Production of histological changes mimicking primary biliary cirrhosis in rabbits by immunization with bile duct antigen.

Histopathological liver changes resembling primary biliary cirrhosis were induced in an experimental animal model. A special strain of rabbit received an antigen prepared from scrapings of bovine gallbladder mucosa. Eventually, 47 out of 84 antigen-treated rabbits displayed histopathological liver features resembling those of chronic non-suppurative destructive cholangitis as seen in humans. In addition, granuloma formation, ductular proliferation and fibrosis were seen in some cases. However, advanced lesions consistent with micronodular cirrhosis have not been found. Lymphocytes seemed to play an important role triggering early pathogenetic mechanisms, judging from the presence of lymphocytes invading the basement membrane of the affected bile ducts. Furthermore, we observed by electron microscopy that the epithelial cells of the involved bile ducts revealed both mitochondrial swelling and dilatation of endoplasmic reticulum cisternae. In summary, our experimental animal model offers interesting possibilities regarding the study of pathogenesis and development of primary biliary cirrhosis.