[Analysis of the complete hepatitis B virus genomes in a patient for repeated seroconversion to anti-HBe antibody due to co-infection with two virus clones].

We report a case of repeated seroconversion to anti-HBe antibody in a patient with chronic hepatitis B. We amplified and cloned sections of the hepatitis B virus (HBV) genes by polymerase chain reaction (PCR), and sequenced the PCR products. The results were analyzed by connecting all of the sequences to generate complete genomes. As a result, we confirmed the coexistence of two different HBV clones, both of which had the same subtype (adr) and genotype (C2). Neither clone had mutations in the S gene region in sequences involved in gene expression or in sequences involved in drug resistance. However, both clones had mutations in the core promoter(A1762T, G1764A). In one HBe antibody-positive clone, a pre-core mutation associated with HBe antigen negativity (G1896A) was found. In addition, pre-S2 deletion and 6 amino acid substitutions in the core protein gene were detected in this clone. The other HBe antigen-positive clone was essentially wild-type. Interestingly, this clone had accumulated mutations, which participated in DNA polymerase inactivation in the P gene region. Therefore, it is expected that this clone cannot replicate its own DNA polymerase. Consequently, this repeated seroconversion phenomenon was suggested to be responsible for the observed findings. In conclusion, analysis of the complete HBV genome has greatly expanded the number of mutations identified, and this method is useful for understanding the causes of rare cases of hepatitis B.