What test should be performed to determine if a person is immune to hepatitis B?

Testing for Hepatitis B Immunity

Order a quantitative hepatitis B surface antibody (anti-HBs) test, with a level ≥10 mIU/mL confirming protective immunity. 1

The Standard Test

• Anti-HBs is the single test required to assess immunity in individuals who have been vaccinated or may have cleared a prior infection. 1
• The test must be quantitative (not qualitative) to determine whether the antibody concentration reaches the protective threshold of ≥10 mIU/mL. 2, 1
• This threshold has been validated by the Advisory Committee on Immunization Practices (ACIP) and represents the minimum level associated with long-term protection against hepatitis B infection. 2, 1

Timing of Testing

• Test 1–2 months after the final vaccine dose when documenting post-vaccination immunity, as this interval allows adequate time for antibody development and provides the most accurate assessment of vaccine response. 2, 1
• For individuals with unknown or uncertain vaccination history, anti-HBs testing can be performed at any time to determine current immune status. 1

Interpretation and Next Steps

If Anti-HBs ≥10 mIU/mL

• The person is immune and requires no further routine testing if immunocompetent. 2, 1
• Immunocompetent individuals maintain long-term protection even if antibody levels later decline below 10 mIU/mL, due to immune memory. 2
• Document this result permanently in the medical record, as it establishes lifelong immunity for most individuals. 2

If Anti-HBs <10 mIU/mL

• Revaccinate with a complete second 3-dose series (or 2-dose series if using Heplisav-B), then retest anti-HBs 1–2 months after the final dose. 2, 1
• If still <10 mIU/mL after two complete series (total of 6 doses), test for HBsAg and anti-HBc to rule out chronic infection. 2, 1
• Individuals who remain non-responders after 6 doses should be counseled about their susceptibility and the need for hepatitis B immune globulin (HBIG) if exposed to HBsAg-positive blood. 2

When to Add Additional Tests

For prevaccination screening in high-risk populations, order a three-test panel (HBsAg, anti-HBs, and total anti-HBc) rather than anti-HBs alone. 1 This applies to:

• Household, sexual, or needle-sharing contacts of HBsAg-positive persons 1
• HIV-positive individuals 1
• Persons born in countries with HBV prevalence ≥2% 1
• Persons who inject drugs 1
• Men who have sex with men 1

The rationale: These populations have higher rates of prior infection, and the three-test panel distinguishes between vaccine-induced immunity (anti-HBs positive, anti-HBc negative) and natural immunity from resolved infection (anti-HBs positive, anti-HBc positive), while also identifying chronic carriers (HBsAg positive). 3, 4

Special Populations Requiring Modified Approaches

Immunocompromised Patients

• Annual anti-HBs testing is recommended for HIV-infected persons, transplant recipients, hemodialysis patients, and those receiving chemotherapy. 1, 5
• Revaccinate when anti-HBs falls below 10 mIU/mL in these populations, as they may lose protective immunity over time. 1, 5

Hemodialysis Patients

• Test anti-HBs annually and administer booster doses when levels fall below 10 mIU/mL. 2, 1, 5
• These patients require higher vaccine doses (40 μg vs. standard 20 μg) and have lower seroconversion rates. 5

Healthcare Personnel

• Postvaccination testing is mandatory for all healthcare workers at high risk for occupational blood exposure, performed 1–2 months after the vaccine series. 2
• This documentation is essential for guiding postexposure prophylaxis decisions if a needlestick or mucosal exposure occurs. 2

Common Pitfalls to Avoid

• Never test anti-HBs in unvaccinated or incompletely vaccinated persons to determine immunity, as the ≥10 mIU/mL correlate of protection has only been validated for those who completed an approved vaccination series. 1, 5
• Do not use anti-HBc alone as a screening test for immunity; it indicates prior exposure but does not confirm protective immunity. 4
• Different assays have different cutoff values—always refer to the specific laboratory's reference range, though ≥10 mIU/mL is the standard protective threshold across most platforms. 1
• Avoid qualitative anti-HBs tests when documenting immunity, as they cannot distinguish between marginally protective and robustly protective antibody levels. 2, 1

Distinguishing Vaccine-Induced from Natural Immunity

If you need to determine whether immunity resulted from vaccination or prior infection:

• Anti-HBs positive + anti-HBc negative = vaccine-induced immunity 3
• Anti-HBs positive + anti-HBc positive = natural immunity from resolved infection 3

This distinction matters for epidemiologic purposes and when counseling patients about their infection history, but both patterns indicate protective immunity. 3