Systematic review and meta-analysis: analysis of variables influencing the interpretation of clinical trial results in NAFLD

[Background] NAFLD clinical trials have shown suboptimal results, particularly for liver fibrosis, despite the robust preclinical drug development. We aimed to assess the histological response after the experimental treatment versus placebo by carrying out a meta-analysis of NAFLD clinical trials.

Detalles Bibliográficos
Autores: Ampuero, Javier, Gallego-Durán, Rocío, Maya-Miles, Douglas, Montero, Rocío, Gato, Sheila, Rojas, Ángela, Gil, Antonio, Muñoz, Rocío, Romero-Gómez, Manuel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/307260
Acceso en línea:http://hdl.handle.net/10261/307260
https://api.elsevier.com/content/abstract/scopus_id/85127116365
Access Level:acceso abierto
Palabra clave:Placebo
Drug
Fibrosis
NAFLD
NASH
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repository_id_str
dc.title.none.fl_str_mv Systematic review and meta-analysis: analysis of variables influencing the interpretation of clinical trial results in NAFLD
title Systematic review and meta-analysis: analysis of variables influencing the interpretation of clinical trial results in NAFLD
spellingShingle Systematic review and meta-analysis: analysis of variables influencing the interpretation of clinical trial results in NAFLD
Ampuero, Javier
Placebo
Drug
Fibrosis
NAFLD
NASH
title_short Systematic review and meta-analysis: analysis of variables influencing the interpretation of clinical trial results in NAFLD
title_full Systematic review and meta-analysis: analysis of variables influencing the interpretation of clinical trial results in NAFLD
title_fullStr Systematic review and meta-analysis: analysis of variables influencing the interpretation of clinical trial results in NAFLD
title_full_unstemmed Systematic review and meta-analysis: analysis of variables influencing the interpretation of clinical trial results in NAFLD
title_sort Systematic review and meta-analysis: analysis of variables influencing the interpretation of clinical trial results in NAFLD
dc.creator.none.fl_str_mv Ampuero, Javier
Gallego-Durán, Rocío
Maya-Miles, Douglas
Montero, Rocío
Gato, Sheila
Rojas, Ángela
Gil, Antonio
Muñoz, Rocío
Romero-Gómez, Manuel
author Ampuero, Javier
author_facet Ampuero, Javier
Gallego-Durán, Rocío
Maya-Miles, Douglas
Montero, Rocío
Gato, Sheila
Rojas, Ángela
Gil, Antonio
Muñoz, Rocío
Romero-Gómez, Manuel
author_role author
author2 Gallego-Durán, Rocío
Maya-Miles, Douglas
Montero, Rocío
Gato, Sheila
Rojas, Ángela
Gil, Antonio
Muñoz, Rocío
Romero-Gómez, Manuel
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Conferencia de Rectores de las Universidades Españolas
Consejo Superior de Investigaciones Científicas (España)
Junta de Andalucía
Ministerio de Ciencia e Innovación (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Placebo
Drug
Fibrosis
NAFLD
NASH
topic Placebo
Drug
Fibrosis
NAFLD
NASH
description [Background] NAFLD clinical trials have shown suboptimal results, particularly for liver fibrosis, despite the robust preclinical drug development. We aimed to assess the histological response after the experimental treatment versus placebo by carrying out a meta-analysis of NAFLD clinical trials.
publishDate 2022
dc.date.none.fl_str_mv 2022
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
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dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/307260
https://api.elsevier.com/content/abstract/scopus_id/85127116365
url http://hdl.handle.net/10261/307260
https://api.elsevier.com/content/abstract/scopus_id/85127116365
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO//PI16%2F01842
info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI17%2F00535
info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI19%2F01404
info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI19%2F00589
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1007/s00535-022-01860-0
https://doi.org/10.1007/s00535-022-01860-0
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
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repository.mail.fl_str_mv
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spelling Systematic review and meta-analysis: analysis of variables influencing the interpretation of clinical trial results in NAFLDAmpuero, JavierGallego-Durán, RocíoMaya-Miles, DouglasMontero, RocíoGato, SheilaRojas, ÁngelaGil, AntonioMuñoz, RocíoRomero-Gómez, ManuelPlaceboDrugFibrosisNAFLDNASH[Background] NAFLD clinical trials have shown suboptimal results, particularly for liver fibrosis, despite the robust preclinical drug development. We aimed to assess the histological response after the experimental treatment versus placebo by carrying out a meta-analysis of NAFLD clinical trials.[Methods] After a systematic review of NAFLD clinical trials to May 2021, applying strict selection criteria, the following primary outcomes were observed: (a) NASH resolution, with no worsening of fibrosis when available; (b) fibrosis improvement  ≥ 1 stage, with no worsening of NAS when available; (c) worsening of NAS; (d) worsening of liver fibrosis  ≥ 1 stage, including the progression to cirrhosis on histopathology. Other histological, clinical, and biochemical outcomes were considered secondary endpoints. Heterogeneity was explored by subgroup and sensitivity analyses, and univariable meta-regression.[Results] Twenty-seven randomized clinical trials were included. The pooled efficacy for NASH resolution receiving experimental therapy was 19% (95%CI 15–23; I2 96.2%) compared with placebo 10% (95%CI 7–12; I2 85.8%) (OR 1.66 (95%CI 1.24–2.21); I2 57.8%), while it was 26% (95%CI 22–29); I2 90%)) versus 18% (95%CI 15–21; I2 59%)) for fibrosis improvement (OR 1.34 (95%CI 1.13–1.58); I2 25.4%). For these outcomes, the therapy showed higher efficacy in trials longer than 48 weeks, with  < 60% of diabetic population, and when it targeted FXR, PPAR, and antidiabetic mechanisms, and with a NAS  < 5 for NASH resolution. Also, NASH (OR 0.57 (95%CI 0.39–0.84); I2 67%) and fibrosis worsening (OR 0.65 (95%CI 0.46–0.92); I2 61.9%) were prevented with the therapy.[Conclusion] This meta-analysis provides information about the efficacy of the therapy versus placebo by comparing different and combined trial outcomes such as NASH resolution, fibrosis improvement, and NAS and fibrosis worsening. Changes in the experimental design and selection criteria of the clinical trials might be suitable to increase the efficacy.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This project has been partially funded by the “Consejería de Salud de la Junta de Andalucía” (PI-0075–2014), the “Spanish Ministry of Economy, Innovation and Competition, Instituto de Salud Carlos III” (PI16/01842, PI17/00535, PI19/01404, PI19/00589, IFI18/00041 and GLD19/00100).Peer reviewedSpringer NatureConferencia de Rectores de las Universidades EspañolasConsejo Superior de Investigaciones Científicas (España)Junta de AndalucíaMinisterio de Ciencia e Innovación (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202320232022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/307260https://api.elsevier.com/content/abstract/scopus_id/85127116365reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO//PI16%2F01842info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI17%2F00535info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI19%2F01404info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI19%2F00589The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1007/s00535-022-01860-0https://doi.org/10.1007/s00535-022-01860-0Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3072602026-05-22T06:33:51Z
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