Association between serum 25-hydroxy vitamin D concentrations and mortality among individuals with metabolic dysfunction-associated fatty liver disease: a prospective cohort study

Am J Clin Nutr. 2022 Sep 15;nqac260. doi: 10.1093/ajcn/nqac260. Online ahead of print.

Abstract

Background: The association between serum 25-hydroxy vitamin D (25(OH)D) concentrations and mortality remains unclear among patients with metabolic dysfunction-associated fatty liver disease (MAFLD) or non-alcoholic fatty liver disease (NAFLD).

Objectives: To evaluate the association between serum 25(OH)D concentrations and mortality among individuals with MAFLD/NAFLD.

Methods: The study included 4651 individuals with fatty liver disease (FLD) (3964 had MAFLD and 3968 had NAFLD) from the Third National Health and Nutrition Examination Survey. Fatty liver disease was identified by ultrasonographic detection of hepatic steatosis. Mortality was ascertained by linkage to the National Death Index up to 31 December 2019. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment of potential confounders.

Results: Of 4651 individuals with FLD, 3427 individuals (69.7%) had both MAFLD and NAFLD. During median follow-ups of 25.8 and 26.1 years, we identified 1809 and 1665 deaths among 3964 participants with MAFLD and 3968 participants with NAFLD, respectively. Compared with participants with serum 25(OH)D concentrations ≤30.0 nmol/L, the multivariable-adjusted HR and 95% CI of all-cause mortality were 0.62 (0.43, 0.89) for participants with MAFLD having serum 25(OH)D >75.0 nmol/L (P-trend = 0.001), and 0.63 (0.42, 0.95) for participants with NAFLD having serum 25(OH)D >75.0 nmol/L (P-trend = 0.002). A nonlinearly inverse association was observed between serum 25(OH)D concentrations and all-cause mortality among participants with MAFLD (Poverall <0.001; Pnonlinear = 0.003) or NAFLD (Poverall <0.001; Pnonlinear = 0.009), with a threshold effect at around 50.0 nmol/L. The inverse association was stronger among participants with MAFLD aged <60 years (P-interaction = 0.001).

Conclusions: This study suggested a nonlinearly inverse association between serum 25(OH)D concentrations and all-cause mortality among patients with MAFLD/NAFLD, with a threshold effect at around 50.0 nmol/L of serum 25(OH)D.

Keywords: MAFLD; NAFLD; cohort study; mortality; vitamin D.