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

Alagille syndrome is an autosomal dominant disorder characterized by abnorm alities in multiple organ systems, including the liver, and is caused by mu tations in JAG1. Chronic cholestasis secondary to paucity of interlobular b ile ducts is traditionally both a clinical and a pathologic hallmark of thi s disease at diagnosis. We describe the biliary changes on serial liver bio psies in a patient who presented with jaundice and extrahepatic stigmata of Alagille syndrome. Her initial specimens at 6 and 10 months of age demonst rated interlobular bile duct proliferation and cholestasis, suggestive of d istal biliary obstruction. A specimen at 2 years of age showed near-total a bsence of interlobular bile ducts, with the classic histologic appearance o f bile duct paucity. We present this case to underscore the potential pitfa lls in interpreting cholestatic liver morphology in the absence of clinical information. The progression of bile duct abnormalities is discussed in th e context of the role postulated for JAG1 in postnatal liver growth and dev elopment.