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BACKGROUND: Hepatitis C is the major cause of posttransfusion hepatitis. Blood components that are positive for antibody to hepatitis C virus (anti-HCV) can transmit posttransfusion hepatitis. STUDY DESIGN AND METHODS: To investigate the effect on posttransfusion hepatitis of screening blood donors with a second-generation test for anti-HCV, 249 transfusion recipients who underwent cardiovascular surgery were prospectively followed. Six recipients who were positive for anti-HCV before transfusion and 51 subjects with incomplete follow-up were excluded from this study. RESULTS: Eleven (13.8%) of 80 subjects who received unscreened blood had two successive serum alanine aminotransferase levels > 90 U per L. Seven (8.8% of total) developed anti-HCV and HCV RNA and two (2.5% of total) developed IgM antibody to cytomegalovirus (IgM anti-CMV). By contrast, 3 (2.7%) of the 112 subjects who received anti-HCV-screened blood had two successive serum alanine aminotransferase levels > 90 U per L. None of these three developed anti-HCV and HCV RNA, but two (1.8% of total) showed the development of IgM anti-CMV. The study shows that screening for anti- HCV in blood donors with a second-generation test almost abrogated posttransfusion viral hepatitis C. CONCLUSION: After anti-HCV screening, other body fluid-transmitted viruses such as CMV may become important in posttransfusion hepatitis.