What is the management approach for a patient with high Hepatitis B (HBV) core antibody and negative Hepatitis B surface antigen (HBsAg) and Hepatitis B surface antibody (HBsAb)?

Management of Isolated Hepatitis B Core Antibody Positivity

Patients with positive hepatitis B core antibody (anti-HBc) but negative hepatitis B surface antigen (HBsAg) and negative hepatitis B surface antibody (anti-HBs) should undergo HBV DNA testing to rule out occult HBV infection and should be monitored for potential viral reactivation if immunosuppressive therapy is planned.

Understanding the Serologic Pattern

This serologic pattern (positive anti-HBc, negative HBsAg, negative anti-HBs) is known as "isolated core antibody" and represents one of several possible interpretations:

• Resolved past HBV infection with waning anti-HBs levels
• Occult HBV infection with low-level viral replication below detection threshold
• False positive anti-HBc test result
• Window period during acute HBV infection resolution 1

Diagnostic Approach

1. Confirm serologic results to rule out laboratory error

2. Test for HBV DNA to identify occult HBV infection 2, 1

   • Positive HBV DNA indicates occult HBV infection requiring management
   • Negative HBV DNA requires further evaluation

3. Consider IgM anti-HBc testing if acute infection is suspected 1

   • Positive IgM anti-HBc suggests recent infection
   • Negative IgM anti-HBc suggests remote infection

Risk Assessment for Reactivation

The risk of HBV reactivation depends on:

1. Immunosuppression status:

   • High risk: Anti-CD20 monoclonal antibodies (e.g., rituximab), stem cell transplantation
   • Moderate risk: TNF inhibitors, high-dose corticosteroids, cytotoxic chemotherapy
   • Low risk: Conventional immunosuppression 2, 1

2. Viral factors:

   • Detectable HBV DNA increases reactivation risk
   • Absence of anti-HBs increases risk 3

Management Recommendations

For Patients Without Planned Immunosuppression:

1. Consider HBV vaccination to induce protective immunity 2, 1

   • A complete vaccination series should be administered
   • Check anti-HBs 1-2 months after completion to confirm response

2. Monitor liver enzymes periodically to detect potential viral activity

For Patients Requiring Immunosuppression:

1. For high-risk immunosuppression (rituximab, stem cell transplantation):

   • Prophylactic antiviral therapy is strongly recommended regardless of HBV DNA status 2
   • Continue for at least 12 months after completing immunosuppressive therapy 1

2. For moderate-risk immunosuppression (other biologics, TNF inhibitors):

   • Frequent monitoring of viral load and liver enzymes is conditionally recommended over prophylactic therapy 2
   • Monitor HBsAg and ALT during treatment
   • Initiate antiviral therapy at first sign of reactivation

3. Preferred antiviral agents:

   • Entecavir or tenofovir are preferred due to high barrier to resistance 1

Special Considerations

• Cancer patients: Universal screening with HBsAg and anti-HBc is recommended prior to systemic anticancer therapy 2

• Rheumatologic patients: Patients with rheumatoid arthritis who are anti-HBc positive should be monitored closely when receiving immunosuppressive therapy 2

• Transplant recipients: HBsAg-negative, anti-HBc-positive patients without anti-HBs have significantly higher rates of HBV reactivation after transplantation compared to those with anti-HBs 3

Pitfalls to Avoid

• Don't assume immunity: The absence of anti-HBs indicates lack of protective immunity, even with negative HBsAg

• Don't overlook occult infection: Negative HBsAg does not rule out HBV infection; HBV DNA testing is essential

• Don't neglect monitoring: Even with negative HBV DNA initially, viral reactivation can occur during immunosuppression

• Don't miss the window period: In rare cases, this pattern could represent resolving acute infection; consider clinical context and potential recent exposures 4

By following these guidelines, clinicians can appropriately manage patients with isolated hepatitis B core antibody positivity and minimize the risk of HBV reactivation, particularly in the setting of immunosuppression.