There is significant unmet need in Primary Biliary Cholangitis (PBC) in patients 
under-responsive to the only approved therapy Ursodeoxycholic Acid (UDCA) who 
are at increased risk of progressing to end-stage liver disease. Obeticholic 
Acid (OCA) is a farnesoid X receptor (FXR) agonist which has been evaluated as a 
second line therapy in PBC and has recently been licenced by the FDA. Areas 
covered: The pharmacology and biology of OCA as an FXR agonist and its clinical 
benefits. A systematic review was undertaken of published literature, meeting 
abstracts and trial registries using the search terms FXR, FGF-19 (& FGF-15), 
Obeticholic Acid and INT-747. Expert commentary: OCA reduces exposure to toxic 
hydrophobic bile acids through reduction in bile acid synthesis (by direct and 
indirect (via enterocyte-released FGF19) actions on Cyp7A1-mediated bile acid 
synthesis) and bile acid excretion by hepatocytes. It significantly improves 
liver biochemical parameters strongly associated with risk of disease 
progression in UDCA under-responsive patients and the key side-effect of 
pruritus can be reduced by optimised dosing. OCA will be the first stratified 
therapy introduced in PBC, however confirmatory trial and real life data are 
needed to confirm that suggestive biochemical improvements are matched by 
improvement in key clinical outcomes.