History and prospects of bile acid therapies

Abstract

Animal bile has been regarded as a potential remedy of liver diseases for millennia in ancient Eastern cultures. The application of bile acids as major organic bile components for gallstone dissolution and of ursodeoxycholic acid (UDCA) for cholestatic liver diseases began in the 2^nd half of the 20^th century. Currently, UDCA is regarded as effective 1^st line treatment of primary biliary cholangitis, the most frequent 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 chenodeoxycholic acid derivative obeticholic acid and derivatives of UDCA such as norucholic acid and various UDCA hybrids are under evaluation for treatment of diverse benign and malignant, genetic and acquired hepatobiliary disorders. Development of new drugs interacting with the enterohepatic bile acid circulation has attracted attention for rare genetic pediatric disorders. The present review describes the current status and future prospects of bile acid-based therapies for hepatobiliary diseases of adults, children and during pregnancy on the basis of historical developments over centuries and millennia.