Hepatitis C virus infection associated with administration of intravenous immune globulin. A cohort study.

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.

Methods: Retrospective cohort study. Methods: An immunology program in a tertiary care hospital. Methods: 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. Methods: 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.

Conclusions: 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.