The developing human biliary system at the porta hepatis level between 11 and 25 weeks of gestation: a way to understanding biliary atresia. Part 2.

In biliary atresia, inflammation and destruction of extrahepatic and intrahepatic bile ducts with eventual fibrous obliteration occurs, causing neonatal obstructive jaundice. The onset of the disorder may start antenatally and progress after birth, and the porta hepatis is a constant site of involvement. To date, little is known about the intrauterine development of the bile ducts at the porta hepatis. The present work gives an account of the developmental pattern of bile ducts at the level of the porta hepatis in the normal human fetus from the 11th to the 25th weeks of gestation. It has been observed that the proximal portion of the hilar bile ducts derives from the intrahepatic biliary ductal plate. This occurs following a predictable remodeling sequence by which, from many ductal plate-derived ductules, those destined to become definitive bile ducts are enveloped in a concentric cuff of mesenchyma. Those which are not are deleted. The distal portions of the right and left main hepatic ducts develop from the extrahepatic bile duct. There was no gestational period in which the extrahepatic bile duct and the intrahepatic biliary system were separated. Furthermore, the developing intrahepatic bile ducts maintain luminal continuity with the common bile duct from the start of organogenesis. Biliary atresia may result from: (i) failure to establish a definitive type of bile duct; (ii) leakage of bile from primitive bile ducts resulting in an interstitial inflammatory reaction in the adjacent mesenchyma; and (iii) continuous proliferation of primitive bile ducts at the level of the porta hepatis beyond the 25th week of gestation, as a failed compensatory mechanism.