In order to establish the virological significance of HBeAg subtypes (HBeAg/1 and HBeAg/2) during hepatitis B virus infection, HBsAg, HBeAg and hepatitis B virus DNA in serum and HBeAg in liver were determined quantitatively in relation to the detection of HBeAg subtypes in agar gel diffusion. Thirty‐eight chronic HBsAg carriers with HBeAg, including 16 non‐specific reactive hepatitis, 8 chronic persistent hepatitis, 11 chronic active hepatitis and 3 liver cirrhosis, who were seen at Tohoku University Hospital from 1983 to 1985, were examined. Significantly larger amounts of HBsAg, HBeAg and hepatitis B virus DNA in serum and HBeAg in liver were found in patients positive for both HBeAg/1 and HBeAg/2 in serum than in those positive for only HBeAg/1 or negative for both subtypes. These results suggest that the presence of HBeAg/2 in serum may reflect the occurrence of active viral replication. When the detection pattern of HBeAg subtypes was examined during serial follow‐up for at least 1 year, three groups of patients were classified with respect to the presence of HBeAg/2, i.e., Type I, consistently positive for HBeAg/2, Type II, consistently negative for HBeAg/2, and Type III, intermittently positive for HBeAg/2. More than 80% of Type I patients were histologically diagnosed having as nonspecific reactive hepatitis, while more than 80% of Type II and III patients had more progressive liver diseases such as chronic persistent hepatitis, chronic active hepatitis and liver cirrhosis. These results suggest that the serial examination of HBeAg subtypes in serum may be important for more detailed evaluations of type B hepatitis.
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