Standardization of Hepatitis C Virus RNA Quantification

Authors

  • Jean-Michel Pawlotsky M.D., Ph.D.,

    Corresponding author
    1. Department of Bacteriology and Virology, Hôpital Henri Mondor, Université Paris XII, Créteil, France
    2. INSERM U99, Hôpital Henri Mondor, Université Paris XII, Créteil, France
    • Service de Bactériologie-Virologie, Hôpital Henri Mondor, 51 avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France. fax: (33) 1 4981 2839.
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  • Magali Bouvier-Alias,

    1. Department of Bacteriology and Virology, Hôpital Henri Mondor, Université Paris XII, Créteil, France
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  • Christophe Hezode,

    1. Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, Université Paris XII, Créteil, France
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  • Francoise Darthuy,

    1. Department of Bacteriology and Virology, Hôpital Henri Mondor, Université Paris XII, Créteil, France
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  • Jocelyne Remire,

    1. Department of Bacteriology and Virology, Hôpital Henri Mondor, Université Paris XII, Créteil, France
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  • Daniel Dhumeaux

    1. INSERM U99, Hôpital Henri Mondor, Université Paris XII, Créteil, France
    2. Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, Université Paris XII, Créteil, France
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Abstract

It was recently recommended that hepatitis C virus (HCV) RNA quantification be used to tailor the duration of combined interferon alfa (IFN-α)/ribavirin therapy in patients infected by HCV genotypes 1, 4, and 5. This recommendation has been difficult to implement in the absence of standardized quantitative units for HCV RNA. The aim of this work was to define clinically relevant HCV RNA loads in standardized international units (IU), for use in routine clinical and research applications based on standardized quantitative assays. Two hepatitis C virus RNA quantitative assays were used: (1) the Superquant assay (National Genetics Institute, Los Angeles, CA), for which possibly relevant thresholds were established; and (2) the semi-automated Cobas Amplicor HCV Monitor assay version 2.0 (Cobas v2.0, Roche Molecular Systems, Pleasanton, CA) that measures HCV RNA loads in IU/mL. Quantification in the Cobas v2.0 assay was linear over the entire range of values tested, including viral loads higher than 850,000 IU/mL after 100-fold dilution. The accuracy and precision of the measures in IU/mL were satisfactory with Cobas v2.0. The results obtained with Superquant and Cobas v2.0 correlated (r = .932; P < .0001). A value of 2,000,000 copies/mL (6.3 log10 copies/mL) with Superquant was converted to nearly 800,000 IU/mL (5.9 log10 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-α/ribavirin treatment duration in patients infected by HCV genotypes 1, 4, and 5.

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