Novel approach to reduce the hepatitis C virus (HCV) window period: Clinical evaluation of a new enzyme-linked immunosorbent assay for HCV core antigen

The window period in hepatitis C virus (HCV) infection is still a major pro blem in ensuring blood safety. HCV RNA detection by nucleic acid amplificat ion technology-based tests has contributed to reduce the infectivity of blo od products, but it is expensive, time-consuming and affected by a high pre valence of false-positive results. The aim of this study-was to assess the performance of a newly developed enzyme immunoassay for the detection of HC V core antigen and its suitability for use in the screening of blood units in order to identify infecting, samples that do not contain specific antibo dies. For evaluation of laboratory performance, different samples were sele cted: to evaluate specificity, we tested 2,586 sera from blood donors, 500 general population samples, and 58 "difficult sera". All samples were teste d by two screening assays, and results were negative. To estimate clinical sensitivity, 103 HCV RNA-positive, anti-HCV-negative samples, 6 natural ser oconversion panels, and 9 commercial seroconversion panels were tested. Int ra- and interassay precision were determined on two HCV-RNA-positive, anti- HCV-negative sera. Seventeen (0.66%) blood donor samples, 2 (0.4%) general population samples, and 2 (3.44%) difficult sera were initially reactive; 3 sera were positive on repetition. These 21 samples tested by reverse trans cription-PCR were negative. The clinical sensitivity calculated with seroco nversion panels and seroconverted patient samples was very similar to PCR s ensitivity: 95% of PCR-positive, antibody-negative samples contained detect able HCV antigen. Data on intra- and interassay precision showed dispersion indices with values of less than 10%. In conclusion, the HCV antigen assay showed high sensitivity and specificity and could become a useful means of improving the safety of blood and blood products.