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


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.
Arnold
Donald M
DM
Department of Medicine, Michael DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada. arnold@mcmaster.ca
Crowther
Mark A
MA
Meyer
Ralph M
RM
Carruthers
Julie
J
Ditomasso
Julie
J
Heddle
Nancy M
NM
McLeod
Anne
A
Kelton
John G
JG
D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000097:blood / Q000276:immunology / Q000494:pharmacology*; D016022:Case-Control Studies; D003951:Diagnostic Errors; D005260:Female; D006509:Hepatitis B / Q000175:diagnosis* / Q000276:immunology; D006510:Hepatitis B Antibodies / Q000097:blood / Q000276:immunology; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D007155:Immunologic Factors / Q000008:administration & dosage / Q000097:blood / Q000276:immunology / Q000494:pharmacology; D008297:Male; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D016032:Randomized Controlled Trials as Topic / Q000592:standards; D012107:Research Design; D012189:Retrospective Studies; D000069283:Rituximab; D012698:Serologic Tests / Q000592:standards
D058846:Antibodies, Monoclonal, Murine-Derived; D006510:Hepatitis B Antibodies; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D000069283:Rituximab