What does it mean to be HBsAg (Hepatitis B surface antigen) negative, anti-HBc (antibody to Hepatitis B core antigen) negative, and anti-HBs (antibody to Hepatitis B surface antigen) positive?

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Last updated: September 15, 2025View editorial policy

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Interpretation of HBsAg Negative, Anti-HBc Negative, and Anti-HBs Positive Serology

A person who is HBsAg negative, anti-HBc negative, and anti-HBs positive has immunity to hepatitis B virus (HBV) due to successful vaccination. 1

Detailed Explanation

This serological pattern represents a classic vaccine-induced immunity profile:

  • HBsAg negative: No hepatitis B surface antigen present, indicating no active HBV infection
  • Anti-HBc negative: No antibodies to hepatitis B core antigen, indicating no previous natural HBV infection
  • Anti-HBs positive: Presence of antibodies to hepatitis B surface antigen, indicating immunity to HBV

When anti-HBs is present without anti-HBc, this specifically indicates immunity acquired through vaccination rather than from resolved natural infection 1. This is an important distinction because:

  1. Vaccine-induced immunity has a different serological pattern than immunity from natural infection
  2. Natural immunity would show positive anti-HBc along with positive anti-HBs 1

Clinical Significance

This serological pattern has several important clinical implications:

  • Protected status: The individual is immune to HBV infection due to successful vaccination 1
  • No risk of transmission: The person cannot transmit HBV to others
  • No monitoring needed: Routine monitoring of hepatitis markers is not necessary in immunocompetent individuals with vaccine-induced immunity 1
  • No reactivation risk: Unlike those with resolved natural infection (who would be anti-HBc positive), vaccinated individuals are not at risk for HBV reactivation during immunosuppressive therapy 1

Anti-HBs Titer Considerations

The level of anti-HBs antibodies is important for determining the degree of protection:

  • >10 mIU/mL: Generally considered protective against HBV infection 2, 1
  • >100 mIU/mL: May provide more robust protection, especially in immunocompromised individuals 1

Anti-HBs levels can decline over time after vaccination, but immune memory often persists even when antibody levels fall below detectable limits 3.

Management Implications

For individuals with this serological pattern:

  • No additional vaccination needed: The presence of anti-HBs indicates successful immunization 1
  • No antiviral prophylaxis needed: Even if undergoing immunosuppressive therapy, vaccinated individuals (anti-HBc negative) are not at risk for HBV reactivation 1
  • Documentation: This serological pattern should be documented in the medical record to avoid unnecessary future testing or vaccination

Common Pitfalls to Avoid

  1. Misinterpreting as natural immunity: Don't confuse vaccine-induced immunity (anti-HBc negative, anti-HBs positive) with immunity from resolved natural infection (anti-HBc positive, anti-HBs positive) 1

  2. Unnecessary revaccination: Individuals with documented protective anti-HBs do not require revaccination, even if levels decline over time 2

  3. Unnecessary monitoring: Unlike those with natural immunity or chronic infection, vaccinated individuals don't require ongoing HBV monitoring unless they become severely immunocompromised 1

  4. Confusing with "window period": This pattern is not consistent with the "window period" of acute HBV infection, which would typically show anti-HBc IgM positivity 2, 4

In summary, this serological pattern represents successful vaccination against hepatitis B virus, with no evidence of past or current infection, and indicates protective immunity against future HBV infection.

References

Guideline

Hepatitis B Virus Infection Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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