Analytical validation of hepatitis B core‐related antigen (HBcrAg) using dried blood spots (DBS)

Limited access to nucleic acid testing (NAT) to quantify HBV DNA levels, an essential tool to determine anti‐HBV treatment eligibility, represents a significant barrier to scale up HBV diagnostic services in resource‐limited countries. Hepatitis B core‐related antigen (HBcrAg) has the potential to b...

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Veröffentlicht in:Journal of viral hepatitis 2021-05, Vol.28 (5), p.837-843
Hauptverfasser: Shimakawa, Yusuke, Vernoux, Laura, Gabassi, Audrey, Mercier‐Delarue, Séverine, Vincent, Jeanne Perpétue, Simon, François, Maylin, Sarah
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container_issue 5
container_start_page 837
container_title Journal of viral hepatitis
container_volume 28
creator Shimakawa, Yusuke
Vernoux, Laura
Gabassi, Audrey
Mercier‐Delarue, Séverine
Vincent, Jeanne Perpétue
Simon, François
Maylin, Sarah
description Limited access to nucleic acid testing (NAT) to quantify HBV DNA levels, an essential tool to determine anti‐HBV treatment eligibility, represents a significant barrier to scale up HBV diagnostic services in resource‐limited countries. Hepatitis B core‐related antigen (HBcrAg) has the potential to become an affordable alternative because of its low cost (US$
doi_str_mv 10.1111/jvh.13489
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Hepatitis B core‐related antigen (HBcrAg) has the potential to become an affordable alternative because of its low cost (US$ &lt;15/assay) and strong correlation with HBV DNA levels in treatment‐naïve patients. However, the current assay requires plasma or serum. To further facilitate its application to decentralized settings, we developed and evaluated a standardized procedure to quantify HBcrAg using dried blood spots as a tool to diagnose HBV‐infected people with high viraemia. We evaluated the following elution method optimized to quantify HBcrAg: suspension of a punched blood‐soaked disc (11 mm) of Whatman 903 Protein Saver Card in 450 µL of PBS 0.05% Tween 20, followed by an incubation for 4 h at room temperature and a centrifugation at 10,000 g for 10 minutes. 150 µL of DBS eluate was used to quantify HBcrAg using chemiluminescent enzyme immunoassay (LUMIPULSE® G600II, Fujirebio). The limit of detection of dried blood spot HBcrAg in relation with HBV DNA levels was 19,115 IU/mL across the five major HBV genotypes (A/B/C/D/E). A strong linear correlation was confirmed between dried blood spot HBcrAg and HBV DNA levels (r = 0.94, p &lt; 0.0001) in samples with high viral loads (range: 3.7–7.0 log IU/mL). The coefficient of variation ranged between 4.0–11.2% for repeatability and 3.9–12.2% for reproducibility. Analytical specificity was 100% (95% CI: 83.9–100%) in HBV‐negative samples. Using our elution method, it may be possible to identify HBV‐infected patients with high viraemia who need antiviral therapy using dried blood spot and HBcrAg. A large‐scale clinical validation is warranted in resource‐limited countries.</description><identifier>ISSN: 1352-0504</identifier><identifier>EISSN: 1365-2893</identifier><identifier>DOI: 10.1111/jvh.13489</identifier><identifier>PMID: 33599049</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>analytical validation ; Antigens ; Antiviral agents ; Blood ; Centrifugation ; Deoxyribonucleic acid ; diagnostic test ; DNA ; dried blood spot ; Elution ; Enzyme immunoassay ; Genotypes ; Hepatitis ; Hepatitis B ; hepatitis B core‐related antigen ; Life Sciences ; Original ; Patients ; resource‐limited country ; Santé publique et épidémiologie ; Viremia</subject><ispartof>Journal of viral hepatitis, 2021-05, Vol.28 (5), p.837-843</ispartof><rights>2021 The Authors. published by John Wiley &amp; Sons Ltd.</rights><rights>2021 The Authors. Journal of Viral Hepatitis published by John Wiley &amp; Sons Ltd.</rights><rights>2021. 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The limit of detection of dried blood spot HBcrAg in relation with HBV DNA levels was 19,115 IU/mL across the five major HBV genotypes (A/B/C/D/E). A strong linear correlation was confirmed between dried blood spot HBcrAg and HBV DNA levels (r = 0.94, p &lt; 0.0001) in samples with high viral loads (range: 3.7–7.0 log IU/mL). The coefficient of variation ranged between 4.0–11.2% for repeatability and 3.9–12.2% for reproducibility. Analytical specificity was 100% (95% CI: 83.9–100%) in HBV‐negative samples. Using our elution method, it may be possible to identify HBV‐infected patients with high viraemia who need antiviral therapy using dried blood spot and HBcrAg. A large‐scale clinical validation is warranted in resource‐limited countries.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33599049</pmid><doi>10.1111/jvh.13489</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-4198-4785</orcidid><oa>free_for_read</oa></addata></record>
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subjects analytical validation
Antigens
Antiviral agents
Blood
Centrifugation
Deoxyribonucleic acid
diagnostic test
DNA
dried blood spot
Elution
Enzyme immunoassay
Genotypes
Hepatitis
Hepatitis B
hepatitis B core‐related antigen
Life Sciences
Original
Patients
resource‐limited country
Santé publique et épidémiologie
Viremia
title Analytical validation of hepatitis B core‐related antigen (HBcrAg) using dried blood spots (DBS)
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