Challenges and Controversies

Recommendations: 1. Check HBV DNA level, but no vaccine if negative.

For the most part I follow the recommendations found in https://www.hepatitisb.uw.edu/page/primary-care-workgroup/guidance. I was in the workgroup that developed this guidance. The workgroup's review of the evidence (as of early 2020) showed no significant evidence that HBV vaccine has benefit for patients who are "isolated core antibody positive". Although this workgroup included primary care and public health experts, it was heavily influenced by the participating specialists, including hepatologists. This was by design -- we wanted input from specialists to help guide primary care clinicians.

Early in my primary care-based hepatitis B managing "career" I sought opinions from any specialist who was too slow to run away from my persistent inquiries. How to manage this kind of case was one of my favorite questions, but perhaps not their favorite. Based on such input I used to routinely give HBV vaccine to these patients (if the HBV DNA was negative). The objective was to try to get a quantitative anti-HBs response. Later I learned about the lack of known benefit for such immunization, so I stopped doing it.

Despite my recommendation above, I do not feel strongly about avoiding HBV immunization in such patients, since it is well-tolerated and generally-available. I suspect that the "absence of evidence for benefit" of this intervention may simply mean that appropriate high-quality studies were simply never done. It would likely be very hard to identify a large number of such cases and then follow them over a long period of time to see what the outcomes are. It seems to me, then, that we probably don't really know if there is benefit. Fortunately, being isolated core positive (if DNA negative) appears to be a low risk situation for the patient. It might only be an issue if someone is, or becomes, immunocompromised in the future, which is hard to predict.

The isolated hepatitis B core antibody serologic profile, defined as a positive anti-HBc with negative HBsAg and anti-HBs, can be seen in anywhere from 1% to 30% of patients depending on the population you are looking at. This is not uncommon in people with chronic hepatitis C or HIV infection, so I would also be sure to evaluate/update her hepatitis C status as well.

An isolated anti-HBc profile can represent: (1) the brief seronegative window in acute hepatitis B (after loss of HBsAg and before detection of anti-HBs), (2) false positive, (3) occult hepatitis B infection (with loss of HBsAg) or (4) natural immunity with waning of anti-HBs. Acute infection can generally be excluded if patient has normal (or not too abnormal) ALT/AST. False positive is less likely in someone who has a history of IDU. Occult HBV is rare but can be screened with HBV DNA particularly if patient comes from an HBV-endemic region (e.g. Asia, Africa) but not usually necessary in most cases.

Most of these individuals (at least in the US) are those with natural immunity. If these patients are given a hep B vaccine booster, they would mount an anamnestic response and return of their anti-HBs. They can be considered protected and do not need the vaccine. This however is different in people with HIV with isolated anti-HBc who don't typically mount an anamnestic response; HBV immunization should be considered in those individuals.