The mechanism of the blunted response to ergocalciferol repletion is uncertain and is likely multifactorial, potentially involving impaired gastrointestinal absorption from gut microbiota change [47] or severe cholestasis or intestinal mucosa edema associated with portal hypertension; it may also involve impaired VDBP synthesis by the cirrhotic liver, as well as impaired hepatic 25-hydroxylation (CYP2R1 activity) [46]. This evidence concerns the gene CYP2R1 and cholestasis.