What is the interpretation of Hepatitis B (HBV) lab results showing a reactive Hepatitis B surface antigen (HBsAg) and low Hepatitis B surface antibody (anti-HBs) initially, followed by normalization and evidence of immunity with a reactive anti-HBs and non-reactive HBsAg in a patient with a history of abnormal HBV labs?

Interpretation of Serial Hepatitis B Laboratory Results

Most Likely Clinical Scenario

This serological pattern most likely represents a false-positive HBsAg result on the initial testing, followed by accurate results showing vaccine-induced or natural immunity. 1

The initial reactive HBsAg with low anti-HBs (<5 mIU/mL) followed by complete reversal to non-reactive HBsAg with reactive anti-HBs within a short timeframe is inconsistent with typical HBV infection patterns and strongly suggests laboratory error or transient false-positivity. 1

Key Diagnostic Considerations

Why This is NOT Acute HBV Infection Followed by Clearance

• Acute HBV infection that spontaneously resolves would require anti-HBc positivity, which should persist for life after true infection. 1, 2 The absence of anti-HBc testing in your results is critical—if the patient truly had acute HBV infection, anti-HBc (both IgM and total) would be positive and remain detectable indefinitely. 1

• The timeline is atypical for natural clearance. True acute HBV infection with spontaneous clearance typically takes months, not the brief interval between your two test dates. 1

• HBsAg persistence defines infection duration. HBsAg positivity lasting >6 months defines chronic infection, while clearance before 6 months indicates acute resolving infection—but both scenarios require anti-HBc positivity. 3

Why This is NOT HBV Reactivation

• Reactivation requires pre-existing resolved or chronic infection, which would show anti-HBc positivity. 3 Without documented prior HBV infection markers, reactivation is not possible.

• The HBV DNA level (<10 IU/mL) is below quantification limits and clinically insignificant in the setting of negative HBsAg. 1 This trace level does not indicate active viral replication or transmissible infection.

Most Probable Explanations

False-positive initial HBsAg result is the leading explanation. 1 HBsAg assays can produce false-positive results that should be confirmed with neutralizing confirmatory testing. 3 The CDC recommends that samples with repeatedly reactive HBsAg results should be tested with an FDA-cleared neutralizing confirmatory test to ensure the result is not false-positive. 3

Transient HBsAg positivity post-vaccination can occur for up to 18 days after hepatitis B vaccination and is clinically insignificant. 3, 1, 4 If the patient received hepatitis B vaccine shortly before the initial testing, this could explain the reactive HBsAg.

Current Immune Status

The patient currently demonstrates immunity to hepatitis B, evidenced by:

• Non-reactive HBsAg rules out active infection. 1
• Reactive anti-HBs indicates protective immunity. 1, 4 Anti-HBs ≥10 mIU/mL confers protection against HBV infection. 4
• HBV DNA <10 IU/mL is below assay quantification and does not indicate active or transmissible infection. 1

Critical Missing Information

Anti-HBc testing is essential to distinguish between vaccine-induced immunity versus resolved natural infection. 1, 4

• If anti-HBc is negative: This confirms vaccine-induced immunity (isolated anti-HBs positivity pattern). 4 This definitively rules out any prior natural HBV infection and confirms the initial HBsAg was false-positive.

• If anti-HBc is positive: This would indicate resolved natural infection with natural immunity. 1, 4 However, this scenario is less likely given the atypical timeline and would raise questions about occult HBV infection.

Recommended Next Steps

Order anti-HBc (total) testing immediately to definitively characterize the patient's HBV exposure history and immune status. 1

Review vaccination history to determine if hepatitis B vaccine was administered near the time of initial testing, which could explain transient HBsAg positivity. 3, 1

If anti-HBc returns negative: The patient has vaccine-induced immunity, the initial HBsAg was false-positive, and no further HBV-specific monitoring is needed unless future immunosuppression is planned. 4

If anti-HBc returns positive: This indicates prior HBV exposure. In this scenario, consider:

• Reviewing for any immunosuppressive conditions or medications that could have caused transient HBV reactivation. 3
• The patient has resolved infection with natural immunity and requires no treatment. 3, 1
• If future immunosuppression is planned, the patient is at risk for HBV reactivation and requires prophylactic antiviral therapy or close monitoring. 3

Clinical Pitfalls to Avoid

Never interpret isolated HBsAg positivity without confirmatory testing. 3 False-positive HBsAg results occur and can cause unnecessary anxiety and inappropriate management.

Do not assume protective immunity based solely on anti-HBs positivity in immunocompromised patients. 3 Anti-HBs titers >100 IU/mL may provide better protection against reactivation, but this threshold is not validated for all clinical scenarios. 3

Recognize that passively acquired anti-HBs from HBIG administration can be detected for 4-6 months and does not represent true immunity. 4, 5 Review recent blood product or HBIG administration history.

Understand that very low HBV DNA levels detectable by sensitive PCR assays can occur in resolved infection and do not indicate active disease when HBsAg is negative. 3