What does a positive Hepatitis B core antibody (HBcAb) test result suggest in a patient with chronic hepatitis B infection?

What Does HBcAb Positive Suggest?

A positive HBcAb (anti-HBc) indicates exposure to hepatitis B virus at some point in time and appears at the onset of acute infection, persisting for life in the majority of persons. 1

Core Interpretation Based on Clinical Context

In Chronic Hepatitis B Infection

In patients with chronic hepatitis B (HBsAg positive for >6 months), the presence of anti-HBc is expected and confirms ongoing chronic infection. 1

• Anti-HBc appears at the onset of symptoms or liver test abnormalities in acute HBV infection and persists for life 1
• In chronic HBV infection, both HBsAg and anti-HBc persist, typically for life 1
• The IgM class of anti-HBc distinguishes acute from chronic infection: IgM anti-HBc persists for up to 6 months in acute infection that resolves 1
• In chronic HBV patients, IgM anti-HBc can persist at low levels during viral replication, though typically not detectable by standard U.S. assays 1

When Anti-HBc is the Only Positive Marker (Isolated Anti-HBc)

Isolated anti-HBc positivity (HBsAg negative, anti-HBs negative or low) most commonly represents resolved HBV infection with waning anti-HBs levels, particularly in high-prevalence populations. 1, 2

This pattern can represent three distinct scenarios:

1. Resolved infection with waned anti-HBs (most common in high-prevalence populations) 1

   • The person recovered from past HBV infection but anti-HBs levels have declined below detectable levels over time

2. Occult chronic infection (most common in high-prevalence populations and HIV/HCV coinfected patients) 1

   • HBsAg is undetectable by commercial assays but virus persists
   • HBV DNA detected in <5% of persons with isolated anti-HBc 1
   • These persons are generally not infectious except through direct percutaneous exposure (blood transfusion, organ transplant) 1

3. False-positive reaction (most common in low-prevalence populations) 1

   • In low-prevalence populations, isolated anti-HBc may represent false positivity in 10-20% of persons with HBV serologic markers 1
   • Most of these persons demonstrate a primary response after hepatitis B vaccination, confirming they were never truly infected 1

Critical Clinical Implications

Risk of HBV Reactivation

Patients with anti-HBc positivity (even if HBsAg negative) face 3-45% risk of HBV reactivation when receiving immunosuppressive therapy and require risk stratification. 3, 2

• Reactivation risk is particularly high with anti-CD20 therapy (rituximab), stem cell transplantation, high-dose corticosteroids, tyrosine kinase inhibitors, and anti-CD52 monoclonal antibodies 3, 4
• HBV DNA testing before immunosuppressive therapy is recommended to define reactivation risk 3, 2
• If HBV DNA is detectable, antiviral prophylaxis should be given similar to HBsAg-positive patients 3
• Reactivation has been reported in renal transplant recipients, HIV-infected patients, bone marrow transplant recipients, and chemotherapy patients 1

Monitoring Recommendations

For anti-HBc positive patients undergoing immunosuppression, monitor HBsAg and ALT every 3 months during therapy if not receiving prophylaxis, or HBV DNA and ALT every 6 months if receiving prophylaxis. 3

• Continue monitoring for at least 12 months after completing immunosuppressive therapy 3
• For immunocompetent patients with isolated anti-HBc not receiving immunosuppression, routine HBV DNA testing is generally not necessary 3, 2

Common Pitfalls to Avoid

• Do not assume anti-HBs positivity eliminates reactivation risk - while it may provide some protection, it does not completely eliminate risk in immunosuppressed patients 3
• Do not use IgM anti-HBc testing in asymptomatic persons - the positive predictive value is low; reserve this test for persons with clinical evidence of acute hepatitis or epidemiologic link to HBV infection 1
• Do not ignore isolated anti-HBc in patients about to start immunosuppression - these patients require HBV DNA testing and potential prophylaxis 3, 2
• Recognize that false-negative HBsAg can occur - in patients with chronic liver disease and isolated anti-HBc, consider HBV DNA testing to rule out occult infection 4