Detection and characterization of hepatitis B virus DNA in serum of HBe antigen-negative HBsAg carriers.

Sera from 153 Israeli patients in various stages of hepatitis B virus (HBV) infection with undetectable hepatitis Be antigen (HBeAg) were studied for the presence of HBV DNA in the serum by molecular hybridization. HBV DNA was detected in 10 patients: 3 with acute hepatitis, 4 asymptomatic hepatitis B surface antigen (HBsAg) carriers, 1 with chronic active hepatitis, 1 with cirrhosis, and 1 with mixed cryoglobulinemia. HBV DNA was detected in 7 of 10 HBeAg-positive control samples tested. Hybridization analysis was used for quantitative comparison of HBV DNA levels in serum. HBV DNA levels, found in HBeAg-negative patients sometimes exceeded the levels found in HBeAg-positive patients. Restriction enzyme analysis of serum HBV DNA from four HBeAg-negative samples gave undistinguishable digestion patterns as compared to 3 HBeAg-positive samples. However, heterogeneity in HBV DNA restriction fragments was detected among HBV genomes in sera of HBeAg-positive samples. These data demonstrate that HBV DNA may be present in the serum at various stages of HBV infection, regardless of HBeAg detection. Failure to detect HBeAg in these patients does not necessarily reflect low serum levels of viral particles, or the occurrence of HBV genome variants.