Origin and involution of hyperplastic bile ductules following total biliary obstruction.

The origin of biliary epithelial cells (BEC) lining hyperplastic bile ductules in the liver in biliary disease is uncertain. Depending on the underlying condition, the hyperplastic BEC may arise by multiplication of existing BEC, transdifferentiation of liver cells to BEC or by both mechanisms. Using histological, autoradiographic and immunohistochemical techniques, the development of these ductules was assessed in rats following total biliary obstruction (TBO) for periods of up to 50 days. Histologically, a biliary cirrhosis developed after 21 days. Apoptosis was observed in both liver cells and BEC at all stages following TBO, and focal involution of hyperplastic ductules by this mode of cell deletion was noted at 50 days. The 3H-thymidine labelling index was approximately 25 times greater (p less than 0.0005) than control values in both liver cells and BEC at all stages following TBO, reaching peak values at 48 h of 6.07 +/- 0.82% for liver cells and 15.99 +/- 1.47% for BEC. In sections stained by the immunoperoxidase technique and using a prekeratin antiserum to identify BEC, an increase in the number of canals of Hering was observed at days 7 and 21. An intermediate-type cell possessing the morphological appearance of a liver cell and expressing prekeratin antigens was seen in an occasional canal of Hering. On the basis of the high cell replication rate of liver cells and BEC and the very occasional intermediate-type cell, it was concluded that hyperplastic BEC are derived essentially from existing BEC by cell division. The contribution to the BEC pool from an intermediate cell type within the canals of Hering was small.