What Hepatitis B Core Antibody (HBcAb) Measures
Hepatitis B core antibody (HBcAb or anti-HBc) is a serologic marker that indicates past or current infection with hepatitis B virus—it appears in all persons who have been infected with HBV, whether the infection was acute, resolved, or chronic. 1
Primary Function and Clinical Significance
- Anti-HBc is the most sensitive indicator of HBV exposure, appearing 1-2 weeks after HBsAg becomes detectable during acute infection 1
- The antibody persists for a lengthy period, often lifelong, making it a permanent marker of HBV exposure 1
- Anti-HBc is present in all phases of HBV infection except in individuals who have never been infected or those with vaccine-derived immunity only 1
Two Forms of Anti-HBc
IgM Anti-HBc
- IgM anti-HBc indicates acute or recent HBV infection (typically within the preceding 1-2 years) 1, 2
- This form often becomes undetectable within 6 months after acute infection 1
- High levels in acute-phase serum confirm recent hepatitis B virus etiology 2
IgG Anti-HBc
- IgG anti-HBc indicates past infection and predominates after the acute phase resolves 1
- This form remains detectable lifelong in most cases 1
- IgG anti-HBc without IgM suggests resolved or chronic infection rather than acute infection 1
Interpretation in Different Clinical Contexts
Distinguishing Vaccine Immunity from Natural Immunity
- Anti-HBc positive with anti-HBs positive (HBsAg negative) = recovered from past natural infection with immunity 1, 3
- Anti-HBc negative with anti-HBs positive = vaccine-derived immunity without prior natural infection 3, 4
- This distinction is critical because individuals with anti-HBc positivity have risk of HBV reactivation under immunosuppression, while those with vaccine-only immunity do not 3
Chronic HBV Infection
- All HBsAg-positive chronic hepatitis B patients should have detectable anti-HBc 1
- Anti-HBc is present in both HBeAg-positive and HBeAg-negative chronic hepatitis cases 5
- Rare cases exist where chronically infected persons do not develop detectable anti-HBc (approximately 75% remain truly negative even with sensitive assays), though this is uncommon 6
Occult HBV Infection
- Anti-HBc may be the only positive marker in occult HBV infection, where HBsAg is undetectable but HBV DNA persists in the liver 1
- Persons with isolated anti-HBc positivity (HBsAg negative, anti-HBs negative) may represent false-positive results, past infection with waning anti-HBs, low-level chronic infection, or passive antibody transfer 1
- All HBcAb-positive individuals who are candidates for immunosuppressive therapy should be evaluated by a hepatologist to rule out occult infection and determine need for pre-emptive antiviral therapy 1
Critical Clinical Applications
Risk Stratification for HBV Reactivation
- Anti-HBc positive patients have up to 68.3% risk of HBV reactivation with rituximab-based chemotherapy, compared to minimal risk in those with vaccine-only immunity 7
- HBV DNA testing and antiviral prophylaxis should be initiated before immunosuppression in anti-HBc positive individuals regardless of HBV DNA level 7
Screening Recommendations
- All individuals exposed to clotting factor concentrates or blood products should be tested for resolved HBV infection by checking HBcAb seropositivity at least once in their lifetime (minimum 6 months after exposure) 1
- Testing should include HBsAg for current infection and HBcAb for resolved infection 1
Common Pitfalls
- Do not assume anti-HBc negativity rules out chronic HBV—always check HBsAg as the primary marker of active infection 1
- Isolated anti-HBc positivity requires further evaluation and cannot be dismissed as simply "past infection" without considering occult HBV, especially before immunosuppression 1, 7
- Anti-HBc does not indicate immunity—only anti-HBs at ≥10 mIU/mL provides protective immunity 1, 4
- The presence of anti-HBc distinguishes natural infection from vaccination, which has major implications for reactivation risk under immunosuppression 3, 7