Association of the Modified Endothelial Activation and Stress Index with MASLD and Liver Fibrosis: Effect Modification by Magnesium Intake

Background/Aims: Few studies have reported the effect of magnesium status on the endothelial dysfunction-related risk for the development of MASLD and liver fibrosis. The current study aimed to explore the association of modified endothelial activation and stress index (mEASIX) with metabolic dysfunction-associated steatotic liver disease (MASLD) and liver fibrosis and to examine the effect of magnesium intake on this association. Materials and Methods: A cross-sectional study was conducted using data from 5960 participants in the National Health and Nutrition Examination Survey 2017-2020. The mEASIX was calculated based on lactate dehydrogenase levels, high-sensitivity C-reactive protein levels, and platelet counts. Metabolic dysfunction-associated steatotic liver disease was defined as the presence of hepatic steatosis along with at least one of the 5 cardiometabolic risk factors. Liver fibrosis was defined as a liver stiffness measurement ≥ 8.0 kPa. Magnesium (Mg) intake was assessed using the 24-hour dietary recall data. Multivariate logistic regression analyses were performed to examine the associations of mEASIX with MASLD and liver fibrosis. Results: The mEASIX was positively associated with MASLD and liver fibrosis (MASLD: odds ratio [OR] in Q2 = 1.62, Q3 = 2.38, and Q4 = 2.70; liver fibrosis: OR in Q3 = 1.84 and Q4 = 2.73; all P < .05). The mEASIX revealed nonlinear relationships with MASLD and liver fibrosis. A significant interaction between magnesium intake and mEASIX was observed in relation to MASLD. Stratified analyses further demonstrated that the association between high mEASIX (≥1.2) and the risk of MASLD and liver fibrosis was more pronounced among participants with low magnesium intake compared to those with high magnesium intake. Conclusion: The current study demonstrated positive nonlinear associations of mEASIX with MASLD and liver fibrosis. Low magnesium intake may exacerbate this endothelial dysfunction-related risk for MASLD and liver fibrosis.