Histological changes of the liver in experimental graft-versus-host disease across minor histocompatibility barriers. VII. A light and electron microscopic study of the large bile duct.

Although morphologic changes of the intrahepatic bile ducts in graft-versus-host disease (GVHD) have been well studied, those of the large extrahepatic bile ducts in the porta hepatis or common bile ducts have not been so well elucidated. In the present study, pathologic changes of the extrahepatic bile ducts in experimental mouse GVHD across minor histocompatibilty barriers were examined up to 14 months after transplantation. Mononuclear cell infiltration was most striking around 2 weeks after transplantation. Although it gradually decreased, infiltration persisted during the entire period of observation. Fibrous thickening and sclerosis of the bile duct wall continued over time following transplantation, especially 3 months after transplantation. The appearance was similar to sclerosing cholangitis, but obliteration of the lumen was not demonstrated. Electron microscopically, the bile duct epithelial layer was frequently infiltrated by lymphocytes, and often accompanied by polymorphonuclear leukocytes, monocytes, and rarely by plasma cells. The epithelial cells in close contact with and in the vicinity of these cells showed a variety of degenerative changes. These results suggest that not only the interlobular and/or small bile ducts but also the large hilar and extrahepatic bile ducts are involved in hepatic GVHD, and thus bile duct injury in GVHD may occur along the full length of the biliary tree.