HISTOLOGICAL-CHANGES OF THE LIVER IN EXPERIMENTAL GRAFT-VERSUS-HOST DISEASE ACROSS MINOR HISTOCOMPATIBILITY BARRIERS .7. A LIGHT AND ELECTRON-MICROSCOPIC STUDY OF THE LARGE BILE-DUCT

Although morphologic changes of the intrahepatic bile ducts in graft-v ersus-host disease (GVHD) have been well studied, those of the large e xtrahepatic 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 histocompatibility barriers were examined up to 14 months after trans plantation. Mononuclear cell infiltration was most striking around 2 w eeks after transplantation. Although it gradually decreased, infiltrat ion persisted during the entire period of observation. Fibrous thicken ing and sclerosis of the bile duct wall continued over time following transplantation, especially 3 months after transplantation. The appear ance was similar to sclerosing cholangitis, but obliteration of the lu men was not demonstrated. Electron microscopically, the bile duct epit helial layer was frequently infiltrated by lymphocytes, and often acco mpanied by polymorphonuclear leukocytes, monocytes, and rarely by plas ma cells. The epithelial cells in close contact with and in the vicini ty of these cells showed a variety of degenerative changes. These resu lts suggest that not only the interlobular and/or small bile ducts but also the large hilar and extrahepatic bile ducts are involved in hepa tic GVHD, and thus bile duct injury in GVHD may occur along the full l ength of the biliary tree.