HBcAg

HBcAg, or hepatitis B core antigen, is the structural protein that forms the nucleocapsid of the hepatitis B virus (HBV). It resides inside the viral core and is not typically secreted into the bloodstream. The core antigen is encoded by the HBV core gene and exists as a 183-amino-acid protein that assembles as dimers into an icosahedral shell containing the viral genome and polymerase. A mature virion contains about 120 core protein dimers, yielding a 240-subunit core particle. The C-terminal, arginine-rich domain binds RNA and is involved in genome packaging; phosphorylation modulates assembly and replication.

Immunology and serology: The immune response targets HBcAg, and serologic testing most often examines antibodies against it. Anti-HBc appears during acute infection (IgM anti-HBc) and persists as total anti-HBc thereafter. HBcAg itself is rarely detectable in serum; when present, it is generally considered a marker of active replication. In clinical practice, anti-HBc is used as a historical marker of exposure to HBV across infection phases. HBcAg is more commonly assessed in liver tissue by histology to evaluate ongoing viral replication.

Clinical significance: In chronic HBV infection, hepatocytes may express HBcAg, reflecting replication activity. Detection of core antigen in liver biopsy can aid assessment of replication status, though it is not a routine serologic marker. Vaccines for hepatitis B target HBsAg rather than HBcAg, so HBcAg is not a component of the standard vaccine. The pre-core region of HBV produces HBeAg, a secreted antigen that is distinct from HBcAg but related in genetic origin and used as a marker of infectivity in some testing protocols.