Neonatal Cholestasis, Biliary Atresia, and Congenital Bile-Duct Disorders

Conjugated hyperbilirubinemia indicates neonatal cholestasis. Direct bilirubin is not neurotoxic, whereas indirect bilirubin can cause neurotoxicity and kernicterus.

Idiopathic neonatal hepatitis, also called giant cell hepatitis, causes cholestatic jaundice. Its cause is unknown. It accounts for about half of intrahepatic cholestasis cases, and its characteristic liver-histology finding is giant cells.

Biliary atresia is obstruction caused by a destructive, sclerosing inflammatory process of unknown cause. It affects the extrahepatic bile ducts and extends into the major intrahepatic ducts. Portal pressure rises by 6–10 weeks, and cirrhosis develops rapidly.

Choledochal cyst is enlargement or dilation of part or all of the extrahepatic biliary system. Type I, dilation of the common bile duct, is most common. Obstructed bile flow can produce intrahepatic changes like biliary atresia and progress to cirrhosis.

Caroli disease is a congenital autosomal recessive disorder with communicating cavernous ectasia of the intrahepatic bile ducts. Multiple cystic structures converge toward the porta hepatis. Intrahepatic communicating dilation distinguishes it from an extrahepatic choledochal cyst.

For conjugated hyperbilirubinemia, consider neonatal hepatitis, intrahepatic or extrahepatic biliary atresia, Alagille syndrome, choledochal cyst, parenchymal disease from rubella, toxoplasmosis, CMV, or herpes, and Dubin–Johnson or Rotor syndrome. Idiopathic infantile hepatitis is identified as the most common cause in newborns.

Alpha-1 antitrypsin deficiency, Alagille syndrome, Byler disease, and viral infections may resemble idiopathic neonatal hepatitis clinically and histologically. In a neonate with jaundice, clay-colored stools, and giant cells on biopsy, the diagnosis given is neonatal hepatitis with extrahepatic biliary atresia.

The first sign is prolonged jaundice. Expect conjugated hyperbilirubinemia, persistently yellow urine, and acholic stools without yellow or green pigment. Consider biliary atresia in every infant who remains jaundiced beyond 14 days.

Choledochal cysts are more common in females. In infancy, they present with neonatal cholestasis. Older children may have recurrent upper abdominal pain, recurrent jaundice, and/or a palpable cystic mass, but this classical triad is rare; the disorder may remain silent until childhood.

Look for the central dot sign on CT. Cholangiography is the most diagnostic test. Associated conditions include congenital hepatic fibrosis and cystic, including polycystic, kidney disease.

In a 2-week-old infant with predominantly direct hyperbilirubinemia, the best study to evaluate bile excretion is hepatobiliary scintigraphy.

Alagille syndrome is autosomal dominant and reflects abnormal development of the bile ducts, heart, central nervous system, and face. Liver biopsy may show bile duct paucity. Neonatal intrahepatic cholestasis, hepatosplenomegaly, and xanthomas may occur.

Biopsy may show bile ductular proliferation, portal tract edema and fibrosis, parenchymal cholestasis, and periportal fibrosis or cirrhosis. Inflammation and fibrosing strictures affect the hepatic or common bile ducts; major intrahepatic ducts may undergo progressive destruction.

Complications include cholangitis, cyst rupture, pancreatitis, gallstones, and carcinoma of the cyst wall. Treatment is surgical removal with biliary drainage via a Roux-en-Y loop.

Associated findings include tetralogy of Fallot, coarctation of the aorta, butterfly-shaped vertebrae, a broad prominent forehead, deep-set eyes, and a small pointed chin. The kidneys and central nervous system may also be affected.

When the biopsy pattern is present in all portal tracts, percutaneous liver biopsy is suggestive. Diagnosis is confirmed at laparotomy.

Initial treatment includes supplementation with vitamins A, D, E, and K plus ursodeoxycholic acid. Liver transplantation is used selectively.

The Kasai operation transforms prognosis. Cholangitis occurs in a significant minority during the first two years after surgery. Portal hypertension is present in almost all cases.