The synthetic BA derivative obeticholic acid, an FXR agonist, is being investigated in phase III clinical trials for the treatment of NAFLD and NASH fibrosis.109 FXR is a key regulator of BA homeostasis that also regulates inflammation and lipid homeostasis.30 The expression of Fxr is down-regulated during NASH.110 Overall, these findings suggest that NASH may promote a luminal environment with a greater proportion of BAs that function as FXR antagonists, but are likely to also interact with other receptors. This evidence concerns the gene NR1H4 and metabolic dysfunction-associated steatohepatitis.