Hepatitis B Virus, Hepatitis Non–A, Non–B Virus and... : Hepatology (original) (raw)

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Hepatitis B Virus, Hepatitis Non–A, Non–B Virus and Hepatitis Delta Virus in Lyophilized Antihemophilic Factor: Relative Sensitivity to Heat

Purcell, Robert H. M.D.*,1; Gerin, John L.1; Popper, Hans1; London, William T.1; Cicmanec, John1; Eichberg, Jorg W.1; Newman, Jack1; Hrinda, Michael E.1

1_Hepatitis Viruses Section, Laboratory of Infectious Diseases, NIAID, and Infectious Diseases Branch, NINCDS, National Institutes of Health, Bethesda, Maryland 20205; Division of Molecular Virology and Immunology, Georgetown University Medical Center, Rockville, Maryland 20852; Stratton Laboratory for the Study of Liver Disease, Mount Sinai School of Medicine, New York, New York 10029; Meloy Laboratories, Inc., Rockville, Maryland 20850; Virology and Immunology Department, Southwest Foundation for Bio–medical Research, San Antonio, Texas 78284; and Revlon Health Care Group, Research and Development Division, Tuckahoe, New York 10707_

* National Institutes of Health, Building 7, Room 202, Bethesda, Maryland 20205.

Received: 11 March 1985; Accepted: 8 July 1985

Abstract

Lyophilized plasma derivatives are more stable to heat than when they are in the liquid state. Commercial Factor VIII (antihemophilic factor) was seeded with a measured quantity of hepatitis B virus. The contaminated material was then lyophilized and subjected to heat of 60°c for 30 hr. Chimpanzees were inoculated with the heat–treated antihemophilic factor or sham–treated antihemophilic factor that had been held at 4°c. Surprisingly, hepatitis B virus survived the heating procedure with no apparent loss in titer: the incubation period to appearance of HBsAg was that expected for the challenge dose of virus. Even more surprising, one chimpanzee (the recipient of the unheated antihemophilic factor) also developed non–A, non–B hepatitis and two chimpanzees (recipients of the heated antihemophilic factor) also developed delta hepatitis. Neither of these agents was a contaminant of the hepatitis B virus challenge pool, since the purity of this hepatitis B virus pool was established previously in chimpanzees. Thus, both a non–A, non–B agent and the delta agent apparently contaminated the commercial antihemophilic factor. This is the first direct evidence for contamination of antihemophilic factor with the delta agent and confirms previous seroepidemiologic evidence for its presence in pooled plasma derivatives. Subsequent inactivation studies were performed with antihemophilic factor experimentally contaminated with the Hutchinson strain of non–A, non–B hepatitis virus. In these studies, heating at 60°c for 30 hr in the dry state rendered antihemophilic factor free of detectable non–A, non–B hepatitis virus.