Metabolomic analysis to discriminate drug-induced liver injury (DILI) phenotypes

Drug-induced liver injury (DILI) is an adverse toxic hepatic clinical reaction associated to the administration of a drug that can occur both at early clinical stages of drug development, as well after normal clinical usage of approved drugs. Because of its unpredictability and clinical relevance, i...

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Detalles Bibliográficos
Autores: Quintás G, Martínez-Sena T, Conde I, Pareja Ibars E, Kleinjans J, Castell JV
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:fisabio.fundanetsuite.com:p10409
Acceso en línea:https://fisabio.portalinvestigacion.com/publicaciones/10409
Access Level:acceso abierto
Palabra clave:Metabolomics
Hepatotoxicity
Drug liver toxicity
DILI
Drug-induced liver injury
Biomarkers
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spelling Metabolomic analysis to discriminate drug-induced liver injury (DILI) phenotypesQuintás GMartínez-Sena TConde IPareja Ibars EKleinjans JCastell JVMetabolomicsHepatotoxicityDrug liver toxicityDILIDrug-induced liver injuryBiomarkersDrug-induced liver injury (DILI) is an adverse toxic hepatic clinical reaction associated to the administration of a drug that can occur both at early clinical stages of drug development, as well after normal clinical usage of approved drugs. Because of its unpredictability and clinical relevance, it is of medical concern. Three DILI phenotypes (hepatocellular, cholestatic, and mixed) are currently recognized, based on serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) values. However, this classification lacks accuracy to distinguish among the many intermediate mixed types, or even to estimate the magnitude and progression of the injury. It was found desirable to have additional elements for better evaluation criteria of DILI. With this aim, we have examined the serum metabolomic changes occurring in 79 DILI patients recruited and monitored using established clinical criteria, along the course of the disease and until recovery. Results revealed that free and conjugated bile acids, and glycerophospholipids were among the most relevant metabolite classes for DILI phenotype characterization. Using an ensemble of PLS-DA models, metabolomic information was integrated into a ternary diagram to display the disease phenotype, the severity of the liver damage, and its progression. The modeling implemented and the use of such compiled information in an easily understandable and visual manner facilitates a straightforward DILI phenotyping and allow to monitor its progression and recovery prediction, usefully complementing the concise information drawn out by the ALT and ALP classification.Springer Verlag2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/10409ARCHIVES OF TOXICOLOGYISSN: 14320738ISSNe: 03405761reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:fisabio.fundanetsuite.com:p104092026-06-11T12:45:17Z
dc.title.none.fl_str_mv Metabolomic analysis to discriminate drug-induced liver injury (DILI) phenotypes
title Metabolomic analysis to discriminate drug-induced liver injury (DILI) phenotypes
spellingShingle Metabolomic analysis to discriminate drug-induced liver injury (DILI) phenotypes
Quintás G
Metabolomics
Hepatotoxicity
Drug liver toxicity
DILI
Drug-induced liver injury
Biomarkers
title_short Metabolomic analysis to discriminate drug-induced liver injury (DILI) phenotypes
title_full Metabolomic analysis to discriminate drug-induced liver injury (DILI) phenotypes
title_fullStr Metabolomic analysis to discriminate drug-induced liver injury (DILI) phenotypes
title_full_unstemmed Metabolomic analysis to discriminate drug-induced liver injury (DILI) phenotypes
title_sort Metabolomic analysis to discriminate drug-induced liver injury (DILI) phenotypes
dc.creator.none.fl_str_mv Quintás G
Martínez-Sena T
Conde I
Pareja Ibars E
Kleinjans J
Castell JV
author Quintás G
author_facet Quintás G
Martínez-Sena T
Conde I
Pareja Ibars E
Kleinjans J
Castell JV
author_role author
author2 Martínez-Sena T
Conde I
Pareja Ibars E
Kleinjans J
Castell JV
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Metabolomics
Hepatotoxicity
Drug liver toxicity
DILI
Drug-induced liver injury
Biomarkers
topic Metabolomics
Hepatotoxicity
Drug liver toxicity
DILI
Drug-induced liver injury
Biomarkers
description Drug-induced liver injury (DILI) is an adverse toxic hepatic clinical reaction associated to the administration of a drug that can occur both at early clinical stages of drug development, as well after normal clinical usage of approved drugs. Because of its unpredictability and clinical relevance, it is of medical concern. Three DILI phenotypes (hepatocellular, cholestatic, and mixed) are currently recognized, based on serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) values. However, this classification lacks accuracy to distinguish among the many intermediate mixed types, or even to estimate the magnitude and progression of the injury. It was found desirable to have additional elements for better evaluation criteria of DILI. With this aim, we have examined the serum metabolomic changes occurring in 79 DILI patients recruited and monitored using established clinical criteria, along the course of the disease and until recovery. Results revealed that free and conjugated bile acids, and glycerophospholipids were among the most relevant metabolite classes for DILI phenotype characterization. Using an ensemble of PLS-DA models, metabolomic information was integrated into a ternary diagram to display the disease phenotype, the severity of the liver damage, and its progression. The modeling implemented and the use of such compiled information in an easily understandable and visual manner facilitates a straightforward DILI phenotyping and allow to monitor its progression and recovery prediction, usefully complementing the concise information drawn out by the ALT and ALP classification.
publishDate 2021
dc.date.none.fl_str_mv 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://fisabio.portalinvestigacion.com/publicaciones/10409
url https://fisabio.portalinvestigacion.com/publicaciones/10409
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 Springer Verlag
publisher.none.fl_str_mv Springer Verlag
dc.source.none.fl_str_mv ARCHIVES OF TOXICOLOGY
ISSN: 14320738
ISSNe: 03405761
reponame:r-FISABIO. Repositorio Institucional de Producción Científica
instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
instname_str Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
reponame_str r-FISABIO. Repositorio Institucional de Producción Científica
collection r-FISABIO. Repositorio Institucional de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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