Hepatitis B Surface Antibody (Anti-HBs): Clinical Interpretation
A positive hepatitis B surface antibody (anti-HBs) indicates immunity to hepatitis B virus, either from successful vaccination or recovery from past infection. 1
Defining Protective Immunity
- Anti-HBs levels ≥10 mIU/mL are considered protective against HBV infection, providing >90% protection against both acute hepatitis B disease and chronic HBV infection in immunocompetent individuals. 2
- The protective threshold is measured 1-2 months after completing the vaccine series using a quantitative assay such as ELISA. 2
Distinguishing Vaccine-Derived vs. Natural Immunity
The complete serologic pattern determines the source of immunity:
Vaccine-Derived Immunity
- HBsAg negative + anti-HBc negative + anti-HBs positive (≥10 mIU/mL) indicates immunity from vaccination, not natural infection. 1, 2
- This pattern definitively confirms no prior natural HBV exposure. 2
- The risk of HBV reactivation is minimal in vaccine-derived immunity because there is no prior natural infection that could reactivate. 1
Natural Immunity (Past Infection)
- HBsAg negative + anti-HBc positive + anti-HBs positive indicates recovered from past HBV infection with natural immunity. 1, 3
- The presence of anti-HBc confirms prior natural infection rather than vaccination alone. 3
Long-Term Protection and Immune Memory
- Immunocompetent individuals who achieve anti-HBs ≥10 mIU/mL after vaccination maintain lifelong protection through immune memory, even when antibody levels subsequently decline below 10 mIU/mL. 2
- Among vaccinated individuals, 15-50% will have anti-HBs levels decline to <10 mIU/mL within 5-15 years, yet they remain protected against clinically significant infection. 2
- Protection persists for at least 30 years among vaccine responders, and likely for life. 2
- 88% of vaccinated individuals mount an anamnestic response when given a challenge dose 30 years after initial vaccination, demonstrating persistent immune memory. 2
When Post-Vaccination Testing Is Recommended
Post-vaccination anti-HBs testing (1-2 months after final dose) is specifically recommended for: 2
- Hemodialysis patients
- HIV-infected persons
- Immunocompromised individuals
- Sexual partners of HBsAg-positive persons
- Infants born to HBsAg-positive mothers
- Healthcare workers (to document immunity before occupational exposure)
For immunocompetent individuals with documented completion of the hepatitis B vaccine series and anti-HBs ≥10 mIU/mL, no further testing or booster doses are currently recommended. 2
Special Populations Requiring Ongoing Monitoring
Annual anti-HBs testing with booster doses when levels fall <10 mIU/mL is recommended for: 2
- Immunocompromised patients
- Hemodialysis patients
- HIV-infected persons
- Hematopoietic stem-cell transplant recipients
- Persons receiving chemotherapy
Common Pitfalls in Interpretation
Passively Acquired Anti-HBs
- Passively acquired anti-HBs (such as after hepatitis B immune globulin administration or intravenous immunoglobulin) does not indicate true immunity and can be detected for 4-6 months. 2
- This can lead to false interpretation of immune status, particularly in recently transfused patients. 2, 4
Transient HBsAg Positivity
- Transient HBsAg positivity can occur up to 18 days following vaccination and is clinically insignificant. 2
Isolated Anti-HBs Positivity
- Isolated anti-HBs positivity definitively indicates vaccine-derived immunity and requires no further testing or management in immunocompetent individuals. 2
Management of Subprotective Levels (Anti-HBs <10 mIU/mL)
If anti-HBs levels are below 10 mIU/mL after initial vaccination series: 2
- Administer a single booster dose of hepatitis B vaccine immediately
- Retest anti-HBs 1-2 months later
- If anti-HBs ≥10 mIU/mL after booster: individual is protected, no further doses needed
- If anti-HBs remains <10 mIU/mL after booster: complete a full second 3-dose vaccine series, then retest 1-2 months after final dose