Isolated Hepatitis B Surface Antigen Positivity Following Vaccination Against Coronavirus Disease A report of two cases
Manar Al Sanaa AlZeedi*, Anwaar Al Lawati, Huda Anwar
Directorate General of Health Services, Ministry of Health, Muscat, Oman.
Manar Al Sanaa AlZeedi, Directorate General of Health Services, Ministry of Health, Muscat, Oman.
Figure 1: Final HBsAg results for Case 1.
A 14-year-old boy underwent hepatitis screening during a routine sports medical evaluation. He had received two doses of the BNT162b2 COVID-19 vaccine (Pfizer/BioNTech), with the last dose received a month beforehand. All routine laboratory findings were within normal limits, except for HBsAg positivity. No hepatitis indicators were found during a physical examination. An HBV profile performed one week later failed to detect HBsAg (0.17 IU/mL) [Figure 2]. The boy had been vaccinated against HBV at one year of age as part of a routine child immunization program.
Figure 2: Final HBsAg results for Case 2.
Figure 3: Serological profile of an acute HBV infection. Reproduced from the Hepatitis B Foundation website.8
False-positive isolated HBsAg seropositivity has been described in other circumstances, including in the setting of malignancy.11,13 Costa et al. reported a 77-year-old female patient with a basal cell carcinoma who demonstrated persistent isolated HBsAg positivity, despite periodic testing over several months.11 Similarly, Tang et al. described a middle-aged female with primary hyperparathyroidism with repeated HBsAg positivity over a 5-week period prior to the surgical removal of a parathyroid adenoma.13 Other instances in which isolated HBsAg seropositivity may occur include mutated HBV variants and underlying immune conditions such as lupus.11,14
Both groups of researchers attributed the HBsAg positivity in their respective cases to heterophilic antibody interference.11,13 Heterophilic antibodies are poorly defined, low-affinity immunoglobulins which can cross-react with a wide range of animal antigens. As such, the presence of heterophilic antibodies have been shown to affect findings from lateral-flow immunoassays by binding to the target antigen, thereby generating false-positive results.15 Consequently, Costa et al. recommended that initial positive HBsAg findings be confirmed using a neutralization technique in which anti-HBs is incubated with HBsAg to block the HBsAg signal.11
Other infections, such as Epstein-Barr virus, may also give rise to low levels of heterophilic antibodies that can persist for up to a year.11,16 Rheumatoid factor cross-reactivity has also been found to result in misleading immunoassay findings.11,17 The two cases of HBsAg positivity described in this report appeared to be isolated, with subsequent testing failing to show persistent antigenemia, lending support to the theory that the false positivity may have been due to an indigenous factor or an exogenous analytical or operational error.17 Appropriate blocking agents are therefore recommended in order to minimize the risk of false-positive reactions.17,18