Misleading hepatitis B test results due to intravenous immunoglobulin administration: implications for a clinical trial of rituximab in immune thrombocytopenia.

Author(s): Arnold DM, Crowther MA, Meyer RM, Carruthers J, Ditomasso J, Heddle NM, McLeod A, Kelton JG

Affiliation(s): Department of Medicine, Michael DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada. arnold@mcmaster.ca

Publication date & source: 2010-12, Transfusion., 50(12):2577-81.

Publication type: Evaluation Studies; Research Support, Non-U.S. Gov't

BACKGROUND: Rituximab may cause reactivation of hepatitis B virus (HBV) even in patients with remote HBV infection. Thus, the presence of hepatitis B core antibodies (anti-HBc) was an exclusion criterion for a randomized trial of rituximab for patients with immune thrombocytopenia. A high seroprevalence of anti-HBc observed among patients screened for the trial prompted this substudy to investigate for an association between anti-HBc seropositivity and exposure to intravenous immunoglobulin (IVIG). STUDY DESIGN AND METHODS: This was a retrospective case-control study that was a substudy of a randomized controlled trial. RESULTS: Of 24 trial participants screened at one center, 11 (45.8%) were anti-HBc positive and of those, 10 (90.0%) had received IVIG in the preceding 4 weeks. Of 13 seronegative patients screened, five (38.5%) had received IVIG (odds ratio, 16; 95% confidence interval, 1.5-166.1). Seven (70%) of 10 seropositive participants subsequently reverted to negative upon repeat testing. Serial testing before and after IVIG (n = 2) demonstrated transient anti-HBc that lasted for up to 11 weeks after the last dose of IVIG. Samples from three of five different IVIG products were found to contain anti-HBc. CONCLUSIONS: Passive transfer of anti-HBc from certain IVIG products may lead to misinterpretation of hepatitis test results with implications for treatment and clinical trial eligibility. To avoid misleading test results, anti-HBc should be measured before or 3 months after IVIG administration; alternatively an IVIG product known to be free of anti-HBc should be used. (c) 2010 American Association of Blood Banks.