Strategies for reliable diagnosis of hepatitis C infection: The need for aserological confirmatory assay

The aim of the study was to examine whether the diagnosis of Hepatitis C (H CV) infection can be obtained reliably without using an immunoblotbased con firmation assay. 1,708 EIA-reactive serum samples were examined retrospecti vely for (i) optical density value in the screening assay, (ii) reactivity in an immunoblot assay, and (iii) result by RT PCR. In 1,394 (81.0%) sample s positive results were obtained by both the HCV EIA and the confirmation a ssay. OD-values greater than or equal to2.2 were observed in 1026 of these samples, but covered the range from 0.4 to 2.1 in the other 368 samples. Th e combination of HCV EIA reactivity and indeterminate immunoblot assay was observed in 134 (7.8%) serum samples. HCV RNA was detected in 58 cases by P CR, The OD-values of these 58 samples ranged from 0.4 to > 2.2. Especially reactivity against the core recombinant protein was indicative of PCR posit ivity. The reactivity by the HCV EIA could not be confirmed by immunoblot a ssay or PCR in 180 (10.5%) sera. These false reactive sera showed OD values by EIA from 0.3 to 2.1, It is concluded that no threshold values can be de fined which would allow differentiation between positive, indeterminate, an d false reactive result by HCV EIA without producing an inacceptably high n umber of false negative diagnoses. Not using immunoblotbased confirmation w ould result in many additional PCR examinations. Therefore, confirmation of reactive HCV EIA results by a serological confirmatory assay must remain a n essential part of the diagnostic procedure. (C) 2001 Wiley-Liss, Inc.