What is the appropriate next step for a patient who is seronegative for hepatitis B surface antibody (no immunity)?

Management of Patient Without Hepatitis B Immunity

Initiate hepatitis B vaccination immediately with one of the approved vaccine series, then test anti-HBs levels 1-2 months after completing the series to document protective immunity (≥10 mIU/mL). 1, 2

Immediate Action: Begin Vaccination

The CDC now recommends universal hepatitis B vaccination for all adults aged 19-59 years, eliminating the need for risk-based screening. 3 You have several vaccine options with different schedules:

• HEPLISAV-B (HepB-CpG): Two-dose series at 0 and 1 month 1
• ENGERIX-B or Recombivax HB: Three-dose series at 0,1, and 6 months 1
• PreHevbrio: Three-dose series at 0,1, and 6 months 1
• Twinrix (HepA-HepB): Three-dose series at 0,1, and 6 months 1

Do not delay vaccination while awaiting any additional test results. 3 The patient is currently susceptible to hepatitis B infection and should receive the first dose immediately. 3

Post-Vaccination Testing Protocol

Test anti-HBs levels 1-2 months after the final vaccine dose using a quantitative assay (ELISA) that detects the protective threshold of ≥10 mIU/mL. 2, 3 This timing is critical because:

• Testing too early may not capture the full immune response 2
• The ≥10 mIU/mL threshold provides >90% protection against both acute hepatitis B disease and chronic HBV infection in immunocompetent individuals 2

Interpreting Post-Vaccination Results

If anti-HBs ≥10 mIU/mL (Responder):

• The patient is considered immune and no further testing or booster doses are needed in immunocompetent individuals. 2, 3
• Protection persists for 30 years or more, and likely for life, even when antibody levels subsequently decline below 10 mIU/mL, due to immune memory (B and T lymphocyte memory cells). 2, 4
• Document this response for future reference, particularly important for healthcare workers or those with occupational exposure risk. 3

If anti-HBs <10 mIU/mL (Non-Responder):

• Administer a complete second 3-dose vaccine series, then retest anti-HBs 1-2 months after the final dose. 2, 3
• 44-100% of initial non-responders will achieve protective levels after revaccination. 2
• If still <10 mIU/mL after two complete series, test for HBsAg to rule out chronic infection. 3

If anti-HBs 1-9 mIU/mL (Low but Detectable):

• Give a single booster dose, then retest 1-2 months later. 3
• 25-50% of persons with low anti-HBs levels respond to a single additional vaccine dose. 3
• If ≥10 mIU/mL after the booster, no further doses are needed. 3
• If still <10 mIU/mL, complete a full second 3-dose series. 3

Special Population Considerations

For immunocompromised patients or those on hemodialysis:

• Use higher-dose vaccine (40 mcg instead of standard 20 mcg). 3
• Perform annual anti-HBs testing. 2, 3
• Give booster doses when levels fall <10 mIU/mL. 2, 3

For pregnant women:

• Use Engerix-B, Recombivax HB, or Twinrix only (not Heplisav-B or PreHevbrio due to insufficient safety data). 3

For patients with inflammatory bowel disease starting immunosuppressive therapy:

• Vaccination is particularly urgent as these patients are at increased risk of HBV reactivation, which can lead to death in approximately 5% of cases. 1

Critical Pitfalls to Avoid

• Do not test for anti-HBs in unvaccinated or incompletely vaccinated persons, as the ≥10 mIU/mL correlate of protection has only been validated for those completing an approved vaccination series. 3
• Do not assume immunity based on vaccination history alone—post-vaccination testing is essential to document response. 2
• Do not confuse passively acquired anti-HBs (from HBIG or IVIG administration) with true immunity, as passive antibody can be detected for 4-6 months but does not indicate protection. 2, 5
• Do not delay vaccination while performing prevaccination serologic testing in low-risk individuals—the first dose should be given immediately. 3