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

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 degrees C for 30 hr. Chimpanzees were inoculated with the heat-treated antihemophilic factor or sham-treated antihemophilic factor that had been held at 4 degrees 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 degrees C for 30 hr in the dry state rendered antihemophilic factor free of detectable non-A, non-B hepatitis virus.

Hepatitis B vaccination of 113 hemophiliacs: Lower antibody response in anti‐LAV/HTLV‐III‐positive patients

“…In theory this could be either because the concentrates were not infected or because of development of protective anti-HBs in the vaccinated patients. As to the first hypothesis, it must be borne in mind that, despite HBsAg screening of single plasma units, unheated commercial concentrates continue to transmit hepatitis B [21,22]. Our own study provides evidence for this, since one patient treated also in the 6-month prevaccination period developed markers of HBV infection.…”

Hepatitis C virus shares amino acid sequence similarity with pestiviruses and flaviviruses as well as members of two plant virus supergroups.

“…Although first discovered over a decade ago the etiological agent has remained elusive (5,6). Studies involving the experimental inoculation of chimpanzees provided evidence that the infectious agent was a lipid-containing virus 30-60 nm in diameter bearing strong resemblance to members of the Togaviridae family (7)(8)(9)(10)(11).…”

The Chimpanzee Model for Hepatitis B Virus Infection

“…For example, chimpanzee blood was used to show that inactivation of HBV in blood products with heat was only partially successful (Shikata et al 1978;Hollinger et al 1984;Purcell et al 1985;Lelie et al 1987). Over the next 15 years, many different inactivation strategies were used, including urea/formalin treatment (Tabor et al 1983a), UV-irradiation alone and in combination with Tween 80 and b-propiolactone (Stephan et al 1981;Prince et al 1983a,b), chloroform treatment (Feinstone et al 1983), exposure to Tween 80 and ether at 4˚C (Prince et al 1984a), glutaraldehyde or ethyl alcohol treatment (Kobayashi et al 1984), exposure to heat (Hollinger et al 1984;Kobayashi et al 1984;Purcell et al 1985;Lelie et al 1987), photochemical treatment (Alter et al 1988;Lin et al 2005), ion exchange chromatography (Zolton et al 1985), various disinfectants (Prince et al 1993), and also antibodies to HBV (Tabor et al 1980a;Brummelhuis et al 1983).…”