorre, Leire Fernández-Rodríguez, Amanda Ángeles Jiménez-Sousa, María Resino, Salvador |
author_facet | Brochado-Kith, Óscar Martínez, Isidoro Berenguer, Juan González-García, Juan Salgüero, Sergio Sepúlveda-Crespo, Daniel Díez, Cristina Hontañón, Víctor Ibañez-Samaniego, Luis Pérez-Latorre, Leire Fernández-Rodríguez, Amanda Ángeles Jiménez-Sousa, María Resino, Salvador |
author_sort | Brochado-Kith, Óscar |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8419228 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84192282021-09-07 HCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients Brochado-Kith, Óscar Martínez, Isidoro Berenguer, Juan González-García, Juan Salgüero, Sergio Sepúlveda-Crespo, Daniel Díez, Cristina Hontañón, Víctor Ibañez-Samaniego, Luis Pérez-Latorre, Leire Fernández-Rodríguez, Amanda Ángeles Jiménez-Sousa, María Resino, Salvador Front Immunol 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. Frontiers Media S.A. 2021-08-23 /pmc/articles/PMC8419228/ /pubmed/34497613 http://dx.doi.org/10.3389/fimmu.2021.723196 Text en Copyright © 2021 Brochado-Kith, Martínez, Berenguer, González-García, Salgüero, Sepúlveda-Crespo, Díez, Hontañón, Ibañez-Samaniego, Pérez-Latorre, Fernández-Rodríguez, Ángeles Jiménez-Sousa and Resino https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Brochado-Kith, Óscar Martínez, Isidoro Berenguer, Juan González-García, Juan Salgüero, Sergio Sepúlveda-Crespo, Daniel Díez, Cristina Hontañón, Víctor Ibañez-Samaniego, Luis Pérez-Latorre, Leire Fernández-Rodríguez, Amanda Ángeles Jiménez-Sousa, María Resino, Salvador HCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients |
title | HCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients |
title_full | HCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients |
title_fullStr | HCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients |
title_full_unstemmed | HCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients |
title_short | HCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients |
title_sort | hcv cure with direct-acting antivirals improves liver and immunological markers in hiv/hcv-coinfected patients |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419228/ https://www.ncbi.nlm.nih.gov/pubmed/34497613 http://dx.doi.org/10.3389/fimmu.2021.723196 |
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