A longitudinal study of histologic and immunohistologic changes in an experimental model of sclerosing cholangitis

A longitudinal study of intra and extrahepatic bile duct injuries was performed in an animal model of secondary sclerosing cholangitis induced by formalin injection into the common bile duct. Lymphocytic infiltration inside and around the bile ducts occurred seven days after injection. The disease later evolved to a fibrous cholangitis of the small bile ducts. Septal intrahepatic and extrahepatic bile duct involvement became evident three months after formalin injection. The ductular proliferation led to a progressive biliary cirrhosis with portal to portal fibrous septa. After formalin injection, bile duct cells expressed the Ia antigen in the cytoplasm and/or on the membrane of bile duct cells. The intensity of staining did not correlate with the duration or severity of the disease. Lymphocytes infiltrating into and around the bile duct were mainly T-cells. This study suggests that a local cell-mediated immune response to the injection of a toxic agent induces pathological features similar to those of sclerosing cholangitis in man.