Characterization of ductular hepatocytes in primary liver allograft failure

Liver regeneration after massive hepatic necrosis is characterized by the presence and formation of ductular hepatocytes (DHs). Several studies suggested that these structures might serve as bipotential progenitor cells, as demonstrated by phenotypic features characteristic of both hepatocytes and biliary epithelial cells. In this investigation, 33 liver allograft explants after primary graft failure 1 to 14 days after orthotopic liver transplantation were examined to study the formation and differentiation of DHs. As demonstrated by earlier studies, antibody to CK-19 defines the biliary epithelial cell lineage, whereas HepPar 1 is hepatocyte specific. Antibodies to CK-19, vimentin and alpha-fetoprotein, HepPar 1, and AE-1 were used for immunoperoxidase staining of 33 failed liver allograft specimens with regeneration. DHs were seen along the limiting plates at Day 1, but reactivity to HepPar 1 started only at Day 4 post injury. Vimentin and alpha-fetoprotein were not detectable in the DHs. The DHs reacted with AE-1 and anti-CK-19 starting at Day 1, but reactivity to HepPar 1 started only at Day 4 post injury. DHs are formed along the limiting plates and acquire phenotypic characteristics of bile duct epithelium as early as Day 1 after liver injury and of hepatocytes only at Day 4 after liver injury. We conclude that DHs might represent bipotential progenitor cells in regenerating liver.