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Keywords:

  • oval cell;
  • hepatitis B surface antigen;
  • hepatitis B virus;
  • stem cell;
  • transforming growth factor-a;
  • hepatocellular carcinoma

Abstract

Recent studies have identified epithelial cell populations in human livers that are similar to the “oval cells” and “transitional cells” seen in rat livers during the early stages of chemical car-cinogenesis. It has been suggested that these cells might be precursors of hepatocytes and theoretically could be involved in hepatocarcino-genesis. The hepatitis B virus (HBV) also is believed to play a role in the etiology of hepatocellular carcinoma (HCC). Therefore, a study was conducted in nontumorous livers adjacent to HCCs obtained from 26 patients from China to determine whether HBV antigens could be identified in oval cells and transitional cells using an immunohistochemical technique. Hepatitis B surface antigen (HBsAg) was detected in the nontumorous livers of 22/26 (85%) patients. HBsAg was detected in oval cells in 18/26 (69%), in transitional cells in 21/26 (81%), and in mature hepatocytes in 22/26 (85%), but not in bile duct or ductule cells. Transforming growth factor-α (TGF-α) was expressed in oval cells, transitional cells, and bile duct cells in 24/26 (92%) patients, an in mature hepatocytes in 25/26 (96%). Coexpression of HBsAg and TGF-α was identified in the same cells in populations of oval cells and transitional cells of selected patients. Because of the possibility that oval cells could be a source of evolving HCC, these findings suggest that expression of TGF-α associated with HBV infection of oval cells could be a mechanism of human hepatocarcinogenesis. Thus, oval cells could be a site (or one of the sites) where HBV participates in the development of HCC. © 1994 Wiley-Liss, Inc.