A value of 2,000,000 copies/mL (6.3 log 10 copies/mL) with Superquant was converted to nearly 800,000 IU/mL (5.9 log 10 IU/mL). In conclusion, all HCV RNA quantitative assays should give HCV RNA loads in international units and be validated with appropriate calibrated panels; 800,000 IU/mL in any of these assays should be used as the decision threshold to tailor the IFN-␣/ribavirin treatment duration in patients infected by HCV genotypes 1, 4, and 5. (HEPATOLOGY 2000;32: 654-659.)Advances in molecular biology-based techniques have recently made it possible to detect and quantify viral genomes in human body fluids. This has helped to understand the pathogenesis of viral infections and to manage both untreated patients and patients receiving antiviral therapy, especially those infected by human immunodeficiency virus, hepatitis B virus, and hepatitis C virus (HCV). 1-3 Initially, "in-house" reverse transcription polymerase chain reaction (RT-PCR) amplification-based techniques were used to quantify HCV RNA, but they lacked standardization, reproducibility, and accuracy. 4 Subsequent development of standardized commercial assays for HCV RNA quantification, namely the noncompetitive PCR-based Amplicor HCV Monitor technique (Roche Molecular Systems, Pleasanton, CA) and the "branched-DNA"-based signal amplification technique (Quantiplex HCV RNA; Bayer Diagnostics, Emeryville, CA), enabled HCV RNA to be quantified in any laboratory equipped for molecular biologybased methods. The performance of these assays has recently been reviewed. 4 In recent years the use of HCV RNA quantification in clinical practice has been hindered for the following reasons: (1) HCV RNA load at a given time has no predictive value for the severity of HCV-induced liver injury and cannot be used as a prognostic indicator of the disease 5,6 ; (2) nonquantitative, qualitative HCV RNA detection assays remain more sensitive than quantitative assays and are thus routinely used to assess the virologic response of chronic hepatitis C to specific treatment 7 ; and (3) although pretreatment HCV RNA load is an independent predictor of sustained virologic responses to interferon alfa (IFN-␣) treatment, 8-10 only one approved therapeutic strategy (IFN-␣, 3 million units [MU] 3 times per week for 6 to 12 months) has been available, hampering the use of pretreatment viral load to tailor treatment schedules.The situation has changed recently with the publication of 2 studies involving more than 1,700 treatment-naive patients with chronic hepatitis C and showing a significant benefit of combination therapy with IFN-␣, 3 MU 3 times per week subcutaneously, and ribavirin, 1,000 to 1,200 mg/d orally, compared with the same dose of 12 In these reports, both pretreatment viral load and the HCV genotype were independent predictors of sustained HCV RNA clearance after combination therapy. 11,12 In addition, the rate of sustained virologic responses was identical after 24 weeks and 48 weeks of the IFN-␣/ribavirin combination, both in patients infected by genotypes 2 an...

The aim of this study was to determine a cost-effective strategy for the diagnosis of hepatitis C virus ( The diagnosis of hepatitis C virus (HCV) infection is based on the detection of anti-HCV antibodies in serum, generally by means of enzyme-linked immunosorbent assays (ELISA). Two different settings must be considered: 1) Blood banks routinely perform anti-HCV testing in blood donors to identify potentially infectious donations and to avoid posttransfusion HCV infection; 2) clinical laboratories routinely search for anti-HCV antibodies in patients with risk factors for parenterally acquired viral infections or clinical symptoms compatible with HCV infection to make appropriate clinical decisions, including therapeutic ones. By analogy with human immunodeficiency virus diagnosis, the French laws have been obliging to perform two different ELISA tests in the routine diagnosis of HCV infection in clinical laboratories for several years, while only one test was needed for blood screening.First-generation anti-HCV ELISAs were lacking sensitivity as well as specificity. This is why first-generation confirmatory assays based on immunoblot testing were developed and systematically used in samples positive in ELISA. 1,2 Since then, ELISA assays have considerably improved, and the second-or third-generation tests available today are both highly sensitive and specific. 3-6 Nevertheless, second-or third-generation immunoblot tests are still used for confirmation in most laboratories. 7,8 The detection of HCV antibodies in serum does not provide information on the replicative status of HCV, a parameter that can be useful in the management of infected patients. Polymerase chain reaction (PCR)-based assays have been developed and are capable of detecting minute amounts of HCV RNA in serum or plasma.The aim of this work was to determine whether a double ELISA determination and confirmation of positive ELISA results with immunoblot assays are still useful in clinical laboratories performing routine diagnosis of HCV infection. MATERIALS AND METHODSFrom January 1 to May 22, 1996, 3,014 consecutive requests for the detection of anti-HCV antibodies were sent to the virology laboratory by the various medical departments of our institution.The serum samples were routinely tested for the presence of anti-HCV antibodies with two different ELISAs: ORTHO HCV 3.0 ELISA Test System (ELISA3.0 HCV; Ortho Clinical Systems, Raritan, NJ), and MONOLISA anti-HCV New Ag (MONOLISA HCV; Sanofi Diagnostics Pasteur, Marnes-la-Coquette, France). ELISA 3.0 detects antibodies directed to core, nonstructural (NS) 3, NS4, and NS5 HCV antigens, while MONOLISA HCV detects antibodies directed to core, NS3, and NS4 antigens. 9 Different peptides are used in the two assays. 9 The assays were perfomed according to the manufacturers' instructions, and, in each sample, the optical density (OD) ratio was calculated by dividing the sample OD by the assay control OD. Samples with an OD ratio Ն2 were considered positive, samples with an OD ratio between 1 and 2 we...

Parameters have been studied to predict responses to interferon (IFN) therapy for chronic hepatitis C, but the definition of a response, the times at which responses were assessed, and the pretreatment parameters considered differ markedly from study to study. Thus, 113 patients with chronic hepatitis C were treated 3-6 months with 3 MU of IFN-alpha 2a three times a week and assessed for pretreatment parameters predictive of responses to IFN. In a multivariate analysis, a biochemical response (normal aminotransferase activity) at the end of treatment was significantly associated with low body weight, normal gamma-glutamyl transpeptidase activity, and a pretreatment hepatitis C virus (HCV) genotype other than 1. Six months after the end of treatment, a low virus burden and a lack of anti-HCV IgM core antibodies were independently associated with sustained virologic response (i.e., normal aminotransferase activity and HCV RNA negativity). Therefore, these pretreatment parameters should be taken into account when individual treatment protocols are designed.

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