Assessment of histologic risk factors for hepatocellular carcinoma in patients with chronic hepatitis B of advanced stage.

Histologic markers of increased risk for hepatocellular carcinoma can provide useful information for the management of patients with chronic hepatitis B. The expression of epithelial cell adhesion molecule (EpCAM, a marker of hepatic progenitor cells), p21 (a marker of hepatocyte senescence), glutamine synthetase (a marker of perivenular hepatocytes) and CD34 (a marker of sinusoidal capillarization) were assessed by immunohistochemistry in 52 liver biopsy specimens from patients with advanced stage chronic hepatitis B. Nineteen patients developed hepatocellular carcinoma during a follow-up period of 133 months. The findings were compared with those of 18 liver biopsy specimens from patients with early-stage chronic hepatitis B and 6 liver biopsy specimens without significant pathologic findings. EpCAM expression in hepatocytes was significantly increased in specimens with advanced stage, as compared with all other specimens. EpCAM positivity in over 30 % of hepatocytes was only seen in 3 specimens from patients who subsequently developed hepatocellular carcinoma. The expression of p21, glutamine synthetase and CD34 was not associated with hepatocellular carcinoma development. Nevertheless, glutamine synthetase immunostains highlighted zonality abnormalities that were useful in chronic hepatitis B staging. In conclusion, extensive immunopositivity of hepatocytes for EpCAM in chronic hepatitis B may represent a marker of increased hepatocellular carcinoma risk. Glutamine synthetase immunostaining represents a useful adjunct in determining the stage of chronic hepatitis B in diagnostic practice.