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2022-04-04

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cc-by-nc-nd (c) Graupera, Isabel et al., 2022
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/201621

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

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Recurs relacionat

https://doi.org/10.1016/j.jhepr.2022.100482

Resum

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.

Matèries

Malalties del fetge, Cirrosi hepàtica, Insuficiència hepàtica, Estructura molecular, Àcids nucleics

Matèries (anglès)

Liver diseases, Hepatic cirrhosis, Liver failure, Molecular structure, Nucleic acids

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Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

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. Molecular characterization of chronic liver disease dynamics: From liver fibrosis to acute-on-chronic liver failure. _Jhep Reports_. 2022. Vol. 4, núm. 6, pàgs. 100482. [consulta: 11 de febrer de 2026]. ISSN: 2589-5559. [Disponible a: https://hdl.handle.net/2445/201621]

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