A new, multiple-antigen enzyme immunoassay (EIA-2) for hepatitis C virus (HCV) antibodies was evaluated in parallel with the previously available c100-3 HCV EIA (EIA-1) in 14,068 volunteer blood donors as well as in 25 cases of transfusion-associated hepatitis C for which recipient and donor samples were available. When compared to EIA-1, the EIA-2 was more sensitive in detecting HCV-infected blood donors. The EIA-2 detected an additional 1 in 1000 EIA-1-negative, surrogate marker-negative donors who were infected with HCV as demonstrated by polymerase chain reaction (PCR). The specificity of the EIA-2 was comparable to that of the EIA-1, but the two tests appear to detect different populations of false-positive donors. Recombinant immunoblot assay-indeterminate donors were detected five times more frequently by the EIA-2; PCR demonstrated that 21 percent of these donors were infected with HCV. The greater sensitivity of EIA-2 was also found in 25 transfusion recipients with non-A, non-B hepatitis; however, in 16 percent of these cases of posttransfusion HCV infection, the EIA-2 failed to detect an HCV-seropositive donor. These data indicate that EIA-2 testing will significantly reduce, but probably not eliminate, the risk of transfusion-associated HCV infection; we estimate this residual per-unit risk to be 1 in 2000 to 1 in 6000 units transfused. On a national level, it is projected that the replacement of the anti-HCV EIA-1 with the EIA-2 will initially prevent up to 40 additional cases of transfusion-associated hepatitis C per day.

This assay should prove useful for the development and quality assurance of increasingly efficient WBC-reduction filters.

If units that test repeatably reactive on EIA but that are not confirmed as positive are almost always from individuals not infected with the virus in question, then these results indicate that there may be sex-, race-, and/or age-linked proteins cross-reacting with the test kit materials. Elucidation of these antigenic determinates and their subsequent removal should be a priority.