Embryologic Correlations

CASE 4: Extrahepatic Biliary Atresia

Clinical History:

A neonate is born at 38 weeks gestation after a normal, uncomplicated vaginal delivery to a 28-year-old primigravida. The prenatal course had been normal except for an elevated IgM titer to cytomegalovirus (CMV). A screening fetal ultrasound at 18 weeks showed no abnormal findings. Following birth the infant is noted to become progressively jaundiced. At 2 weeks, the neonatal serum bilirubin is 15 mg/dL. A CBC shows a Hgb of 14 g/dL, Hct 42%, and MCV 96 fL. A direct and indirect antiglobulin test are both negative. The mother's blood type is O+. A liver biopsy of the neonate shows marked cholestasis but no inflammation.

  1. What is the probable cause for these findings?

  2. There is biliary tract obstruction from extrahepatic biliary atresia -- a segment of common bile duct is atretic.

  3. What is the embryologic abnormality?

  4. A liver primordium buds off the developing foregut in the 3rd week, extending into the mesodermal plate between the yolk sac and the developing heart, and forms the liver. The connection of the liver to the foregut narrows to form the common bile duct. A small outgrowth from this duct forms the gallbladder and cystic duct. The vitelline and umbilical veins give rise to the sinusoids that form around the developing plates of hepatocytes.

    In development, the common bile duct temporarily becomes a solid structure that then has a central lumen form. If this lumen fails to reopen, then atresia occurs.

  5. Can this be fixed?

  6. If the atresia is intrahepatic and extensive, nothing can be done, other than liver transplantation. More localized extrahepatic lesions may be amenable to surgical repair. A re-anastomosis can be done if a segment of bile duct >200 microns can be found in the porta hepatis with an operating microscope. Surgery must be done as soon as possible, before significant hepatic damage with fibrosis has occurred.

  7. Is there a chromosomal abnormality?

  8. No.

  9. What is the recurrence risk?

  10. This is a sporadic condition in most cases, with no defined recurrence risk.

  11. What is the significance of the CMV serologic test finding?

  12. Though the exact mechanisms for biliary atresia is not known, some cases are associated with congenital CMV, reovirus, or rotavirus infection. An infection may trigger an immunologic reaction with inflammation of the biliary tree.

  13. Name some other causes for neonatal jaundice.

  14. The baby could have erythroblastosis fetalis, a condition in which maternal circulating antibodies cross the placenta and attack fetal red blood cells. Most cases are due to Rh incompatibility, so in this case, the O+ blood type of the mother and the fact that this is her first pregnancy virtually rules out this possibility (there are much rarer antibodies that can occur). There may be mild transient hyperbilirubinemia in babies born prematurely.

    The major differential diagnosis for extrahepatic biliary atresia is neontal giant cell hepatitis, a rare condition that results from inflammation of the liver, not obstruction. It may be caused by a number of infectious agents such as cytomegalovirus, rubella, and hepatitis B virus, by metabolic disorders, or by unknown causes. Most affected babies with giant cell hepatitis recover uneventfully.