NR1H4 and cholangiocarcinoma: ​​Concerning carcinogenic risk, chronic FXR activation displays a complex tissue-selective duality:​​ while systemic FXR loss promotes hepatocarcinogenesis and tumor-specific FXR silencing characterizes the HCC/CCA microenvironment (131), hyperactivation within specific gastrointestinal tissues may drive β-catenin-dependent oncogenesis (132).