MORPHOMETRIC AND IMMUNOHISTOCHEMICAL CHARACTERIZATION OF HUMAN LIVER-REGENERATION

Regeneration in human liver is characterized in part by the formation of ductular structures, so-called ductular hepatocytes in massive hepa tic necrosis and bile ductules in mechanical biliary obstruction. lit an attempt to characterize the liver regenerative process, we performe d image analysis and immunohistochemical staining of the ductular stru ctures in these well defined human liver disorders, 13 cases of massiv e hepatic necrosis and 9 cases of mechanical biliary obstruction. The proliferation index was determined and the expression of several antig ens was localized by immunohistochemical staining using antibodies to cr-fetoprotein, alpha-1-antitrypsin, albumin, and cytokeratin 13 The d uctular structures in adult human liver were compared with the develop ing ductal plates in 11 fetal livers, ranging in age from 9 to 36 week s of gestation. Image analysis demonstrated that the mean total area, mean nuclear area, and mean cell size of ductular hepatocytes were sig nificantly larger than those of bile ductules (p < 0.05). The prolifer ation index of ductular hepatocytes and bib ductules was significantly higher than that of hepatocytes of normal livers (p < 0.02). Bile duc ts, bile ductules in mechanical biliary obstruction, ductular hepatocy tes in massive hepatic necrosis, and the ductal plate cells in fetal l iver shouted strong staining for cytokeratin 13, which characterizes i ntermediate filaments associated with bile duct epithelial cells. Albu min, a liver-specific protein, and alpha-1-antitrypsin, a protease inh ibitor were strongly expressed in ductal plate cells of fetal liver, h epatocytes, and ductular hepatocytes, whereas bile duct cells and bile ductules were negative for albumin. In summary, ductular hepatocytes demonstrate morphometric and immunophenotypic features of both hepatoc ytes and biliary epithelial cells, whereas bile ductules share charact eristics primarily with fetal ductal plates and mature bile ducts. The se findings suggest that ductular hepatocytes in massive hepatic necro sis may serve as bipotential progenitor cells, and bile ductules in me chanical biliary obstruction are related to ductal plates of fetal liv er.