Performance of two HCV RNA assays during protease inhibitor-based triple therapy in patients with advanced liver fibrosis and cirrhosis

PLoS One. 2014 Nov 12;9(11):e110857. doi: 10.1371/journal.pone.0110857. eCollection 2014.

Abstract

Introduction: On-treatment HCV RNA measurements are crucial for the prediction of a sustained virological response (SVR) and to determine treatment futility during protease inhibitor-based triple therapies. In patients with advanced liver disease an accurate risk/benefit calculation based on reliable HCV RNA results can reduce the number of adverse events. However, the different available HCV RNA assays vary in their diagnostic performance.

Aim: To investigate the clinical relevance of concordant and discordant results of two HCV RNA assays during triple therapy with boceprevir and telaprevir in patients with advanced liver fibrosis/cirrhosis.

Methods: We collected on-treatment samples of 191 patients with advanced liver fibrosis/cirrhosis treated at four European centers for testing with the Abbott RealTime (ART) and COBAS AmpliPrep/COBAS TaqMan HCV v2.0 (CTM) assays.

Results: Discordant test results for HCV RNA detectability were observed in 23% at week 4, 17% at week 8/12 and 9% at week 24 on-treatment. The ART detected HCV RNA in 41% of week 4 samples tested negative by the CTM. However, the positive predictive value of an undetectable week 4 result for SVR was similar for both assays (80% and 82%). Discordance was also found for application of stopping rules. In 27% of patients who met stopping rules by CTM the ART measured levels below the respective cut-offs of 100 and 1000 IU/ml, respectively, which would have resulted in treatment continuation. In contrast, in nine patients with negative HCV RNA by CTM at week 24 treatment would have been discontinued due to detectable residual HCV RNA by the ART assay. Importantly, only 4 of these patients failed to achieve SVR.

Conclusion: Application of stopping rules determined in approval studies by one assay to other HCV RNA assays in clinical practice may lead to over and undertreatment in a significant number of patients undergoing protease inhibitor-based triple therapy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Retroviral Agents / therapeutic use*
  • Clinical Laboratory Techniques
  • Europe
  • Genotype
  • Hepacivirus / drug effects
  • Hepacivirus / enzymology
  • Hepatitis C / drug therapy*
  • Humans
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / virology
  • Oligopeptides / administration & dosage
  • Predictive Value of Tests
  • Proline / administration & dosage
  • Proline / analogs & derivatives
  • Protease Inhibitors / therapeutic use*
  • RNA, Viral / analysis*
  • Reproducibility of Results
  • Treatment Outcome
  • Viremia

Substances

  • Anti-Retroviral Agents
  • Oligopeptides
  • Protease Inhibitors
  • RNA, Viral
  • telaprevir
  • N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide
  • Proline

Grants and funding

This work was partially supported by research grants from the Endoprogress Foundation, Pécs Hungary, and by the Foundation for Patients with Liver Diseases, Budapest, Hungary. Abbott Molecular provided HCV RNA tests and covered the publication fees. The funder provided support in the form of salaries for authors (GC; Abbott Molecular), but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.