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

Benjamin Maasoumy, B. Hunyady, Vincenza Calvaruso, Mihály Makara, Johannes Vermehren, Attila Haragh, Simone Susser, Birgit Bremer, Gavin Cloherty, Michael P. Manns, Antonio Craxì, Heiner Wedemeyer, Christoph Sarrazin

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Article numbere110857
JournalPLoS One
Volume9
Issue number11
DOIs
Publication statusPublished - Nov 12 2014

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liver cirrhosis
proteinase inhibitors
Protease Inhibitors
Liver Cirrhosis
Liver
Assays
RNA
therapeutics
assays
Therapeutics
Medical Futility
liver diseases
Liver Diseases
testing
sampling
prediction

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Performance of two HCV RNA assays during protease inhibitor-based triple therapy in patients with advanced liver fibrosis and cirrhosis. / Maasoumy, Benjamin; Hunyady, B.; Calvaruso, Vincenza; Makara, Mihály; Vermehren, Johannes; Haragh, Attila; Susser, Simone; Bremer, Birgit; Cloherty, Gavin; Manns, Michael P.; Craxì, Antonio; Wedemeyer, Heiner; Sarrazin, Christoph.

In: PLoS One, Vol. 9, No. 11, e110857, 12.11.2014.

Research output: Contribution to journalArticle

Maasoumy, B, Hunyady, B, Calvaruso, V, Makara, M, Vermehren, J, Haragh, A, Susser, S, Bremer, B, Cloherty, G, Manns, MP, Craxì, A, Wedemeyer, H & Sarrazin, C 2014, 'Performance of two HCV RNA assays during protease inhibitor-based triple therapy in patients with advanced liver fibrosis and cirrhosis', PLoS One, vol. 9, no. 11, e110857. https://doi.org/10.1371/journal.pone.0110857
Maasoumy, Benjamin ; Hunyady, B. ; Calvaruso, Vincenza ; Makara, Mihály ; Vermehren, Johannes ; Haragh, Attila ; Susser, Simone ; Bremer, Birgit ; Cloherty, Gavin ; Manns, Michael P. ; Craxì, Antonio ; Wedemeyer, Heiner ; Sarrazin, Christoph. / Performance of two HCV RNA assays during protease inhibitor-based triple therapy in patients with advanced liver fibrosis and cirrhosis. In: PLoS One. 2014 ; Vol. 9, No. 11.
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AU - Vermehren, Johannes

AU - Haragh, Attila

AU - Susser, Simone

AU - Bremer, Birgit

AU - Cloherty, Gavin

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