Diffuse biliary tract involvement mimicking primary sclerosing cholangitis in an experimental model of chronic graft-versus-host disease in mice

Experimental graft-versus-host disease (GVHD) across minor histocompatibility antigens was developed by injecting spleen and bone marrow cells (9 :1)of congenic B10.D2 mice into sublethally irradiated BALB/c mice, and the histologic features of the liver were studied for up to 14 months after transplantation. Both intrahepatic and extrahepatic bile ducts were severely involved in the GVHD process and showed features of non-suppurative cholangitis. Inflammatory cells, mainly lymphocytes, abutted the bile ducts and infiltrated into the duct epithelial layer together with a variety of degenerative changes in the epithelial cells. The peak inflammatory activity occurred about 2-3 weeks after transplantation. Thereafter, the inflammatory cell infiltration around the bile ducts and in the bile duct epithelial layer gradually became reduced in severity, although the infiltration persisted during the entire 14 month observation period. Periductal and duct wall fibroplasia began about 1 week after transplantation and gradually progressed. After 23 months post-transplantation, distinct ductal and periductal fibrosis of both intrahepatic and extrahepatic bile ducts was observed. This histologic feature resembled that of primary sclerosing cholangitis (PSC). These results suggest that PSC lesions might develop as a result of chronic cellular immunologic mechanisms in GVHD across minor histocompatibility barriers.