Metabolic Dysfunction-Associated Fatty Liver Disease-Cardiovascular-Kidney-Metabolic (MAFLD-CKM): A Modified Framework to Predict Long-Term Mortality.
5 affiliations
- 1Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Minia University, Minia, Egypt.
- 2National Liver Institute, Menoufia University, Szibin al-Kaum, Egypt.
- 3Department of Internal Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt.
- 4Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia.
- 5Liver Research Unit, Medica Sur Clinic and Foundation, National Autonomous University of Mexico, Mexico City, Mexico.
Abstract
BACKGROUND Cardiovascular-kidney-metabolic (CKM) syndrome reframes cardio-renal-metabolic risk but omits hepatic dysfunction, particularly metabolic dysfunction-associated fatty liver disease (MAFLD). This study assesses whether integrating MAFLD into the CKM framework improves mortality risk discrimination compared with the original CKM framework. MATERIAL AND METHODS We used data of 10 335 adults aged 20 to 74 years from the third National Health and Nutrition Examination Survey (NHANES III) with mortality follow-up through 2019. CKM was classified based on the American Heart Association framework, and MAFLD was identified based on hepatic steatosis and metabolic dysfunction according to established criteria. A modified CKM score was proposed, incorporating MAFLD into CKM staging. We compared the association of each staging system with all-cause and cardiovascular mortality using Cox regression. RESULTS While both staging systems are significantly associated with mortality, the proposed modified CKM staging showed superior risk stratification than the original definition, particularly in stage 3. The modified CKM system showed a notably higher hazard ratio than the original CKM system in all-cause mortality (3.84, 95% CI: 3.38-4.37 vs 3.49, 95% CI: 3.07-3.95) and CVD-related mortality (6.38, 95% CI: 4.80-8.48 vs 5.41, 95% CI: 4.12-7.12). CONCLUSIONS Integrating MAFLD into the CKM framework (modified CKM) provided an incremental improvement in prognostic discrimination for allcause and cardiovascular mortality, with stronger risk stratification observed in stage 3, highlighting the key role of the liver in the cardio-renal-metabolic axis. These findings underscore the need for a broader, multi-organ approach to provide incremental refinement for defining and managing metabolic risk.
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BibTeX
@article{mostafa2026metabolic,
title = {{Metabolic Dysfunction-Associated Fatty Liver Disease-Cardiovascular-Kidney-Metabolic (MAFLD-CKM): A Modified Framework to Predict Long-Term Mortality.}},
author = {Alaa M Mostafa and Yasser Fouad and Eman Abdelsameea and Reem Ezzat Mahdy and Ziayn Pan and Nahum Méndez-Sánchez and Mohammed Eslam},
journal = {Medical science monitor : international medical journal of experimental and clinical research},
year = {2026},
month = oct,
doi = {10.12659/msm.954116},
url = {https://europepmc.org/article/MED/42888835},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Metabolic Dysfunction-Associated Fatty Liver Disease-Cardiovascular-Kidney-Metabolic (MAFLD-CKM): A Modified Framework to Predict Long-Term Mortality.
AU - Alaa M Mostafa
AU - Yasser Fouad
AU - Eman Abdelsameea
AU - Reem Ezzat Mahdy
AU - Ziayn Pan
AU - Nahum Méndez-Sánchez
AU - Mohammed Eslam
PY - 2026
DA - 2026/10/17
JO - Medical science monitor : international medical journal of experimental and clinical research
DO - 10.12659/msm.954116
UR - https://europepmc.org/article/MED/42888835
AB - BACKGROUND Cardiovascular-kidney-metabolic (CKM) syndrome reframes cardio-renal-metabolic risk but omits hepatic dysfunction, particularly metabolic dysfunction-associated fatty liver disease (MAFLD). This study assesses whether integrating MAFLD into the CKM framework improves mortality risk discrimination compared with the original CKM framework. MATERIAL AND METHODS We used data of 10 335 adults aged 20 to 74 years from the third National Health and Nutrition Examination Survey (NHANES III) with mortality follow-up through 2019. CKM was classified based on the American Heart Association framework, and MAFLD was identified based on hepatic steatosis and metabolic dysfunction according to established criteria. A modified CKM score was proposed, incorporating MAFLD into CKM staging. We compared the association of each staging system with all-cause and cardiovascular mortality using Cox regression. RESULTS While both staging systems are significantly associated with mortality, the proposed modified CKM staging showed superior risk stratification than the original definition, particularly in stage 3. The modified CKM system showed a notably higher hazard ratio than the original CKM system in all-cause mortality (3.84, 95% CI: 3.38-4.37 vs 3.49, 95% CI: 3.07-3.95) and CVD-related mortality (6.38, 95% CI: 4.80-8.48 vs 5.41, 95% CI: 4.12-7.12). CONCLUSIONS Integrating MAFLD into the CKM framework (modified CKM) provided an incremental improvement in prognostic discrimination for allcause and cardiovascular mortality, with stronger risk stratification observed in stage 3, highlighting the key role of the liver in the cardio-renal-metabolic axis. These findings underscore the need for a broader, multi-organ approach to provide incremental refinement for defining and managing metabolic risk.
SN - 1234-1010
SN - 1643-3750
ER -