Chronic hepatitis B virus infection in an anti-HBc-nonreactive blood donor: variant virus or defective immune response?

Viral sequence and host immune response were investigated in an unusual, asymptomatic chronic hepatitis B virus carrier (human leukocyte antigen type A24, Bw61, Bw62, Bw6, DRw11, DRw52, DQw7) who was consistently nonreactive for antibody to HBc and had a normal ALT level over a 5-yr study period. The precore and core region DNA sequences of virus isolated from his serum had seven silent mutations that resulted in no changes in the amino acid sequence of the adr HBsAg subtype. He had no abnormalities in the number of peripheral blood T or B cells and no HBcAg-specific suppressor T cells. His lymphocytes proliferated in vitro in response to phytohemagglutinin, pokeweed mitogen, Staphylococcus aureus and tetanus toxoid but not to recombinant HBcAg. Unlike other HBsAg carriers and hepatitis B virus-immune individuals, his monocytes did not ingest beads coated with HBcAg. Failure to produce antibody to HBc was not due to an hepatitis B virus variant but to a selective immune system defect in this asymptomatic HBsAg carrier.