Targeted lipidomics reveals extensive changes in circulating lipid mediators in patients with acutely decompensated cirrhosis

Acute-on-chronic liver failure (ACLF) is a newly described syndrome, which develops in patients with acutely decompensated cirrhosis, and is characterized by intense systemic inflammation, multi-organ failure and high short-term mortality. The profile of circulating lipid mediators, which are endoge...

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Authors: López Vicario, Cristina, Checa, Antonio, Urdangarin, Arantxa, Aguilar, Ferran, Alcaraz-Quiles, José, Caraceni, Paolo, Amorós, Àlex, Pavesi, Marco, Gomez Cabrero, David, Trebicka, Jonel, Oettl, Karl, Moreau, Richard, Planell, Núria, Arroyo, Vicente, Wheelock, Craig E., Clària i Enrich, Joan
Format: article
Status:Versión aceptada para publicación
Publication Date:2020
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/188684
Online Access:https://hdl.handle.net/2445/188684
Access Level:Open access
Keyword:Cirrosi hepàtica
Insuficiència hepàtica
Inflamació
Hepatic cirrhosis
Liver failure
Inflammation
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spelling Targeted lipidomics reveals extensive changes in circulating lipid mediators in patients with acutely decompensated cirrhosisLópez Vicario, CristinaCheca, AntonioUrdangarin, ArantxaAguilar, FerranAlcaraz-Quiles, JoséCaraceni, PaoloAmorós, ÀlexPavesi, MarcoGomez Cabrero, DavidTrebicka, JonelOettl, KarlMoreau, RichardPlanell, NúriaArroyo, VicenteWheelock, Craig E.Clària i Enrich, JoanCirrosi hepàticaInsuficiència hepàticaInflamacióHepatic cirrhosisLiver failureInflammationAcute-on-chronic liver failure (ACLF) is a newly described syndrome, which develops in patients with acutely decompensated cirrhosis, and is characterized by intense systemic inflammation, multi-organ failure and high short-term mortality. The profile of circulating lipid mediators, which are endogenous signaling molecules generated from polyunsaturated fatty acids released from membrane phospholipids that play a major role in inflammation and immunity, is poorly characterized in ACLF. In the current study, we assessed the profile of lipid mediators by liquid chromatography coupled to tandem mass spectrometry in plasma from patients with acutely decompensated cirrhosis, with (n=119) and without (n=127) ACLF, and from healthy subjects (HS, n=18). Measurements were prospectively repeated in 191 patients with acutely decompensated cirrhosis during a 28-day follow-up period. Fifty-nine lipid mediators (out of 100) were detected in plasma from cirrhotic patients, of which, 16 were significantly associated with the disease status. Among these, 11 lipid mediators distinguished patients at any stage from HS, whereas two lipid mediators (leukotriene [LT] E4 and 12-hydroxyheptadecatrienoic acid, both derived from arachidonic acid) shaped a minimal plasma fingerprint that discriminated patients with ACLF from those without. Levels of LTE4 distinguished ACLF grade 3 from ACLF grades 1 and 2, followed the clinical course of the disease (increased with worsening and decreased with improvement) and positively correlated with markers of inflammation and non-apoptotic cell death. Moreover, LTE4 together with LXA5 (derived from eicosapentaenoic acid) and EKODE (derived from linoleic acid) associated with short-term mortality. Interestingly, LXA5 and EKODE formed a signature profile associated with coagulation and liver failures. Taken together, these findings uncover specific lipid mediator profiles associated with severity and prognosis of patients with acutely decompensated cirrhosis.2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/188684Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1016/j.jhep.2020.03.046Journal of Hepatology, 2020, vol.73, num. 4, p. 817-828https://doi.org/10.1016/j.jhep.2020.03.046info:eu-repo/grantAgreement/EC/H2020/825694cc by-nc-nd (c) Elsevier, 2020http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1886842026-05-27T06:46:51Z
dc.title.none.fl_str_mv Targeted lipidomics reveals extensive changes in circulating lipid mediators in patients with acutely decompensated cirrhosis
title Targeted lipidomics reveals extensive changes in circulating lipid mediators in patients with acutely decompensated cirrhosis
spellingShingle Targeted lipidomics reveals extensive changes in circulating lipid mediators in patients with acutely decompensated cirrhosis
López Vicario, Cristina
Cirrosi hepàtica
Insuficiència hepàtica
Inflamació
Hepatic cirrhosis
Liver failure
Inflammation
title_short Targeted lipidomics reveals extensive changes in circulating lipid mediators in patients with acutely decompensated cirrhosis
title_full Targeted lipidomics reveals extensive changes in circulating lipid mediators in patients with acutely decompensated cirrhosis
title_fullStr Targeted lipidomics reveals extensive changes in circulating lipid mediators in patients with acutely decompensated cirrhosis
title_full_unstemmed Targeted lipidomics reveals extensive changes in circulating lipid mediators in patients with acutely decompensated cirrhosis
title_sort Targeted lipidomics reveals extensive changes in circulating lipid mediators in patients with acutely decompensated cirrhosis
dc.creator.none.fl_str_mv López Vicario, Cristina
Checa, Antonio
Urdangarin, Arantxa
Aguilar, Ferran
Alcaraz-Quiles, José
Caraceni, Paolo
Amorós, Àlex
Pavesi, Marco
Gomez Cabrero, David
Trebicka, Jonel
Oettl, Karl
Moreau, Richard
Planell, Núria
Arroyo, Vicente
Wheelock, Craig E.
Clària i Enrich, Joan
author López Vicario, Cristina
author_facet López Vicario, Cristina
Checa, Antonio
Urdangarin, Arantxa
Aguilar, Ferran
Alcaraz-Quiles, José
Caraceni, Paolo
Amorós, Àlex
Pavesi, Marco
Gomez Cabrero, David
Trebicka, Jonel
Oettl, Karl
Moreau, Richard
Planell, Núria
Arroyo, Vicente
Wheelock, Craig E.
Clària i Enrich, Joan
author_role author
author2 Checa, Antonio
Urdangarin, Arantxa
Aguilar, Ferran
Alcaraz-Quiles, José
Caraceni, Paolo
Amorós, Àlex
Pavesi, Marco
Gomez Cabrero, David
Trebicka, Jonel
Oettl, Karl
Moreau, Richard
Planell, Núria
Arroyo, Vicente
Wheelock, Craig E.
Clària i Enrich, Joan
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cirrosi hepàtica
Insuficiència hepàtica
Inflamació
Hepatic cirrhosis
Liver failure
Inflammation
topic Cirrosi hepàtica
Insuficiència hepàtica
Inflamació
Hepatic cirrhosis
Liver failure
Inflammation
description Acute-on-chronic liver failure (ACLF) is a newly described syndrome, which develops in patients with acutely decompensated cirrhosis, and is characterized by intense systemic inflammation, multi-organ failure and high short-term mortality. The profile of circulating lipid mediators, which are endogenous signaling molecules generated from polyunsaturated fatty acids released from membrane phospholipids that play a major role in inflammation and immunity, is poorly characterized in ACLF. In the current study, we assessed the profile of lipid mediators by liquid chromatography coupled to tandem mass spectrometry in plasma from patients with acutely decompensated cirrhosis, with (n=119) and without (n=127) ACLF, and from healthy subjects (HS, n=18). Measurements were prospectively repeated in 191 patients with acutely decompensated cirrhosis during a 28-day follow-up period. Fifty-nine lipid mediators (out of 100) were detected in plasma from cirrhotic patients, of which, 16 were significantly associated with the disease status. Among these, 11 lipid mediators distinguished patients at any stage from HS, whereas two lipid mediators (leukotriene [LT] E4 and 12-hydroxyheptadecatrienoic acid, both derived from arachidonic acid) shaped a minimal plasma fingerprint that discriminated patients with ACLF from those without. Levels of LTE4 distinguished ACLF grade 3 from ACLF grades 1 and 2, followed the clinical course of the disease (increased with worsening and decreased with improvement) and positively correlated with markers of inflammation and non-apoptotic cell death. Moreover, LTE4 together with LXA5 (derived from eicosapentaenoic acid) and EKODE (derived from linoleic acid) associated with short-term mortality. Interestingly, LXA5 and EKODE formed a signature profile associated with coagulation and liver failures. Taken together, these findings uncover specific lipid mediator profiles associated with severity and prognosis of patients with acutely decompensated cirrhosis.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/188684
url https://hdl.handle.net/2445/188684
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1016/j.jhep.2020.03.046
Journal of Hepatology, 2020, vol.73, num. 4, p. 817-828
https://doi.org/10.1016/j.jhep.2020.03.046
info:eu-repo/grantAgreement/EC/H2020/825694
dc.rights.none.fl_str_mv cc by-nc-nd (c) Elsevier, 2020
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc-nd (c) Elsevier, 2020
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300724

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