Borderline and/or discordant Cobas Amplicor HCV Test version 2.0 results: clinical significance.

BACKGROUND: The Cobas Amplicor HCV Test Version 2.0 (Roche Diagnostics, Mannheim, Germany) allows highly sensitive detection of hepatitis C virus (HCV) RNA in patient samples (> or =100 copies/ml with 100% reproducibility) and yields reproducible, unambiguous results that correlate well with relevant serological and clinical parameters. Occasionally, however, results are borderline (defined by Roche Diagnostics as optical density 0.15-1.0) and/or discordant upon repetition. Such results are difficult to interpret: do they represent false-positives or reflect very low-level viremia (<100 copies/ml)? OBJECTIVE: To determine whether low-level viremia could be a plausible explanation for the borderline/discordant results observed with this test. STUDY DESIGN: (1) Analyse serial dilutions of two HCV standards and one HCV quantitated patient serum; and (2) correlate ambiguous results from 21 patients with available clinical and laboratory data. RESULTS: (1) All dilutions containing >100 copies/ml yielded 100% concordant positive results, whereas dilutions with <100 copies/ml yielded discordant results, often with borderline values. (2) All patients had either a confirmed HCV infection (n=14, seropositive, most undergoing therapy with interferon-alpha) or had a history of confirmed or suspected contact with HCV without confirmed HCV infection (seronegative): three needle-stick injuries, one newborn of an HCV seropositive mother, one woman with liver cirrhosis of unknown etiology, one iv drug abuser, and one nurse with a prior blood transfusion and "indeterminant HCV results" at a blood donation center. CONCLUSION: Based on our experience to date, borderline results and/or discordant replicates obtained with the Cobas Amplicor HCV Test Version 2.0 are indicative of very low level viremia (<100 copies/ml) due either to an HCV infection (patients will be seropositive) or to transient contact with the virus with or without subsequent HCV infection (patients will be seronegative and may remain so). Follow-up of such patients is mandatory.