What does it mean if hepatitis B (HBV) core antibodies are positive, HBV surface antibodies (HBsAb) are reactive, and HBV surface antigen (HBsAg) is negative?

Hepatitis B Serological Pattern Interpretation

The pattern of positive hepatitis B core antibodies (anti-HBc), reactive surface antibodies (anti-HBs), and negative surface antigen (HBsAg) indicates a resolved past hepatitis B virus (HBV) infection with natural immunity. 1

Understanding This Serological Profile

This specific combination of serological markers represents:

• Negative HBsAg: Indicates no active HBV infection is present
• Positive anti-HBc: Shows previous exposure to the hepatitis B virus
• Positive anti-HBs: Demonstrates immunity to HBV

This pattern differs from vaccine-induced immunity, which would show positive anti-HBs but negative anti-HBc 1. The presence of both antibodies confirms that the person was previously infected with HBV but has successfully cleared the virus and developed natural immunity.

Clinical Implications

Immunity Status

• The person has natural immunity to HBV and does not require hepatitis B vaccination 1
• Anti-HBs levels ≥10 mIU/mL are considered protective 1
• This immunity is typically long-lasting, though monitoring may be needed in certain situations

Risk of Reactivation

• Despite resolved infection, HBV DNA may persist in hepatocytes in an inactive form
• Risk of reactivation exists primarily during immunosuppressive therapy 1
• The presence of anti-HBs alongside anti-HBc provides significant protection against reactivation compared to anti-HBc positivity alone 2

Management Considerations

Routine Follow-up

• No specific follow-up is required for immunocompetent individuals with this serological pattern
• Normal liver function tests would further confirm resolved infection

Before Immunosuppressive Therapy

HBV reactivation risk varies by immunosuppressive regimen:

Immunosuppression Regimen	Risk Level	Recommended Action
Anti-CD20 monoclonal antibodies	High	Prophylactic antiviral therapy
Stem cell transplantation	High	Prophylactic antiviral therapy
TNF inhibitors	Moderate	Close monitoring or prophylactic antivirals
High-dose corticosteroids	Moderate	Close monitoring or prophylactic antivirals
Cytotoxic chemotherapy	Moderate	Close monitoring or prophylactic antivirals

• HBV DNA testing should be performed before starting immunosuppressive therapy to rule out occult infection 1
• Preferred prophylactic agents include entecavir or tenofovir due to their high barrier to resistance 1
• Prophylaxis should continue for 6-12 months after completing immunosuppressive therapy 1

Monitoring During Immunosuppression

• If monitoring approach is chosen (instead of prophylaxis), check HBV DNA and liver enzymes every 1-3 months 1
• Initiate antivirals promptly if HBV DNA becomes detectable 1

Patient Education

Patients should be informed that:

• They have recovered from a past HBV infection and now have immunity
• They should inform future healthcare providers about their HBV status
• They are at risk for HBV reactivation if they undergo certain immunosuppressive therapies
• No hepatitis B vaccination is needed 1

Common Pitfalls to Avoid

1. Misinterpreting as vaccine-induced immunity: This pattern indicates natural infection and recovery, not vaccination
2. Failing to screen before immunosuppression: Always check HBV DNA before starting high-risk immunosuppressive therapies
3. Overlooking the protective effect of anti-HBs: The presence of anti-HBs alongside anti-HBc significantly reduces reactivation risk compared to anti-HBc alone 2
4. Assuming complete viral clearance: Despite resolved infection, viral DNA may persist in hepatocytes, creating risk for reactivation during immunosuppression