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Impact of steatosis and inflammation definitions on the performance of NASH tests

BACKGROUND AND AIM: One of the unmet needs in subjects with metabolic risks is the prediction of metabolic liver disease by noninvasive tests. The construction of performant tests is dependent on the appropriateness of the histological reference definition. The aim of this study was to analyze the l...

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Autores principales: Poynard, Thierry, Munteanu, Mona, Charlotte, Frederic, Perazzo, Hugo, Ngo, Yen, Deckmyn, Olivier, Pais, Raluca, Mathurin, Philippe, Ratziu, Vlad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams And Wilkins 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865485/
https://www.ncbi.nlm.nih.gov/pubmed/29280921
http://dx.doi.org/10.1097/MEG.0000000000001033
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author Poynard, Thierry
Munteanu, Mona
Charlotte, Frederic
Perazzo, Hugo
Ngo, Yen
Deckmyn, Olivier
Pais, Raluca
Mathurin, Philippe
Ratziu, Vlad
author_facet Poynard, Thierry
Munteanu, Mona
Charlotte, Frederic
Perazzo, Hugo
Ngo, Yen
Deckmyn, Olivier
Pais, Raluca
Mathurin, Philippe
Ratziu, Vlad
author_sort Poynard, Thierry
collection PubMed
description BACKGROUND AND AIM: One of the unmet needs in subjects with metabolic risks is the prediction of metabolic liver disease by noninvasive tests. The construction of performant tests is dependent on the appropriateness of the histological reference definition. The aim of this study was to analyze the limitations of similar European (Fatty Liver Inhibition of Progression) and USA (Clinical-Research-Network) standard definitions and their impact on the construction of tests. METHODS: We hypothesized that a simpler histological definition of non-alcoholo steato-hepatitis (NASH), which does not require the presence of steatosis and the presence of both lobular inflammation and ballooning, should improve the concordance rates with previously validated blood tests. We reviewed the landmark studies in metabolic liver disease, sources of the standard definitions, and we compared the adequacy of these standards to other possible definitions in 1081 subjects with biopsies, by concordance and accuracy rates. RESULTS: The limitations of standard definitions included the presence of appropriate controls in only 6.6% of landmark studies, an arbitrary definition of steatosis and NASH covering only four (15%) out of 27 possible combinations of features, compared with 18 (67%) for a simplified NASH definition, which did not require steatosis. A total of 39/1081 (3.6%) cases were not identified by standard definition, but were identified by the simplified definition as significant active disease, including 15 cases with significant fibrosis. The simplified definition increased the κ concordance (P<0.0001) between test prediction and histological reference. CONCLUSION: A simplified definition of NASH could help in the construction of biomarkers with higher performances.
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spelling pubmed-58654852018-04-04 Impact of steatosis and inflammation definitions on the performance of NASH tests Poynard, Thierry Munteanu, Mona Charlotte, Frederic Perazzo, Hugo Ngo, Yen Deckmyn, Olivier Pais, Raluca Mathurin, Philippe Ratziu, Vlad Eur J Gastroenterol Hepatol Original Articles: Nonalcoholic Steatohepatitis BACKGROUND AND AIM: One of the unmet needs in subjects with metabolic risks is the prediction of metabolic liver disease by noninvasive tests. The construction of performant tests is dependent on the appropriateness of the histological reference definition. The aim of this study was to analyze the limitations of similar European (Fatty Liver Inhibition of Progression) and USA (Clinical-Research-Network) standard definitions and their impact on the construction of tests. METHODS: We hypothesized that a simpler histological definition of non-alcoholo steato-hepatitis (NASH), which does not require the presence of steatosis and the presence of both lobular inflammation and ballooning, should improve the concordance rates with previously validated blood tests. We reviewed the landmark studies in metabolic liver disease, sources of the standard definitions, and we compared the adequacy of these standards to other possible definitions in 1081 subjects with biopsies, by concordance and accuracy rates. RESULTS: The limitations of standard definitions included the presence of appropriate controls in only 6.6% of landmark studies, an arbitrary definition of steatosis and NASH covering only four (15%) out of 27 possible combinations of features, compared with 18 (67%) for a simplified NASH definition, which did not require steatosis. A total of 39/1081 (3.6%) cases were not identified by standard definition, but were identified by the simplified definition as significant active disease, including 15 cases with significant fibrosis. The simplified definition increased the κ concordance (P<0.0001) between test prediction and histological reference. CONCLUSION: A simplified definition of NASH could help in the construction of biomarkers with higher performances. Lippincott Williams And Wilkins 2018-04 2018-03-14 /pmc/articles/PMC5865485/ /pubmed/29280921 http://dx.doi.org/10.1097/MEG.0000000000001033 Text en Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/) (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Original Articles: Nonalcoholic Steatohepatitis
Poynard, Thierry
Munteanu, Mona
Charlotte, Frederic
Perazzo, Hugo
Ngo, Yen
Deckmyn, Olivier
Pais, Raluca
Mathurin, Philippe
Ratziu, Vlad
Impact of steatosis and inflammation definitions on the performance of NASH tests
title Impact of steatosis and inflammation definitions on the performance of NASH tests
title_full Impact of steatosis and inflammation definitions on the performance of NASH tests
title_fullStr Impact of steatosis and inflammation definitions on the performance of NASH tests
title_full_unstemmed Impact of steatosis and inflammation definitions on the performance of NASH tests
title_short Impact of steatosis and inflammation definitions on the performance of NASH tests
title_sort impact of steatosis and inflammation definitions on the performance of nash tests
topic Original Articles: Nonalcoholic Steatohepatitis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865485/
https://www.ncbi.nlm.nih.gov/pubmed/29280921
http://dx.doi.org/10.1097/MEG.0000000000001033
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