What are the recommended management steps for a patient who has completed a full hepatitis B vaccination series (standard 20 µg recombinant hepatitis B surface antigen at 0, 1, 6 months) but has anti‑hepatitis B surface antibody (anti‑HBs) titers <10 mIU/mL, particularly if the patient is immunocompromised?

Management of Hepatitis B Vaccine Non-Responders

Immediate Action: Revaccinate with a Complete Second Series

Patients who fail to develop protective anti-HBs levels (≥10 mIU/mL) after a complete hepatitis B vaccination series should receive a full second 3-dose vaccine series (0,1, and 6 months), followed by anti-HBs testing 1-2 months after the final dose. 1, 2

This approach is supported by evidence showing that 44-100% of initial non-responders will achieve protective antibody levels after revaccination with a complete second series. 1, 2

Pre-Revaccination Testing

Before proceeding with revaccination, you must:

• Test for HBsAg to rule out chronic HBV infection, particularly if the patient has risk factors for HBV exposure (household contacts of HBsAg-positive persons, persons who inject drugs, men who have sex with men, or persons born in endemic regions). 1, 2
• Do not delay revaccination while waiting for test results—the first vaccine dose can be administered immediately after blood collection for serologic testing. 1

Standard Revaccination Protocol

For Immunocompetent Adults

• Administer three doses of standard hepatitis B vaccine (20 µg) at 0,1, and 6 months. 1, 2
• If the series is interrupted, do not restart—simply continue with the next dose when able, ensuring at least 8 weeks between the second and third doses. 1
• Test anti-HBs levels 1-2 months after the final dose to document response. 1, 2

For Immunocompromised Patients

• Consider using double-dose vaccine (40 µg per dose) for patients on hemodialysis or those who are significantly immunocompromised. 3, 4
• For hemodialysis patients specifically, use a 4-dose regimen (40 µg at 0,1,2, and 6 months), which achieves seroprotection in 67% of patients. 3
• After successful vaccination, perform annual anti-HBs testing and administer booster doses when levels fall below 10 mIU/mL. 1

Alternative Approach for Healthcare Workers

For healthcare workers with documented completion of a primary series but anti-HBs <10 mIU/mL:

• Give one additional vaccine dose immediately, followed by anti-HBs testing 1-2 months later. 1, 2
• If anti-HBs remains <10 mIU/mL after this single dose, complete the full second series (total of 6 doses when accounting for the original series). 1
• This staged approach may be more practical for recently vaccinated healthcare workers. 1

Management After Second Complete Series

If Anti-HBs ≥10 mIU/mL After Revaccination

• Document the response for future reference. 1, 2
• No further routine testing or booster doses are needed for immunocompetent individuals, as they will maintain long-term protection through immune memory even if antibody levels subsequently decline. 1

If Anti-HBs Remains <10 mIU/mL After Two Complete Series

• The patient is considered a confirmed non-responder. 1
• Do not administer additional vaccine doses, as repeated vaccinations beyond two complete series do not improve immune responses. 5
• Counsel the patient that they remain susceptible to HBV infection. 1
• If exposed to HBV-positive blood or body fluids, administer two doses of HBIG (0.06 mL/kg): the first dose as soon as possible after exposure and the second dose 1 month later. 1

Special Considerations for Immunocompromised Patients

The management differs significantly for immunocompromised individuals:

• Annual anti-HBs testing is recommended for HIV-infected persons, hematopoietic stem-cell transplant recipients, and persons receiving chemotherapy. 1
• Administer booster doses when anti-HBs levels decline to <10 mIU/mL. 1
• Unlike immunocompetent persons, immunocompromised patients cannot rely on immune memory alone and require maintained circulating antibody levels. 1
• For hemodialysis patients, the threshold for protection may need to be higher than 10 mIU/mL, as weak responders (10-99.9 mIU/mL) lose protective levels much faster than strong responders (≥100 mIU/mL). 4

Critical Pitfalls to Avoid

• Do not test anti-HBs levels years after childhood vaccination and assume non-response—antibody levels naturally wane over time in responders who remain protected through immune memory. 1
• Do not restart the vaccine series if doses are delayed—simply continue from where you left off with appropriate intervals. 1, 2
• Do not delay revaccination while conducting extensive risk stratification—begin the series promptly. 2
• Do not give more than two complete vaccine series to immunocompetent non-responders, as this does not improve response rates. 5
• Do not assume all non-responders have immune defects—most have functional immune systems and respond normally to other antigens. 5

Documentation Requirements

• Maintain written, dated records of all vaccine doses and serologic test results. 1, 2
• Schedule the post-vaccination testing appointment (1-2 months after final dose) at the time of administering the final vaccine dose to ensure compliance. 2
• For healthcare workers, document vaccine response status for management of future occupational exposures. 1