Enzymatic amplification and sequence analysis of precore/core DNA in HBsAg-positive patients

Serum or plasma from 69 HBsAg-positive patients was tested for the presence of precore core gene specific DNA by the polymerase chain reaction (PCR). In both healthy individuals (n = 26) and chronic carriers (n = 25), there was a strong correlation between presence of circulating anti-HBe and the absence of detectable HBV genome in serum. In 18 serum samples where HBsAg was the only detectable marker, i.e., anti-HBc-negative specimens, HBV DNA could be detected in three samples. HBV strains from 21 of the 24 PCR-positive samples were sequenced over the precore/core junction. A stop codon at the end of the precore region, described by other workers, was found in strains from two blood donors, one of whom had detectable HBeAg in serum. Conversely, HBV strains from the three anti-HBc-negative patients where DNA of the HBV precore region could be amplified and who had no detectable serum HBeAg or anti-HBe did not have this stop codon. The study indicates that further investigations are required before lack of HBeAg can be correlated with evidence of mutations in the precore region.