Immunohistochemical study for the origin of ductular reaction in chronic liver disease

Int J Clin Exp Pathol. 2014 Jun 15;7(7):4076-85. eCollection 2014.

Abstract

The appearance of proliferating bile ductular structures, which is called the "atypical ductular reaction" is frequently observed in various chronic liver diseases associated. However, the origin of these increased bile ductules has been a matter of controversy. In this study, we investigated the origin of ductular cells as an aspect of relation between epithelial to mesenchymal transition (EMT) and epithelial members of liver parenchyme, such as hepatocyte and cholangiocyte by immunohistochemical staining of human liver. Thirteen specimens of surgically resected liver with biliary cirrhosis were selected. Three sets of double immunohistochemical stains were done; Hep-Par 1 - cytokeratin 19 (CK19), Hep-Par 1 - α-sm ooth mus cle actin (α-SMA) and CK19 - α-SMA. As a result, we investigated the dual expression of the markers of hepatocyte and cholangiocyte in the same cell; in ductular cell and surrounding hepatocyte. However, there seems to be no dual expression of markers for EMT with epithelial markers. This study suggests a possibility of phenotypic change of mature hepatocyte into cholangiocyte. Future studies will be necessary to determine the role that proliferating cholangiocytes play in the pathogenesis of biliary fibrosis and how cholangiocytes interact with other cell types of the liver such as hepatic stellate cells or Kupffer cells.

Keywords: Liver; bile duct cell; ductular reaction; hepatocyte; immunohistochemistry; transdifferentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bile Ducts / pathology*
  • Biomarkers / analysis
  • Cell Transdifferentiation*
  • Epithelial-Mesenchymal Transition*
  • Female
  • Hepatocytes / pathology*
  • Humans
  • Immunohistochemistry
  • Liver Cirrhosis, Biliary / pathology*
  • Male
  • Middle Aged

Substances

  • Biomarkers