Vitamin D metabolism is changed and FGF23 levels are increased in patients with cirrhosis

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Background: Vitamin D (VD) deficiency, assessed by plasma 25-Hydroxyvitamin-D (25(OH)D), is highly prevalent in chronic liver disease (CLD) and associated with disease progression and complications. However, the variable response of individuals to VD supplementation indicates the limitation of 25(OH)D levels to provide insights into the metabolic situation, especially in severely ill patients. Therefore, the aim of the current project was to evaluate different VD metabolites and Fibroblast Growth Factor 23 (FGF23), a hormone that regulates the synthesis of the active VD metabolite calcitriol, in different stages of CLD. Methods: Thirty-nine patients (74% male, mean age: 58 years) of the Jena University Hospital with decompensated liver cirrhosis as well as 88 participants of the prospective multicenter cohort study “German National Cohort (NAKO)” with hepatic steatosis (n=44) and controls without hepatic steatosis (n=44), matched in age, gender and season of blood collection, were included in the current analysis. 7-Dehydrocholesterol (7-DHC), VD 3 , 25(OH)D 3 and 24,25-dihydroxyvitamin D 3 (24,25(OH) 2 D 3 ) plasma levels were analyzed using liquid chromatography-tandem mass spectrometry. Concentrations of calcitriol, VD-binding protein (DBP) and intact FGF23 (iFGF23) were determined in plasma by commercial ELISA kits. Results: None of the parameters assessed differed between the two NAKO groups. In cirrhosis patients, plasma levels of 7-DHC (-45%), 25(OH)D 3 (-70%) and DBP (-55%) were markedly reduced compared to controls and participants with steatosis (7-DHC: -50%, 25(OH)D 3 : -70%, DBP: -55%) (all p<0.0001). Additionally, in contrast to the NAKO groups, only a small number of cirrhosis patients had quantifiable plasma concentrations of VD 3 (n=17) and 24,25(OH) 2 D 3 (n=6) (LOQ: 0.075 ng/ml for VD 3 and 0.43 ng/ml for 24,25(OH) 2 D 3 , respectively), Interestingly, despite being tightly regulated, calcitriol plasma levels were also substantially lower in cirrhosis patients (-65%, and -63%) when compared to controls and individuals with steatosis, respectively (both: p<0.0001). Furthermore, subjects having liver cirrhosis showed higher plasma iFGF23 levels in comparison to controls (+70%) and compared to individuals with steatosis (+47%; both: p<0.0001). Conclusion: Our data point out that liver cirrhosis patients were characterized by marked changes in VD metabolism, and elevated iFGF23 concentrations. Publication History Article published online: 22 May 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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