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Serum Level of Cytokeratin 18 (M65) as a Prognostic Marker of High Cardiovascular Disease Risk in Individuals with Non-Alcoholic Fatty Liver Disease

Alterations in apoptosis, as reflected by circulating Cytokeratin 18 (CK18), are involved in the progression of non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis and atherogenesis. We aimed to explore the discriminant accuracy of Cytokeratin 18 (CK18, including M65 and M30 f...

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Autores principales: Pagano, Sabrina, Bakker, Stephan J. L., Juillard, Catherine, Dullaart, Robin P. F., Vuilleumier, Nicolas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377236/
https://www.ncbi.nlm.nih.gov/pubmed/37509164
http://dx.doi.org/10.3390/biom13071128
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author Pagano, Sabrina
Bakker, Stephan J. L.
Juillard, Catherine
Dullaart, Robin P. F.
Vuilleumier, Nicolas
author_facet Pagano, Sabrina
Bakker, Stephan J. L.
Juillard, Catherine
Dullaart, Robin P. F.
Vuilleumier, Nicolas
author_sort Pagano, Sabrina
collection PubMed
description Alterations in apoptosis, as reflected by circulating Cytokeratin 18 (CK18), are involved in the progression of non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis and atherogenesis. We aimed to explore the discriminant accuracy of Cytokeratin 18 (CK18, including M65 and M30 forms) for an elevated fatty liver index (FLI) as a validated proxy of NAFLD, and cardiovascular disease (CVD) risk in the general population. Both serum CK18 forms were measured using a commercial immunoassay in randomly selected samples from 312 participants of the PREVEND general population cohort. FLI ≥ 60 was used to indicate NAFLD. Framingham Risk Score (FRS) and the SCORE2 were used to estimate the 10-year risk of CVD. The Receiver Operating Characteristic (ROC) curve, linear/logistic regression models, and Spearman’s correlations were used. Intricate associations were found between CK18, FLI, and CVD risk scores. While M30 was the only independent predictor of FLI ≥ 60, M65 best discriminated NAFLD individuals at very-high 10-year CVD risk according to SCORE2 (AUC: 0.71; p = 0.001). Values above the predefined manufacturer cutoff (400 U/L) were associated with an independent 5-fold increased risk (adjusted odds ratio: 5.44, p = 0.01), with a negative predictive value of 93%. Confirming that NAFLD is associated with an increased CVD risk, our results in a European general population-based cohort suggest that CK18 M65 may represent a candidate biomarker to identify NAFLD individuals at low CVD risk.
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spelling pubmed-103772362023-07-29 Serum Level of Cytokeratin 18 (M65) as a Prognostic Marker of High Cardiovascular Disease Risk in Individuals with Non-Alcoholic Fatty Liver Disease Pagano, Sabrina Bakker, Stephan J. L. Juillard, Catherine Dullaart, Robin P. F. Vuilleumier, Nicolas Biomolecules Article Alterations in apoptosis, as reflected by circulating Cytokeratin 18 (CK18), are involved in the progression of non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis and atherogenesis. We aimed to explore the discriminant accuracy of Cytokeratin 18 (CK18, including M65 and M30 forms) for an elevated fatty liver index (FLI) as a validated proxy of NAFLD, and cardiovascular disease (CVD) risk in the general population. Both serum CK18 forms were measured using a commercial immunoassay in randomly selected samples from 312 participants of the PREVEND general population cohort. FLI ≥ 60 was used to indicate NAFLD. Framingham Risk Score (FRS) and the SCORE2 were used to estimate the 10-year risk of CVD. The Receiver Operating Characteristic (ROC) curve, linear/logistic regression models, and Spearman’s correlations were used. Intricate associations were found between CK18, FLI, and CVD risk scores. While M30 was the only independent predictor of FLI ≥ 60, M65 best discriminated NAFLD individuals at very-high 10-year CVD risk according to SCORE2 (AUC: 0.71; p = 0.001). Values above the predefined manufacturer cutoff (400 U/L) were associated with an independent 5-fold increased risk (adjusted odds ratio: 5.44, p = 0.01), with a negative predictive value of 93%. Confirming that NAFLD is associated with an increased CVD risk, our results in a European general population-based cohort suggest that CK18 M65 may represent a candidate biomarker to identify NAFLD individuals at low CVD risk. MDPI 2023-07-14 /pmc/articles/PMC10377236/ /pubmed/37509164 http://dx.doi.org/10.3390/biom13071128 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pagano, Sabrina
Bakker, Stephan J. L.
Juillard, Catherine
Dullaart, Robin P. F.
Vuilleumier, Nicolas
Serum Level of Cytokeratin 18 (M65) as a Prognostic Marker of High Cardiovascular Disease Risk in Individuals with Non-Alcoholic Fatty Liver Disease
title Serum Level of Cytokeratin 18 (M65) as a Prognostic Marker of High Cardiovascular Disease Risk in Individuals with Non-Alcoholic Fatty Liver Disease
title_full Serum Level of Cytokeratin 18 (M65) as a Prognostic Marker of High Cardiovascular Disease Risk in Individuals with Non-Alcoholic Fatty Liver Disease
title_fullStr Serum Level of Cytokeratin 18 (M65) as a Prognostic Marker of High Cardiovascular Disease Risk in Individuals with Non-Alcoholic Fatty Liver Disease
title_full_unstemmed Serum Level of Cytokeratin 18 (M65) as a Prognostic Marker of High Cardiovascular Disease Risk in Individuals with Non-Alcoholic Fatty Liver Disease
title_short Serum Level of Cytokeratin 18 (M65) as a Prognostic Marker of High Cardiovascular Disease Risk in Individuals with Non-Alcoholic Fatty Liver Disease
title_sort serum level of cytokeratin 18 (m65) as a prognostic marker of high cardiovascular disease risk in individuals with non-alcoholic fatty liver disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377236/
https://www.ncbi.nlm.nih.gov/pubmed/37509164
http://dx.doi.org/10.3390/biom13071128
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