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Abstract

A recent increased incidence of hepatitis A in the hemophilia populations of Italy, Germany, Belgium and Ireland was studied. The first well-documented outbreak occurred in Italy, where 51 patients with severe hemophilia contracted hepatitis A between the years 1989 and 1992. A case-control study by Mannucci et al. of the first 29 consecutive cases of hemophilia patients with jaundice led to the conclusion that hepatitis A was transmitted to Italian hemophilia patients by solvent-detergent-treated, ion-exchange-purified concentrate. In a retrospective serologic study of the German epidemic, Brakmann et al. isolated 18 seroconversions in a study group of 195 hemophilia patients over a 5-year period. Although several types of concentrate were used in Germany during this time, all but 1 infected patient received large doses of solvent-detergent, ion-exchange product. It was revealed that the 1 exception had a brother with hemophilia who had received solvent-detergent-prepared concentrate and had developed hepatitis A. Transmission to the study patient was therefore attributed to household contact. The Belgian experience corroborated the findings of the Italian and German investigators: several batches of factor VIII, prepared from plasma of Belgian donors in Lille, France, and Vienna, Austria, appeared to be associated with hepatitis A infection, mainly in hemophilia patients who had received large infusions. An interesting observation in the later (1993) case-control portion of the Belgian study was that hepatitis A virus antibodies were less prevalent in hemophilia patients than in age-matched controls. A possible explanation for this phenomenon is that the hemophilia patients had been passively protected through the immunoglobulin contained in the cryoprecipitate they had received in early treatments, and that they had lost this immunity as a result of their more recent treatment with solvent-detergent, ion-exchange concentrate, which contains almost no immunoglobulin. Solvent-detergent, ion-exchange product was likewise implicated in the Irish epidemic of hepatitis A in which the highest incidence was observed: 30 of 215 Irish hemophilia patients became infected between May and December 1992. In Ireland, geographic clustering was also a factor, since all of the plasma used to prepare the 3 implicated lots of factor VIII originated in donors from the same geographic area. It was concluded that the solvent-detergent, ion-exchange chromatography-purified method of factor VIII preparation was responsible for the recent epidemics of hepatitis A among hemophilia populations in Europe.