The history and future of bile acid therapies.

Animal bile has been regarded as a potential remedy for liver diseases for millennia in ancient Eastern cultures. The application of bile acids, as major organic components of bile, for gallstone dissolution and of ursodeoxycholic acid (UDCA) for cholestatic liver diseases began in the second half of the 20th century. Currently, UDCA is regarded as an effective first-line treatment for primary biliary cholangitis, the most common chronic cholestatic liver disease, and is also applied in other cholestatic disorders, including primary sclerosing cholangitis and intrahepatic cholestasis of pregnancy. For the past two decades, nuclear receptor agonists - such as the farnesoid X receptor agonist and the chenodeoxycholic acid derivative obeticholic acid - as well as derivatives of UDCA, such as norucholic acid and various UDCA hybrids, have been under investigation for the treatment of a wide range of benign and malignant, genetic and acquired hepatobiliary disorders. The development of new drugs that interact with the enterohepatic bile acid circulation has attracted attention for rare genetic paediatric disorders. In the present review, we describe the current status and future prospects of bile acid-based therapies for hepatobiliary diseases in adults, children, and during pregnancy, on the basis of historical developments over centuries and millennia.