Hepatitis C Infection in Patients with Primary Hypogammaglobulinemia after Treatment with Contaminated Immune Globulin

Abstract

In patients with primary hypogammaglobulinemia there was a high rate of HCV infection after treatment with contaminated immune globulin. In these immunocompromised patients HCV infection has a severe and rapidly progressive course, and responses to interferon are poor.

Hepatitis C viral infection in the immunosuppressed patient

“…3 This high rate of progression to cirrhosis was confirmed by a Swedish study. Six of 17 (35%) infected patients were reported as cirrhotic within 10 years of infection, two of whom developed liver failure 4 within this time period. In a further study of non-A, non-B hepatitis in patients with hypogammaglobulinaemia who received hepatitis C infected immunoglobulin G, 3 of 12 (25%) developed cirrhosis within 5 years of infection.…”

“…In a further study of non-A, non-B hepatitis in patients with hypogammaglobulinaemia who received hepatitis C infected immunoglobulin G, 3 of 12 (25%) developed cirrhosis within 5 years of infection. 6 In immunocompetent subjects, factors recognized as associated with more progressive hepatitis C, namely in males, the onset of infection Ͼ40 years and alcohol intake Ͼ50 g/day 7 were not relevant in these studies of hypogammaglobulinaemic patients infected with hepatitis C. 3,4 While initial infecting viral load may be important, 8 other viral factors, such as HCV quasispecies, have not been studied in these patients.…”

“…Most patients with hypogammaglobulinaemia who are also infected with HCV acquired their infection from batched contaminated immunoglobulin [2][3][4][5] and were already immune incompetent at the time of infection. These include individuals with isolated immunoglobulin deficiencies and combined immunodeficiency syndromes.…”

“…Symptomatic hepatitis with icterus was observed in 25%. 3,5 Histologically proven chronic hepatitis developed in 75% 3,4 and the rate of progression to cirrhosis was high (31%). 3 This high rate of progression to cirrhosis was confirmed by a Swedish study.…”

Safety and availability of immunoglobulin replacement therapy in relation to potentially transmissable agents

“…In contrast, where there were full data on batch usage, prompt detection of transmitted infection 34 and early treatment with interferon alpha were possible; early treatment was shown to be more effective than treatment in the chronic phase. 35,36 Post-licensing monitoring by manufacturers is obligatory; manufacturers are required to keep aliquots of each batch of immunoglobulin produced so that an individual virus can be traced retrospectively by genotyping. This allows good epidemiological investigation, both within a patient population and, more importantly, to identify a contaminated donor or an unsafe manufacturing process.…”