INTRODUCTION: Primary biliary cholangitis (PBC) is an autoimmune disease of the 
liver characterized by destruction and inflammation of the intrahepatic bile 
ducts. The disease affects mainly women. The disease is often discovered through 
abnormal alkaline phosphatase (ALP) activity, and is confirmed when 
anti-mitochondrial antibodies (AMA) are present. The etiology of PBC is poorly 
understood. Cigarette smoking, immune dysregulation, nail polish, urinary tract 
infections, and low socioeconomic status have been implicated but none have been 
confirmed. Genome wide association studies (GWAS) have disclosed strong 
associations between certain human leukocyte antigen (HLA) alleles and PBC. PBC 
can progress to cirrhosis and end-stage liver disease. Hepatocellular carcinoma 
(HCC) develops in up to 3.5% of PBC patients. Ursodeoxycholic acid (UDCA) is the 
only medication approved for the treatment of PBC. The use of UDCA in PBC delays 
histological progression and extends the transplant-free survival. 40% of PBC 
patients do not respond adequately to UDCA, and these patients are at high risk 
for serious complications. Therefore, there is a critical need for more 
effective therapies for this problematic disease. Multiple other agents have 
either been or are currently being studied as therapeutic options in UDCA 
non-responder PBC patients. Six-ethyl chenodeoxycholic acid (6-ECDCA), a potent 
farnesoid X receptor (FXR) agonist, has shown anti-cholestatic activity in 
rodent models of cholestasis. Obeticholic acid (OCA, 6-ECDCA, or INT-747), a 
first-in-class FXR agonist, has been examined in PBC patients with inadequate 
response to UDCA, and shown promising results. Particularly, initial clinical 
trials have demonstrated that the use of OCA (in addition to UDCA) in PBC 
patients with inadequate response to UDCA led to significant reduction of serum 
alkaline phosphatase (ALP, an important prognostic marker in PBC). More 
recently, the results of a randomized clinical trial of OCA monotherapy in PBC 
reported significant reduction of ALP in the treatment group compared to 
placebo.
AREAS COVERED: This review covers the preclinical and clinical studies of OCA in 
PBC. In addition, other alternative therapies that are currently being examined 
in PBC patients will also be discussed in this review. A literature search was 
carried out using the PubMed database.
EXPERT OPINION: If approved by the U.S. FDA, OCA will likely be an important 
alternative add-on therapy in PBC patients who have inadequate response to UDCA.