What are the management and treatment options for a patient who is Hepatitis B surface antigen (HepBsAg) negative and Hepatitis B core antibody (HepBcAb) positive?

Management of HBsAg Negative, HBcAb Positive Patients

Patients who are HBsAg negative and HBcAb positive should undergo HBV DNA testing and be monitored regularly, with antiviral prophylaxis only needed if they require immunosuppressive therapy or show evidence of viral reactivation. 1

Understanding the Serological Profile

This serological pattern (HBsAg negative, HBcAb positive) typically indicates one of four possibilities:

• Resolved past HBV infection with immunity (most common)
• Occult HBV infection with low-level viral replication
• False positive anti-HBc result
• Window period during acute infection resolution

Additional testing should include:

• HBV DNA quantification to rule out occult infection
• Anti-HBs to determine if protective antibodies are present
• Liver function tests to assess for active liver disease

Management Algorithm

Step 1: Assess Immune Status

• If anti-HBs positive (≥10 IU/L): Indicates resolved infection with immunity
• If anti-HBs negative: Consider occult infection or waned immunity

Step 2: Evaluate for Occult Infection

• Test for HBV DNA
• If HBV DNA positive: Manage as chronic HBV infection
• If HBV DNA negative: Monitor periodically, especially if immunosuppression is planned

Step 3: Risk Assessment for Reactivation

The risk of HBV reactivation in HBsAg negative, HBcAb positive patients varies based on:

Immunosuppression Regimen	Risk Level	Recommended Action
Anti-CD20 antibodies (e.g., rituximab)	High	Prophylactic antiviral therapy
Stem cell transplantation	High	Prophylactic antiviral therapy
TNF inhibitors	Moderate	Close monitoring or prophylaxis
High-dose corticosteroids	Moderate	Close monitoring or prophylaxis
Cytotoxic chemotherapy	Moderate	Close monitoring or prophylaxis

Monitoring Recommendations

For patients not receiving immunosuppression:

• Routine monitoring of liver function tests
• No antiviral prophylaxis needed
• HBV DNA testing only if liver enzymes become elevated

For patients requiring immunosuppression:

• Test HBV DNA before starting immunosuppressive therapy 1
• Monitor HBsAg or HBV DNA (or both) every 1-3 months during and for at least 6 months after stopping immunosuppression 1
• If reactivation occurs (detectable HBV DNA or HBsAg seroconversion), promptly initiate antiviral therapy 1

Antiviral Prophylaxis

Antiviral prophylaxis is not routinely recommended for HBsAg negative, HBcAb positive patients unless:

1. They are undergoing high-risk immunosuppressive therapy (especially anti-CD20 agents like rituximab)
2. They have detectable HBV DNA
3. They show evidence of HBV reactivation

When prophylaxis is indicated, preferred agents include:

• Entecavir or tenofovir due to high barrier to resistance 1, 2
• Continue for at least 12 months after completion of immunosuppressive therapy 2

Special Considerations

Cancer Patients

The risk of HBV reactivation in HBsAg negative, HBcAb positive cancer patients ranges from 3-45%, with higher risk in those receiving rituximab-containing regimens 1. The NCCN recommends HBV DNA testing before starting therapy to define reactivation risk 1.

Inflammatory Bowel Disease Patients

In IBD patients, the reactivation rate is much lower (approximately 0.28%) 1. Pre-emptive therapy approach is recommended rather than routine prophylaxis.

Vaccination Considerations

• If anti-HBs is negative, some experts suggest a single booster dose of HBV vaccine to assess for anamnestic response 3
• Strong anamnestic response (>90%) suggests intact immune memory even in those with anti-HBs <10 IU/L 4

Common Pitfalls to Avoid

1. Misinterpreting serology: Don't assume active infection based solely on HBcAb positivity
2. Unnecessary prophylaxis: Avoid routine antiviral prophylaxis in low-risk patients
3. Inadequate monitoring: Failure to monitor during immunosuppression can lead to missed reactivation
4. Overlooking occult infection: Always consider HBV DNA testing before immunosuppression
5. Confusing with vaccination status: Vaccinated individuals typically have positive anti-HBs but negative anti-HBc

By following this structured approach, clinicians can appropriately manage patients with this serological profile while minimizing both the risk of HBV reactivation and unnecessary antiviral treatment.