51 Hepatocyte FXR activation also induces the expression of BA efflux transporters, such as Bsep and Ostα/β, in the liver to promote enterohepatic BA circulation and prevent cholestasis.54,55 Because of the lack of FXR specificity for primary and secondary BAs and BA dose-dependent cellular toxicity, the generation of synthetic ligands for FXR activation has been of increased interest. This evidence concerns the gene NR1H4 and cholestasis.