Strikingly, INT-767 administration in Abcb4−/− mice stimulates intestinal Fgf15 induction and inhibits hepatic Cyp7a1 expression, promoting endogenous BA reduction, indicating that protection from HCC development is mediated by FXR and not TGR5 and underscoring the potential of FXR activation in disease with BA-associated HCC development. Here, GPBAR1 is linked to hepatocellular carcinoma.