Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 22 June 2023 / Approved: 23 June 2023 / Online: 23 June 2023 (10:36:14 CEST)

A peer-reviewed article of this Preprint also exists.

Pagano, S.; Bakker, S.J.L.; Juillard, C.; Dullaart, R.P.F.; Vuilleumier, N. Serum Level of Cytokeratin 18 (M65) as a Prognostic Marker of High Cardiovascular Disease Risk in Individuals with Non-Alcoholic Fatty Liver Disease. Biomolecules 2023, 13, 1128. Pagano, S.; Bakker, S.J.L.; Juillard, C.; Dullaart, R.P.F.; Vuilleumier, N. Serum Level of Cytokeratin 18 (M65) as a Prognostic Marker of High Cardiovascular Disease Risk in Individuals with Non-Alcoholic Fatty Liver Disease. Biomolecules 2023, 13, 1128.

Abstract

Background and aim: 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 Non-Alcoholic Fatty Liver Disease (NAFLD), and cardiovascular disease (CVD) risk in the general population. Methods: 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. Receiver Operating Characteristic (ROC) curve, linear/logistic regression models and Spearman's correlations were used. Results: Intricate associations were found between CK18, FLI and CVD risk scores. While M30 was the only independent predictor of FLI≥60, M65 discriminated best NAFLD individuals at very-high 10-years CVD risk according to SCORE2 (AUC:0.71; p=0.001). Values above the predefined manufacturer cut-off (400 U/l), were associated with an independent 5-fold increased risk (adjusted odds ratio: 5.44, p=0.01), with negative predictive value of 93%. Conclusions: Confirming that NAFLD is associated with an increased CVD risk, our results point to CK18 M65 as a candidate biomarker to identify NAFLD individuals at low CVD risk in European general population.

Keywords

Cytokeratin 18; Non-Alcoholic Fatty Liver Disease; Fatty liver index; Framingham risk score; Systematic COronary Risk Evaluation 2

Subject

Medicine and Pharmacology, Internal Medicine

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