The International Consensus Conference on Hepatitis C recently recommended that hepatitis C virus (HCV) RNA quantification be used to tailor the duration of combined interferon alfa and ribavirin therapy in patients infected by HCV genotypes 1, 4, and 5. The decision threshold has been set at 2,000,000 copies/mL. The recommendation has been difficult to implement in the absence of standardized quantitative units for HCV RNA. Consequently, clinically relevant HCV RNA loads must now be defined in standardized international units (IU) for use in routine clinical and research applications. The semi-automated Cobas Amplicor HCV Monitor TM assay version 2.0 (Roche Molecular Systems) measures HCV RNA loads in IU/mL. Quantification in the Cobas version 2.0 assay is linear between 650 and 850,000 IU/mL, and the accuracy and precision of the measures in IU/mL are satisfactory. A value of 2,000,000 copies/mL (6.3 log 10 copies/mL) converts to nearly 800,000 IU/mL (5.9 log 10 IU/mL). All HCV RNA quantitative assays should now express viral loads in international units and be validated with appropriate calibrated panels.
Standardization opens the way to the widespread use of HCV RNA quantification to guide treatment for patients with chronic hepatitis C. Two potential applications appear particularly promising. First, HCV RNA load can be used to establish treatment schedules, with 800,000 IU/mL in any standardized assay designated as the decision threshold for extending the duration of combination therapy – interferon alfa plus ribavirin – for patients infected by HCV genotypes 1, 4, and 5. Relevant decision thresholds will have to be determined prospectively for all new therapeutic schedules using these and/or other drugs. Second, HCV RNA quantification can be used to monitor early viral replication dynamics in order to elucidate the mechanisms of action underlying the antiviral activities of the drugs and to help tailor treatment to true antiviral effect throughout the therapeutic interval. In the end, researchers, practicing physicians, and patients will benefit from the enhanced transparency achieved through standardization of testing measures around international units.
JEAN-MICHEL PAWLOTSKY, MD, PHD
Professor of Medicine
University of Paris XII
Chief, Virology Unit
Department of Bacteriology
Henri Mondor University Hospital