Outbreak of Hepatitis C Virus Infection in Patients With Hematologic Disorders Treated With Intravenous Immunoglobulins: Different Prognosis According to the Immune Status

Abstract

The influence of immunodeficiency on the course of hepatitis C virus (HCV) infection is still debated, although a worsening effect has been suggested. We compared the characteristics of hepatitis C in two groups of hematologic patients with different levels of immunocompetence who acquired the same virus strain after treatment with contaminated intravenous immunoglobulins (IVIG). Indications for IVIG therapy were idiopathic thrombocytopenic purpura (ITP) in six patients and hypogammaglobulinemia in 7 patients with various hematologic disorders, who were defined immunodeficient (ID). Infection rate was 100%. Five ID patients never developed HCV antibodies despite serum HCV-RNA positivity. The same HCV genotype was shown in 10 patients tested. Moreover, E1-E2 gene partial nucleotide sequencing, performed in four patients, showed identical or closely related amino acid sequences, thus strongly supporting the hypothesis of a common source of infection. Clinical acute infection did not differ significantly between the two groups, but subsequent liver failure developed in five of the seven ID patients and in none of the ITP patients (P = .04). Liver biopsy, performed in three cases, documented HCV as the only cause of liver damage. Six ID patients died, with liver disease being the primary cause of death in four cases and a contributory cause in two cases. Their median survival after IVIG was 12 months, significantly worse than that of ITP patients (P = .0028). We conclude that immunodeficiency markedly worsens the course of IVIG-acquired HCV infection in hematologic patients.

Response to splenectomy is durable after a certain point in time in adult patients with chronic immune thrombocytopenic purpura

“…Four patients were tested positive for hepatitis C virus (HCV), and all received IVIg treatment between 1983 and 1990. The HCV was probably transmitted via IVIg preparations used during this time period (15).…”

Acute pulmonary embolism caused by highly aggregated intravenous immunoglobulin

“…Pulmonary embolism , myocardial infarction and cerebrovascular accidents were found in patients receiving IVIG therapy with pathological findings of plasma expansion and increased viscosity . Moreover, platelet activation , procoagulant activity , anaphylaxis in IgA‐deficient recipients and hepatitis C virus transmission were also reported. However, the incidence of IVIG‐induced thrombosis was reported to average from 3 to 13% , but the proposed mechanism seems to be irrelevant to the aggregate .…”

Virus reduction in the preparation of intravenous immune globulin: in vitro experiments

“…As noted in the Introduction, the development of chronic HCV infection has been observed in patients treated with some preparations of IGIV, 4–7 and HCV RNA has been reported to be present in some IGIV preparations 8 . Although there was apparent seroconversion as the result of the passive transfer of antibodies in IGIV manufactured from plasma collected before screening for anti‐HCV became routine, 22,23 certain IGIV preparations manufactured since that time (some experimental and some commercial) have transmitted HCV, leading to clinical disease 4–7 . It has therefore become necessary to incorporate virus inactivation and/or removal steps into the manufacturing process of IGIV.…”

“…These preparations have an excellent safety record with respect to the transmission of viral disease 2,3 . Nevertheless, concern regarding the viral safety of these preparations has been raised by reports of transmission of hepatitis C virus (HCV) and the development of chronic hepatitis C in patients treated with IGIV 4–7 . Genetic material for HCV (HCV RNA) has been detected in IGIV preparations 8 .…”