How should patients who have completed the hepatitis B vaccine series but now have low anti‑HBs titers (<10 mIU/mL) be managed?

Management of Patients with Low Hepatitis B Antibody Titers

For patients with low anti-HBs titers (<10 mIU/mL) after completing the hepatitis B vaccine series, administer a single booster dose immediately, then retest anti-HBs 1–2 months later to determine if additional doses are needed. 1

Understanding Low Antibody Levels

• Anti-HBs levels below 10 mIU/mL indicate subprotective immunity and classify the patient as a non-responder to the initial vaccine series, making them susceptible to HBV infection. 1
• Levels between 1–9 mIU/mL represent measurable but subprotective antibody response, and these patients have better response to revaccination than those with no detectable anti-HBs. 1
• Among persons with low anti-HBs levels (1–9 mIU/mL) after initial vaccination, 25–50% respond to a single additional vaccine dose. 1

Immediate Management Algorithm

Step 1: Administer Single Booster Dose

• Give one dose of hepatitis B vaccine immediately (standard adult dose: 20 mcg for Engerix-B; 10 mcg for children ≤10 years). 1, 2
• This single-dose approach is more practical than immediately starting a complete second series. 1
• For hemodialysis patients, use a higher-dose vaccine (40 mcg); for immunocompromised individuals, consider 40 mcg dose. 1, 2

Step 2: Retest After Booster

• Wait 1–2 months after the booster dose, then measure anti-HBs levels to assess response. 1, 3
• This timing is critical to accurately assess vaccine-induced immunity. 3

Step 3: Interpret Results and Proceed

If anti-HBs ≥10 mIU/mL after the booster:

• The patient is now protected and no further doses are needed. 1
• Document this response permanently in the medical record, particularly important for healthcare workers or those with occupational exposure risk. 1, 4

If anti-HBs remains <10 mIU/mL after the booster:

• Complete a full second 3-dose vaccine series (the remaining doses administered at 1 and 6 months after the booster). 1, 3
• Retest anti-HBs 1–2 months after the final dose of this second complete series. 1, 3
• Between 44–100% of initial non-responders achieve protective levels after a complete second series. 1, 3

Pre-Revaccination Testing Considerations

• Before revaccination, test for HBsAg to exclude chronic HBV infection, especially in persons with risk factors (household contacts of HBsAg-positive individuals, injection drug users, men who have sex with men, or those born in endemic regions). 3
• Do not postpone the first revaccination dose while awaiting HBsAg results; the dose can be administered immediately after blood collection. 3

Management of Confirmed Non-Responders

• If anti-HBs remains <10 mIU/mL after two complete vaccine series (total of six doses), the patient is classified as a confirmed non-responder. 3, 4
• Test for HBsAg and anti-HBc to determine if the person is chronically infected. 3, 4
• If HBsAg-negative, counsel the patient that they remain susceptible to HBV infection. 3, 4
• Following occupational or accidental exposure to HBV-positive blood or body fluids, administer two doses of hepatitis B immune globulin (HBIG) at 0.06 mL/kg: the first as soon as possible and the second one month later. 3

Special Population Considerations

Immunocompromised Patients

• Perform annual anti-HBs testing for HIV-infected persons, hemodialysis patients, hematopoietic stem-cell transplant recipients, and patients receiving chemotherapy. 1, 3, 2
• Provide booster vaccine doses whenever anti-HBs falls below 10 mIU/mL. 1, 3, 2
• Immunocompromised individuals cannot rely on immune memory alone and require maintained circulating antibody levels for protection. 3

Healthcare Workers

• For healthcare workers who completed the primary series but have anti-HBs <10 mIU/mL, give one additional vaccine dose immediately and retest anti-HBs 1–2 months later. 3, 4
• If anti-HBs remains <10 mIU/mL after this single dose, complete the full second series. 3, 4
• Mandatory postvaccination serologic testing must be performed for all healthcare workers at high risk for occupational percutaneous or mucosal exposure to blood or body fluids. 4
• Document vaccine-response status to guide future occupational exposure management. 3, 4

Critical Pitfalls to Avoid

• Do not interpret low anti-HBs levels measured years after childhood vaccination as non-response in immunocompetent individuals. Waning antibodies are expected in individuals who retain immune memory; immunocompetent persons who initially achieved anti-HBs ≥10 mIU/mL after completing the 3-dose vaccine series maintain lifelong protection through immune memory, regardless of subsequent antibody decline. 1, 3
• Do not restart the vaccine series if doses are delayed. Simply continue with the next scheduled dose, ensuring at least an 8-week interval between the second and third doses. 3
• Do not delay revaccination while waiting for additional testing or risk stratification. 3

Documentation Requirements

• Maintain written, dated records of every vaccine dose administered and all serologic test results. 3, 4
• Schedule the 1–2 month post-vaccination testing appointment at the time of the final vaccine dose to ensure compliance. 3