Development and validation of the AMMON-OHE model to predict risk of overt hepatic encephalopathy occurrence in outpatients with cirrhosis.

BACKGROUND AND AIMS: Neuropsychological and psychophysical tests are recommended for the risk assessment for overt hepatic encephalopathy (OHE), but their accuracy is limited. Hyperammonaemia is central in the pathogenesis of OHE, but its predictive utility is unknown. This study aimed to determine...

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Autores: Ballester, Maria Pilar, Tranah, Thomas H, Balcar, Lorenz, Fiorillo, Alessandra, Ampuero, Javier, Kerbert, Annarein J C, Thomsen, Karen L, Escudero, Maria Desamparados, Mandorfer, Mattias, Reiberger, Thomas, Shawcross, Debbie L, Romero-Gomez, Manuel, Montoliu, Carmina, Carbonell-Asins, Juan Antonio, Jalan, Rajiv
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p17506
Acceso en línea:https://incliva.portalinvestigacion.com/publicaciones/17506
Access Level:acceso abierto
Palabra clave:Ammonia
Cirrhosis
Critical flicker frequency
Overt hepatic encephalopathy
Psychometric hepatic encephalopathy score
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spelling Development and validation of the AMMON-OHE model to predict risk of overt hepatic encephalopathy occurrence in outpatients with cirrhosis.Ballester, Maria PilarTranah, Thomas HBalcar, LorenzFiorillo, AlessandraAmpuero, JavierKerbert, Annarein J CThomsen, Karen LEscudero, Maria DesamparadosMandorfer, MattiasReiberger, ThomasShawcross, Debbie LRomero-Gomez, ManuelMontoliu, CarminaCarbonell-Asins, Juan AntonioJalan, RajivAmmoniaCirrhosisCritical flicker frequencyOvert hepatic encephalopathyPsychometric hepatic encephalopathy scoreBACKGROUND AND AIMS: Neuropsychological and psychophysical tests are recommended for the risk assessment for overt hepatic encephalopathy (OHE), but their accuracy is limited. Hyperammonaemia is central in the pathogenesis of OHE, but its predictive utility is unknown. This study aimed to determine the role of neuropsychological or psychophysical tests and ammonia and to develop the AMMON-OHE model for risk stratification regarding subsequent OHE development in outpatients with cirrhosis.; METHODS: This observational, prospective study included 426 outpatients without previous OHE from 3 liver units followed for a median of 2.5 years. Psychometric hepatic encephalopathy score (PHES) <-4 or critical flicker frequency (CFF) <39 was considered abnormal. Ammonia was normalized to upper limit of normal (AMM-ULN) at the respective reference laboratory. Multivariable frailty competing risk analyses and random survival forest were performed to predict future OHE and to develop the AMMON-OHE model. External validation was carried out using 267 and 381 patients from two independent units.; RESULTS: Significant differences were found in time-to-OHE (log-rank p<0.001) according to PHES or CFF and ammonia, with the highest risk in patients with abnormal PHES plus high AMM-ULN (HR: 4.4; 95% CI: 2.4-8.1, p<0.001 compared with normal PHES and AMM-ULN). On multivariable analysis, AMM-ULN but not PHES or CFF was an independent predictor for development of OHE (HR: 1.4; 95%CI: 1.1-1.9; p=0.015). The AMMON-OHE model included sex, diabetes, albumin, creatinine and AMM-ULN, and showed a C-index of 0.844 and 0.728 in the two external validation cohorts.; CONCLUSIONS: This study developed and validated the AMMON-OHE model, comprising readily available clinical and biochemical variables that can be used to identify outpatients at highest risk for developing a first episode of OHE. Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.ELSEVIER2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://incliva.portalinvestigacion.com/publicaciones/17506JOURNAL OF HEPATOLOGYISSN: 01688278ISSNe: 16000641reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVAinstname:INCLIVAInglésinfo:eu-repo/semantics/openAccessoai:incliva.fundanetsuite.com:p175062026-06-07T16:35:31Z
dc.title.none.fl_str_mv Development and validation of the AMMON-OHE model to predict risk of overt hepatic encephalopathy occurrence in outpatients with cirrhosis.
title Development and validation of the AMMON-OHE model to predict risk of overt hepatic encephalopathy occurrence in outpatients with cirrhosis.
spellingShingle Development and validation of the AMMON-OHE model to predict risk of overt hepatic encephalopathy occurrence in outpatients with cirrhosis.
Ballester, Maria Pilar
Ammonia
Cirrhosis
Critical flicker frequency
Overt hepatic encephalopathy
Psychometric hepatic encephalopathy score
title_short Development and validation of the AMMON-OHE model to predict risk of overt hepatic encephalopathy occurrence in outpatients with cirrhosis.
title_full Development and validation of the AMMON-OHE model to predict risk of overt hepatic encephalopathy occurrence in outpatients with cirrhosis.
title_fullStr Development and validation of the AMMON-OHE model to predict risk of overt hepatic encephalopathy occurrence in outpatients with cirrhosis.
title_full_unstemmed Development and validation of the AMMON-OHE model to predict risk of overt hepatic encephalopathy occurrence in outpatients with cirrhosis.
title_sort Development and validation of the AMMON-OHE model to predict risk of overt hepatic encephalopathy occurrence in outpatients with cirrhosis.
dc.creator.none.fl_str_mv Ballester, Maria Pilar
Tranah, Thomas H
Balcar, Lorenz
Fiorillo, Alessandra
Ampuero, Javier
Kerbert, Annarein J C
Thomsen, Karen L
Escudero, Maria Desamparados
Mandorfer, Mattias
Reiberger, Thomas
Shawcross, Debbie L
Romero-Gomez, Manuel
Montoliu, Carmina
Carbonell-Asins, Juan Antonio
Jalan, Rajiv
author Ballester, Maria Pilar
author_facet Ballester, Maria Pilar
Tranah, Thomas H
Balcar, Lorenz
Fiorillo, Alessandra
Ampuero, Javier
Kerbert, Annarein J C
Thomsen, Karen L
Escudero, Maria Desamparados
Mandorfer, Mattias
Reiberger, Thomas
Shawcross, Debbie L
Romero-Gomez, Manuel
Montoliu, Carmina
Carbonell-Asins, Juan Antonio
Jalan, Rajiv
author_role author
author2 Tranah, Thomas H
Balcar, Lorenz
Fiorillo, Alessandra
Ampuero, Javier
Kerbert, Annarein J C
Thomsen, Karen L
Escudero, Maria Desamparados
Mandorfer, Mattias
Reiberger, Thomas
Shawcross, Debbie L
Romero-Gomez, Manuel
Montoliu, Carmina
Carbonell-Asins, Juan Antonio
Jalan, Rajiv
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ammonia
Cirrhosis
Critical flicker frequency
Overt hepatic encephalopathy
Psychometric hepatic encephalopathy score
topic Ammonia
Cirrhosis
Critical flicker frequency
Overt hepatic encephalopathy
Psychometric hepatic encephalopathy score
description BACKGROUND AND AIMS: Neuropsychological and psychophysical tests are recommended for the risk assessment for overt hepatic encephalopathy (OHE), but their accuracy is limited. Hyperammonaemia is central in the pathogenesis of OHE, but its predictive utility is unknown. This study aimed to determine the role of neuropsychological or psychophysical tests and ammonia and to develop the AMMON-OHE model for risk stratification regarding subsequent OHE development in outpatients with cirrhosis.; METHODS: This observational, prospective study included 426 outpatients without previous OHE from 3 liver units followed for a median of 2.5 years. Psychometric hepatic encephalopathy score (PHES) <-4 or critical flicker frequency (CFF) <39 was considered abnormal. Ammonia was normalized to upper limit of normal (AMM-ULN) at the respective reference laboratory. Multivariable frailty competing risk analyses and random survival forest were performed to predict future OHE and to develop the AMMON-OHE model. External validation was carried out using 267 and 381 patients from two independent units.; RESULTS: Significant differences were found in time-to-OHE (log-rank p<0.001) according to PHES or CFF and ammonia, with the highest risk in patients with abnormal PHES plus high AMM-ULN (HR: 4.4; 95% CI: 2.4-8.1, p<0.001 compared with normal PHES and AMM-ULN). On multivariable analysis, AMM-ULN but not PHES or CFF was an independent predictor for development of OHE (HR: 1.4; 95%CI: 1.1-1.9; p=0.015). The AMMON-OHE model included sex, diabetes, albumin, creatinine and AMM-ULN, and showed a C-index of 0.844 and 0.728 in the two external validation cohorts.; CONCLUSIONS: This study developed and validated the AMMON-OHE model, comprising readily available clinical and biochemical variables that can be used to identify outpatients at highest risk for developing a first episode of OHE. Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
publishDate 2023
dc.date.none.fl_str_mv 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://incliva.portalinvestigacion.com/publicaciones/17506
url https://incliva.portalinvestigacion.com/publicaciones/17506
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv ELSEVIER
publisher.none.fl_str_mv ELSEVIER
dc.source.none.fl_str_mv JOURNAL OF HEPATOLOGY
ISSN: 01688278
ISSNe: 16000641
reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
instname:INCLIVA
instname_str INCLIVA
reponame_str r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
collection r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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