Hepatitis C virus infection associated with administration of intravenous immune globulin. A cohort study
J. S. Bresee, E. E. Mast, P. J. Coleman, M. J. Baron, L. B. Schonberger, M. J. Alter, M. M. Jonas, M. Y. Yu, P. M. Renzi and L. C. Schneider
Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Ga 30333, USA.
OBJECTIVE: To determine the risk of and risk factors for hepatitis C virus
(HCV) infection among persons with immune deficiencies who had received
intravenous immune globulin (IGIV) between March 1993 and February 1994.
DESIGN: Retrospective cohort study. SETTING: An immunology program in a
tertiary care hospital. PATIENTS: Of 341 persons who had received IGIV
between March 1, 1993, and February 22, 1994, 278 (82%) were enrolled. The
mean age for the enrolled persons was 9 years, and 99% had primary immune
deficiencies. MAIN OUTCOME MEASURES: Evidence of HCV infection by detection
in sera of antibody to HCV and/or HCV RNA by reverse transcriptase
polymerase chain reaction. RESULTS: Twenty-three (11%) of 210 persons who
received the IGIV Gammagard (Baxter Healthcare Corporation, Deerfield, Ill)
became infected compared with none of 52 persons who received exclusively
other IGIV products (P=.01). In a multivariate analysis, HCV infection was
associated only with Gammagard produced from plasma screened by
second-generation (multiantigen) anti-HCV tests (P=.03). Hepatitis C virus
RNA was detected in Gammagard, and the risk of transmission to recipients
increased with increasing quantity of HCV RNA infused, from 0 for those who
received no HCV RNA-positive lots to 29% for the quartile of patients
receiving the greatest amount (P<.001). At least 9 different lots of
Gammagard were required to account for all cases. CONCLUSION: Gammagard was
the only IGIV product implicated in the transmission of HCV. Infection was
associated with higher quantities of HCV RNA in Gammagard produced from
second-generation anti-HCV-screened plasma. Further studies are needed to
determine reasons for the infectivity of Gammagard, and viral inactivation
and removal steps are needed to ensure the safety of IGIV products.
