Immune pathogenesis of sclerosing cholangitis in biliary atresia.

Biliary atresia (BA) is the most frequent single life-threatening hepatic disorder in early childhood in Japan, Europe and North America. It affects one in 9000 live-born infants in our country. BA is characterized by complete inability to excrete bile associated with obstruction, destruction or absence of the extrahepatic bile ducts. Pathologic study of tissues removed from the porta hepatis and of the proximal extrahepatic bile ducts suggests that BA in the vast majority of infants results from a sclerosing, inflammatory lesion initiated in ductular tissues. Kasai procedure (KP) is in the first line of treatment for BA infants in the developed countries all over the world. In KP, bile duct remnants or fibrous tissues in front of the hepatic artery are dissected and a Roux-en -Y anastomosis is fashioned between the area of the porta hepatic and the jejunum. KP has provided opportunities to survive years for some infants with BA with reasonable quality of life. However in BA, bile duct injury and sclerosing inflammation is ongoing even after apparently successful KP. A 10-year survival rates with native liver is still 53% in 1999 according to multi-centre analysis in Japan. BA is still the leading cause of paediatric liver transplantation. Poor prognosis of BA is, of course, due to unknown aetiology. Potential aetiologies for more common perinatal form of BA include viral infections, immune-mediated injuries and autoimmune disease involving biliary systems. Details of each theory including our updated findings will be reviewed and discussed.