We have separated circulating HBeAg into small and large molecular forms by agarose gel electrophoresis and analyzed the relationship between the two forms and other clinical features of chronic hepatitis B, especially in regard to liver cell damage. The large HBeAg accounted for 7.3% 2 3.4% of serum HBeAg in 9 subjects with normal liver histological findings or nonspecific reactive hepatitis, 38.0% 2 27.8% in 32 patients with chronic persistent hepatitis and 65.6% f 23.3% in 21 patients with chronic active hepatitis (p < 0.01). A positive correlation was seen between the height of aminotransferase elevations and the percentage of large HBeAg. Three patients who progressed from histologically normal liver or nonspecific reactive hepatitis to chronic active hepatitis had dramatic increases in the percentage of large HBeAg. The finding that the presence of large HBeAg in serum correlated with the severity of hepatitis suggests that HBeAg may play an important role in determining the degree of liver injury in chronic hepatitis B. (HEPATOLOGY 1991;13:1057-1060.)
HBeAg, which was first described by Magnius and Espmark (1) in 1972, exists in the core of Dane particles in the liver or serum or as soluble protein in serum (2-41, and both forms consist of identical polypeptides (p15.5) (4). Two types of HBeAg, namely the IgG-free small molecular form and the IgG-bound large molecular form, have been identified in serum (5).
The relationship between the two molecular forms of HBeAg and the clinical course of HBV infection has been described in several reports (5-8). A shift in predominance often occurs from the small to the large forms during the course of acute HBV infection, followed by the loss of large HBeAg forms and the development of antibody to HBeAg (anti-HBe) (6). A positive correlation between the ratio of small to large HBeAg and HBVassociated DNA polymerase activity has been reported (7), as well as a higher level of large HBeAg in association