Diagnosis and monitoring of HCV infection using the cobas® HCV test for use on the cobas® 6800/8800 systems

Joseph D. Yao, Stephen Young, Gabrielle M. Heilek, Enrique Marino, Ellen E. Paxinos, Ed G. Marins, Alexandra Valsamakis

Research output: Contribution to journalArticle

Abstract

Background and objectives: Accurate, sensitive, and specific tests for detection and monitoring of hepatitis C virus (HCV) RNA concentrations are essential for diagnosis and management of HCV infections. We evaluated the next-generation reverse-transcription real-time PCR test, cobas® HCV test for use with the cobas® 6800/8800 systems (“cobas HCV”) by determining its analytical performance characteristics and clinical utility for the diagnosis and therapeutic monitoring of chronic HCV infections. Methods: The limit of detection (LOD), linearity, precision, specificity, matrix equivalence of plasma and serum, and quantitative agreement with the COBAS® AmpliPrep/COBAS® TaqMan® HCV Test version 2.0 (“CAP/CTM HCV v2”) were evaluated. Clinical utility for the diagnosis of chronic HCV infection was demonstrated by testing plasma from HCV seropositive individuals and comparing results to a nucleic acid amplification test (NAAT) approved for use in the diagnosis of chronic hepatitis C. Clinical specificity was investigated by testing plasma from HCV antibody negative subjects with non-HCV related liver diseases. Utility for monitoring treatment response was defined by testing plasma collected during treatment of HCV genotypes (GT) 1, 2, and 3 and determining positive predictive value (PPV), negative predictive value (NPV) and the odds ratio (OR) for predicting cure (sustained virologic response 12 weeks after treatment cessation, “SVR12”). Results: The cobas HCV test demonstrated an LOD of at least 15 IU/mL and measurable range from 15 to at least 1.0E + 08 IU/mL (1.2–8.0 log10 IU/mL) for GT 1–6, with high accuracy (≤0.16 log10 difference) and precision (standard deviation 0.04–0.14 log10) throughout the linear range. Paired plasma and serum samples showed highly correlated performance (R2 = 0.97). Quantification was 100% specific for HCV in analytical studies. Correlation with CAP/CTM HCV v2 was high in patient samples (mean titer difference: 0.05 log10 with a 95% CI: 0.03–0.06 log10). For the diagnosis of chronic HCV, positive and negative percent agreement between cobas HCV and the comparator NAAT were 98.8–100% on the cobas 6800 and 8800 systems. Clinical specificity of cobas HCV using samples from HCV antibody negative subjects with non-HCV related liver diseases was 99.6% and 100% on cobas 6800 and 8800 systems. In therapeutic monitoring and SVR12 prediction during experimental treatment for chronic HCV GT 1 infections, undetectable HCV RNA by cobas HCV at different on-treatment weeks had a PPV 76.8%–79.4%, NPV 29.9%–100%, and OR 1.64–47.52. During therapy of HCV GT 2 and GT 3, treatment week 4 and 12 results were: PPV, 84.7% and 75.3%; NPV, 47.8% and 50.0%; OR, 5.09 and 3.05. Conclusions: The cobas HCV test is highly sensitive, specific, and accurate HCV RNA test for GT 1–6. It demonstrates excellent correlation with the FDA-approved CAP/CTM HCV v2 test. It is useful clinically for detection of active HCV infection in individuals that have had a positive anti-HCV antibody test result and in monitoring treatment response.

Original languageEnglish (US)
Pages (from-to)63-69
Number of pages7
JournalJournal of Clinical Virology
Volume102
DOIs
StatePublished - May 1 2018

Fingerprint

Virus Diseases
Hepacivirus
Chronic Hepatitis C
Genotype
Hepatitis C Antibodies
Nucleic Acid Amplification Techniques
Therapeutics
Odds Ratio
RNA
Limit of Detection
Liver Diseases
Viruses

Keywords

  • Chronic hepatitis C
  • cobas 6800/8800
  • cobas HCV test
  • HCV RNA quantification
  • Hepatitis C virus

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Yao, J. D., Young, S., Heilek, G. M., Marino, E., Paxinos, E. E., Marins, E. G., & Valsamakis, A. (2018). Diagnosis and monitoring of HCV infection using the cobas® HCV test for use on the cobas® 6800/8800 systems. Journal of Clinical Virology, 102, 63-69. https://doi.org/10.1016/j.jcv.2018.02.017

Diagnosis and monitoring of HCV infection using the cobas® HCV test for use on the cobas® 6800/8800 systems. / Yao, Joseph D.; Young, Stephen; Heilek, Gabrielle M.; Marino, Enrique; Paxinos, Ellen E.; Marins, Ed G.; Valsamakis, Alexandra.

In: Journal of Clinical Virology, Vol. 102, 01.05.2018, p. 63-69.

Research output: Contribution to journalArticle

Yao, Joseph D. ; Young, Stephen ; Heilek, Gabrielle M. ; Marino, Enrique ; Paxinos, Ellen E. ; Marins, Ed G. ; Valsamakis, Alexandra. / Diagnosis and monitoring of HCV infection using the cobas® HCV test for use on the cobas® 6800/8800 systems. In: Journal of Clinical Virology. 2018 ; Vol. 102. pp. 63-69.
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T1 - Diagnosis and monitoring of HCV infection using the cobas® HCV test for use on the cobas® 6800/8800 systems

AU - Yao, Joseph D.

AU - Young, Stephen

AU - Heilek, Gabrielle M.

AU - Marino, Enrique

AU - Paxinos, Ellen E.

AU - Marins, Ed G.

AU - Valsamakis, Alexandra

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Background and objectives: Accurate, sensitive, and specific tests for detection and monitoring of hepatitis C virus (HCV) RNA concentrations are essential for diagnosis and management of HCV infections. We evaluated the next-generation reverse-transcription real-time PCR test, cobas® HCV test for use with the cobas® 6800/8800 systems (“cobas HCV”) by determining its analytical performance characteristics and clinical utility for the diagnosis and therapeutic monitoring of chronic HCV infections. Methods: The limit of detection (LOD), linearity, precision, specificity, matrix equivalence of plasma and serum, and quantitative agreement with the COBAS® AmpliPrep/COBAS® TaqMan® HCV Test version 2.0 (“CAP/CTM HCV v2”) were evaluated. Clinical utility for the diagnosis of chronic HCV infection was demonstrated by testing plasma from HCV seropositive individuals and comparing results to a nucleic acid amplification test (NAAT) approved for use in the diagnosis of chronic hepatitis C. Clinical specificity was investigated by testing plasma from HCV antibody negative subjects with non-HCV related liver diseases. Utility for monitoring treatment response was defined by testing plasma collected during treatment of HCV genotypes (GT) 1, 2, and 3 and determining positive predictive value (PPV), negative predictive value (NPV) and the odds ratio (OR) for predicting cure (sustained virologic response 12 weeks after treatment cessation, “SVR12”). Results: The cobas HCV test demonstrated an LOD of at least 15 IU/mL and measurable range from 15 to at least 1.0E + 08 IU/mL (1.2–8.0 log10 IU/mL) for GT 1–6, with high accuracy (≤0.16 log10 difference) and precision (standard deviation 0.04–0.14 log10) throughout the linear range. Paired plasma and serum samples showed highly correlated performance (R2 = 0.97). Quantification was 100% specific for HCV in analytical studies. Correlation with CAP/CTM HCV v2 was high in patient samples (mean titer difference: 0.05 log10 with a 95% CI: 0.03–0.06 log10). For the diagnosis of chronic HCV, positive and negative percent agreement between cobas HCV and the comparator NAAT were 98.8–100% on the cobas 6800 and 8800 systems. Clinical specificity of cobas HCV using samples from HCV antibody negative subjects with non-HCV related liver diseases was 99.6% and 100% on cobas 6800 and 8800 systems. In therapeutic monitoring and SVR12 prediction during experimental treatment for chronic HCV GT 1 infections, undetectable HCV RNA by cobas HCV at different on-treatment weeks had a PPV 76.8%–79.4%, NPV 29.9%–100%, and OR 1.64–47.52. During therapy of HCV GT 2 and GT 3, treatment week 4 and 12 results were: PPV, 84.7% and 75.3%; NPV, 47.8% and 50.0%; OR, 5.09 and 3.05. Conclusions: The cobas HCV test is highly sensitive, specific, and accurate HCV RNA test for GT 1–6. It demonstrates excellent correlation with the FDA-approved CAP/CTM HCV v2 test. It is useful clinically for detection of active HCV infection in individuals that have had a positive anti-HCV antibody test result and in monitoring treatment response.

AB - Background and objectives: Accurate, sensitive, and specific tests for detection and monitoring of hepatitis C virus (HCV) RNA concentrations are essential for diagnosis and management of HCV infections. We evaluated the next-generation reverse-transcription real-time PCR test, cobas® HCV test for use with the cobas® 6800/8800 systems (“cobas HCV”) by determining its analytical performance characteristics and clinical utility for the diagnosis and therapeutic monitoring of chronic HCV infections. Methods: The limit of detection (LOD), linearity, precision, specificity, matrix equivalence of plasma and serum, and quantitative agreement with the COBAS® AmpliPrep/COBAS® TaqMan® HCV Test version 2.0 (“CAP/CTM HCV v2”) were evaluated. Clinical utility for the diagnosis of chronic HCV infection was demonstrated by testing plasma from HCV seropositive individuals and comparing results to a nucleic acid amplification test (NAAT) approved for use in the diagnosis of chronic hepatitis C. Clinical specificity was investigated by testing plasma from HCV antibody negative subjects with non-HCV related liver diseases. Utility for monitoring treatment response was defined by testing plasma collected during treatment of HCV genotypes (GT) 1, 2, and 3 and determining positive predictive value (PPV), negative predictive value (NPV) and the odds ratio (OR) for predicting cure (sustained virologic response 12 weeks after treatment cessation, “SVR12”). Results: The cobas HCV test demonstrated an LOD of at least 15 IU/mL and measurable range from 15 to at least 1.0E + 08 IU/mL (1.2–8.0 log10 IU/mL) for GT 1–6, with high accuracy (≤0.16 log10 difference) and precision (standard deviation 0.04–0.14 log10) throughout the linear range. Paired plasma and serum samples showed highly correlated performance (R2 = 0.97). Quantification was 100% specific for HCV in analytical studies. Correlation with CAP/CTM HCV v2 was high in patient samples (mean titer difference: 0.05 log10 with a 95% CI: 0.03–0.06 log10). For the diagnosis of chronic HCV, positive and negative percent agreement between cobas HCV and the comparator NAAT were 98.8–100% on the cobas 6800 and 8800 systems. Clinical specificity of cobas HCV using samples from HCV antibody negative subjects with non-HCV related liver diseases was 99.6% and 100% on cobas 6800 and 8800 systems. In therapeutic monitoring and SVR12 prediction during experimental treatment for chronic HCV GT 1 infections, undetectable HCV RNA by cobas HCV at different on-treatment weeks had a PPV 76.8%–79.4%, NPV 29.9%–100%, and OR 1.64–47.52. During therapy of HCV GT 2 and GT 3, treatment week 4 and 12 results were: PPV, 84.7% and 75.3%; NPV, 47.8% and 50.0%; OR, 5.09 and 3.05. Conclusions: The cobas HCV test is highly sensitive, specific, and accurate HCV RNA test for GT 1–6. It demonstrates excellent correlation with the FDA-approved CAP/CTM HCV v2 test. It is useful clinically for detection of active HCV infection in individuals that have had a positive anti-HCV antibody test result and in monitoring treatment response.

KW - Chronic hepatitis C

KW - cobas 6800/8800

KW - cobas HCV test

KW - HCV RNA quantification

KW - Hepatitis C virus

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