The combination of TMAO and a high-fat diet (HFD) seems to have a synergistic effect on NAFLD development since TMAO could influence BA metabolism towards the increased synthesis of FXR-antagonists [113]; as we mentioned above [90], FXR inhibition is associated with spontaneous HCC development through the Wnt/β-catenin pathway. This evidence concerns the gene NR1H4 and hepatocellular carcinoma.