Abstract
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.
Methods
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.
Results
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).
Conclusion
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.
Abbreviations
- ALT:
-
Alanine aminotransferase
- APRI:
-
AST to platelet ratio index
- AST:
-
Serum aspartate aminotransferase
- CAC:
-
Coronary artery calcification
- CVD:
-
Cardiovascular disease
- FIB-4:
-
Fibrosis-4
- FPG:
-
Fasting plasma glucose
- HDL-C:
-
High-density lipoprotein cholesterol
- hsCRP:
-
High-sensitivity C reactive protein
- MAFLD:
-
Metabolic dysfunction-associated fatty liver disease
- NAFLD:
-
Non-alcoholic fatty liver disease
- NFS:
-
NAFLD fibrosis score
- T2DM:
-
Type 2 diabetes mellitus
- WC:
-
Waist circumference
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Funding
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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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.
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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). https://doi.org/10.1007/s12072-023-10517-w
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DOI: https://doi.org/10.1007/s12072-023-10517-w