False Positive Hepatitis B Surface Antigen Results
Yes, hepatitis B surface antigen (HBsAg) tests can produce false positive results in several clinical scenarios, and confirmatory testing is essential before making a diagnosis of HBV infection.
Causes of False Positive HBsAg Results
Recent Vaccination
- HBsAg may be transiently positive for up to 18 days following hepatitis B vaccination 1
- Studies have shown false positive rates of up to 50% when testing is performed within days of vaccination 2
- This occurs because the vaccine contains recombinant HBsAg that can be detected by screening tests 3
Technical and Assay-Related Factors
- Specificity of HBsAg rapid diagnostic tests varies from 98.0% to 99.5%, meaning false positives can occur 4
- Different testing platforms may produce different results for the same sample 5
- Some assays are more prone to false positives than others, particularly with certain patient populations 6
Biological Factors
- Administration of granulocyte-colony stimulating factor (G-CSF) has been associated with false positive HBsAg results 6
- Endogenous antibodies can cause interference in some immunoassays 5
Confirmation of HBsAg Results
CDC and MMWR Recommendations
- To ensure an HBsAg-positive test result is not false positive, samples with repeatedly reactive HBsAg results should be tested with an FDA-cleared neutralizing confirmatory test 1
- The CDC recommends this confirmatory testing as standard practice for all positive HBsAg results 1
Interpretation of Serologic Test Results
Complete Serologic Profile
- A complete serologic profile including HBsAg, total anti-HBc, IgM anti-HBc, and anti-HBs provides the most accurate assessment of HBV status 1
- The following interpretations are possible:
| HBsAg | Total anti-HBc | IgM anti-HBc | Anti-HBs | Interpretation |
|---|---|---|---|---|
| + | − | − | − | Early acute infection; transient (≤18 days) after vaccination |
| + | + | + | − | Acute infection |
| − | + | + | − | Acute resolving infection |
| − | + | − | + | Recovered from past infection and immune |
| + | + | − | − | Chronic infection |
| − | + | − | − | Past infection; low-level chronic infection; passive transfer to infant born to HBsAg-positive mother; false positive (no infection) |
| − | − | − | + | Immune if concentration is >10 mIU/mL after vaccination |
Clinical Approach to Positive HBsAg Results
When to Suspect a False Positive
- Recent hepatitis B vaccination (within 18 days) 1
- No risk factors for HBV infection
- Discordant results (e.g., positive HBsAg with positive anti-HBs) 5
- Patient receiving G-CSF or other biological therapies 6
Recommended Steps
- Check for recent hepatitis B vaccination history
- Perform confirmatory neutralizing test for HBsAg
- Test for other HBV serologic markers (anti-HBc, IgM anti-HBc, anti-HBs)
- If results remain unclear, repeat testing after 1-2 weeks
- Consider testing with an alternative assay platform if available 5
Clinical Implications
Importance of Accurate Diagnosis
- False positive results can lead to unnecessary anxiety, additional testing, and potentially inappropriate treatment
- Misdiagnosis of HBV infection may impact:
- Patient management decisions
- Screening of contacts
- Eligibility for certain treatments or procedures
Special Populations
- Patients awaiting immunosuppressive therapy require accurate HBV status determination to guide prophylaxis decisions 1
- Pregnant women need accurate HBV status to determine need for infant immunoprophylaxis 1
- Healthcare workers may face occupational restrictions based on HBsAg status 1
Prevention of Misdiagnosis
- Avoid HBsAg testing immediately after vaccination when possible
- Use confirmatory testing for all positive HBsAg results
- Consider the complete clinical picture and risk factors when interpreting results
- When in doubt, repeat testing after an appropriate interval
Remember that while false positive HBsAg results do occur, the consequences of missing true HBV infection can be significant. Therefore, thorough evaluation of positive results is essential for accurate diagnosis and appropriate patient management.