2026-06-14T02:28:52Zhttps://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

00925njm 22002777a 4500 dc 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 author 2026-02-02 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. 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 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.