Cell death markers in patients with cirrhosis and acute decompensation

The aims of this study were to determine the role of cell death in patients with cirrhosis and acute decompensation (AD) and acute on chronic liver failure (ACLF) using plasma‐based biomarkers. The patients studied were part of the CANONIC (CLIF Acute‐on‐Chronic Liver Failure in Cirrhosis) study (N...

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Autores: Macdonald, Stewart, Andreola, Fausto, Bachtiger, Patrik, Amorós, Àlex, Pavesi, Marco, Mookerjee, Rajeshwar P., Zheng, Yu Bao, Grønbaek, Henning, Gerbes, Alexander L., Solà, Elsa, Caraceni, Paolo, Moreau, Richard, Ginès i Gibert, Pere, Arroyo, Vicente, Jalan, Rajiv
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2018
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:2445/139697
Acceso en línea:https://hdl.handle.net/2445/139697
Access Level:acceso abierto
Palabra clave:Cirrosi hepàtica
Cèl·lules hepàtiques
Marcadors bioquímics
Malalties del fetge
Insuficiència hepàtica
Hepatic cirrhosis
Liver cells
Biochemical markers
Liver diseases
Liver failure
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oai_identifier_str oai:recercat.cat:2445/139697
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network_name_str España
repository_id_str
spelling Cell death markers in patients with cirrhosis and acute decompensationMacdonald, StewartAndreola, FaustoBachtiger, PatrikAmorós, ÀlexPavesi, MarcoMookerjee, Rajeshwar P.Zheng, Yu BaoGrønbaek, HenningGerbes, Alexander L.Solà, ElsaCaraceni, PaoloMoreau, RichardGinès i Gibert, PereArroyo, VicenteJalan, RajivCirrosi hepàticaCèl·lules hepàtiquesMarcadors bioquímicsMalalties del fetgeInsuficiència hepàticaHepatic cirrhosisLiver cellsBiochemical markersLiver diseasesLiver failureThe aims of this study were to determine the role of cell death in patients with cirrhosis and acute decompensation (AD) and acute on chronic liver failure (ACLF) using plasma‐based biomarkers. The patients studied were part of the CANONIC (CLIF Acute‐on‐Chronic Liver Failure in Cirrhosis) study (N = 337; AD, 258; ACLF, 79); additional cohorts included healthy volunteers, stable patients with cirrhosis, and a group of 16 AD patients for histological studies. Caspase‐cleaved keratin 18 (cK18) and keratin 18 (K18), which reflect apoptotic and total cell death, respectively, and cK18:K18 ratio (apoptotic index) were measured in plasma by enzyme‐linked immunosorbent assay. The concentrations of cK18 and K18 increased and the cK18:K18 ratio decreased with increasing severity of AD and ACLF (P < 0.001, respectively). Alcohol etiology, no previous decompensation, and alcohol abuse were associated with increased cell death markers whereas underlying infection was not. Close correlation was observed between the cell death markers and, markers of systemic inflammation, hepatic failure, alanine aminotransferase, and bilirubin, but not with markers of extrahepatic organ injury. Terminal deoxynucleotidyl transferase dUTP nick‐end labeling staining confirmed evidence of greater hepatic cell death in patients with ACLF as opposed to AD. Inclusion of cK18 and K18 improved the performance of the CLIF‐C AD score in prediction of progression from AD to ACLF (P < 0.05). Conclusion: Cell death, likely hepatic, is an important feature of AD and ACLF and its magnitude correlates with clinical severity. Nonapoptotic forms of cell death predominate with increasing severity of AD and ACLF. The data suggests that ACLF is a heterogeneous entity and shows that the importance of cell death in its pathophysiology is dependent on predisposing factors, precipitating illness, response to injury, and type of organ failure.Wiley2019201920182019info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion14 p.application/pdfhttps://hdl.handle.net/2445/139697Articles 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)InglésVersió postprint del document publicat a: https://doi.org/10.1002/hep.29581Hepatology, 2018, vol. 67, num. 3, p. 989-1002https://doi.org/10.1002/hep.29581(c) American Association for the Study of Liver Diseases, 2018info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1396972026-05-29T05:05:01Z
dc.title.none.fl_str_mv Cell death markers in patients with cirrhosis and acute decompensation
title Cell death markers in patients with cirrhosis and acute decompensation
spellingShingle Cell death markers in patients with cirrhosis and acute decompensation
Macdonald, Stewart
Cirrosi hepàtica
Cèl·lules hepàtiques
Marcadors bioquímics
Malalties del fetge
Insuficiència hepàtica
Hepatic cirrhosis
Liver cells
Biochemical markers
Liver diseases
Liver failure
title_short Cell death markers in patients with cirrhosis and acute decompensation
title_full Cell death markers in patients with cirrhosis and acute decompensation
title_fullStr Cell death markers in patients with cirrhosis and acute decompensation
title_full_unstemmed Cell death markers in patients with cirrhosis and acute decompensation
title_sort Cell death markers in patients with cirrhosis and acute decompensation
dc.creator.none.fl_str_mv Macdonald, Stewart
Andreola, Fausto
Bachtiger, Patrik
Amorós, Àlex
Pavesi, Marco
Mookerjee, Rajeshwar P.
Zheng, Yu Bao
Grønbaek, Henning
Gerbes, Alexander L.
Solà, Elsa
Caraceni, Paolo
Moreau, Richard
Ginès i Gibert, Pere
Arroyo, Vicente
Jalan, Rajiv
author Macdonald, Stewart
author_facet Macdonald, Stewart
Andreola, Fausto
Bachtiger, Patrik
Amorós, Àlex
Pavesi, Marco
Mookerjee, Rajeshwar P.
Zheng, Yu Bao
Grønbaek, Henning
Gerbes, Alexander L.
Solà, Elsa
Caraceni, Paolo
Moreau, Richard
Ginès i Gibert, Pere
Arroyo, Vicente
Jalan, Rajiv
author_role author
author2 Andreola, Fausto
Bachtiger, Patrik
Amorós, Àlex
Pavesi, Marco
Mookerjee, Rajeshwar P.
Zheng, Yu Bao
Grønbaek, Henning
Gerbes, Alexander L.
Solà, Elsa
Caraceni, Paolo
Moreau, Richard
Ginès i Gibert, Pere
Arroyo, Vicente
Jalan, Rajiv
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cirrosi hepàtica
Cèl·lules hepàtiques
Marcadors bioquímics
Malalties del fetge
Insuficiència hepàtica
Hepatic cirrhosis
Liver cells
Biochemical markers
Liver diseases
Liver failure
topic Cirrosi hepàtica
Cèl·lules hepàtiques
Marcadors bioquímics
Malalties del fetge
Insuficiència hepàtica
Hepatic cirrhosis
Liver cells
Biochemical markers
Liver diseases
Liver failure
description The aims of this study were to determine the role of cell death in patients with cirrhosis and acute decompensation (AD) and acute on chronic liver failure (ACLF) using plasma‐based biomarkers. The patients studied were part of the CANONIC (CLIF Acute‐on‐Chronic Liver Failure in Cirrhosis) study (N = 337; AD, 258; ACLF, 79); additional cohorts included healthy volunteers, stable patients with cirrhosis, and a group of 16 AD patients for histological studies. Caspase‐cleaved keratin 18 (cK18) and keratin 18 (K18), which reflect apoptotic and total cell death, respectively, and cK18:K18 ratio (apoptotic index) were measured in plasma by enzyme‐linked immunosorbent assay. The concentrations of cK18 and K18 increased and the cK18:K18 ratio decreased with increasing severity of AD and ACLF (P < 0.001, respectively). Alcohol etiology, no previous decompensation, and alcohol abuse were associated with increased cell death markers whereas underlying infection was not. Close correlation was observed between the cell death markers and, markers of systemic inflammation, hepatic failure, alanine aminotransferase, and bilirubin, but not with markers of extrahepatic organ injury. Terminal deoxynucleotidyl transferase dUTP nick‐end labeling staining confirmed evidence of greater hepatic cell death in patients with ACLF as opposed to AD. Inclusion of cK18 and K18 improved the performance of the CLIF‐C AD score in prediction of progression from AD to ACLF (P < 0.05). Conclusion: Cell death, likely hepatic, is an important feature of AD and ACLF and its magnitude correlates with clinical severity. Nonapoptotic forms of cell death predominate with increasing severity of AD and ACLF. The data suggests that ACLF is a heterogeneous entity and shows that the importance of cell death in its pathophysiology is dependent on predisposing factors, precipitating illness, response to injury, and type of organ failure.
publishDate 2018
dc.date.none.fl_str_mv 2018
2019
2019
2019
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/2445/139697
url https://hdl.handle.net/2445/139697
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/10.1002/hep.29581
Hepatology, 2018, vol. 67, num. 3, p. 989-1002
https://doi.org/10.1002/hep.29581
dc.rights.none.fl_str_mv (c) American Association for the Study of Liver Diseases, 2018
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Association for the Study of Liver Diseases, 2018
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 14 p.
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
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 15,812455

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