The demonstration that FXR agonists PX-102 in healthy subjects [32] or MET409 and Cilofexor in NASH patients [35,36] reduce bile acid synthesis, with no significant increase in circulating FGF19 concentration, indicates that the activation of hepatic FXR might inhibit bile acid synthesis independently of FGF19. The gene discussed is NR1H4; the disease is metabolic dysfunction-associated steatohepatitis.