NR1H4 and cholestasis: For example, in PBC patients, repression of BA uptake systems (NTCP, OATP2) together with induction of basolateral efflux systems (MRP3, MRP4, and OSTα/β) support the elimination of retained BAs from the liver as cholestasis progresses with advanced disease.41,60–65 Experimental studies in rodents have uncovered a complex interplay of several regulatory pathways under control of FXR and other NRs that are activated by accumulating biliary constituents mediating these transporter changes.42