W. R. Treem, G. A. Krzymowski, R. W. Cartun, C. A. Pedersen, J. S. Hyams, M. Berman

Cytokeratin Immunohistochemical Examination of Liver Biopsies in Infants with Alagille Syndrome and Biliary Atresia

  • Gastroenterology
  • Pediatrics, Perinatology and Child Health
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SummaryIdentifying bile duct epithelium is sometimes difficult with standard histologie techniques. The availability of antibodies to specific cy tokeratin (CK) intermediate filaments has allowed identification of CK expressed by bile duct epithelium. Formalin‐fixed, paraffin‐embedded liver tissue from five infants (aged 1–12 months) with Alagille syndrome and five infants with biliary atresia (aged 1.5–11 months) were pepsin digested then reacted with a combination of anti‐cytokeratin monoclonal antibodies using an avidin‐biotin immunoper‐oxidase technique. Liver tissue obtained at autopsy from infants without primary liver disease (aged 22 weeks gestation to 24 months) was treated similarly for comparison. Control specimens showed progression from prominent immunoreactivity of the ductal plate cells at the rim of the portal tract (22–24 weeks gestation) to incorporation of tubular ductal structures into portal tract mesenchymal tissue (26–34 weeks gestation) and formation of intensely immunoreactive mature discrete interlobular ducts with progressive loss of cytokeratin immunoreactivity of the ductal plate cells (1–24 months). In contrast, biopsies from infants with Alagille syndrome showed few immunoreactive interlobular ducts. Biopsies from infants with Alagille syndrome less than 2 months old showed only immunoreactivity of single ductal plate cells or small ductules at the periphery of the portal tracts. Biopsies from some infants greater than 3 months old showed increased numbers of immunoreactive cells in groups and anastomosing bands lacking true lumens and extending into the fibrous bridges between adjacent portal areas (neoductular proliferation). Biopsies from infants with biliary atresia showed strongly immunoreactive interlobular bile ducts and prominent peripheral ductules. Neoductular proliferation was already present in the earliest biopsies, and as fibrosis and cirrhosis increased, interlobular duct staining decreased, and ductal plate cells extending into fibrous bands became more immunoreactive. Anti‐cytokeratin monoclonal antibodies appear to be a useful tool for identification of bile duct epithelium in infants with a paucity of interlobular bile ducts and biliary atresia. Compared to age‐matched controls and patients with biliary atresia, infants with Alagille syndrome may fail to fully develop interlobular ducts. In both Alagille syndrome and biliary atresia, chronic cholestasis is a stimulus for proliferation of epithelium at the limiting plate which expresses a bile ductular cytokeratin pheno‐type.

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