G Model
ARTICLE IN PRESS
JCV 3037 1–4
Journal of Clinical Virology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Journal of Clinical Virology journal homepage: www.elsevier.com/locate/jcv
Short Communication
1
Clinical utility of hepatitis C virus core antigen quantification in patients with chronic hepatitis C
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3
4 5 6 7
Q1
Stéphane Chevaliez a,b,∗ , Alexandre Soulier a,b , Lila Poiteau a,b , Magali Bouvier-Alias a,b , Jean-Michel Pawlotsky a,b a b
National Reference Center for Viral Hepatitis B, C and Delta, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France INSERM U955, Créteil, France
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a r t i c l e
i n f o
a b s t r a c t
10 11 12 13 14
Article history: Received 28 March 2014 Received in revised form 21 May 2014 Accepted 26 May 2014
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Keywords: Hepatitis C HCV core antigen HCV RNA
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1. Background
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22 23 24 25 26 27 28 29 30 31 32 33
Background: Hepatitis C virus (HCV) core antigen has been proposed as a surrogate marker of HCV replication. HCV core antigen detection and quantification can thus theoretically be used instead of nucleic acid testing (NAT) to diagnose infection and manage antiviral therapy, with several advantages compared to HCV RNA assays. HCV core antigen can now be easily detected and quantified by means of a chemiluminescent microparticle immunoassay on the Abbott Architect device. Objective: The aim of the present study was to evaluate the clinical performance of the Architect HCV Ag assay for the detection and quantification of HCV core antigen in patients with chronic HCV genotype 1–6 infections. Results: The Architect HCV Ag assay had a specificity of 100% (95%CI: 97.8–100%). HCV core antigen levels were not influenced by the HCV genotype. The lower limit of detection of 3 fmol/L corresponded to approximately 1000 IU/mL of HCV RNA, regardless of the real-time PCR assay used. HCV core antigen and HCV RNA levels correlated for HCV genotype 1–4 (r = 0.89 and r = 0.88 for the m2000 and the CAP/CTM v2.0 assay, respectively). Conclusions: The Architect HCV Ag assay is highly specific and easy to perform. It represents a valuable screening, diagnostic and monitoring tool, especially in the era of new all-oral, interferon-free antiviral strategies that do not require high analytical sensitivity. © 2014 Published by Elsevier B.V.
Chronic hepatitis C virus (HCV) infection is estimated to affect 130–170 million individuals worldwide [1,2]. Chronic hepatitis C is a progressive liver disease leading to cirrhosis and hepatocellular carcinoma in a substantial proportion of patients. Nucleic acid testing (NAT) is mandatory for the diagnosis of ongoing infection and the management of chronic hepatitis C therapy. Assays based on real-time polymerase chain reaction (PCR) are now recommended for HCV RNA detection and quantification by International Clinical Practice Guidelines and widely used in clinical virology laboratories [3–5]. However, these assays are expensive, automated platforms and experienced personnel must be available and the time required for generating the results is long. In the context
∗ Corresponding author at: Department of Virology, Hôpital Henri Mondor, 51 avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France. Tel.: +33 1 4981 2828; fax: +33 1 4981 2839. E-mail address: [email protected] (S. Chevaliez).
of the arrival of a number of new highly active anti-HCV therapies, access to care may be limited by the lack of accessibility to NAT testing, in particular, but not only, in resource-constrained areas. HCV core antigen detection and quantification represents an alternative to NAT testing. Indeed, HCV core antigen has been shown to be a surrogate of HCV replication. HCV core antigen levels correlate with HCV RNA levels in various populations, including HCV-monoinfected, HBV- or HIV-coinfected, hemodialysis patients and patients after liver and kidney transplantation [6–9]. HCV core antigen detection and quantification can now be performed within less than 60 min on the Architect device, by means of a fully automated chemiluminescent microparticle immunoassay (CMIA), the Architect HCV Ag assay (Abbott Diagnostics, Chicago, IL). Importantly, HCV core antigen testing is less expensive than NAT testing. A potential disadvantage, however, is the lower analytical sensitivity of HCV core antigen quantification compared to real-time PCR assays. The Abbott Architect HCV Ag assay is European Conformity (CE)-marked, but has not been approved by the FDA and is available for “Research use only” in the US.
http://dx.doi.org/10.1016/j.jcv.2014.05.014 1386-6532/© 2014 Published by Elsevier B.V.
Please cite this article in press as: Chevaliez S, et al. Clinical utility of hepatitis C virus core antigen quantification in patients with chronic hepatitis C. J Clin Virol (2014), http://dx.doi.org/10.1016/j.jcv.2014.05.014
34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53
G Model JCV 3037 1–4
ARTICLE IN PRESS
2
S. Chevaliez et al. / Journal of Clinical Virology xxx (2014) xxx–xxx
relationship between quantitative variables was studied by means of regression analysis. Comparisons between groups were made using the Kruskal–Wallis test or Mann–Whitney test. p values 800,000 IU/mL) was found in 50.5% and 64.7% of them with the two real-time PCR assays, respectively. Based on sequencing of a portion of the nonstructural 5B gene of HCV followed by phylogenetic analysis, 59.3% of patients from group C were infected with HCV genotype 1, 19.2% with genotype 4, 12.3% with genotype 3, 5.0% with genotype 2, 1.3% with genotype 6 and 1.0% with genotype 5. The HCV genotype was not determined in 6 (1.9%) patients due to low-level HCV RNA (≤2.70 Log IU/mL). The
HCV RNA level (Log IU/mL), mean ± SD HCV RNA >800,000 IU/mL, n (%) HCV RNA undetectable, n (%) HCV genotype, n (%) 1 2 3a 4 5a 6 Not determined HCV core antigen level (Log fmol/L), mean ± SD
78 79 80
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None of the HCV-seronegative individuals from group A had detectable HCV core antigen. Specificity was thus 100% [95%confidence interval (CI): 97.8–100%]. HCV RNA and HCV core antigen were both undetectable in patients from group B. Both markers were detectable in all patients with chronic hepatitis C from group C but six, who had an HCV RNA level
ARTICLE IN PRESS
JCV 3037 1–4
Journal of Clinical Virology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Journal of Clinical Virology journal homepage: www.elsevier.com/locate/jcv
Short Communication
1
Clinical utility of hepatitis C virus core antigen quantification in patients with chronic hepatitis C
2
3
4 5 6 7
Q1
Stéphane Chevaliez a,b,∗ , Alexandre Soulier a,b , Lila Poiteau a,b , Magali Bouvier-Alias a,b , Jean-Michel Pawlotsky a,b a b
National Reference Center for Viral Hepatitis B, C and Delta, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France INSERM U955, Créteil, France
8
9 20
a r t i c l e
i n f o
a b s t r a c t
10 11 12 13 14
Article history: Received 28 March 2014 Received in revised form 21 May 2014 Accepted 26 May 2014
15
19
Keywords: Hepatitis C HCV core antigen HCV RNA
21
1. Background
16 17 18
22 23 24 25 26 27 28 29 30 31 32 33
Background: Hepatitis C virus (HCV) core antigen has been proposed as a surrogate marker of HCV replication. HCV core antigen detection and quantification can thus theoretically be used instead of nucleic acid testing (NAT) to diagnose infection and manage antiviral therapy, with several advantages compared to HCV RNA assays. HCV core antigen can now be easily detected and quantified by means of a chemiluminescent microparticle immunoassay on the Abbott Architect device. Objective: The aim of the present study was to evaluate the clinical performance of the Architect HCV Ag assay for the detection and quantification of HCV core antigen in patients with chronic HCV genotype 1–6 infections. Results: The Architect HCV Ag assay had a specificity of 100% (95%CI: 97.8–100%). HCV core antigen levels were not influenced by the HCV genotype. The lower limit of detection of 3 fmol/L corresponded to approximately 1000 IU/mL of HCV RNA, regardless of the real-time PCR assay used. HCV core antigen and HCV RNA levels correlated for HCV genotype 1–4 (r = 0.89 and r = 0.88 for the m2000 and the CAP/CTM v2.0 assay, respectively). Conclusions: The Architect HCV Ag assay is highly specific and easy to perform. It represents a valuable screening, diagnostic and monitoring tool, especially in the era of new all-oral, interferon-free antiviral strategies that do not require high analytical sensitivity. © 2014 Published by Elsevier B.V.
Chronic hepatitis C virus (HCV) infection is estimated to affect 130–170 million individuals worldwide [1,2]. Chronic hepatitis C is a progressive liver disease leading to cirrhosis and hepatocellular carcinoma in a substantial proportion of patients. Nucleic acid testing (NAT) is mandatory for the diagnosis of ongoing infection and the management of chronic hepatitis C therapy. Assays based on real-time polymerase chain reaction (PCR) are now recommended for HCV RNA detection and quantification by International Clinical Practice Guidelines and widely used in clinical virology laboratories [3–5]. However, these assays are expensive, automated platforms and experienced personnel must be available and the time required for generating the results is long. In the context
∗ Corresponding author at: Department of Virology, Hôpital Henri Mondor, 51 avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France. Tel.: +33 1 4981 2828; fax: +33 1 4981 2839. E-mail address: [email protected] (S. Chevaliez).
of the arrival of a number of new highly active anti-HCV therapies, access to care may be limited by the lack of accessibility to NAT testing, in particular, but not only, in resource-constrained areas. HCV core antigen detection and quantification represents an alternative to NAT testing. Indeed, HCV core antigen has been shown to be a surrogate of HCV replication. HCV core antigen levels correlate with HCV RNA levels in various populations, including HCV-monoinfected, HBV- or HIV-coinfected, hemodialysis patients and patients after liver and kidney transplantation [6–9]. HCV core antigen detection and quantification can now be performed within less than 60 min on the Architect device, by means of a fully automated chemiluminescent microparticle immunoassay (CMIA), the Architect HCV Ag assay (Abbott Diagnostics, Chicago, IL). Importantly, HCV core antigen testing is less expensive than NAT testing. A potential disadvantage, however, is the lower analytical sensitivity of HCV core antigen quantification compared to real-time PCR assays. The Abbott Architect HCV Ag assay is European Conformity (CE)-marked, but has not been approved by the FDA and is available for “Research use only” in the US.
http://dx.doi.org/10.1016/j.jcv.2014.05.014 1386-6532/© 2014 Published by Elsevier B.V.
Please cite this article in press as: Chevaliez S, et al. Clinical utility of hepatitis C virus core antigen quantification in patients with chronic hepatitis C. J Clin Virol (2014), http://dx.doi.org/10.1016/j.jcv.2014.05.014
34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53
G Model JCV 3037 1–4
ARTICLE IN PRESS
2
S. Chevaliez et al. / Journal of Clinical Virology xxx (2014) xxx–xxx
relationship between quantitative variables was studied by means of regression analysis. Comparisons between groups were made using the Kruskal–Wallis test or Mann–Whitney test. p values 800,000 IU/mL) was found in 50.5% and 64.7% of them with the two real-time PCR assays, respectively. Based on sequencing of a portion of the nonstructural 5B gene of HCV followed by phylogenetic analysis, 59.3% of patients from group C were infected with HCV genotype 1, 19.2% with genotype 4, 12.3% with genotype 3, 5.0% with genotype 2, 1.3% with genotype 6 and 1.0% with genotype 5. The HCV genotype was not determined in 6 (1.9%) patients due to low-level HCV RNA (≤2.70 Log IU/mL). The
HCV RNA level (Log IU/mL), mean ± SD HCV RNA >800,000 IU/mL, n (%) HCV RNA undetectable, n (%) HCV genotype, n (%) 1 2 3a 4 5a 6 Not determined HCV core antigen level (Log fmol/L), mean ± SD
78 79 80
81
None of the HCV-seronegative individuals from group A had detectable HCV core antigen. Specificity was thus 100% [95%confidence interval (CI): 97.8–100%]. HCV RNA and HCV core antigen were both undetectable in patients from group B. Both markers were detectable in all patients with chronic hepatitis C from group C but six, who had an HCV RNA level
