S2553 Impact of Vitamin D Deficiency on Progression From Metabolic Dysfunction-Associated Fatty Liver Disease to Cirrhosis: A Retrospective Cohort Study

Introduction: While vitamin D deficiency is associated with MAFLD, long-term evidence on its impact is limited. Methods: We conducted a retrospective cohort study using de-identified TriNetX data to evaluate whether vitamin D deficiency (25[OH]D < 20 ng/mL or International Classification of Diseases, Tenth Revision E55) predicts progression from MAFLD to cirrhosis in adults diagnosed between 2012 and 2018. After excluding those with preexisting cirrhosis, other chronic liver diseases, alcohol use disorder, advanced chronic kidney disease, HIV, malabsorptive or granulomatous conditions, recent pregnancy, or use of medications affecting vitamin D metabolism, we used propensity score matching to balance baseline characteristics and followed patients for up to 6 years to assess cirrhosis and related outcomes. Results: In matched cohorts (n = 37,438; mean age 52.8 y; 34.2% vs 33.8% man), vitamin D deficiency showed no 1-year difference in MACE (RR 1.058; P = 0.125), mortality (0.979; P = 0.708), liver transplant (1.192; P = 0.251), HCC (0.881; P = 0.506), or non-alcoholic cirrhosis (0.973; P = 0.577), but lower decompensated cirrhosis (0.831; P = 0.008) and cholangiocarcinoma (0.532; P = 0.009), with higher hospitalization (1.143; P < 0.001). At 2 years, MACE (1.087; P = 0.006) and hospitalization (1.145; P < 0.001) increased, while decompensated cirrhosis (0.862; P = 0.011), cholangiocarcinoma (0.525; P = 0.003), and HCC (0.660; P = 0.007) decreased; mortality (1.025; P = 0.587), non-alcoholic cirrhosis (0.987; P = 0.748), and liver transplant (1.209; P = 0.191) remained unchanged. At 4 years, higher MACE (1.060; P = 0.014) and hospitalization (1.151; P < 0.001) persisted, with continued reductions in decompensated cirrhosis (0.865; P = 0.002), cholangiocarcinoma (0.513; P < 0.001), and HCC (0.628; P < 0.001), but no difference in mortality (0.961; P = 0.254), liver transplant (0.953; P = 0.704), or non-alcoholic cirrhosis (1.025; P = 0.465). By 6 years, mortality (0.937; P = 0.034) and decompensated cirrhosis (0.910; P = 0.027) were lower, non-alcoholic cirrhosis (1.067; P = 0.034) and hospitalization (1.127; P < 0.001) higher, with no change in MACE (1.005; P = 0.814), HCC (0.801; P = 0.078), cholangiocarcinoma (0.700; P = 0.075), or liver transplant (1.031; P = 0.804). Conclusion: In MAFLD, vitamin D deficiency over 6 years was linked to lower risks of decompensated cirrhosis, cholangiocarcinoma, HCC (from year 2), and mortality (year 6), but higher hospitalization, MACE, and non-alcoholic cirrhosis risks by year 6.