Elevated Relative Levels of the C-3 Epimer of 25-Hydroxyvitamin D in Patients with Cirrhosis

Background: Elevated levels of the C-3 epimer (3-epi-25(OH)D) of 25-hydroxyvitamin D (25(OH)D) have been identified in premature infants as compared to most adults, and an immature liver has been suggested as a possible cause. We hypothesised that patients with cirrhosis might present with elevated C-3 epimerisation due to impaired liver function. The aim was to assess whether 3-epi-25(OH)D levels differ in patients with chronic liver disease with cirrhosis vs. those without cirrhosis. Methods: A total of 309 patients were included (254 patients with cirrhosis vs. 55 without cirrhosis). Serum 25(OH)D and 3-epi-25(OH)D levels were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Patients with cirrhosis had significantly higher median relative 3-epi-25(OH)D concentrations, as compared to patients without cirrhosis (7.4% (5.5-10.4) vs. 4.8% (2.4-5.7), respectively; p < 0.001). They also had similar absolute 3-epi-25(OH)D levels (despite having lower 25(OH)D serum concentrations) than patients without cirrhosis. A progressive increase in relative 3-epi-25(OH)D levels was observed with more advanced cirrhosis (p < 0.001). An analysis of the ROC area under the curve determined 6% as the optimal cut-off for relative 3-epi-25(OH)D. All patients with Child-Pugh stage C and 88.6% with stage B were above the 6% cut-off and had significantly higher absolute serum 3-epi-25(OH)D concentrations (0.9 ng/mL vs. 0.6 ng/mL; p < 0.05) and lower serum 25(OH)D levels (9.3 vs. 14.1 ng/mL; p < 0.001) than patients <6% cut-off. Conclusions: These results reflect the marked increases in relative 3-epi-25(OH)D levels that occur with cirrhosis. The specific hepatic metabolic alterations still need to be unravelled, including whether cirrhosis might lead to reduced epimer clearance.