Ultrastructural lesions of bile ducts in primary biliary cirrhosis: A comparison with the lesions observed in graft versus host disease

Abstract

Intrahepatic bile duct destruction is a characteristic feature of primary biliary cirrhosis and hepatic graft versus host disease. Lymphocytotoxicity against antigens on the surface of biliary cells is one of the cell mediated immune mechanisms debated in the pathogenesis of persistent bile duct destruction during primary biliary cirrhosis. Immune complex injury has also been hypothesized. In graft versus host disease, damage to bile duct cells is also believed to be due to a cytotoxic reaction of the grafted lymphoid cells against the host histocompatibility antigens, and immune complex deposition is likely to occur. The aim in this comparative ultrastructural study of intrahepatic bile ducts in 10 patients with primary biliary cirrhosis and six patients with hepatic graft versus host disease was to investigate whether identical or different ultrastructural lesions were detected in both diseases. Features of conspicuous necrosis of biliary cells, including cytolysosomes, apoptosis, and basement membrane disruption, were observed in both diseases. Numerous lymphocytes established close membrane contacts with biliary cells, especially with the necrotic ones. They had cytoplasmic pseudopods, and some of them displayed a uropod or contained lysosomal vesicles. Abnormalities of the bile duct basement membrane, also observed in both diseases, included thickening or multilayering and numerous lucent areas of rarefaction often containing osmiophilic inclusions. The striking similarity of the ultrastructural lesions in both diseases provides an additional morphological argument to suggest that certain common pathogenic mechanisms might be involved in the destruction of bile ducts in primary biliary cirrhosis as well as in hepatic graft versus host disease.