This increased sensitivity of the last-generation assays has dramatically reduced the risk of HCV transmission by blood components by reducing the window period from 82 days (5) to 66 days (3, 12). assay. The HCV Ag/Ab assay did not detect HCV contamination as early as the HCV RNA assay (mean delay, 30.3 days) or HCV Ag assay (mean delays, 27.9, and 16.3 days by the HCV core Ag quantification assay and the HCV Ag blood screening assay, respectively). This new assay provides a notable improvement for the early detection of HCV contamination during the so-called windows period compared with anti-HCV Ab assays and could be a useful alternative to HCV RNA detection or HCV core Ag assays for diagnosis or blood screening when nucleic acid technologies or HCV core Ag detection are not implemented. Since the development of the first assay in 1989 (20), assays for detection 8-Hydroxyguanine of hepatitis C computer virus (HCV) antibodies (Ab) have allowed progress in the early detection of HCV contamination (46). This increased sensitivity of the last-generation assays has dramatically reduced the risk of HCV transmission by blood components by reducing the windows period from 82 days (5) to 66 days (3, 12). To further reduce the residual risk (2, 5, 16, 18, 36, 37, 41, 48), nucleic acid testing (NAT) for HCV RNA was introduced in several high-income countries (2, 14, 15, 21, 30, 39). In some countries, an assay for the detection of HCV core antigen 8-Hydroxyguanine (Ag) by use of the enzyme immunoassay (EIA) technology has been chosen as an alternative to NAT for the early diagnosis of contamination (1, 8, 25, 38). In addition, 8-Hydroxyguanine some authors emphasized the clinical advantage of HCV core Ag quantification as a direct marker of viral replication in the chronic phase of contamination (4) and as a relevant marker for predicting and monitoring the response to therapy (7, 29, 31). Indeed, the HCV core Ag assays have sensitivities close to that of NAT, with mean detection differences of 1 1 to 2 2 days in the windows period with the specific assay developed for blood screening (11, 32, 35, 45) and 0.29 day with the immunoassay capable of detecting and quantifying HCV core Ag (23). A bHLHb38 recent study reported that a prototype assay based on the simultaneous detection of HCV core Ag and anti-HCV Ab significantly closed the time gap between HCV RNA detection and the first appearance of detectable anti-HCV Ab (42). However, this assay is not yet available for routine use. More recently, a new combination assay has been developed and licensed in Europe (Monolisa HCV Ag/Ab ULTRA; Bio-Rad, Marnes la Coquette, France). To assess its sensitivity for the detection of HCV contamination during the windows period or at the early phase after seroconversion, we tested two panels and compared the results with those obtained using the two available assays for HCV Ag (HCV core Ag EIA blood screening assay and trak-C assay) and HCV RNA. The overall objective was to determine if this new test could constitute an alternative to NAT for the diagnosis of HCV contamination during the windows period and whether the sensitivity for antibody detection is preserved. MATERIALS AND METHODS Panels. (i) Panel 1: individual samples from volunteer blood donors. Panel 1 (Table ?(Table1)1) consisted of 12 blood donor samples which were unfavorable for anti-HCV Ab (Ortho HCV 3.0 EIA test system Enhanced SAVe; Ortho Clinical Diagnostics, Raritan, NJ) but positive for HCV RNA. The plasma from each of these blood donations was immediately aliquoted and stored at ?30C until it was used. All these samples were subsequently found to be positive for HCV core Ag by the trak-C assay (23), and 9 of the 11 samples tested were also positive by the HCV core Ag blood screening assay. Eight samples had been collected before the seroconversion (among these, five had been identified by the French Fractionation and Biotechnology Laboratory by detection of HCV RNA in plasma pools, and three had been identified by NAT in a pool of 8 or 24 donations after its implementation in blood donation centers),.