Transmission of Non-A, Non-B Hepatitis by pH4-Treated Intravenous Immunoglobulin

Abstract

Four patients (2 with X-linked, one with common variable hypogammaglobulinaemia, and 1 with ulcerative colitis) developed non-A, non-B hepatitis (NANBH) following administration of a specific batch of intravenous immunoglobulin (IV IgG) manufactured by the Scottish National Blood Transfusion Service using the pH4/mild pepsin method. Each patient had normal serum ALT levels over a preceding period of 12-67 months, with raised values developing within 4-18 weeks of first administration of the implicated batch. Two patients had very mild symptoms of hepatitis, the other 2 being asymptomatic. Over a follow-up period of 8-12 months, ALT levels returned to normal in 3 patients, but biopsy-proven chronic NANBH developed in the fourth. The level of NANBH virus in the starting plasma used to manufacture this batch may have exceeded the capacity of the process to inactivate the virus. The transmission of NANBH by one of approximately 110 batches administered demonstrates the importance of continued close surveillance of recipients of IV IgG, even if asymptomatic, by regular monitoring of liver function tests and recording of all batches received.

Virus Inactivation during Intravenous Immunoglobulin Production

“…Intramuscular immunoglobulin (IMIG) has a good rec ord of viral safety whereas many intravenous immunglobulin (IVIG) products have transmitted posttransfusion hepatitis (PTH) [1][2][3][4][5][6][7]. In many IVIG processes plasma is first fractionated by the Cohn ethanol method which is also used for preparing conventional IMIG.…”

Human monoclonal antibodies against a plethora of viral pathogens from single combinatorial libraries.

“…Human monoclonal antibody preparations for disease therapy and prophylaxis overcome many of the problems inherent in pooled sera (12,13). In particular, the concentration of virus-specific antibodies is several orders of magnitude higher than in pooled sera, thereby decreasing the amount of immunoglobulin required for prophylaxis and therapy.…”

A prospective controlled crossover trial of a new heat-treated intravenous immunoglobulin

“…Although still based on the Cohn ethanol method, manufacturing processes differ between companies. There have been transmissions of non-A non-B hepatitis with some products, causing severe hepatitis and deaths from cirrhosis within 5-10 years in some patients [5][6][7][8], Using polymerase chain reaction (PCR) technology on patients' sera and immunoglobulin preparations, these outbreaks have now been linked to HCV infeclion [9]. Current licensed products available in the UK do nol have a specific viral inactivation step in the manufacturing process, although tnost of these products have a good record of safety in regard to HCV transmission.…”