HCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients.

Autor:	Brochado-Kith Ó; Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain., Martínez I; Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain., Berenguer J; Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario 'Gregorio Marañón', Madrid, Spain.; Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain., González-García J; Unidad de VIH, Servicio de Medicina Interna, Hospital Universitario 'La Paz', Madrid, Spain.; Instituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, Spain., Salgüero S; Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.; Unidad de Análisis Clínicos, Hospital Universitario Fundación Alcorcón, Alcorcón, Spain., Sepúlveda-Crespo D; Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain., Díez C; Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario 'Gregorio Marañón', Madrid, Spain.; Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain., Hontañón V; Unidad de VIH, Servicio de Medicina Interna, Hospital Universitario 'La Paz', Madrid, Spain.; Instituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, Spain., Ibañez-Samaniego L; Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain.; Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Madrid, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain., Pérez-Latorre L; Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario 'Gregorio Marañón', Madrid, Spain.; Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain., Fernández-Rodríguez A; Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain., Ángeles Jiménez-Sousa M; Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain., Resino S; Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2021 Aug 23; Vol. 12, pp. 723196. Date of Electronic Publication: 2021 Aug 23 (Print Publication: 2021).
DOI:	10.3389/fimmu.2021.723196
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Brochado-Kith, Martínez, Berenguer, González-García, Salgüero, Sepúlveda-Crespo, Díez, Hontañón, Ibañez-Samaniego, Pérez-Latorre, Fernández-Rodríguez, Ángeles Jiménez-Sousa and Resino.)
Databáze:	MEDLINE
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