What does a Hepatitis B (Hep B) surface antibody quantification of less than 3.5 indicate?

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Last updated: May 19, 2025 • View editorial policy

From the Guidelines

A hepatitis B surface antibody (anti-HBs) level less than 3.5 mIU/mL indicates you do not have immunity against hepatitis B virus and should consider vaccination or a booster dose, as levels above 10 mIU/mL indicate protection 1. To determine the best course of action, consider the following:

  • If you have not been previously vaccinated, you should receive the standard hepatitis B vaccination series, which consists of three doses: an initial dose, followed by a second dose 1 month later, and a third dose 6 months after the first 2.
  • If you have previously been vaccinated but your levels are now low, you may need a booster dose, particularly if you have risk factors such as healthcare work, dialysis, immunocompromised status, or close contact with infected individuals 1.
  • After completing the vaccination series or receiving a booster dose, you should have your antibody levels checked again 1-2 months later to confirm immunity (levels above 10 mIU/mL indicate protection) 2. Some key points to consider:
  • The presence of anti-HBs is generally indicative of immunity to HBV infection, and levels above 10 mIU/mL are considered seroprotective 3.
  • If you have risk factors such as healthcare work, dialysis, immunocompromised status, or close contact with infected individuals, it is particularly important to ensure you have adequate immunity against HBV infection 4.
  • The body produces these antibodies in response to vaccination or after recovery from natural infection, and their presence at adequate levels provides protection against future hepatitis B infection 2.

From the Research

Hepatitis B Surface Antibody Quantification

  • A hepatitis B surface antibody quantification of less than 3.5 may indicate a low level of immunity to hepatitis B virus (HBV) 5.
  • Studies have shown that isolated anti-HBs levels can be low and may not persist, with 22 subjects losing detectable anti-HBs within 19 months 5.
  • The immunologic specificity and protective value of anti-HBs, especially when levels are low, remain questionable 5.

Comparison of Assay Performance

  • A study comparing the performance of Chemiluminescence Immunoassay (CLIA) and Enzyme-linked Immunosorbent Assay (ELISA) in detecting antibodies to hepatitis B surface antigen found good analytical agreement between the two immunoassays 6.
  • However, there were some discrepancies in quantitative measurement, which may be due to variation in standard calibrators used in each assay 6.

Immune Determinants and Maintenance of Antibody

  • Research has shown that durable and sufficient titers of antibodies to hepatitis B surface antigen (anti-HBs) are desirable for vaccinees to gain resistance to HBV exposure 7.
  • The acquisition and maintenance of vaccine-induced anti-HBs in healthy adults involve the coordinated activation of Tfh and B-cell lineages after HB vaccination 7.
  • Higher anti-HBs antibody titer acquisition is related to the longer term maintenance of anti-HBs, which is positively correlated with prevaccination levels of serum interferon-γ and related chemokines 7.

Clinical Significance of Antibody to Hepatitis B Surface Antigen

  • Anti-HBs is recognized as a protective immune marker, both for HBV infection clearance and following vaccination, and is also considered an important indicator of functional cure for chronic hepatitis B (CHB) 8.
  • The restoration of HBV-specific B cell function, along with the induction of an anti-HBs antibody response, is regarded as pivotal for terminating chronic HBV infection and achieving functional cure 8.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.