The results of this study confirm that transient HBsAg positivity can occur in patients who have recent HBV vaccination. In our academic medical center population, we found 11 cases out of 11,719 total tests (0.085%) where vaccination caused weakly positive (grayzone) HBsAg results. These 11 cases arose out of 34 instances where HBV vaccine was administered within 14 days of HBsAg testing. Ten of the 11 cases involved the higher (40 mcg) of the two doses available for the Engerix-B® vaccine.
In all 11 patients, HBsAg testing was for screening purposes (either for dialysis patients or pre-travel laboratory tests) and not for work-up of clinically suspected viral hepatitis infection. In addition, except for one patient who received vaccination and HBsAg testing in the same outpatient visit, the other ten patients were all hemodialysis patients who had the HBsAg test ordered as part of ongoing surveillance and the HBV vaccine administered during an outpatient visit to a different provider (usually a primary care physician or registered nurse practitioner). Our study is consistent with other studies demonstrating hepatitis B vaccine-induced reactive HBsAg test in hemodialysis patients
This study highlights why vaccine-induced positivity for the HBsAg test is a persistent problem that is difficult to eliminate. One would predict that the challenge is even greater if a patient is seen in two different healthcare systems that do not share a common electronic medical record. In our own medical center, we have now instituted a “Best Practice Alert” in our electronic medical record that alerts the physician when a HBsAg test is ordered within 14 days of a HBV vaccine order and advises delaying HBsAg testing until at least 15 days after vaccination.
The hemodialysis population is particularly challenging with regard to HBsAg testing as patients often undergo regular HBsAg testing and may be seen by other providers for a variety of other medical issues. In addition, hemodialysis patients tend to respond poorly to hepatitis B vaccines and thus frequently receive a higher dose of vaccine than used in other patient populations. Hemodialysis patients may even require additional doses of vaccine to achieve adequate levels of antibodies against HBsAg
There are two main limitations to the analysis presented in this paper. First, although pediatric patients 18 years old or less comprised 28.1% of the total HBsAg tests, there were no pediatric patients that received hepatitis B vaccine within 14 days of HBsAg testing. Consequently, the results related to recent vaccine administration are only applicable to adult patients. However, the sample size of this study exceeds that of previous studies and contains a patient population that likely is similar to that analyzed by clinical laboratories at many academic medical centers, and has produced results comparable to other similar studies of academic medical center patient populations
[4, 11–13]. Second, although nutritional status was not examined in detail, it is likely that most patients in the study were well-nourished and thus the findings are most applicable to other well-nourished populations.
Our study also demonstrates that weakly positive HBsAg results uncommonly reflect actual HBV infection. Of the overall 43 grayzone results out of 11,719 total tests, only 4 patients were found to have active HBV infection by additional confirmatory laboratory work-up, e.g., HBV DNA although it should be pointed out that not all patients had detailed confirmatory work-up performed. Reactive (not grayzone) HBsAg tests were often markedly higher than the upper limit of the grayzone (COI = 20) and generally had COIs of greater than 1,000. We believe our results should prompt caution in interpretation of weakly positive HBsAg results, at least for the Roche Diagnostics assay used, and also highlights the importance of follow-up confirmatory testing to ascertain true infection status and avoid the downstream consequences of false positives.