Ursodeoxycholic Acid Treatment of Vanishing Bile Duct Syndromes
Vanishing bile duct syndromes (VBDS) are characterized by progressive destruction of intrahepatic and sometimes extrahepatic branches of the biliary tree. A common symptom of all VBDS is chronic cholestasis, which is often progressive and leads to biliary cirrhosis and its sequelae. VBDS are heterogeneous in their etiology. The most common VBDS diseases in adults are primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). In children, biliary atresia, Byler’s disease and Alagille syndrome classify as VBDS, but they are rare. Ursodeoxycholic acid (UDCA), a naturally occurring dihydroxy bile acid, is the only drug currently approved for the treatment of patients with PBC, and has been studied for several other cholestatic syndromes. Effectiveness of UDCA in patients with PBC has been shown. In addition, beneficial effects have also been observed in patients with other VBDS including PSC, cystic fibrosis and chronic graft-versus-host-disease (GVHD). Several potential mechanisms of action of UDCA have been proposed including biophysical effects and intracellular modulation of signaling events and secretion. Of these, cholangiocyte protection, stimulation of impaired hepatocellular secretion, and anti-apoptotic effects are probably the most relevant mechanisms currently under investigation.