Magnesium Depletion Score and Mortality in Individuals with Metabolic Dysfunction Associated Steatotic Liver Disease over a Median Follow-Up of 26 Years.

UNLABELLED: Metabolic dysfunction associated steatotic liver disease (MASLD) has been associated with increased risks of all-cause and cardiovascular disease (CVD) mortality. Identification of modifiable risk factors that may contribute to higher risks of mortality could facilitate targeted and intensive intervention strategies in this population. This study aims to examine whether the magnesium depletion score (MDS) is associated with all-cause and CVD mortality among individuals with MASLD or metabolic and alcohol associated liver disease (MetALD).

METHODS: A total of 3802 participants with MASLD or MetALD were followed up over a median of 26 years in the National Health and Nutrition Examination Survey (NHANES) III cohort. The MDS was calculated by aggregating four factors influencing the reabsorption capability of the kidneys. The associations between MDS and all-cause, CVD, and cancer mortality were quantified using Cox proportional hazard regression models.

RESULTS: In the combined MASLD + MetALD cohort, a higher MDS (>2) was associated with increased all-cause mortality (HR, 2.52; 95%CI, 1.77-3.61; p-trend < 0.0001) and CVD mortality (HR, 3.01; 1.87-4.86; p-trend < 0.0001) compared to MDS = 0; this association became stronger among participants who did not meet the estimated average requirement level of Mg intake (2.72; 1.69-4.37; p-trend = 0.0014) and those with a Fibrosis-4 index (FIB-4) < 1.3 (2.95; 1.69-5.15; p-trend = 0.0006).

CONCLUSIONS: In individuals with MASLD or MetALD, higher MDS, indicative of worse global Mg status, was associated with an increased risk of all-cause and CVD mortality. Correcting global Mg deficiency in high-risk MASLD/MetALD patients may have long-term health benefits.