What are the implications and management strategies for a patient with a low Hepatitis B surface antibody (HBs) titre, potentially indicating waning immunity or chronic infection?

Management of Low Hepatitis B Surface Antibody (Anti-HBs) Titre

If the anti-HBs titre is less than 10 mIU/mL, the patient lacks protective immunity against hepatitis B and requires either revaccination (if previously vaccinated) or initiation of the vaccine series (if never vaccinated), as this threshold is the established protective level according to the CDC and AASLD. 1, 2

Immediate Assessment Required

When encountering a low anti-HBs titre, you must first determine the patient's hepatitis B status through complete serologic testing:

• Check HBsAg immediately to rule out chronic hepatitis B infection, as HBsAg positivity indicates active infection rather than immunity 2, 3
• Measure total anti-HBc to distinguish between:
  • Never exposed (anti-HBc negative): true vaccine non-responder or waning immunity
  • Previously exposed (anti-HBc positive): resolved infection with waning antibody 2, 3
• Verify vaccination history to determine if this represents primary vaccine failure or waning immunity over time 4

Clinical Interpretation by Serologic Pattern

Pattern 1: Anti-HBs <10 mIU/mL + HBsAg Negative + Anti-HBc Negative

This indicates lack of immunity and no prior exposure. The patient is susceptible to HBV infection and requires vaccination. 2

• Administer the complete hepatitis B vaccine series (3 doses at 0,1, and 6 months) 1
• Recheck anti-HBs titre 1-2 months after completing the series 4
• Approximately 5% of immunocompetent adults will not respond to standard vaccination and may require higher doses or alternative strategies 1

Pattern 2: Anti-HBs <10 mIU/mL + HBsAg Negative + Anti-HBc Positive

This indicates resolved prior infection with waning antibody. 2, 3

• These patients retain immunologic memory despite low antibody levels 2
• Revaccination is generally not necessary for immunocompetent individuals, as anamnestic response will occur upon HBV exposure 1
• Exception: If the patient will undergo immunosuppressive therapy or chemotherapy, measure HBV DNA and consider prophylactic antiviral therapy (entecavir or tenofovir) regardless of anti-HBs level, as reactivation risk is 3-45% depending on the regimen 3

Pattern 3: Anti-HBs <10 mIU/mL + HBsAg Positive

This indicates chronic hepatitis B infection, not waning immunity. 2

• Proceed with complete CHB evaluation: HBeAg/anti-HBe, HBV DNA quantification, and ALT levels 1, 2
• Measure ALT every 3-4 months for at least 1 year to determine disease phase 1, 2
• Refer to hepatologist for consideration of antiviral therapy based on HBV DNA levels, ALT elevation, and fibrosis assessment 1

High-Risk Populations Requiring Aggressive Management

Immunocompromised patients (chemotherapy, biologics, chronic steroids, HIV, transplant recipients):

• Even "weakly positive" anti-HBs levels (10-100 mIU/mL) may not provide adequate protection during immunosuppression 5
• Administer a booster dose if anti-HBs is <100 mIU/mL before starting immunosuppressive therapy 5
• If anti-HBc positive (any titre), measure HBV DNA before immunosuppression and strongly consider prophylactic antiviral therapy regardless of anti-HBs level 2, 3

Healthcare workers and high-exposure individuals:

• Maintain anti-HBs >10 mIU/mL through regular monitoring and booster vaccination 4
• Check anti-HBs annually if ongoing high-risk exposure 4
• Administer booster dose when titre falls below 10 mIU/mL 4

Critical Pitfalls to Avoid

Passively acquired antibody: If the patient received blood products, IVIG, or hepatitis B immunoglobulin within the past 3-6 months, the anti-HBs may be passively acquired and does not indicate true immunity. 6

• Repeat testing 6 months after last blood product exposure 6
• Do not rely on this antibody for protection 6

False-positive HBsAg: Isolated HBsAg positivity without other markers (anti-HBc negative, HBV DNA undetectable) may represent heterophilic antibody interference. 7

• Confirm with repeat testing using a different assay platform 7
• Check HBV DNA to verify true infection 7

Window period confusion: During acute resolving hepatitis B, patients may be HBsAg negative, anti-HBs negative, but IgM anti-HBc positive. 3

• This is not low immunity—this is acute infection in the "window period" 3
• Repeat serologies in 3-6 months to confirm resolution 3

Monitoring After Revaccination

• Recheck anti-HBs 1-2 months after completing vaccine series 4
• If anti-HBs remains <10 mIU/mL after standard 3-dose series, consider the patient a non-responder 1
• Non-responders may benefit from:
  • Repeat full 3-dose series with double-dose vaccine 1
  • Intradermal administration in select cases 1
  • If still no response, counsel regarding susceptibility and need for hepatitis B immunoglobulin if exposed 1