What is the protocol for a patient who has received a Hepatitis B (HBV) booster and does not respond?

Protocol for Hepatitis B Vaccine Non-Responders

If a patient does not respond to a hepatitis B booster (anti-HBs <10 mIU/mL after additional vaccination), administer a complete second 3-dose series, retest 1-2 months after the final dose, and if still non-responsive, test for HBsAg to rule out chronic infection. 1, 2

Initial Management After Non-Response to Booster

When a patient receives a booster dose and fails to achieve protective antibody levels:

• Administer a full 3-dose revaccination series using the standard schedule (0,1, and 6 months) 1, 2
• Retest anti-HBs levels 1-2 months after completing the third dose of the revaccination series 1, 2
• Between 25-50% of non-responders will respond to a single additional dose, while 44-100% respond to a complete 3-dose revaccination series 1

Testing After Revaccination

After completing the second 3-dose series:

• If anti-HBs remains <10 mIU/mL, test for HBsAg and anti-HBc to rule out chronic HBV infection 1, 2
• Persons who test HBsAg-positive require appropriate management for chronic hepatitis B 1
• Persons who test HBsAg-negative are confirmed as primary non-responders 1

Management of Confirmed Non-Responders

For patients who remain non-responsive after two complete vaccine series:

• Counsel the patient that they are susceptible to HBV infection and require HBIG for any known exposure 1
• Document non-responder status clearly in the medical record 1
• Educate about precautions to prevent HBV exposure 1
• For future HBsAg-positive exposures, administer HBIG (0.06 mL/kg) as soon as possible, preferably within 24 hours 1, 3

Enhanced Revaccination Strategies

Consider these approaches to improve response rates in non-responders:

• Double-dose vaccination (e.g., 40 mcg instead of 20 mcg for standard adult formulation) may enhance response rates, though evidence is mixed 1, 4
• Persons with measurable but low antibody levels (<10 mIU/mL) after the initial series respond better to revaccination than those with undetectable levels 1
• A double dose of combined hepatitis A and B vaccine achieved 95% seroconversion in previous non-responders in one study 4

Special Population Considerations

Immunocompromised patients (HIV-infected persons, hemodialysis patients, transplant recipients):

• Modified dosing regimens with doubled antigen doses or additional doses may increase response rates 1
• These patients have reduced humoral response and may require more aggressive revaccination protocols 1
• Annual anti-HBs testing is recommended for hemodialysis patients, with boosters when levels fall below 10 mIU/mL 2

Critical Pitfalls to Avoid

• Do not assume a patient is a non-responder without confirming they completed the full primary series with appropriate intervals (minimum 4 weeks between doses 1 and 2,8 weeks between doses 2 and 3, and 16 weeks between doses 1 and 3) 1
• Do not forget to test for HBsAg in persistent non-responders, as they may have unrecognized chronic infection 1, 2
• Do not delay HBIG administration while awaiting serologic results in non-responders with known HBsAg-positive exposure 3
• Genetic factors may contribute to non-response, and some individuals will never mount an adequate antibody response despite multiple vaccination attempts 1