A phase II trial published in 2013, showed that administration of OCA at 25 mg or 50 mg daily for six weeks reduced markers of liver inflammation and fibrosis and increased insulin sensitivity.The Farnesoid X Receptor Ligand Obeticholic Acid in Nonalcoholic Steatohepatitis Treatment (FLINT) trial, sponsored by NIDDK, was halted early in January 2014, after about half of the 283 subjects had completed the study, when a planned interim analysis showed that a) the primary endpoint had been met and b) lipid abnormalities were detected and arose safety concerns. Treatment with OCA (25 mg/day for 72 weeks) resulted in a highly statistically significant improvement in the primary histological endpoint, defined as a decrease in the NAFLD Activity Score of at least two points, with no worsening of fibrosis. 45% (50 of 110) of the treated group had this improvement compared with 21% (23 of 109) of the placebo-treated controls. However concerns about longterm safety issues such as increased cholesterol and adverse cardiovascular events may warrant the concomitant use of statins in OCA-treated patients. Portal hypertension
Animal studies suggest that OCA improves intrahepatic vascular resistance and so may be of therapeutic benefit in portal hypertension. An open label phase IIa clinical study is under way. Bile acid diarrhea
Bile acid diarrhea (also called bile acid malabsorption) can be secondary to Crohns disease or be a primary condition. Reduced median levels of FGF19, an ileal hormone that regulates increased hepatic bile acid synthesis, have been found in this condition. FGF19 is potently stimulated by bile acids and especially by OCA.
Additional studies are being required to prove its clinical benefit. Primary biliary cholangitis
Primary biliary cholangitis (PBC), also known as primary biliary cirrhosis, is an auto-immune, inflammatory liver disease which produces bile duct injury, fibrosis, cholestasis and eventual cirrhosis. It is much more common in women than men and can cause jaundice, itching (pruritus) and fatigue. Ursodeoxycholic acid therapy is beneficial, but the disease often progresses and may require liver transplantation. Animal studies suggested that treatment with FXR agonists should be beneficial in cholestatic diseases such as PBC. OCA at doses between 10 mg and 50 mg was shown to provide significant biochemical benefit, but pruritus was more frequent with higher doses. The results of a randomized, double-blind phase III study of OCA, 5 mg or 10 mg, compared to placebo (POISE) were presented in April 2014, and showed that the drug met the trials primary endpoint of a significant reduction in serum alkaline phosphatase, a biomarker predictive of disease progression, liver transplantation or death. Nonalcoholic steatohepatitis (NASH)
Non-alcoholic steatohepatitis is a common cause of abnormal liver function with histological features of fatty liver,  inflammation and fibrosis. It may progress to cirrhosis and is becoming an increasing indication for liver transplantation. It is increasing in prevalence. OCA is proposed to treat NASH.