HCV RNA detection by TMA during the hepatitis C antiviral long-term treatment against cirrhosis (Halt-C) trial

Authors


  • Potential conflicts of interest: Of the authors who have financial relationships with Hoffmann-La Roche, Inc., Timothy R. Morgan is on the speakers' bureau and receives research support; Herbert L. Bonkovsky is a consultant, on the speakers' bureau, and receives research support; Mitchell L. Shiffman is a consultant, on the speakers' bureau, and receives research support; Gregory T. Everson is a consultant, on the speakers' bureau, and receives research support; Karen L. Lindsay is a consultant and receives research support; Anna S. F. Lok is a consultant and receives research support; Adrian M. Di Bisceglie is a consultant, on the speakers' bureau, and receives research support; and William M. Lee is on the speakers' bureau and receives research support. The authors who have other financial relationships related to this project are Chihiro Morishima, David R. Gretch, Herbert L. Bonkovsky, and William M. Lee, who receive research support from Bayer Diagnostics. The authors with no financial relationships related to this project are James E. Everhart, Jules L. Dienstag, and Marc G. Ghany.

  • This is publication number 16 from the HALT-C Trial Group.

Abstract

For making treatment decisions related to chronic hepatitis C, the utility of HCV RNA tests with increased sensitivity has not been defined. Prior interferon nonresponders with advanced fibrosis (n = 1,145) were retreated with peginterferon alpha-2a and ribavirin. Patients who were HCV RNA-negative by a polymerase chain reaction (PCR)-based assay (Roche COBAS Amplicor™ HCV Test, v. 2.0; lower limit of detection [LOD] 100 IU/mL) at week 20 (W20) received treatment for 48 weeks. Stored specimens were tested using the Bayer VERSANT® HCV RNA Qualitative (TMA) Assay (LOD 9.6 IU/mL) and compared to PCR results for the ability to predict sustained virological response (SVR; defined as undetectable HCV RNA by PCR at W72). Nearly all PCR-positive samples (1006/1007, 99.9%) were positive as assessed by TMA. Among 1,294 PCR-negative samples, 22% were TMA-positive. Negative TMA results were more predictive of SVR than were negative PCR results at W12 (82% vs. 64%, P < .001) and at W20 (66% vs. 52%, P = 0.001). SVR was more likely the earlier TMA had become negative during treatment (82% at W12, 44% at W20, 20% at W24). Among 45 patients who were TMA-positive but were PCR-negative at W20 and W24, none achieved SVR (95% CI: 0%-8%). Approximately 10% of patients with a single positive TMA result at the end of treatment still achieved SVR. In conclusion, negative TMA results at or after W12 were superior to negative PCR results for predicting SVR. In patients with negative PCR results during treatment, a single positive TMA test did not exclude SVR, although persistently positive tests did. (HEPATOLOGY 2006;44:360–367.)

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