Epidemiology most frequent surgical cause of cholestatic jaundice that presents in the neonatal period 5/100,000 live births in The Netherlands, 5.1/100,000 in France, 6/100,000 in the British Isles, 6.5/100,000 in Texas, 7/100,000 in Victoria Australia, 7.4/100,000 in Atlanta USA and in Japan, 10.6/100,000 in Hawaii, to 32/100,000 in French Polynesia occurs in approximately 1/18,000 live births in Western Europe In the world, the reported incidence varies from 5/100,000 to 32/100,000 live births, and is highest in Asia and the Pacific region; occurs in black infants, with an incidence approximately 2 times higher than that observed among white infants Chardot, Christope (2006). Biliary Atresia. Orphanet Journal of Rare Dis. 2006; 1: 28 Schwarz, Steven M (2009). Pediatric Biliary Atresia. Reitrieved last April 2, 2011 at overview#a0199

Epidemiology Females > males Prior to the development of liver transplantation, the long-term survival rate for infants with biliary atresia following portoenterostomy was 47-60% at 5 years and 25-35% at 10 years. 1/3 of all patients, bile flow is inadequate following surgery, and these children succumb to complications of biliary cirrhosis in the first few years of life unless liver transplantation is performed. Following portoenterostomy, complications include cholangitis (50%) and portal hypertension (>60%) Chardot, Christope (2006). Biliary Atresia. Orphanet Journal of Rare Dis. 2006; 1: 28 Schwarz, Steven M (2009). Pediatric Biliary Atresia. Reitrieved last April 2, 2011 at overview#a0199

Etiology & Pathogenesis Karrer, F. et. al. (2003). Pathogenesis and Outcome of Biliary Atresia: Current Concepts. Journal of Pediatric Gastroenterology and Nutrition 37:4–21 Lippincott Williams & Wilkins, Inc., Philadelphia

Viral Infection Cytomegalovirus (CMV) Reovirus & Rotavirus HPV & HHV6 (?) Karrer, F. et. al. (2003). Pathogenesis and Outcome of Biliary Atresia: Current Concepts. Journal of Pediatric Gastroenterology and Nutrition 37:4–21 Lippincott Williams & Wilkins, Inc., Philadelphia

Immune Injury in Biliary Atresia “multihit” pathologic process (viral/toxic insult) to biliary epithelium to newly expressed or altered antigens on the surface of bile duct epithelia newly expressed or altered antigens on the surface of bile duct epithelia bile duct epithelial injury  fibrosis and occlusion of the extrahepatic bile duct Cytotoxic T cells then elicit a TH1 cellular response Karrer, F. et. al. (2003). Pathogenesis and Outcome of Biliary Atresia: Current Concepts. Journal of Pediatric Gastroenterology and Nutrition 37:4–21 Lippincott Williams & Wilkins, Inc., Philadelphia

Karrer, F. et. al. (2003). Pathogenesis and Outcome of Biliary Atresia: Current Concepts. Journal of Pediatric Gastroenterology and Nutrition 37:4–21 Lippincott Williams & Wilkins, Inc., Philadelphia

Autoimmunity in Biliary Atresia Vasiliauskas et al. (75) have reported that 10 of 11 patients with biliary atresia were positive for serum IgG and IgM antineutrophil cytoplasmic antibodies (ANCA), with higher levels of the IgMANCA in patients with biliary atresia compared with children and adults with other liver diseases. Karrer, F. et. al. (2003). Pathogenesis and Outcome of Biliary Atresia: Current Concepts. Journal of Pediatric Gastroenterology and Nutrition 37:4–21 Lippincott Williams & Wilkins, Inc., Philadelphia

Vascular Etiology Intrahepatic and extrahepatic bile duct blood supply: hepatic arterial circulation hepatic arterial ischemia causes bile duct strictures Causative or consequential nature still unclear Karrer, F. et. al. (2003). Pathogenesis and Outcome of Biliary Atresia: Current Concepts. Journal of Pediatric Gastroenterology and Nutrition 37:4–21 Lippincott Williams & Wilkins, Inc., Philadelphia

Defective Morphogenesis Intrahepatic bile duct development depends on interactions between mesenchyme and portal venous radicals Primitive hepatic precursor cells  single layer of cells  double layer (the ductal plate) as the primitive intrahepatic bile ductule anlage  cells scatter and remodel as a single layer around the lumen to form the portal tract bile ducts Abnormal remodeling leads to the ductal plate malformation (believed to be responsible for the liver lesion of congenital hepatic fibrosis and other bile duct dysplasias) Abnormalities in induction of hepatocyte growth factor, or defects in scatter factor and/or receptors Karrer, F. et. al. (2003). Pathogenesis and Outcome of Biliary Atresia: Current Concepts. Journal of Pediatric Gastroenterology and Nutrition 37:4–21 Lippincott Williams & Wilkins, Inc., Philadelphia