Immunoelectron microscopic observation of intrahepatic HBeAg in patients with chronic hepatitis B

Immune light and electron microscopic studies using monoclonal antibodies have been applied to localize HBeAg in liver biopsy specimens of 19 patients with chronic hepatitis B. Under the light microscope, HBeAg was demonstrated in nuclei, cytoplasm and on the cell surface of hepatocytes. The number of HBeAg-positive hepatocytes correlated well with the serum levels of HBeAg (enzyme immunoassay) and DNA-polymerase. Of 11 patients in whom high numbers of HBeAg-positive hepatocytes were found at the light microscopic level, HBeAg was also studied in hepatocytes at the electron microscopic level. The HBeAg in nuclei was either found as aggregates or dispersed diffusely. In the aggregates of HBeAg, the 27-nm core particles were frequently found. In addition, the antigen was found in the cytosol of some hepatocytes as amorphous mass and in some hepatocytes in the cisternae of perinuclear space, endoplasmic reticulum and Golgi saccules. Occasionally the antigen was found on the membranes of the cell organelles and on the plasma membranes that faced the intercellular and the Disse spaces. These findings suggest that cytoplasmic HBeAg in hepatocytes may be ultrastructurally classified into two different patterns by its distribution, mainly in endoplasmic reticulum or in cytosol. The ratio varied between hepatocytes with these two types of patterns. The titer of serum HBeAg tended to be higher when the corresponding liver biopsy specimens contained more hepatocytes with HBeAg in endoplasmic reticulum than those with HBeAg in the cytosol. (HEPATOLOGY 1990;12:133–140).