Immune and Endothelial-Related Extracellular Vesicles Are Associated with Corticosteroid Response and Mortality in Alcohol-Associated Hepatitis
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...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2026 |
| País: | España |
| Institución: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repositorio: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:dnet:r-iibsantpa_::120979d6439d1c916b414c1074f1925d |
| Acceso en línea: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=21302 |
| Access Level: | acceso abierto |
| Palabra clave: | alcohol-associated hepatitis extracellular vesicles corticosteroid response |
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Immune and Endothelial-Related Extracellular Vesicles Are Associated with Corticosteroid Response and Mortality in Alcohol-Associated HepatitisGuinart-Cuadra, ABrujats, ASzafranska, JGuerrero, RDinamarca, FCantó, EPoca, MRomán, ESánchez-Ardid, EFajardo, JCamps, MMulet, MSoriano, GEscorsell, AFalcon-Perez, JMGonzalez, EFerrero-Gregori, AGely, CVillalba, JBataller, RArgemi, JOsuna-Gómez, RVidal, SAlvarado-Tapias, Ealcohol-associated hepatitisextracellular vesiclescorticosteroid responseAlcohol-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.MDPI2026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=21302INTERNATIONAL JOURNAL OF MOLECULAR SCIENCESISSN: 16616596ISSNe: 14220067reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:dnet:r-iibsantpa_::120979d6439d1c916b414c1074f1925d2026-06-14T12:41:47Z |
| dc.title.none.fl_str_mv |
Immune and Endothelial-Related Extracellular Vesicles Are Associated with Corticosteroid Response and Mortality in Alcohol-Associated Hepatitis |
| title |
Immune and Endothelial-Related Extracellular Vesicles Are Associated with Corticosteroid Response and Mortality in Alcohol-Associated Hepatitis |
| spellingShingle |
Immune and Endothelial-Related Extracellular Vesicles Are Associated with Corticosteroid Response and Mortality in Alcohol-Associated Hepatitis Guinart-Cuadra, A alcohol-associated hepatitis extracellular vesicles corticosteroid response |
| title_short |
Immune and Endothelial-Related Extracellular Vesicles Are Associated with Corticosteroid Response and Mortality in Alcohol-Associated Hepatitis |
| title_full |
Immune and Endothelial-Related Extracellular Vesicles Are Associated with Corticosteroid Response and Mortality in Alcohol-Associated Hepatitis |
| title_fullStr |
Immune and Endothelial-Related Extracellular Vesicles Are Associated with Corticosteroid Response and Mortality in Alcohol-Associated Hepatitis |
| title_full_unstemmed |
Immune and Endothelial-Related Extracellular Vesicles Are Associated with Corticosteroid Response and Mortality in Alcohol-Associated Hepatitis |
| title_sort |
Immune and Endothelial-Related Extracellular Vesicles Are Associated with Corticosteroid Response and Mortality in Alcohol-Associated Hepatitis |
| dc.creator.none.fl_str_mv |
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 |
| author |
Guinart-Cuadra, A |
| author_facet |
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 |
| author_role |
author |
| author2 |
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 |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
alcohol-associated hepatitis extracellular vesicles corticosteroid response |
| topic |
alcohol-associated hepatitis extracellular vesicles corticosteroid response |
| description |
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. |
| publishDate |
2026 |
| dc.date.none.fl_str_mv |
2026 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=21302 |
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https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=21302 |
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Inglés |
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Inglés |
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info:eu-repo/semantics/openAccess |
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openAccess |
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MDPI |
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MDPI |
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES ISSN: 16616596 ISSNe: 14220067 reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
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Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
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r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
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r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
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