What does a hepatitis B surface antigen (HBsAg) nonreactive and total antibody (anti-HB) reactive result indicate in terms of hepatitis B virus (HBV) infection?

Interpretation of HBsAg Nonreactive with Total Anti-HB Reactive

This serologic pattern (HBsAg negative with total anti-HB reactive) indicates past hepatitis B virus infection with recovery and immunity. 1

Primary Interpretation

The combination of a nonreactive (negative) HBsAg with reactive (positive) total hepatitis B antibody most commonly represents one of two scenarios:

• Resolved past infection with immunity: When both anti-HBc and anti-HBs are positive, this indicates the patient recovered from a previous HBV infection and developed natural immunity 1, 2
• Vaccine-induced immunity: When only anti-HBs is positive (without anti-HBc), this indicates immunity from successful HBV vaccination 1

Complete Serologic Assessment Required

To fully interpret "total anti-HB reactive," you must determine which specific antibodies are present:

• If anti-HBs positive AND anti-HBc positive: This pattern confirms recovered from past infection with natural immunity 1, 2
• If anti-HBs positive BUT anti-HBc negative: This pattern indicates vaccine-induced immunity only 1
• If anti-HBc positive BUT anti-HBs negative (isolated anti-HBc): This represents a more complex scenario requiring additional evaluation 1

Clinical Significance of Resolved Infection Pattern

When the pattern shows HBsAg negative, anti-HBc positive, and anti-HBs positive:

• The patient is not currently infectious and cannot transmit HBV to others 2
• Protective immunity is present when anti-HBs levels are ≥10 mIU/mL 1
• No active viral replication is occurring, as HBV DNA should be undetectable 1
• The patient is generally not at risk for developing chronic HBV infection 2

Important Clinical Caveat: Reactivation Risk

Despite resolved infection, HBV reactivation can occur under specific circumstances:

• Immunosuppressive therapy poses significant risk: Patients with this serologic pattern have a 3-45% risk of HBV reactivation when receiving immunosuppressive therapy, particularly with anti-CD20/CD52 monoclonal antibodies or high-dose corticosteroids 2
• Pre-immunosuppression evaluation is critical: Before initiating immunosuppressive therapy, obtain HBV DNA testing to assess reactivation risk 2
• Antiviral prophylaxis may be warranted: Consider prophylactic antiviral therapy if HBV DNA is detectable or if high-risk immunosuppression is planned 2
• Monitor liver function tests during any immunosuppressive therapy in these patients 2

Isolated Anti-HBc Pattern (Special Consideration)

If only anti-HBc is positive (without anti-HBs or HBsAg), this isolated pattern has multiple possible interpretations:

• Most commonly: Past infection with waning anti-HBs levels over time 1
• Less commonly: False-positive result, low-level chronic infection, or passive antibody transfer in infants born to HBsAg-positive mothers 1
• HBV DNA is detectable in less than 10% of persons with isolated anti-HBc, though levels may fluctuate 1
• These individuals are unlikely to transmit infection except in large-volume exposures like blood transfusion 1

Management Recommendations

For immunocompetent individuals with resolved infection (HBsAg negative, anti-HBc positive, anti-HBs positive):

• No specific treatment is needed in the absence of planned immunosuppression 2
• No routine HBV vaccination is required as natural immunity is present 1
• Document the serologic status for future reference, particularly before any potential immunosuppressive therapy 2

For patients requiring future immunosuppression:

• Obtain baseline HBV DNA testing before initiating immunosuppressive therapy 2
• Consider antiviral prophylaxis based on the type and intensity of immunosuppression and HBV DNA status 2
• Monitor liver enzymes regularly during immunosuppressive treatment 2

Common Pitfalls to Avoid

• Do not assume all "total anti-HB" tests are the same: Always clarify whether anti-HBs, anti-HBc, or both are positive to make accurate clinical decisions 1
• Do not overlook reactivation risk: Even with resolved infection, patients receiving immunosuppressive therapy require careful monitoring and possible prophylaxis 2
• Do not confuse with vaccine response: Patients with natural immunity (anti-HBc positive) have different implications than those with vaccine-only immunity (anti-HBc negative) 1
• Do not ignore isolated anti-HBc: This pattern requires additional evaluation and may indicate occult infection in some cases 1