NR1H4 and hepatocellular carcinoma: A weakened defense against potential carcinogenic BAs, subsequent hepatic inflammation, together with the absence of direct regulatory effects on the cell cycle, may explain the carcinogenic potential resulting from loss of FXR and SHP.69,72,73 A direct role of FXR on cell proliferation and apoptosis is underlined by the fact that not only does FXR play a crucial role in hepatocellular cancer, but also its alterations have also been implicated in colorectal and breast carcinogenesis.74,75