What are the next steps for someone with non-reactive Hepatitis B (Hep B) lab results?

Management of Non-Reactive Hepatitis B Lab Results

If your patient has non-reactive (negative) hepatitis B serology, they are susceptible to HBV infection and should receive the complete hepatitis B vaccination series immediately, with the first dose administered at the current visit. 1

Immediate Action Steps

Initiate Vaccination Without Delay

• Administer the first dose of hepatitis B vaccine immediately, even if concerns exist about completing the series 1
• Do not delay vaccination while awaiting additional testing or patient follow-up 2
• Vaccination of persons who may already be immune is not harmful and does not increase adverse event risk 1

Complete the Vaccination Series

• Standard 3-dose schedule: 0,1, and 6 months 3
• Alternative options include Heplisav-B (2-dose series) or other approved vaccines with varying schedules 2
• Ensure documentation of each dose with written, dated records 1

Post-Vaccination Testing Protocol

Who Requires Testing After Vaccination

Post-vaccination serologic testing is NOT routinely necessary for most healthy adolescents and adults 1. However, testing IS required for:

• Healthcare personnel and public safety workers 1
• Persons with HIV infection 1
• Sexual and needle-sharing partners of HBsAg-positive persons 1
• Hemodialysis patients (including predialysis, peritoneal dialysis, home dialysis) 1
• Other immunocompromised persons (hematopoietic stem-cell transplant recipients, chemotherapy patients) 1

Testing Timing and Interpretation

• Test anti-HBs levels 1-2 months after the final vaccine dose 1, 2
• Use a method that detects protective concentrations ≥10 mIU/mL 2
• Anti-HBs ≥10 mIU/mL indicates immunity; no further testing needed in immunocompetent persons 2

Management of Inadequate Response

If Anti-HBs <10 mIU/mL After Primary Series

• Revaccinate with a complete second 3-dose series 1, 3
• Retest anti-HBs 1-2 months after the third dose of the repeat series 1
• Most non-responders (44-100%) will develop protective antibodies after a second complete series 3

If Still Non-Responsive After Two Complete Series

• Test for HBsAg and anti-HBc to rule out chronic HBV infection 1, 3
• If HBsAg positive: refer for management of chronic hepatitis B 1
• If HBsAg negative: consider the person susceptible to HBV 1
• Counsel about precautions for preventing HBV infection 1
• Advise about the need for hepatitis B immune globulin (HBIG) for any known exposure 1

Special Population Considerations

Immunocompromised Patients

• Annual anti-HBs testing is warranted to assess antibody concentrations 2
• Revaccinate when anti-HBs falls <10 mIU/mL 2
• This includes transplant candidates/recipients, HIV-infected persons, and those on immunosuppressive therapy 2

Hemodialysis Patients

• Require higher vaccine doses (40 μg) 3
• Annual monitoring with booster doses if anti-HBs <10 mIU/mL 2, 3

Pregnant Women

• Use Engerix-B, Recombivax HB, or Twinrix only 3
• Avoid Heplisav-B or PreHevbrio due to insufficient safety data 3

Critical Pitfalls to Avoid

Common Errors in Testing

• Do not test for anti-HBs in unvaccinated or incompletely vaccinated persons 2, 3
• The ≥10 mIU/mL correlate of protection has only been validated for those completing an approved vaccination series 2, 3
• Testing before completion of the series is potentially misleading 2

Vaccination Barriers

• Do not allow serologic testing to become a barrier to vaccination 1
• In settings where universal vaccination is recommended, provide the first dose immediately after blood draw 1
• Do not assume protection based solely on vaccination history without documented serologic response 3

Immunologic Memory Considerations

• Immunocompetent persons with documented anti-HBs ≥10 mIU/mL after completing the vaccine series have long-term protection 2
• Routine booster doses are NOT needed for immunocompetent individuals who achieved adequate response 2
• Cellular immune memory may persist even when antibody levels decline below 10 mIU/mL in immunocompetent persons 4

Contact Management if Exposure Risk Exists

If Patient Has Known Exposure to HBsAg-Positive Person

• Identify all household, sexual, and needle-sharing contacts 1
• Administer both HBIG (0.06 mL/kg) and hepatitis B vaccine at separate anatomic sites as soon as possible, preferably within 24 hours 1
• The maximum effective interval is unlikely to exceed 7 days for percutaneous exposures or 14 days for sexual exposures 1