There was a publication of some results of clinical use of solvent detergent product in Thrombosis and Haemostasis in 1987 and a fuller and more detailed publication in the Lancet, 23 July 1988, "Virus Safety of Solvent/detergent-treated Anti-haemophilic Factor Concentrate", Horowitz & Others. The Lancet article showed no transmission of NANB hepatitis or HIV to sixteen and seventeen patients respectively treated with solvent detergent product. No reference was made to the possible existence of a non-lipid enveloped strain of NANB virus and it seems from the evidence of Dr. Prince and Dr. Horowitz that they were satisfied by this time that such a strain did not exist.
Monoclonal Concentrates Fractionation processes using monoclonal antibodies were developed. The primary purpose was to achieve a highly purified and concentrated product with high specific activity but there was also some degree of viral inactivation. The process of immunoaffinity chromatography utilising monoclonal antibodies was thus described in Kasper & Others, "Recent evolution of clotting factor concentrates for haemophilia A and B", Transfusion Volume 33 No. 5, "Immunoaffinity chromatography was assisted by the development of monoclonal antibodies to specific clotting factors, such as Factor VIII. The antibodies can be coupled to a matrix through which plasma or one of its fractions is poured, thus attaching the targeted clotting factor. The matrix can then be rinsed to decrease contamination with unwanted proteins and viruses and the clotting factor can be eluted. Other chromatographic purification steps may follow. Such extensive purification in itself results in a high degree of separation from viruses." Factors fractionated using the monoclonal method and treated with various forms of viral inactivation were licensed in the United States from 1987 and 1988 onwards.
Appreciation of the Clinical Significance of NANB Hepatitis The Tribunal has already traced the developing state of knowledge of the clinical significance of non-A non-B hepatitis up to June 1982. In the period after that date the results of further studies were published tending to show the condition to have potentially serious long term consequences. One such study was an article by Hay, Preston & Others in the Lancet, 29 June 1985, "Progressive Liver Disease in Haemophilia: An Understated Problem?" In their introduction the authors referred to the hitherto generally benign view of non-A non-B hepatitis:"Little concern has been expressed about the long term implications of liver disease associated with haemophilia; few clinical features of chronic liver disease have been reported in haemophiliacs and few deaths attributed to it. Liver biopsy studies have shown chronic persistent hepatitis in most of these patients, leading various workers to conclude that liver disease in haemophilia is benign and non-progressive." In their discussion the authors reported:"Our observations show that progressive liver disease is a potentially serious problem in haemophilia. Of seventy-nine haemophilic patients, selected solely on the basis of previous exposure to blood products, seventeen had evidence of progressive liver disease (nine cirrhosis, eight chronic active hepatitis). Serial liver biopsies showed progression of chronic persistent hepatitis to chronic active hepatitis and cirrhosis within a period of two to six years." - 96 -