Reduction in risk of hepatitis transmission by heat-treatment of a human Factor VIII concentrate.

A human Factor VIII concentrate containing both a non-A, non-B hepatitis agent and 300 or 30,000 chimpanzee infectious doses of added hepatitis B virus (HBV) was heated to 60 C in the lyophilized state for more than 10 hr. None of the four test chimpanzees that received the heated concentrate developed biochemical or ultrastructural evidence of non-A, non-B hepatitis, whereas both control animals receiving unheated product acquired the disease four to five weeks after infusion. In one of these animals the alanine aminotransferase level remained elevated, a finding indicating unresolved or persistent liver disease. Challenge inoculations with unheated Factor VIII base product (without HBV) resulted in the development of non-A, non-B hepatitis in one of two chimpanzees that previously received the heated product. Hepatitis B infection developed in the control animal that resolved its non-A, non-B hepatitis infection but not in the non-A, non-B hepatitis carrier chimpanzee. Both chimpanzees receiving the heated Factor VIII containing 300 chimpanzee infectious doses of HBV failed to develop hepatitis B until 32 and 40 weeks postinoculation, whereas the two chimpanzees that received heated concentrate containing 30,000 infectious doses of HBV became infected within the expected time. Product characterization and human safety trials have revealed no significant difference between the heated and unheated Factor VIII lots and recovery of product has been exceptionally good.