Therefore, dysregulation of BA metabolism can also affect the function of BSEP through FXR and upregulate the expression of efflux transporter genes, MDR1 and MRP1, which can cause HCC cells to pump regorafenib out of the cell more quickly, reduce intracellular drug concentration, and cause drug insensitivity. Here, NR1H4 is linked to hepatocellular carcinoma.