Molecular characterization of chronic liver disease dynamics: From liver fibrosis to acute-on-chronic liver failure

Background & aims: The molecular mechanisms driving the progression from early-chronic liver disease (CLD) to cirrhosis and, finally, acute-on-chronic liver failure (ACLF) are largely unknown. Our aim was to develop a protein network-based approach to investigate molecular pathways driving progr...

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Autores: Graupera, Isabel, Isus, Laura, Coll, Mar, Pose Méndez, Elisa, Díaz, Alba, Vallverdú, Julia, Rubio Tomás, Teresa, Martínez-Sánchez, Celia, Huelin, Patricia, Llopis, Marta, Solé, Cristina, Fondevila Campo, Constantino, Lozano Salvatella, Juan José, Sancho Bru, Pau, Ginès i Gibert, Pere, Aloy, Patrick, 1972-
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/201621
Acceso en línea:https://hdl.handle.net/2445/201621
Access Level:acceso abierto
Palabra clave:Malalties del fetge
Cirrosi hepàtica
Insuficiència hepàtica
Estructura molecular
Àcids nucleics
Liver diseases
Hepatic cirrhosis
Liver failure
Molecular structure
Nucleic acids
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spelling Molecular characterization of chronic liver disease dynamics: From liver fibrosis to acute-on-chronic liver failureGraupera, IsabelIsus, LauraColl, MarPose Méndez, ElisaDíaz, AlbaVallverdú, JuliaRubio Tomás, TeresaMartínez-Sánchez, CeliaHuelin, PatriciaLlopis, MartaSolé, CristinaFondevila Campo, ConstantinoLozano Salvatella, Juan JoséSancho Bru, PauGinès i Gibert, PereAloy, Patrick, 1972-Malalties del fetgeCirrosi hepàticaInsuficiència hepàticaEstructura molecularÀcids nucleicsLiver diseasesHepatic cirrhosisLiver failureMolecular structureNucleic acidsBackground & aims: The molecular mechanisms driving the progression from early-chronic liver disease (CLD) to cirrhosis and, finally, acute-on-chronic liver failure (ACLF) are largely unknown. Our aim was to develop a protein network-based approach to investigate molecular pathways driving progression from early-CLD to ACLF. Methods: Transcriptome analysis was performed on liver biopsies from patients at different liver disease stages, including fibrosis, compensated cirrhosis, decompensated cirrhosis and ACLF, and control healthy livers. We created 9 liver-specific disease-related protein-protein interaction networks capturing key pathophysiological processes potentially related to CLD. We used these networks as a framework and performed gene set-enrichment analysis (GSEA) to identify dynamic gene profiles of disease progression. Results: Principal component analyses revealed that samples clustered according to the disease stage. GSEA of the defined processes showed an upregulation of inflammation, fibrosis and apoptosis networks throughout disease progression. Interestingly, we did not find significant gene expression differences between compensated and decompensated cirrhosis, while ACLF showed acute expression changes in all the defined liver disease-related networks. The analyses of disease progression patterns identified ascending and descending expression profiles associated with ACLF onset. Functional analyses showed that ascending profiles were associated with inflammation, fibrosis, apoptosis, senescence and carcinogenesis networks, while descending profiles were mainly related to oxidative stress and genetic factors. We confirmed by qPCR the upregulation of genes of the ascending profile and validated our findings in an independent patient cohort. Conclusion: ACLF is characterized by a specific hepatic gene expression pattern related to inflammation, fibrosis, apoptosis, senescence and carcinogenesis. Moreover, the observed profile is significantly different from that of compensated and decompensated cirrhosis, supporting the hypothesis that ACLF should be considered a distinct entity.Elsevier2023202320222023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion12 p.application/pdfhttps://hdl.handle.net/2445/201621Articles publicats en revistes (Medicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1016/j.jhepr.2022.100482Jhep Reports, 2022, vol. 4, num. 6, p. 100482https://doi.org/10.1016/j.jhepr.2022.100482cc-by-nc-nd (c) Graupera, Isabel et al., 2022https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2016212026-05-29T05:05:01Z
dc.title.none.fl_str_mv Molecular characterization of chronic liver disease dynamics: From liver fibrosis to acute-on-chronic liver failure
title Molecular characterization of chronic liver disease dynamics: From liver fibrosis to acute-on-chronic liver failure
spellingShingle Molecular characterization of chronic liver disease dynamics: From liver fibrosis to acute-on-chronic liver failure
Graupera, Isabel
Malalties del fetge
Cirrosi hepàtica
Insuficiència hepàtica
Estructura molecular
Àcids nucleics
Liver diseases
Hepatic cirrhosis
Liver failure
Molecular structure
Nucleic acids
title_short Molecular characterization of chronic liver disease dynamics: From liver fibrosis to acute-on-chronic liver failure
title_full Molecular characterization of chronic liver disease dynamics: From liver fibrosis to acute-on-chronic liver failure
title_fullStr Molecular characterization of chronic liver disease dynamics: From liver fibrosis to acute-on-chronic liver failure
title_full_unstemmed Molecular characterization of chronic liver disease dynamics: From liver fibrosis to acute-on-chronic liver failure
title_sort Molecular characterization of chronic liver disease dynamics: From liver fibrosis to acute-on-chronic liver failure
dc.creator.none.fl_str_mv Graupera, Isabel
Isus, Laura
Coll, Mar
Pose Méndez, Elisa
Díaz, Alba
Vallverdú, Julia
Rubio Tomás, Teresa
Martínez-Sánchez, Celia
Huelin, Patricia
Llopis, Marta
Solé, Cristina
Fondevila Campo, Constantino
Lozano Salvatella, Juan José
Sancho Bru, Pau
Ginès i Gibert, Pere
Aloy, Patrick, 1972-
author Graupera, Isabel
author_facet Graupera, Isabel
Isus, Laura
Coll, Mar
Pose Méndez, Elisa
Díaz, Alba
Vallverdú, Julia
Rubio Tomás, Teresa
Martínez-Sánchez, Celia
Huelin, Patricia
Llopis, Marta
Solé, Cristina
Fondevila Campo, Constantino
Lozano Salvatella, Juan José
Sancho Bru, Pau
Ginès i Gibert, Pere
Aloy, Patrick, 1972-
author_role author
author2 Isus, Laura
Coll, Mar
Pose Méndez, Elisa
Díaz, Alba
Vallverdú, Julia
Rubio Tomás, Teresa
Martínez-Sánchez, Celia
Huelin, Patricia
Llopis, Marta
Solé, Cristina
Fondevila Campo, Constantino
Lozano Salvatella, Juan José
Sancho Bru, Pau
Ginès i Gibert, Pere
Aloy, Patrick, 1972-
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Malalties del fetge
Cirrosi hepàtica
Insuficiència hepàtica
Estructura molecular
Àcids nucleics
Liver diseases
Hepatic cirrhosis
Liver failure
Molecular structure
Nucleic acids
topic Malalties del fetge
Cirrosi hepàtica
Insuficiència hepàtica
Estructura molecular
Àcids nucleics
Liver diseases
Hepatic cirrhosis
Liver failure
Molecular structure
Nucleic acids
description Background & aims: The molecular mechanisms driving the progression from early-chronic liver disease (CLD) to cirrhosis and, finally, acute-on-chronic liver failure (ACLF) are largely unknown. Our aim was to develop a protein network-based approach to investigate molecular pathways driving progression from early-CLD to ACLF. Methods: Transcriptome analysis was performed on liver biopsies from patients at different liver disease stages, including fibrosis, compensated cirrhosis, decompensated cirrhosis and ACLF, and control healthy livers. We created 9 liver-specific disease-related protein-protein interaction networks capturing key pathophysiological processes potentially related to CLD. We used these networks as a framework and performed gene set-enrichment analysis (GSEA) to identify dynamic gene profiles of disease progression. Results: Principal component analyses revealed that samples clustered according to the disease stage. GSEA of the defined processes showed an upregulation of inflammation, fibrosis and apoptosis networks throughout disease progression. Interestingly, we did not find significant gene expression differences between compensated and decompensated cirrhosis, while ACLF showed acute expression changes in all the defined liver disease-related networks. The analyses of disease progression patterns identified ascending and descending expression profiles associated with ACLF onset. Functional analyses showed that ascending profiles were associated with inflammation, fibrosis, apoptosis, senescence and carcinogenesis networks, while descending profiles were mainly related to oxidative stress and genetic factors. We confirmed by qPCR the upregulation of genes of the ascending profile and validated our findings in an independent patient cohort. Conclusion: ACLF is characterized by a specific hepatic gene expression pattern related to inflammation, fibrosis, apoptosis, senescence and carcinogenesis. Moreover, the observed profile is significantly different from that of compensated and decompensated cirrhosis, supporting the hypothesis that ACLF should be considered a distinct entity.
publishDate 2022
dc.date.none.fl_str_mv 2022
2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/201621
url https://hdl.handle.net/2445/201621
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1016/j.jhepr.2022.100482
Jhep Reports, 2022, vol. 4, num. 6, p. 100482
https://doi.org/10.1016/j.jhepr.2022.100482
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Graupera, Isabel et al., 2022
https://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Graupera, Isabel et al., 2022
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 12 p.
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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