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

JAMA. 1996 Nov 20;276(19):1563-7.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alanine Transaminase / blood
  • Child
  • Cohort Studies
  • Drug Contamination*
  • Female
  • Hepacivirus / isolation & purification*
  • Hepatitis C / diagnosis
  • Hepatitis C / etiology*
  • Humans
  • Immunoenzyme Techniques
  • Immunoglobulins, Intravenous / adverse effects*
  • Immunologic Deficiency Syndromes / drug therapy
  • Logistic Models
  • Male
  • Multivariate Analysis
  • Polymerase Chain Reaction
  • Retrospective Studies
  • Risk

Substances

  • Immunoglobulins, Intravenous
  • Alanine Transaminase