Precore region mutation in hepatitis B virus genome in "healthy" asymptomatic anti-HBe positive carriers

The precore region mutation of hepatitis B virus (HBV) genome characterized from G to A at nucleotide 83 resulting a stop codon in codon 28 has been identified in severe chronic or fulminant hepatitis suggesting that the mutant might be more pathogenic. Since little is known about the mutant in asymptomatic carriers, we investigated the mutant HBV in 19 "healthy" asymptomatic anti-HBe positive carriers by direct sequencing of viral DNA amplified by polymerase chain reaction from serum. Among 18 cases in whom viral DNA could be sequence, wild type HBV was found in only one case. Seventeen cases including three with co-infection of wild type showed a point mutation resulting in a stop codon from TGG to TAG in codon 28 of precore region. This mutation is identical as that found in severe liver disease by other investigators. HBeAg positive patients used as positive control showed only wild type HBV. In conclusion, the precore mutation was found also in the "healthy" asymptomatic carriers. Although this mutation was tightly associated with the lack of HBeAg in serum, it dose not seem to have pathogenic potential compared with wild type HBV.