Minority of Hematology Patients Receive Hepatitis B Screening Prior to Intravenous Immunoglobulin Exposure

A small portion of hematology patients had a baseline hepatitis B core antibody (anti-HBc) screening before exposure to intravenous immunoglobulin (IVIG), which can lead to difficulty with interpretation of a patient’s anti-HBc status and treatment complications, according to the results of a study published in Transfusion.¹

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IVIG is commonly utilized for a wide range of hematological indications. The treatment has a low rate of infective viral transmission, though in many centers, plasma donors are excluded based on various present antibodies, including any that indicate hepatitis B.¹

Anti-HBc indicates an active or previously treated hepatitis B infection. For recipients of IVIG, it is impossible to definitively distinguish their endogenous IgG antibodies from those acquired from IVIG donors. This phenomenon can lead to difficulty in hepatitis B interpretation, as these antibodies can remain detectable for up to 12 weeks^.1

Furthermore, an indication of positive anti-HBc can complicate and limit the use of typical chemotherapeutic or immunosuppressive agents due to the potential for hepatitis B reactivation. The investigators sought to examine the prevalence of anti-HBc screening prior to IVIG in patients at an Irish health center over 6 months.¹ The observational, retrospective study evaluated 43 cases. Researchers assessed multiple serological markers pre- and post-IVIG, including anti-HBc, hepatitis B surface antigen (HBsAG), and hepatitis B surface antibody (anti-HBs).¹

Overall, 58.1% (n = 25/43) of patients had some type of hepatitis B viral serological testing prior to treatment with IVIG. The least common test performed was anti-HBc, which was administered in 21% (n = 9/43) of patients.¹

In all cases where an anti-HBc test was recorded prior to IVIG administration, the results were negative. Contrastingly, 60% of patients had an anti-HBc recorded after being administered IVIG.¹

Of the patients who received hepatitis B testing, 15.3% (n = 4/26) were observed to have a positive or equivocal anti-HBc indication following IVIG treatment. In all 4 of these cases, the antibodies were found to be transient, and all had a correspondingly positive anti-HBs and negative HBsAg.¹

Misleading anti-HBc results following IVIG administration have been described in previous literature. Arnold et al. found that of 24 trial participants at a single center, 11 (45.8%) were anti-HBc positive. Of those patients, 10 (90.0%) had received IVIG treatment in the preceding 4 weeks.²

Additionally, 70% of seropositive participants in that study had subsequently reverted to negative upon repeat testing, indicating a wide array of inaccuracies in anti-HBc testing for IVIG patients. Arnold et al. also advocated for the establishment of anti-HBc statis before administering IVIG, and said positive results up to 3 months following treatment should be analyzed cautiously.²

Although the current study focused on intravenous preparations, in some instances, such as when frequent immunoglobulin replacement in patients with immunoglobulin deficiency occurs, subcutaneous delivery is preferred. Despite the difference in administration, previous reviews have indicated that detectable anti-HBc can also be found with a subcutaneous method.¹

Despite the small sample size of the study, other larger data assessments have been consistent with these results. Notably, although screening virology before IVIG was requested in many cases, the most clinically significant serological test was the least likely to be requested in this cohort.¹

“It is important that clinicians are aware of the potential down-stream effects of this for patients, particularly when urgent immunosuppressive therapy is likely to be required,” the study authors wrote.¹

REFERENCES

1. Liston K, Prior AR, McHugh J, et al. Hepatitis B screening in hematology patients receiving intravenous immunoglobulin. Transfusion. 2024. doi:10.1111/trf.17938

2. Arnold DM, Crowther MA, Meyer RM, et al. Misleading hepatitis B test results due to intravenous immunoglobulin administration: implications for a clinical trial of rituximab in immune thrombocytopenia. Transfusion. 2010. doi:10.1111/j.1537-2995.2010.02766.x