Integrating MAFLD into the CKM framework (modified CKM) provided an incremental improvement in prognostic discrimination for all-cause and cardiovascular mortality, with stronger risk stratification observed in stage 3, highlighting the key role of the liver in the cardio-renal-metabolic axis.
The modified CKM staging system showed higher hazard ratios for all-cause mortality than the original CKM system.
The modified CKM staging system showed higher hazard ratios for cardiovascular disease-related mortality than the original CKM system.
Superior risk stratification of the modified CKM system over the original was particularly observed at stage 3.
The study population consisted of 10,335 adults from the NHANES III dataset with long-term mortality follow-up.
The original CKM framework was identified as omitting hepatic dysfunction, specifically MAFLD, from cardio-renal-metabolic risk assessment.
This research suggests that adding liver disease information to an existing heart-kidney-metabolic risk scoring system makes it better at predicting who is likely to die from all causes or from cardiovascular disease. The existing system, called CKM (Cardiovascular-Kidney-Metabolic) syndrome, was developed by the American Heart Association to assess combined risks from heart, kidney, and metabolic conditions — but it does not account for fatty liver disease (called MAFLD). The researchers used health data from over 10,000 American adults tracked for several decades to test whether including MAFLD would improve the system's ability to identify high-risk individuals. The modified scoring system that included MAFLD predicted a higher risk of death compared to the original system, particularly among people classified at stage 3 of disease severity. For example, people in the highest risk category had about 3.84 times the risk of dying from any cause under the modified system, compared to 3.49 times under the original. For cardiovascular deaths specifically, the modified system predicted 6.38 times the risk versus 5.41 times with the original system. This research suggests that the liver plays an important role in the web of metabolic diseases affecting the heart and kidneys, and that ignoring liver health in risk assessments may lead to underestimating a person's true health risks. Including fatty liver disease in clinical risk frameworks could potentially help doctors identify more people who need closer monitoring or earlier intervention for metabolic and cardiovascular conditions.
Mostafa A, Fouad Y, Abdelsameea E, Mahdy R, Pan Z, Méndez-Sánchez N, et al.. (2026). Metabolic Dysfunction-Associated Fatty Liver Disease-Cardiovascular-Kidney-Metabolic (MAFLD-CKM): A Modified Framework to Predict Long-Term Mortality.. Medical science monitor : international medical journal of experimental and clinical research. https://doi.org/10.12659/MSM.954116