chimpanzees. The virus itself was not identified until 1989, and is now referred to as HCV.

Following the identification of the etiologic agent of the majority of cases of NANB hepatitis in 1988, the natural history and severity of this infection became better known. In prospective studies, 50–70 percent of persons with acute hepatitis C infection were shown to become carriers of chronic HCV. It is known now that chronic hepatitis C infection is often silent, is one of the major causes of cirrhosis, hepatocellular carcinoma, or both, in the United States, and is a common precipitant of liver failure necessitating liver transplantation.

Viral Inactivation of AHF Concentrate

Early Methods

According to a Department of Health, Education and Welfare Conference on Hemophilia in 1976, research at that time had already begun to develop alternate means, other than testing for HBsAg, of removing HBV from final products while maintaining the therapeutic activity of the clotting treatment. Pilot studies had been undertaken to evaluate two methods of viral removal: solidphase immunoabsorption and polyethylene glycol precipitation. However, results of inoculating chimpanzees with the treated products were equivocal (Barker and Dodd 1989). In 1978, hepatitis continued to present a major risk in the use of pooled plasma products, including fibrinogen, AHF concentrates (i.e., Factors VIII and IX), and Factors II, VII, and X (Trepo, et al. 1978).

Two other methods of viral inactivation were also being developed during the 1970s. These methods provided the foundation for most of the subsequent development in this area. First, Dr. Edward Shanbrom, the codeveloper of Factor VIII concentrates, who by this time had left Hyland Laboratories (Baxter Healthcare) and was self-employed, developed a nonionic detergent method for treating plasma before it was fractionated into Factor VIII and the other plasma derivatives (Shanbrom interview). Second, a German pharmaceutical company, Behringwerke, A.G., initiated studies in 1977 on heat inactivation methods for AHF concentrate (Weidmann and Hoechst 1993).

Dr. Shanbrom's method required adding a detergent to the fractionation column, and this method was chosen for experimentation because it was known that viruses containing lipid membranes are readily inactivated by detergentinduced disruption of membrane integrity (Shanbrom pers. com. 1995). The application of the inactivation process before the plasma was fractionated, however, would have required relicensure of all the products of fractionation (Bacich, Shanbrom interviews). Although Dr. Shanbrom tried to interest the



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