Hepatitis B virus DNA in serum of healthy black African adults positive for hepatitis B surface antibody alone: Possible association with recombination between genotypes A and D

In some patients with chronic liver disease induced by hepatitis B virus, v iral DNA is known to persist in low concentration in serum after seroconver sion to hepatitis B surface antibody-positivity. This phenomenon has, howev er, not been documented in asymptomatic black African carriers of hepatitis B virus. Using nested amplification by the polymerase chain reaction, we d etected low concentrations of hepatitis B virus DNA in the serum of 6 of 23 (26%) healthy black African adults with normal liver function and with hep atitis B virus surface antibody as the only serological marker of the virus . This finding offers one explanation for the earlier observation of integr ated hepatitis B virus DNA in hepatocellular carcinomas in black Africans w hose serum was positive for surface antibody alone. A number of genetic cha nges were found in the six isolates that might be responsible for evasion o f the immune response and persistence of the virus. Isolated mutations were detected in the "a" determinant of the surface gene and in the encapsidati on signal. In all five isolates sequenced in the core promoter, mutations w ere present in the upstream regulatory region. Recombination between genoty pes A and D was present in three of the isolates, including both of those i n which the entire genome was sequenced, This change in genotype also overl apped the amino end of the polymerase domain and may result in sufficiently low levels of replication to allow viral persistence. Topoisomerase 1 spec ific trinucleotides were concentrated in the vicinity of the recombination breakpoints. J. Med. Virol. 64:441-454, 2001. (C) 2001 Wiley-Liss, Inc.