Hepatitis C virus transmission through quarantine fresh-frozen plasma

In 1994, quarantine fresh-frozen plasma (Q-FFP) was introduced in Germany i n order to reduce the risk of HIV and HCV transmission In 1998, an acute HC V infection of a patient was reported to us. The look-back revealed that th is patient had received two Q-FFP from a donor who had seroconverted for HC V in the meantime. Recipients of further plasma donations from this donor w ere identified. Back-up specimens of these donations were investigated in s everal laboratories. A total of 25 additional HCV-PCR positive plasma units had been transfused to 12 further patients. HCV infections were diagnosed in seven of these recipients, three patients had already been deceased. One of the remaining two recipients was already HCV positive prior to transfus ion, in the other patient, no HCV infection was detectable. This patient ha d received three units of an "early" plasma donation, which was tested nega tive by PCR in one laboratory, but positive in the other. The subsequent, c linically infectious donation had the same discrepant PCR results. Thus, ei ght cases of HCV transmission were revealed and classified as "certain" wit h regard to causality, also due to an identical HCV genotype, i.e. 3e. Some of these infections would have been prevented by application of a differen t anti-HCV assay. The assay used in the respective plasmapheresis station w as in-sensitive in this individual case for more than 400 days after the fi rst PCR positive donation. This caused the release of the above mentioned i nfectious units. Upon re-testing the backups, three of four other anti-HCV assays revealed a positive result already 104 days after the first PCR-posi tive donation. The donor had increased ALAT levels (> 23 IU/L) at nine of 2 8 donations, two of these were higher than 2.5 times the upper normal limit , and two were higher than 68 IU/L, which is the cut-off value for male blo od donors in Germany. The results of these (look-back) studies arouse sever al queries, i.e, differences in the diagnostic sensitivity between current anti-HCV and PCR tests, the accuracy of risk-estimates (especially when bas ed on hemovigilance studies for Q-FFP), the value of ALAT testing, and curr ently practised release algorithms for Q-FFP.