Paucity of Intrahepatic Bile Ducts (Syndromic)

 Cardiac abnormalities, particularly pulmonary stenosis

image Skeletal abnormalities, particularly butterfly vertebrae

image Ocular abnormalities, particularly posterior embryotoxon

image Characteristic facies


• Mutations in J AG1 gene, which encodes ligand for Notch receptor

• Interaction between JAG1 and NOTCH2 may be necessary for bile duct maturation

Clinical Issues

• Presents as jaundice before age of 6 months


• Hepatobiliary scan
image Excretion of technetium-labeled iminodiacetic dye typically absent, mimicking extrahepatic biliary atresia

• Cholangiography
image May show bile duct hypoplasia


• Early in life, bile duct destruction, bile ductular reaction, and inspissated bile in ductules can be confused with biliary atresia

• As patient ages, liver shows evolving ductopenia

Top Differential Diagnoses

• Extrahepatic biliary atresia

• Paucity of intrahepatic bile ducts (nonsyndromic)

Diagnostic Checklist

• Liver biopsies in infants with neonatal cholestasis due to Alagille syndrome may be indistinguishable from biliary atresia

Gross Appearance
Explanted cirrhotic liver from an adult with Alagille syndrome shows a nodular, distorted external surface.

Gross Appearance
Cut surface of cirrhotic liver from an adult with Alagille syndrome shows micronodular cirrhosis, extensive fibrosis, and green discoloration.

Absence of Bile Duct
Portal tract from a patient with Alagille syndrome shows arterioles and veins but no interlobular bile duct.

Bile Ductular Reaction
The edge of a fibrous septum in cirrhotic liver in Alagille syndrome shows bile ductular reaction with inspissated bile in bile ductules image .



• Alagille syndrome

• Arteriohepatic dysplasia


• Syndrome characterized by intrahepatic bile duct hypoplasia and loss, along with at least 3 of the following major clinical features or 2 features in patients with family history
image Chronic cholestasis

image Cardiac abnormalities

– Peripheral pulmonary stenosis, pulmonary valve stenosis, tetralogy of Fallot, aortic stenosis, ventricular septal defects

image Skeletal abnormalities

– Butterfly vertebrae, curved phalanges, short ulna

image Ocular abnormalities

– Posterior embryotoxon, optic nerve drusen

image Characteristic facies

– Broad forehead, deep-set eyes, straight nose, pointed chin


Genetic Disorder

• Mutations in JAG1 gene that encodes ligand for Notch receptor seen in up to 90% of patients
image Interaction between JAG1 and NOTCH2 may be important in bile duct formation and maturation to more differentiated state

– Mutations lead to impaired ductal plate remodeling and subsequent impaired postnatal intrahepatic bile duct development

image Alternatively, interaction between JAG1 and NOTCH4 may be involved in vascular remodeling, and abnormal portal blood vessel remodeling could lead to ductopenia

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Apr 20, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Paucity of Intrahepatic Bile Ducts (Syndromic)

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