Extrahepatic biliary atresia demonstrates abnormal persistence of HES1 protein in neonatal biliary epithelium: an immunohistochemical study.

Extrahepatic biliary atresia (EHBA) is an important cause of conjugated hyperbilirubinemia in neonates. It is a progressive disease with a poor prognosis, requiring early surgical intervention to control morbidity and mortality. The exact pathogenesis of this disorder is not known, although genetic, infectious, toxic, and/or environmental factors are thought to play a role in the causation. The Notch signaling pathway plays diverse and critical roles in development of extrahepatic and intrahepatic biliary tree. The HES family of bHLH proteins is involved in downstream signaling in the Notch pathway. We demonstrate that HES1, a principal member of this family, is normally expressed in the nuclei of human biliary epithelial cells up to 16 weeks of gestation, but not in later gestation or in the neonatal period. On the contrary, in EHBA, there is anomalous persistence of this protein for up to 3 months of postnatal life. We suggest that aberrant HES1 expression in EHBA may represent a compensatory feedback upregulation due to a putative downstream molecular defect. Further studies should be performed to evaluate the role of HES1 immunohistochemistry as a diagnostic tool in extrahepatic biliary atresia.