Hepatitis B Vaccination for Individuals with Positive HBcAb and Negative HBsAb
Persons who are positive only for anti-HBc (HBcAb) and negative for HBsAb should receive the full series of hepatitis B vaccine. 1
Understanding the Serological Profile
When a person tests positive for hepatitis B core antibody (HBcAb) but negative for hepatitis B surface antibody (HBsAb), this serological pattern can have several interpretations:
- Resolved infection with waning immunity
- False positive anti-HBc test
- "Window period" during acute infection
- Occult hepatitis B infection with low-level viremia
Vaccination Recommendation Algorithm
Step 1: Confirm Serological Status
- Verify HBcAb positive status
- Confirm HBsAb negative status
- Test for HBsAg to rule out active infection
Step 2: Administer Hepatitis B Vaccine
- The CDC and AASLD explicitly recommend that "persons who are positive only for anti-HBc and who are from a low endemic area with no risk factors for HBV should be given the full series of hepatitis B vaccine." 1
- Follow standard vaccination schedule: 0,1, and 6 months
- Alternative accelerated schedules may be considered: 0,1, and 4 months or 0,2, and 4 months 2
Step 3: Post-Vaccination Testing
- Perform anti-HBs testing 1-2 months after completing the vaccination series
- This helps determine if the person:
- Had prior immunity (anamnestic response)
- Was a true non-responder
- Had a false positive anti-HBc result
Expected Responses to Vaccination
Research shows several possible responses to vaccination in individuals with isolated anti-HBc:
Anamnestic (Booster) Response: Rapid development of high anti-HBs levels after a single dose, suggesting previous infection with waning antibodies. Studies show this occurs in approximately 34% of individuals with low-level anti-HBs and 6% of those negative for anti-HBs 3.
Primary Response: Normal response to complete vaccination series, suggesting the initial anti-HBc was a false positive. About 79% of those who don't show a booster response will develop protective anti-HBs levels after completing the three-dose series 3.
Non-response: Failure to develop protective antibody levels despite complete vaccination. This is uncommon but may indicate occult HBV infection or other immune issues.
Evidence-Based Rationale
The recommendation to vaccinate individuals with isolated anti-HBc is supported by multiple studies:
A study of 33 subjects with isolated anti-HBc showed that 90.9% developed protective antibody levels after the complete vaccination series 4.
Another study demonstrated that vaccination of individuals with isolated anti-HBc helped distinguish between those with prior immunity (anamnestic response) and those with false positive results 5.
Even in the absence of detectable anti-HBs, some vaccinated individuals may have cellular immunity that provides protection against clinical disease 6, 7.
Important Considerations
- Vaccination is safe even if the person has previously been infected with HBV 1.
- For individuals at high risk of exposure (healthcare workers, sexual partners of HBsAg-positive persons), post-vaccination testing is particularly important 1.
- If the person remains a non-responder after a complete second series (6 doses total), they should be considered susceptible to HBV infection and counseled about precautions and the need for HBIG post-exposure prophylaxis 1.
By following this evidence-based approach, clinicians can ensure appropriate protection against hepatitis B for individuals with this serological pattern while also potentially clarifying their true HBV status.