The vitamin D receptor genotype is associated with Vitamin D- and Interleukin-6 concentrations in liver cirrhosis and acute-on-chronic liver failure

Background: Vitamin D (25(OH)D3)-deficiency is highly prevalent in liver cirrhosis. Moreover, 25(OH)D3-status correlates with systemic inflammation and decompensation risk in liver cirrhosis. This study aimed to evaluate how single nucleotide polymorphisms (SNPs) of the Vitamin D receptor (VDR) influence 25(OH)D3-status and 25(OH)D3-mediated immunological effects in liver cirrhosis and acute-on-chronic liver failure (ACLF).

Method: Compensated and decompensated liver cirrhosis patients with or without ACLF were recruited from a monocentric, prospective cohort study (N=355). Clinical data were analysed, 25(OH)D3-plasma-concentrations were quantified by ADVIA Centaur Immunoassay and cytokine levels were determined by ELISA. The VDR was examined for distinct SNPs (rs7968585, rs731236, rs7975232, rs2239179, rs2228570) using pyrosequencing.

Results: Patients mean 25(OH)D3-concentrations were 15.3ng/mL underlining the high prevalence of 25(OH)D3-deficiency. 25(OH)D3-levels decreased significantly with liver cirrhosis progression (compensated vs. ACLF: P=0.007). Furthermore, 25(OH)D3-supplementation proved to be highly effective in compensated and decompensated liver cirrhosis, whereas 25(OH)D3-levels could not be increased significantly in ACLF by supplementation (ACLF supplemented vs. unsupplemented P>0.99). Inflammatory markers, e.g. Interleukin-6 (IL-6) increased with cirrhosis progression (compensated vs. ACLF: P<0.0001). Overall, 25(OH)D3- and IL-6-concentrations correlated inversely. Of note, a trend of an opposing association between IL-6-levels and the genotype of the VDR haplotype rs731236/rs7975232/rs7968585 and rs2239179 was identified in compensated liver cirrhosis and ACLF. rs2239179 was moreover associated with 25(OH)D3-status (AG vs. GG: P=0,002) and its GG-genotype showed lower prevalence in ACLF (P=0.0003).

Conclusion: According to this analysis the VDR-genotype may affect inflammatory molecules, 25(OH)D3-status and the success of a supplementary therapy in liver cirrhosis and ACLF.

Publication History

Article published online:
20 January 2025