What does a negative surface antibody qualitative test for Hepatitis B (HBV) indicate and what are the next steps?

Interpretation of Negative Surface Antibody Qualitative Test for Hepatitis B

A negative surface antibody qualitative test for Hepatitis B (HBsAg) indicates lack of immunity to HBV infection, and the individual should receive hepatitis B vaccination if not previously vaccinated, or revaccination if previously vaccinated but without documented immune response.

Understanding Hepatitis B Serologic Markers

Hepatitis B serologic testing involves several markers that help determine infection status and immunity:

• A negative hepatitis B surface antibody (anti-HBs) test indicates the person does not have detectable antibodies against the hepatitis B virus surface antigen, meaning they are likely not immune to HBV infection 1
• This lack of immunity could be due to:
  • Never being infected with HBV and never being vaccinated 1
  • Previous vaccination that didn't produce sufficient antibody response 1
  • Waning antibody levels after previous vaccination or resolved infection 2, 3

Interpretation Based on Vaccination History

For Unvaccinated Individuals:

• A negative anti-HBs result indicates susceptibility to HBV infection 1
• Next step: Complete the hepatitis B vaccination series (typically 3 doses) 1
• Post-vaccination testing should be performed 1-2 months after the final dose to confirm immunity (anti-HBs ≥10 mIU/mL) 1

For Previously Vaccinated Individuals:

• A negative anti-HBs result may indicate:
  • Inadequate initial response to vaccination 1
  • Waning antibody levels over time 3
• Next step: Administer a booster dose or complete revaccination 1
  • For healthy individuals who previously responded to vaccination, immunologic memory may persist despite undetectable antibody levels 3
  • For high-risk individuals (healthcare workers, immunocompromised patients), revaccination is recommended 1

Additional Testing Considerations

• To fully understand immune status, additional testing may be warranted:
  • Test for HBsAg to rule out current infection 1
  • Test for total anti-HBc to determine if there was previous exposure 1
• The complete serologic profile helps distinguish between:
  • Never infected (HBsAg negative, anti-HBc negative, anti-HBs negative) 1
  • Immune due to natural infection (HBsAg negative, anti-HBc positive, anti-HBs positive) 1
  • Immune due to vaccination (HBsAg negative, anti-HBc negative, anti-HBs positive) 1
  • Chronically infected (HBsAg positive, anti-HBc positive, anti-HBs negative) 1

Special Populations and Considerations

• For healthcare personnel (HCP):

  • Testing for anti-HBs upon hire is recommended for those with documented hepatitis B vaccination 1
  • HCP with anti-HBs <10 mIU/mL should receive additional doses of vaccine 1

• For immunocompromised individuals:

  • More likely to have inadequate response to vaccination 1, 4
  • May require annual testing to assess anti-HBs levels 1
  • Higher vaccine doses may be needed 1

• For sex partners of HBsAg-positive persons:

  • Should be tested and vaccinated if found to be seronegative 1
  • First vaccine dose should be administered immediately after blood collection for serologic testing 1

Important Caveats

• Some individuals with negative anti-HBs may still have immune protection:

  • T-cell mediated immunity and memory B cells can provide protection even with undetectable antibody levels 2, 3
  • In one study, 25-38% of samples initially negative for anti-HBs showed positive results when tested with different assays 2
  • Anamnestic responses (rapid antibody production upon re-exposure) may occur in individuals with prior exposure despite negative anti-HBs 5

• Different assays may have different cutoff values:

  • The protective level of anti-HBs is generally considered to be ≥10 mIU/mL 1
  • Results may vary depending on the specific assay used 1

Next Steps Algorithm

1. For negative anti-HBs result:

   • Check vaccination history
   • Test for HBsAg and total anti-HBc to determine infection status 1

2. If never vaccinated:

   • Administer complete hepatitis B vaccine series 1
   • Test anti-HBs 1-2 months after final dose 1

3. If previously vaccinated:

   • Administer one booster dose of hepatitis B vaccine 1
   • Test anti-HBs 1-2 months after booster 1
   • If still <10 mIU/mL, complete a second vaccine series 1
   • Test again 1-2 months after final dose 1

4. If still non-responsive after revaccination:

   • Test for HBsAg to rule out chronic infection 1
   • Counsel about precautions to prevent HBV infection 1
   • Consider need for HBIG prophylaxis for any future exposures 1