How should hepatitis B surface antigen (HBsAg) and surface antibody (anti‑HBs) results be interpreted, and what are the appropriate next steps for treatment, vaccination, or monitoring?

Hepatitis B Surface Antigen and Antibody Interpretation

All patients should be screened with a complete hepatitis B panel including HBsAg, anti-HBs, and anti-HBc to determine infection status, immunity, and guide appropriate management. 1

Initial Screening Panel

The Centers for Disease Control and Prevention and Centers for Medicare & Medicaid Services mandate testing for three markers before determining next steps: 1

• HBsAg (Hepatitis B Surface Antigen) - identifies active infection (acute or chronic) 1, 2
• Anti-HBs (Antibody to Surface Antigen) - indicates immunity from vaccination or past infection 1
• Anti-HBc (Antibody to Core Antigen) - distinguishes natural infection from vaccine-induced immunity 1

Interpretation of Common Serologic Patterns

Pattern 1: HBsAg Negative, Anti-HBc Negative, Anti-HBs Positive (≥10 mIU/mL)

This indicates vaccine-induced immunity. 3, 4

• No further action needed in immunocompetent individuals 4
• Protective immunity is defined as anti-HBs ≥10 mIU/mL 1, 4
• Lifelong protection is maintained even when antibody levels subsequently decline below 10 mIU/mL in immunocompetent persons 4
• No booster doses or routine retesting required for immunocompetent individuals 4

Pattern 2: HBsAg Negative, Anti-HBc Positive, Anti-HBs Positive (≥10 mIU/mL)

This indicates recovered from past HBV infection with natural immunity. 1, 3

• No treatment or vaccination needed 1
• These patients are immune to reinfection 1
• No routine monitoring required unless immunosuppression is planned 3

Pattern 3: HBsAg Positive (Regardless of Other Markers)

This indicates active HBV infection (acute or chronic). 1, 2

• Immediate referral to hepatology or infectious disease specialist 3
• HBV DNA quantitative testing required to assess viral load 3, 2
• Liver function tests (ALT, AST, bilirubin, albumin) needed 3
• Consider antiviral therapy based on viral load and liver disease activity 2

Pattern 4: HBsAg Negative, Anti-HBc Positive, Anti-HBs Negative or <10 mIU/mL

This suggests past infection with waning immunity or occult HBV infection. 3

• HBV DNA testing is mandatory to rule out occult hepatitis B infection 3
• If HBV DNA is negative and liver function tests are normal, no specific monitoring needed unless immunosuppression is planned 3
• Consider vaccination if HBV DNA is negative 1

Pattern 5: All Markers Negative

This indicates susceptibility to HBV infection. 1

• Vaccination is strongly recommended 1
• Standard 3-dose series at 0,1, and 6 months 1
• Post-vaccination testing 1-2 months after final dose for high-risk groups 1

Pattern 6: HBsAg Negative, Anti-HBc Negative, Anti-HBs Indeterminate or Low (1-9 mIU/mL)

This indicates subprotective immunity requiring revaccination. 3, 4

• Administer single booster dose of hepatitis B vaccine 4
• Retest anti-HBs 1-2 months after booster 4
• If anti-HBs remains <10 mIU/mL, complete a second full 3-dose series 1, 4

Special Populations Requiring Different Management

Hemodialysis Patients

• Annual anti-HBs testing is mandatory 1, 4
• Administer booster dose when anti-HBs falls <10 mIU/mL 1
• Higher vaccine dose (40 mcg) may be needed 4
• Monthly HBsAg screening if susceptible 1

Immunocompromised Patients (HIV, Chemotherapy, Transplant Recipients)

• Annual anti-HBs monitoring required 1, 4
• Booster vaccination when levels fall <10 mIU/mL 1, 4
• HBV DNA testing mandatory before any immunosuppressive therapy, regardless of serologic pattern 1, 3
• If anti-HBc positive, antiviral prophylaxis required even with negative HBV DNA for high-risk therapies 1, 3

Healthcare Workers and Occupational Exposure Risk

• Post-vaccination testing 1-2 months after final dose to document immunity 1
• If anti-HBs <10 mIU/mL, complete second 3-dose series and retest 1
• For known nonresponders with occupational exposure to HBsAg-positive source: HBIG × 1 and initiate revaccination or HBIG × 2 1

Infants Born to HBsAg-Positive Mothers

• HBsAg-negative infants with anti-HBs <10 mIU/mL should receive single booster dose and retest 1-2 months later 1
• If anti-HBs remains <10 mIU/mL after booster, complete second full series 1

Critical Pitfalls to Avoid

Passive Antibody Transfer

• Recent IVIG or fresh frozen plasma administration can cause passive transfer of anti-HBs or anti-HBc, leading to false-positive results 3, 5
• Repeat testing 3-6 months after IVIG/plasma administration to assess true immune status 3
• Passively acquired anti-HBs does not indicate true immunity and can be detected for 4-6 months 3

Occult HBV Infection

• Never assume resolved infection without HBV DNA testing, especially if immunosuppression is planned 3
• Occult HBV infection can occur with negative HBsAg but positive HBV DNA 2
• This is particularly important in patients with isolated anti-HBc positivity 3

Assay Variability

• Different commercial assays have varying cutoff values and sensitivities for anti-HBs 3
• Indeterminate results near detection threshold may require repeat testing with quantitative assay 3

Post-Vaccination Timing

• Transient HBsAg positivity can occur up to 18 days following vaccination and is clinically insignificant 3
• Anti-HBs response to vaccine cannot be accurately assessed if HBIG was received in the previous 3-4 months 1

Management Algorithm for Non-Responders to Initial Vaccination

For patients with anti-HBs <10 mIU/mL after completing the primary 3-dose series: 1, 4

1. Administer complete second 3-dose vaccine series (0,1, and 6 months) 1
2. Retest anti-HBs 1-2 months after final dose of second series 1
3. 44-100% of initial non-responders will achieve protective levels after revaccination 4
4. If still <10 mIU/mL after 6 total doses, consider patient a non-responder 1
5. Non-responders require HBIG for post-exposure prophylaxis if exposed to HBsAg-positive source 1