Proliferation to paucity: evolution of bile duct abnormalities in a case of Alagille syndrome

Alagille syndrome is an autosomal dominant disorder characterized by abnormalities in multiple organ systems, including the liver, and is caused by mutations in JAG1. Chronic cholestasis secondary to paucity of interlobular bile ducts is traditionally both a clinical and a pathologic hallmark of this disease at diagnosis. We describe the biliary changes on serial liver biopsies in a patient who presented with jaundice and extrahepatic stigmata of Alagille syndrome. Her initial specimens at 6 and 10 months of age demonstrated interlobular bile duct proliferation and cholestasis, suggestive of distal biliary obstruction. A specimen at 2 years of age showed near-total absence of interlobular bile ducts, with the classic histologic appearance of bile duct paucity. We present this case to underscore the potential pitfalls in interpreting cholestatic liver morphology in the absence of clinical information. The progression of bile duct abnormalities is discussed in the context of the role postulated for JAG1 in postnatal liver growth and development.