Clinical and molecular characterization of steatotic liver disease in the setting of immune-mediated inflammatory diseases

Background & Aims: Growing evidence suggests an increased prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in the context of immune-mediated inflammatory diseases (IMIDs). We aimed to clinically and mechanistically characterize steatotic liver disease (SLD) in a pro...

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Autores: García Nieto, Enrique, Rodríguez Duque, Juan Carlos, Rivas Rivas, Coral, Iruzubieta Coz, Paula, García, María José, Rasines, Laura, Álvarez Cancelo, Laura, García Blanco, Agustín, Fortea, José Ignacio, Puente, Ángela, Castro, Beatriz, Cagigal, María Luisa, Rueda-gotor, Javier, Blanco, Ricardo, Vaqué Díez, José Pedro|||0000-0002-3913-2495, Crespo, Javier, Arias-Loste, María Teresa
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad de Cantabria (UC)
Repositorio:UCrea Repositorio Abierto de la Universidad de Cantabria
Idioma:inglés
OAI Identifier:oai:repositorio.unican.es:10902/34182
Acceso en línea:https://hdl.handle.net/10902/34182
Access Level:acceso abierto
Palabra clave:MASLD
SLD
IMID
Advanced fibrosis
Transcriptome
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spelling Clinical and molecular characterization of steatotic liver disease in the setting of immune-mediated inflammatory diseasesGarcía Nieto, EnriqueRodríguez Duque, Juan CarlosRivas Rivas, CoralIruzubieta Coz, PaulaGarcía, María JoséRasines, LauraÁlvarez Cancelo, LauraGarcía Blanco, AgustínFortea, José IgnacioPuente, ÁngelaCastro, BeatrizCagigal, María LuisaRueda-gotor, JavierBlanco, RicardoVaqué Díez, José Pedro|||0000-0002-3913-2495Crespo, JavierArias-Loste, María TeresaMASLDSLDIMIDAdvanced fibrosisTranscriptomeBackground & Aims: Growing evidence suggests an increased prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in the context of immune-mediated inflammatory diseases (IMIDs). We aimed to clinically and mechanistically characterize steatotic liver disease (SLD) in a prospective cohort of patients with IMID compared to controls. Methods: Cross-sectional, case-control study including a subset of patients with IMID. Controls from the general population were age-, sex-, type 2 diabetes-, and BMI-matched at a 1:2 ratio. SLD was established using controlled attenuation parameter. Liver biopsies were obtained when significant liver fibrosis was suspected. Total RNA was extracted from freshly frozen cases and analyzed by RNA-seq. Differential gene expression was performed with ‘limma-voom’. Gene set-enrichment analysis was per formed using the fgsea R package with a preranked “limma t-statistic” gene list. Results: A total of 1,456 patients with IMID and 2,945 controls were included. Advanced SLD (liver stiffness measurement ≥9.7 kPa) (13.46% vs. 3.79%; p <0.001) and advanced MASLD (12.8% vs. 2.8%; p <0.001) prevalence were significantly higher among patients with IMID than controls. In multivariate analysis, concomitant IMID was an independent, and the strongest, predictor of advanced SLD (adjusted odds ratio 3.318; 95% CI 2.225-4.947; p <0.001). Transcriptomic data was obtained in 109 patients and showed 87 significant genes differentially expressed between IMID-MASLD and control-MASLD. IMID-MASLD cases displayed an enriched expression of genes implicated in pro-tumoral activities or the control of the cell cycle concomitant with a negative expression of genes related to metabolism. Conclusions: The prevalence of advanced SLD and MASLD is disproportionately elevated in IMID cohorts. Our findings suggest that IMIDs may catalyze a distinct MASLD pathway, divergent from classical metabolic routes, highlighting the need for tailored clinical management strategies.Acknowledgments: This work was fully suported by grants from the Spanish Instituto de Salud Carlos III (ISCIII-FEDER). Grant numbers: PI18/01304, PI20/01279, and PI19/00204This work was fully suported by grants from the Spanish Instituto de Salud Carlos III (ISCIII-FEDER). Grant numbers: PI18/01304, PI20/01279, and PI19/00204.ElsevierUniversidad de Cantabria20242024-01-01journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articlehttps://hdl.handle.net/10902/34182JHEP Reports, 2024, 6 (10), 101167reponame:UCrea Repositorio Abierto de la Universidad de Cantabriainstname:Universidad de Cantabria (UC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repositorio.unican.es:10902/341822026-06-02T12:39:31Z
dc.title.none.fl_str_mv Clinical and molecular characterization of steatotic liver disease in the setting of immune-mediated inflammatory diseases
title Clinical and molecular characterization of steatotic liver disease in the setting of immune-mediated inflammatory diseases
spellingShingle Clinical and molecular characterization of steatotic liver disease in the setting of immune-mediated inflammatory diseases
García Nieto, Enrique
MASLD
SLD
IMID
Advanced fibrosis
Transcriptome
title_short Clinical and molecular characterization of steatotic liver disease in the setting of immune-mediated inflammatory diseases
title_full Clinical and molecular characterization of steatotic liver disease in the setting of immune-mediated inflammatory diseases
title_fullStr Clinical and molecular characterization of steatotic liver disease in the setting of immune-mediated inflammatory diseases
title_full_unstemmed Clinical and molecular characterization of steatotic liver disease in the setting of immune-mediated inflammatory diseases
title_sort Clinical and molecular characterization of steatotic liver disease in the setting of immune-mediated inflammatory diseases
dc.creator.none.fl_str_mv García Nieto, Enrique
Rodríguez Duque, Juan Carlos
Rivas Rivas, Coral
Iruzubieta Coz, Paula
García, María José
Rasines, Laura
Álvarez Cancelo, Laura
García Blanco, Agustín
Fortea, José Ignacio
Puente, Ángela
Castro, Beatriz
Cagigal, María Luisa
Rueda-gotor, Javier
Blanco, Ricardo
Vaqué Díez, José Pedro|||0000-0002-3913-2495
Crespo, Javier
Arias-Loste, María Teresa
author García Nieto, Enrique
author_facet García Nieto, Enrique
Rodríguez Duque, Juan Carlos
Rivas Rivas, Coral
Iruzubieta Coz, Paula
García, María José
Rasines, Laura
Álvarez Cancelo, Laura
García Blanco, Agustín
Fortea, José Ignacio
Puente, Ángela
Castro, Beatriz
Cagigal, María Luisa
Rueda-gotor, Javier
Blanco, Ricardo
Vaqué Díez, José Pedro|||0000-0002-3913-2495
Crespo, Javier
Arias-Loste, María Teresa
author_role author
author2 Rodríguez Duque, Juan Carlos
Rivas Rivas, Coral
Iruzubieta Coz, Paula
García, María José
Rasines, Laura
Álvarez Cancelo, Laura
García Blanco, Agustín
Fortea, José Ignacio
Puente, Ángela
Castro, Beatriz
Cagigal, María Luisa
Rueda-gotor, Javier
Blanco, Ricardo
Vaqué Díez, José Pedro|||0000-0002-3913-2495
Crespo, Javier
Arias-Loste, María Teresa
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad de Cantabria
dc.subject.none.fl_str_mv MASLD
SLD
IMID
Advanced fibrosis
Transcriptome
topic MASLD
SLD
IMID
Advanced fibrosis
Transcriptome
description Background & Aims: Growing evidence suggests an increased prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in the context of immune-mediated inflammatory diseases (IMIDs). We aimed to clinically and mechanistically characterize steatotic liver disease (SLD) in a prospective cohort of patients with IMID compared to controls. Methods: Cross-sectional, case-control study including a subset of patients with IMID. Controls from the general population were age-, sex-, type 2 diabetes-, and BMI-matched at a 1:2 ratio. SLD was established using controlled attenuation parameter. Liver biopsies were obtained when significant liver fibrosis was suspected. Total RNA was extracted from freshly frozen cases and analyzed by RNA-seq. Differential gene expression was performed with ‘limma-voom’. Gene set-enrichment analysis was per formed using the fgsea R package with a preranked “limma t-statistic” gene list. Results: A total of 1,456 patients with IMID and 2,945 controls were included. Advanced SLD (liver stiffness measurement ≥9.7 kPa) (13.46% vs. 3.79%; p <0.001) and advanced MASLD (12.8% vs. 2.8%; p <0.001) prevalence were significantly higher among patients with IMID than controls. In multivariate analysis, concomitant IMID was an independent, and the strongest, predictor of advanced SLD (adjusted odds ratio 3.318; 95% CI 2.225-4.947; p <0.001). Transcriptomic data was obtained in 109 patients and showed 87 significant genes differentially expressed between IMID-MASLD and control-MASLD. IMID-MASLD cases displayed an enriched expression of genes implicated in pro-tumoral activities or the control of the cell cycle concomitant with a negative expression of genes related to metabolism. Conclusions: The prevalence of advanced SLD and MASLD is disproportionately elevated in IMID cohorts. Our findings suggest that IMIDs may catalyze a distinct MASLD pathway, divergent from classical metabolic routes, highlighting the need for tailored clinical management strategies.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10902/34182
url https://hdl.handle.net/10902/34182
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv JHEP Reports, 2024, 6 (10), 101167
reponame:UCrea Repositorio Abierto de la Universidad de Cantabria
instname:Universidad de Cantabria (UC)
instname_str Universidad de Cantabria (UC)
reponame_str UCrea Repositorio Abierto de la Universidad de Cantabria
collection UCrea Repositorio Abierto de la Universidad de Cantabria
repository.name.fl_str_mv
repository.mail.fl_str_mv
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