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Impact of metabolic factors on risk of cardiovascular disease in nondiabetic metabolic dysfunction-associated fatty liver disease

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Background and aim

Changing terminology of non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) is recently proposed by expert panels based on metabolic dysregulations. However, clinical evidences for the risk of cardiovascular disease (CVD) in MAFLD are limited. The aim of this study is evaluating the association of cardiovascular risk in these two terminology and subgroups of MAFLD.


A total of 2133 individuals who underwent ultrasound and cardiac computed tomography contemporaneously were included at a single medical checkup center. Ultrasound was used to define fatty liver, and coronary artery calcification (CAC) defined a coronary artery calcium score above 0 was used to estimate the cardiovascular risk.


Overall, 911 participants were diagnosed with fatty liver. In the unadjusted analysis, NAFLD (OR = 1.4, 95% confidence interval [CI] = 1.05–1.85, p = 0.019) and MAFLD (OR = 1.55, 95% CI = 1.29–1.86, p = 0.046) were significantly associated with CAC. However, in sex and age-adjusted analyses, only MAFLD was associated with CAC (adjusted OR [aOR] = 1.38, 95% CI = 1.14–1.69, p = 0.001). Of the three subgroups of MAFLD (diabetic, nondiabetic overweight/obese, and nondiabetic normal weight/lean with at least two metabolic abnormalities), only diabetic MAFLD was associated with CAC (aOR = 2.65, 95% CI = 1.98–3.55, p < 0.001). When the minimal number of metabolic risk abnormalities increased to three, nondiabetic normal-weight/lean MAFLD was associated with CAC (aOR = 1.35, 95% CI = 1.02–1.77, p = 0.034).


Diabetic MAFLD predicted high-risk CVD phenotypes the best. Metabolic risk abnormalities in nondiabetic MAFLD patients were independently associated with the risk of CVD. The proposed diagnostic criteria for nondiabetic MAFLD need further investigation in terms of CVD risk.

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Data availability

The data supporting findings of this study are available from the corresponding authors upon reasonable request.



Alanine aminotransferase


AST to platelet ratio index


Serum aspartate aminotransferase


Coronary artery calcification


Cardiovascular disease




Fasting plasma glucose


High-density lipoprotein cholesterol


High-sensitivity C reactive protein


Metabolic dysfunction-associated fatty liver disease


Non-alcoholic fatty liver disease


NAFLD fibrosis score


Type 2 diabetes mellitus


Waist circumference


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JGP receives funding supported by the 2022 Yeungnam University Research Grant. RL receives funding support from NCATS (5UL1TR001442), NIDDK (U01DK061734, U01DK130190, R01DK106419, R01DK121378, R01DK124318, P30DK120515), NHLBI (P01HL147835), and NIAAA (U01AA029019).

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Authors and Affiliations



JGP and SYP is guarantor of integrity of the entire study. JGP designed the study and partially supervised by RL. All authors except RL collected data, which were reviewed by GJP, and analyzed by GJP based on the statistical analysis plan. GJP, MKG, and YLR drafted the manuscript, which was critically revised by SYP. All authors were responsible for collecting and interpretation of the data and approved the final version of manuscript.

Corresponding authors

Correspondence to Soo Young Park or Jung Gil Park.

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Conflict of interest

RL serves as a consultant for Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myer Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse bio, Hightide, Inipharm, Intercept, Inventiva, Ionis, Janssen Inc., Madrigal, Metacrine, Inc., NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 bio, and Viking Therapeutics. In addition, his institution has received grant support from Allergan, Astrazeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Galmed Pharmaceuticals, Genfit, Gilead, Intercept, Inventiva, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Pfizer, and Sonic Incytes. He is also co-founder of Liponexus, Inc.

Ethical approval

This study was performed in accordance with the ethical guidelines of the 1975 Declaration of Helsinki as revised in 2013. The study protocol was approved by the institutional review board of the study center (IRB No. KNUH-2021-07-057-001). The requirement for informed consent from the study participants was waived by the ethics committee because of the retrospective nature of this study.

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Kang, M.K., Lee, Y.R., Jang, S.Y. et al. Impact of metabolic factors on risk of cardiovascular disease in nondiabetic metabolic dysfunction-associated fatty liver disease. Hepatol Int 17, 626–635 (2023).

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