2026-06-14T03:54:07Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/273502026-03-26T01:17:57Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud author Martín-Escolano, Rubén author Fernandez-Rodriguez, Amanda author Tarancon-Diez, Laura author Berenguer, Juan author Codina Márquez, Helena author Amigot-Sánchez, Rafael author González-García, Juan author Hontañón, Víctor author Pérez-Latorre, Leire author Ibañez-Samaniego, Luis author Llop-Herrera, Elba author Olveira, Antonio author Díaz, Laura author Martinez, Isidoro author Jimenez-Sousa, Maria Angeles author Resino, Salvador funder Instituto de Salud Carlos III funder Agencia Estatal de Investigación (España) funder Unión Europea. Comisión Europea. NextGenerationEU funder Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas) funder Comunidad de Madrid (España) 2026-03-25T15:16:09Z 2026-03-25T15:16:09Z 2026-02-02 Martín-Escolano R, Fernández-Rodríguez A, Tarancon-Diez L, Berenguer J, Codina H, Amigot-Sánchez R, González-García J, Hontañón V, Pérez-Latorre L, Ibañez-Samaniego L, Llop-Herrera E, Olveira A, Díaz L, Martínez I, Jiménez-Sousa MÁ and Resino S (2026) HIV status defines distinct immunological drivers of persistent portal hypertension after HCV cure in people with advanced cirrhosis. Front. Immunol. 17:1683092. doi: 10.3389/fimmu.2026.1683092. 10.3389/fimmu.2026.1683092 Frontiers in Immunology 41705254 https://hdl.handle.net/20.500.12105/27350 Introduction: The immunological drivers of portal hypertension regression after hepatitis C virus (HCV) cure are poorly understood, particularly in the context of human immunodeficiency virus (HIV) coinfection We aimed to identify baseline immune signatures predicting the evolution of the hepatic venous pressure gradient (HVPG) in people with and without HIV (PWH/PWoH). Methods: We prospectively followed 41 individuals with advanced cirrhosis (18 PWoH, 23 PWH) who were cured of HCV with direct-acting antivirals (DAA). Baseline plasma and cellular immune markers were extensively profiled using multiplex assays and flow cytometry. We used mixed-effects modeling to test for associations between these baseline immune features and the change in HVPG over a 48-week follow-up period, with q-values controlling for false discoveries. Results: Two distinct immunological profiles of impaired HVPG regression emerged. In PWoH, impaired regression was linked to a broad proinflammatory profile [TNF-α (AMR = 1.13; q=0.012), IL17A (AMR = 1.28; q=0.012), and IL10 (AMR = 1.2; q=0.028)], a widespread total CD4+ T-cell activation [HLA-DR+ (AMR = 1.44; q<0.001) and CD38+HLA-DR+ (AMR = 1.3; q=0.007)], and robust activation across central memory (CM) and effector memory (EM) subsets. Conversely, in PWH, impaired HVPG regression was associated with sVCAM-1 (AMR = 1.58; q=0.096), and a more focused activation within EM (HLA-DR+, AMR = 1.08; q=0.030) and TemRA (CD38+HLA-DR+, AMR = 1.12; q=0.030) CD4+ T-cells. Discussion: HIV coinfection fundamentally reshapes the immunological landscape of post-cure portal hypertension recovery. The shift from systemic inflammation in PWoH to endothelial dysfunction and T-cell exhaustion in PWH reveals distinct pathological pathways. Understanding these signatures is a crucial step toward developing targeted therapies to promote complete hepatic recovery. eng DAA therapy HIV HVPG regression Biomarkers Chronic hepatitis C Immunological profile HIV status defines distinct immunological drivers of persistent portal hypertension after HCV cure in people with advanced cirrhosis. research article 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 URL https://repisalud.isciii.es/bitstreams/350b94ba-e04a-4cc6-9ab2-002cfbbb1898/download File MD5 7d892e1dd555e3a3d6c412de3ea0b20e 593103 application/pdf HIV_StatusDefinesDistinct_2026.pdf URL https://repisalud.isciii.es/bitstreams/53392c05-e142-42d6-9598-4e9497cdf3a9/download File MD5 50a8828935b976c6572880e4f9cf43ed 691286 application/vnd.openxmlformats-officedocument.wordprocessingml.document Supplementary_HIV_StatusDefinesDistinct_2026.docx