• 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
Imaging
• Hepatobiliary scan
Excretion of technetium-labeled iminodiacetic dye typically absent, mimicking extrahepatic biliary atresia
• Cholangiography
May show bile duct hypoplasia
Microscopic
• 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 .
TERMINOLOGY
Synonyms
• Alagille syndrome
• Arteriohepatic dysplasia
Definitions
• 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
• Mutations in JAG1 gene that encodes ligand for Notch receptor seen in up to 90% of patients
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
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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Interaction between JAG1 and NOTCH2 may be important in bile duct formation and maturation to more differentiated state
Alternatively, interaction between JAG1 and NOTCH4 may be involved in vascular remodeling, and abnormal portal blood vessel remodeling could lead to ductopenia
