Molecular Profiling of Decompensated Cirrhosis by a Novel MicroRNA Signature

Noninvasive staging of decompensated cirrhosis is an unmet clinical need. The aims of this study were to characterize and validate a novel microRNA (miRNA) signature to stage decompensated cirrhosis and predict the portal pressure and systolic cardiac response to nonselective beta-blockers (NSBBs)....

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Autores: García García de Paredes, Ana, Manicardi, Nicolo, Tellez, Luis, Ibañez, Luis, Royo, Felix, Bermejo, Javier, Blanco, Carolina, Fondevila Campo, Constantino, Fernández Lanza, Val, García Bermejo, Laura, Falcón Pérez, Juan Manuel, Bañares, Rafael, Gracia Sancho, Jordi, Albillos, Agustín
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Recursos: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:2445/177844
Acesso em linha:https://hdl.handle.net/2445/177844
Access Level:acceso abierto
Palavra-chave:Cirrosi hepàtica
Micro RNAs
Marcadors bioquímics
Hepatic cirrhosis
MicroRNAs
Biochemical markers
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spelling Molecular Profiling of Decompensated Cirrhosis by a Novel MicroRNA SignatureGarcía García de Paredes, AnaManicardi, NicoloTellez, LuisIbañez, LuisRoyo, FelixBermejo, JavierBlanco, CarolinaFondevila Campo, ConstantinoFernández Lanza, ValGarcía Bermejo, LauraFalcón Pérez, Juan ManuelBañares, RafaelGracia Sancho, JordiAlbillos, AgustínCirrosi hepàticaMicro RNAsMarcadors bioquímicsHepatic cirrhosisMicroRNAsBiochemical markersNoninvasive staging of decompensated cirrhosis is an unmet clinical need. The aims of this study were to characterize and validate a novel microRNA (miRNA) signature to stage decompensated cirrhosis and predict the portal pressure and systolic cardiac response to nonselective beta-blockers (NSBBs). Serum samples from patients with decompensated cirrhosis (n = 36) and healthy controls (n = 36) were tested for a novel signature of five miRNAs (miR-452-5p, miR-429, miR-885-5p, miR-181b-5p, and miR-122-5p) identified in the secretome of primary human hepatocytes and for three miRNAs (miR-192-5p, miR-34a-5p, and miR-29a-5p) previously discovered as biomarkers of chronic liver disease. All patients had ascites, which was refractory in 18 (50%), and were placed on NSBBs for variceal bleeding prophylaxis. In all patients, serum miRNAs, hepatic venous pressure gradient, and an echocardiogram study were performed before and 1 month after NSBBs. Patients with cirrhosis had lower serum levels of miR-429, miR-885-5p, miR-181b-5p, miR-122-5p, miR-192-5p, and miR-29a-5p (P < 0.05). Baseline serum miR-452-5p and miR-429 levels were lower in NSBB responders (P = 0.006). miR-181b-5p levels were greater in refractory ascites than in diuretic-sensitive ascites (P = 0.008) and correlated with serum creatinine. miR-452-5p and miR-885-5p were inversely correlated with baseline systemic vascular resistance (ρ = −0.46, P = 0.007; and ρ = −0.41, P = 0.01, respectively) and with diminished systolic contractility (ρ = −0.55, P = 0.02; and ρ = −0.55, P = 0.02, respectively) in patients with refractory ascites after NSBBs. Conclusion: Analysis of a miRNA signature in serum discriminates between patients with decompensated cirrhosis who show more severe systemic circulatory dysfunction and compromised systolic function after beta-blockade and those more likely to benefit from NSBBs.John Wiley & Sons2021202120202021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion14 p.application/pdfhttps://hdl.handle.net/2445/177844Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)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/10.1002/hep4.1642Hepatology Communications, 2020, vol. 5, num. 2, p. 309-322https://doi.org/10.1002/hep4.1642cc-by (c) García García de Paredes, Ana et al., 2020https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1778442026-05-29T05:05:01Z
dc.title.none.fl_str_mv Molecular Profiling of Decompensated Cirrhosis by a Novel MicroRNA Signature
title Molecular Profiling of Decompensated Cirrhosis by a Novel MicroRNA Signature
spellingShingle Molecular Profiling of Decompensated Cirrhosis by a Novel MicroRNA Signature
García García de Paredes, Ana
Cirrosi hepàtica
Micro RNAs
Marcadors bioquímics
Hepatic cirrhosis
MicroRNAs
Biochemical markers
title_short Molecular Profiling of Decompensated Cirrhosis by a Novel MicroRNA Signature
title_full Molecular Profiling of Decompensated Cirrhosis by a Novel MicroRNA Signature
title_fullStr Molecular Profiling of Decompensated Cirrhosis by a Novel MicroRNA Signature
title_full_unstemmed Molecular Profiling of Decompensated Cirrhosis by a Novel MicroRNA Signature
title_sort Molecular Profiling of Decompensated Cirrhosis by a Novel MicroRNA Signature
dc.creator.none.fl_str_mv García García de Paredes, Ana
Manicardi, Nicolo
Tellez, Luis
Ibañez, Luis
Royo, Felix
Bermejo, Javier
Blanco, Carolina
Fondevila Campo, Constantino
Fernández Lanza, Val
García Bermejo, Laura
Falcón Pérez, Juan Manuel
Bañares, Rafael
Gracia Sancho, Jordi
Albillos, Agustín
author García García de Paredes, Ana
author_facet García García de Paredes, Ana
Manicardi, Nicolo
Tellez, Luis
Ibañez, Luis
Royo, Felix
Bermejo, Javier
Blanco, Carolina
Fondevila Campo, Constantino
Fernández Lanza, Val
García Bermejo, Laura
Falcón Pérez, Juan Manuel
Bañares, Rafael
Gracia Sancho, Jordi
Albillos, Agustín
author_role author
author2 Manicardi, Nicolo
Tellez, Luis
Ibañez, Luis
Royo, Felix
Bermejo, Javier
Blanco, Carolina
Fondevila Campo, Constantino
Fernández Lanza, Val
García Bermejo, Laura
Falcón Pérez, Juan Manuel
Bañares, Rafael
Gracia Sancho, Jordi
Albillos, Agustín
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cirrosi hepàtica
Micro RNAs
Marcadors bioquímics
Hepatic cirrhosis
MicroRNAs
Biochemical markers
topic Cirrosi hepàtica
Micro RNAs
Marcadors bioquímics
Hepatic cirrhosis
MicroRNAs
Biochemical markers
description Noninvasive staging of decompensated cirrhosis is an unmet clinical need. The aims of this study were to characterize and validate a novel microRNA (miRNA) signature to stage decompensated cirrhosis and predict the portal pressure and systolic cardiac response to nonselective beta-blockers (NSBBs). Serum samples from patients with decompensated cirrhosis (n = 36) and healthy controls (n = 36) were tested for a novel signature of five miRNAs (miR-452-5p, miR-429, miR-885-5p, miR-181b-5p, and miR-122-5p) identified in the secretome of primary human hepatocytes and for three miRNAs (miR-192-5p, miR-34a-5p, and miR-29a-5p) previously discovered as biomarkers of chronic liver disease. All patients had ascites, which was refractory in 18 (50%), and were placed on NSBBs for variceal bleeding prophylaxis. In all patients, serum miRNAs, hepatic venous pressure gradient, and an echocardiogram study were performed before and 1 month after NSBBs. Patients with cirrhosis had lower serum levels of miR-429, miR-885-5p, miR-181b-5p, miR-122-5p, miR-192-5p, and miR-29a-5p (P < 0.05). Baseline serum miR-452-5p and miR-429 levels were lower in NSBB responders (P = 0.006). miR-181b-5p levels were greater in refractory ascites than in diuretic-sensitive ascites (P = 0.008) and correlated with serum creatinine. miR-452-5p and miR-885-5p were inversely correlated with baseline systemic vascular resistance (ρ = −0.46, P = 0.007; and ρ = −0.41, P = 0.01, respectively) and with diminished systolic contractility (ρ = −0.55, P = 0.02; and ρ = −0.55, P = 0.02, respectively) in patients with refractory ascites after NSBBs. Conclusion: Analysis of a miRNA signature in serum discriminates between patients with decompensated cirrhosis who show more severe systemic circulatory dysfunction and compromised systolic function after beta-blockade and those more likely to benefit from NSBBs.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
2021
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/2445/177844
url https://hdl.handle.net/2445/177844
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/10.1002/hep4.1642
Hepatology Communications, 2020, vol. 5, num. 2, p. 309-322
https://doi.org/10.1002/hep4.1642
dc.rights.none.fl_str_mv cc-by (c) García García de Paredes, Ana et al., 2020
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) García García de Paredes, Ana et al., 2020
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 14 p.
application/pdf
dc.publisher.none.fl_str_mv John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
dc.source.none.fl_str_mv Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)
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 15,228081

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