Appearance of hepatocytelike cells in the interlobular bile ducts of human liver in various liver disease states



Among 1,098 liver biopsy specimens obtained from patients with various liver diseases characterized by liver injury, 58 epithelial cells whose cytoplasms stained positively by the periodic acid–Schiff stain (digested with diastase) were recognized in the interlobular bile ducts of 37 specimens from 36 patients. Light microscopic study revealed that the cytoplasms of these cells were clear or stained weakly eosinophilic on hematoxylin and eosin staining and that the cell limits were distinct. From their reaction with periodic acid–Schiff stain and from electron microscopic observation it was clear that these cells contained an abundance of glycogen and were located among the normal bile duct cells surrounded by basement membrane. On electron microscopy, these cells had microvilli of equal sizes on their luminal surfaces and many irregularly sized microvilluslike cell membrane projections on their basal surfaces. They rested on basement membrane with basal spaces. These cells varied in size from 25.0 to 452.2 μm2 (mean = 212.2 μm2). In contrast, the sizes of normal bile duct cells and hepatocytes ranged from 20.0 to 69.3 μm2 (mean = 34.2 μm2) and from 113.0 to 860.3 μm2 (mean = 447.0 μm2), respectively. Immunohistochemical study with antiserum to cytokeratin 19, albumin and α1-antitrypsin on serially cut frozen sections showed that some of these cells expressed markers of bile duct cells and hepatocytes. Some cells expressed only the markers of hepatocytes. Computer graphic three-dimensional reconstruction clearly demonstrated that these cells were located sparsely (but sometimes in groups) among normal interlobular bile duct cells, without any connection to the surrounding parenchymal hepatocytes. This pathognomonic significance of these cells is unknown, but they may represent the transformation or metaplasia of bile duct cells to hepatocytes. (HEPATOLOGY 1992;16:1199–1205.)