Excess HBcAg in HBc antibody-negative chronic hepatitis B virus carriers

HBcAg and antibody to HBcAg were assayed in chronic hepatitis B virus carriers who were not reactive for HBc antibodies on available commercial tests. HBc antibody-negative sera, collected before the onset of the acute phase in recovering patients, were used as controls. A high level of HBcAg was detected in HBc antibody-negative chronic hepatitis B virus carriers after dissociative treatment. HBcAg levels were correlated with serum hepatitis B virus DNA levels. Precipitation of immune complexes increased the amount of detected HBcAg. HBc antibodies were detected in some patients only after sucrose gradient fractionation of serum and dissociative treatment. All HBsAg-positive chronic carriers who lacked HBc antibody were immunocompromised. Our results show that in HBc antibody-negative chronic hepatitis B virus carriers with active replication, HBc antibodies may be complexed by the excess of antigen and become undetectable by the available commercial tests. Unresponsiveness to HBcAg cannot always be ascribed to infection by another hepatitis B virus-related virus or hepatitis B virus variant.