Immune and Endothelial-Related Extracellular Vesicles Are Associated with Corticosteroid Response and Mortality in Alcohol-Associated Hepatitis
Por:
Guinart-Cuadra, A, Brujats, A, Szafranska, J, Guerrero, R, Dinamarca, F, Cantó, E, Poca, M, Román, E, Sánchez-Ardid, E, Fajardo, J, Camps, M, Mulet, M, Soriano, G, Escorsell, A, Falcon-Perez, JM, Gonzalez, E, Ferrero-Gregori, A, Gely, C, Villalba, J, Bataller, R, Argemi, J, Osuna-Gómez, R, Vidal, S, Alvarado-Tapias, E
Publicada:
27 ene 2026
Resumen:
Alcohol-associated hepatitis (AH) is the most severe clinical manifestation of alcohol-associated liver disease. Corticosteroids are the only disease-specific therapy shown to improve short-term survival. Currently, no non-invasive markers are available to predict patient response to corticosteroids or long-term survival in AH. This study investigates whether surface antigens on plasma extracellular vesicles (EVs), key mediators of intercellular communication, can reflect the underlying immune dysregulation in AH and serve as prognostic markers. Patients with AH were prospectively enrolled between 2020 and 2024. Blood samples were collected before corticosteroid initiation during the first 24 h of hospitalization. EVs were characterized using nanoparticle tracking analysis, cryo-electron microscopy, and flow cytometry. Interleukin-6 (IL-6), soluble (s)CD62p, Circulating Vascular Cell Adhesion Molecule-1 (sVCAM), tumor necrosis factor receptor superfamily member 1 (TNRFS1a), and Intercellular Adhesion Molecule 1 (ICAM-1) were quantified by ELISA. Key outcome variables included response to corticosteroids and mortality. A total of 46 patients with AH and 28 healthy donors (HD) were included. EV concentration was significantly higher in AH patients than in HD (9.3 x 1011 [IQR 4-24] versus 2.4 x 1011 [IQR 2-4], p = 0.03). Specific EV antigens were associated with key clinical outcomes: CD20 and CD2 levels differed between patients with or without infections (bacterial, viral, and fungal) developed during hospitalization; CD40 and CD146 were elevated in patients who developed acute kidney injury. EVs enriched in monocyte (CD14) and T-reg (CD25) markers were associated with plasma IL-6 levels, while endothelial markers CD105 and CD146 correlated with sVCAM and sCD62p. EVs enriched in platelet (CD49e) and endothelial (CD31) markers were associated with corticosteroid response, whereas EVs enriched with endothelial (CD105 and CD146) and B lymphocyte (CD19) markers were associated with mortality. Overall, EVs enriched in endothelial and monocyte markers may represent a candidate non-invasive tool for predicting corticosteroid response and mortality in AH, aiding risk stratification and early identification of non-responders for timely transplant evaluation.
Filiaciones:
Guinart-Cuadra, A:
Inst Recerca St Pau, Grp Inflammatory Dis, Barcelona 08041, Spain
Inst Salud Carlos III, Ctr Biomed Res Liver & Digest Dis Network CIBERehd, Madrid 28029, Spain
Univ Autonoma Barcelona, Dept Biol Cellular Fisiol & Immunol, Campus UAB, Cerdanyola Del Valles 08193, Spain
Brujats, A:
Inst Salud Carlos III, Ctr Biomed Res Liver & Digest Dis Network CIBERehd, Madrid 28029, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Gastroenterol & Hepatol Dept, Dept Med, Barcelona 08025, Spain
Szafranska, J:
Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona 08041, Spain
Guerrero, R:
Hosp Santa Creu & Sant Pau, Dept Intervent Radiol, Barcelona 08041, Spain
Dinamarca, F:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau, Dept Psychiat, Barcelona 08041, Spain
Cantó, E:
Inst Recerca St Pau, Grp Inflammatory Dis, Barcelona 08041, Spain
Poca, M:
Inst Salud Carlos III, Ctr Biomed Res Liver & Digest Dis Network CIBERehd, Madrid 28029, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Gastroenterol & Hepatol Dept, Dept Med, Barcelona 08025, Spain
Román, E:
Inst Salud Carlos III, Ctr Biomed Res Liver & Digest Dis Network CIBERehd, Madrid 28029, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Gastroenterol & Hepatol Dept, Dept Med, Barcelona 08025, Spain
Sánchez-Ardid, E:
Inst Salud Carlos III, Ctr Biomed Res Liver & Digest Dis Network CIBERehd, Madrid 28029, Spain
Fajardo, J:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Gastroenterol & Hepatol Dept, Dept Med, Barcelona 08025, Spain
Camps, M:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Gastroenterol & Hepatol Dept, Dept Med, Barcelona 08025, Spain
Mulet, M:
Inst Recerca St Pau, Grp Inflammatory Dis, Barcelona 08041, Spain
Soriano, G:
Inst Salud Carlos III, Ctr Biomed Res Liver & Digest Dis Network CIBERehd, Madrid 28029, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Gastroenterol & Hepatol Dept, Dept Med, Barcelona 08025, Spain
Escorsell, A:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Gastroenterol & Hepatol Dept, Dept Med, Barcelona 08025, Spain
Falcon-Perez, JM:
Inst Salud Carlos III, Ctr Biomed Res Liver & Digest Dis Network CIBERehd, Madrid 28029, Spain
Basque Res & Technol Alliance, Ctr Cooperat Res Biosci C bioGUNE, Exosomes Lab, Elaxalde Derio 48160, Bizkaia, Spain
IKERBasque Basque Fdn Sci, Bilbao 48009, Spain
Gonzalez, E:
Basque Res & Technol Alliance, Ctr Cooperat Res Biosci C bioGUNE, Exosomes Lab, Elaxalde Derio 48160, Bizkaia, Spain
Ferrero-Gregori, A:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Gastroenterol & Hepatol Dept, Dept Med, Barcelona 08025, Spain
Gely, C:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Gastroenterol & Hepatol Dept, Dept Med, Barcelona 08025, Spain
Villalba, J:
Hosp Santa Creu & Sant Pau, Dept Intervent Radiol, Barcelona 08041, Spain
Bataller, R:
Hosp Clin Barcelona, Dept Digest & Metab Dis, Liver Unit, Barcelona 08036, Spain
Argemi, J:
Inst Salud Carlos III, Ctr Biomed Res Liver & Digest Dis Network CIBERehd, Madrid 28029, Spain
Clin Univ Navarra, Liver Unit & HPB Oncol Area, Pamplona 31008, Spain
Univ Navarra, Ctr Appl Med Res CIMA, Computat Biol & Translat Genom Program, Pamplona 31008, Spain
Inst Invest Sanitaria Navarra IdiSNA, Pamplona 31008, Spain
Univ Navarra, Ctr Appl Med Res CIMA, Solid Tumors Program, Hepatol Lab, Pamplona 31009, Spain
Osuna-Gómez, R:
Inst Recerca St Pau, Grp Inflammatory Dis, Barcelona 08041, Spain
Vidal, S:
Inst Recerca St Pau, Grp Inflammatory Dis, Barcelona 08041, Spain
Alvarado-Tapias, E:
Inst Recerca St Pau, Grp Inflammatory Dis, Barcelona 08041, Spain
Inst Salud Carlos III, Ctr Biomed Res Liver & Digest Dis Network CIBERehd, Madrid 28029, Spain
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Gastroenterol & Hepatol Dept, Dept Med, Barcelona 08025, Spain
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