Z Gastroenterol 2016; 54 - KV187
DOI: 10.1055/s-0036-1586963

Vitamin D metabolic chemotyping in patients with chronic liver diseases

CS Stokes 1, M Müller 2, DA Volmer 2, F Lammert 1
  • 1Universitätsklinikum des Saarlandes, Innere Medizin II, Homburg, Deutschland
  • 2Universität des Saarlandes, Bioanalytische Chemie, Saarbrücken, Deutschland

Background: Patients with chronic liver diseases (CLD) often have low serum 25-hydroxyvitamin D (25(OH)D) concentrations. The vitamin D receptor is expressed in immune and non-parenchymal liver cells, and 25(OH)D influences defense against bacterial infections and survival in CLD. The role of other vitamin D metabolites remains largely unknown. The aim herein was to quantify multiple, including downstream vitamin D metabolites (the vitamin D "chemotype") in CLD patients.

Methods: Overall, we included 86 CLD patients, who we treated with 20,000 IU vitamin D3 weekly for 6 months if they had low vitamin D serum levels (defined by serum 25(OH)D concentrations < 30 ng/ml). We assessed patients' vitamin D chemotype at baseline, after 3 and 6 months (during treatment) and at 6 months post-treatment. We availed of a novel liquid chromatography mass spectrometry (LC-MS/MS) method, which offers lower detection limits to measure multiple vitamin D metabolites simultaneously.

Results: The cohort comprised 52.3% women, median age 55 years (range 27 – 81) and BMI 26.1 kg/m2 (17.0 – 54.5). Median baseline 25(OH)D3 and 1,25(OH)2D3 concentrations were 16.1 ng/ml (3.0 – 44.8) and 0.03 ng/ml (0.01 – 0.08), respectively; 24,25(OH)D3 was tenfold lower than 25(OH)D3 (1.7 ng/ml, 0.2 – 9.9). The 3-epi-25(OH)D3 epimer species was detected in all samples (0.8 ng/ml, 0.01 – 3.6), equivalent to 0.3 – 12% of individuals' baseline 25(OH)D3. Baseline 25(OH)D3 correlated inversely with response to supplementation (rs=-0.53; P < 0.001). In general, lower baseline 24,25(OH)D3 correlated with larger changes to 25(OH)D3 concentrations (rs=-0.48; P < 0.001). Individual women with extremely low vitamin D levels (but no men) had higher baseline 24,25(OH)D3 concentrations (5.7, 6.6, 9.9 ng/ml); all 3 attained normal post-treatment serum 25(OH)D3. This coincided with decreased 24,25(OH)D3 levels, indicating reduced 24-hydroxylase activity.

Conclusions: Our findings support a novel method for quantifying the vitamin D chemotype which has potential to be used to predict response to vitamin D substitution. The differences in the 3-epi-25(OH)D3 concentrations reinforce the importance of separating the epimer from 25(OH)D3 to avoid overestimation of 25(OH)D concentrations and consequently, vitamin D status.