Vitamin D supplementation is associated with reduced risk of hepatobiliary malignancy in patients with primary sclerosing cholangitis

BACKGROUND: Vitamin D deficiency has been implicated in cancer risk across several organ systems, but its role in hepatobiliary malignancy (HBM) remains unclear. We evaluated whether vitamin D supplementation (VDS) was associated with a lower risk of HBM specifically in patients with primary sclerosing cholangitis (PSC). METHODS: Patients enrolled in the PSC registry at our quaternary care and liver transplant (LT) center from 2010 to 2020 were analyzed. The primary exposure was VDS, modeled as a time-dependent variable. The primary outcome was HBM. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics, and Cox proportional hazards models were employed to estimate marginal hazard ratios (HRs). Cumulative incidence functionsfor HBM were estimated using a competing risks analysis treating death, and LT was as competing events. RESULTS: A total of 160 patients (mean age 42 years; 66% male) were included, of whom 76 (47.5%) reported baseline VDS. Over a median follow-up of 7 years, 15 patients developed HBM, corresponding to an incidence rate of 12.3 per 1000 person-years. VDS was associated with a significantly lower risk of HBM in both conventional (HR 0.16, 95% CI 0.05-0.57) and IPTW (HR 0.15, 95% CI 0.03-0.41) analyses. This association was consistent across baseline vitamin D strata, including <30 ng/mL (HR 0.12, 95% CI 0.02-0.79) and ≥30 ng/mL (HR 0.18, 95% CI 0.05-0.65). Accounting for competing risks, the 5-year cumulative incidence of HBM was 1.1% among patients receiving VDS versus 11.5% without VDS (p<0.01). DISCUSSION: VDS was associated with a significantly lower risk of HBM in this longitudinally followed cohort of patients with PSC. These findings support the consideration of VDS in all patients with PSC and underscore the need for mechanistic and interventional studies to further evaluate this association.