Ultrastructural Aspects of Primary Biliary Cirrhosis and Other Types of Cholestatic Liver Disease

Abstract

Seven patients with primary biliary cirrhosis were studied clinically, biochemically, and by light and electron microscopy. Serial liver biopsies were examined. The electron-microscopic findings were compared with those in 5 patients with extrahepatic obstructive jaundice, 3 with cholestatic viral hepatitis, 2 with chronic aggressive hepatitis, and 2 with other types of cirrhosis. Distinctive features were observed in patients with primary biliary cirrhosis in the small and medium-sized bile ducts. These consisted of the following: the bile duct epithelium shows intracytoplasmic filamentous structures grouped into bundles which become progressively more abundant and prominent. The mitochondria are swollen and exhibit fewer circular cristae. The cytoplasm in addition is occupied by numerous cytophagosomes which decrease with progression of disease. The rough endoplasmic reticulum is vesicular and ribosomes are scanty. The luminal microvilli are at first blunted and scanty and finally disappear. In the final stage, the basement membranes of the bile ducts are disrupted and invaded by polymorphonuclear leukocytes. Changes were observed in hepatocytes as well. At the early stage they contain numerous cytophagosomes, and the mitochondria show homogenization of their matrix with curling and disappearance of cristae, granules, and prominent crystalline inclusions. These findings vary with progression of disease and do not appear to be characteristic. Evidence from the literature supporting this interpretation is discussed. Some of the changes observed in the bile ducts are also seen to a minor degree in other pathological entities, but their prominence and progression are distinctive in primary biliary cirrhosis and possibly make them features of diagnostic significance. However, comparative studies of larger series are necessary in order to assess the significance of the findings reported here.