Evaluating Outcomes in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease and Vitamin D...

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease (CLD) globally and is closely linked to metabolic risk factors and systemic inflammation. Emerging evidence suggests that vitamin D deficiency may influence MASLD severity and outcomes, though limited real-world data often assess long-term clinical outcomes in MASLD patients stratified by vitamin D status. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network (2006-2025). Adult patients with MASLD were stratified into two cohorts based on serum 25-hydroxyvitamin D levels: normal (≥30 ng/mL) and deficient (<20 ng/mL). Patients with other CLD, malignancy, decompensated cirrhosis, and relevant confounding conditions were excluded. Primary outcomes included all-cause mortality, hospital readmissions, and ICU admissions at 1-year and 5-year follow-up. Results: After propensity score matching, 6959 patients were included in each cohort. Compared with patients with normal vitamin D levels, those with vitamin D deficiency had significantly higher rates of hospital readmissions, ICU admissions, and all-cause mortality at both 1-year and 5-year follow-up. A 1 year, readmissions occurred in 10% vs. 6%, ICU admissions 2.6% vs. 1.2%, and mortality 1.5% vs. 0.5% of patients (p = 0.01). Similar findings were observed at 5 years, with higher rates of readmissions 15% vs. 10%, ICU admissions 4.4% vs. 2.4% and mortality 3.2% vs. 1.3% in the vitamin D-deficient cohort (p = 0.01). Conclusions: Vitamin D deficiency was associated with significantly increased mortality, hospital readmissions, and ICU admissions among patients with MASLD. Our findings suggest that vitamin D status may represent a valuable prognostic indicator in this population. Although the observational nature of this study precluded establishing causality, our results support the consideration of routine assessment of vitamin D levels in patients with MASLD. Further prospective and mechanistic studies are needed to determine whether vitamin D supplementation can improve outcomes in this population.