Kyoko Yoshida1, Alice Desbiolles2, Sarah F Feldman2, Sang Hoon Ahn3, Enagnon K Alidjinou4, Masanori Atsukawa5, Laurence Bocket4, Maurizia R Brunetto6, Maria Buti7, Ivana Carey8, Gian Paolo Caviglia9, En-Qiang Chen10, Markus Cornberg11, Masaru Enomoto12, Masao Honda13, Christoph Höner Zu Siederdissen11, Masatoshi Ishigami14, Harry L A Janssen15, Benjamin Maasoumy11, Takeshi Matsui16, Akihiro Matsumoto17, Shuhei Nishiguchi18, Mar Riveiro-Barciela7, Akinobu Takaki19, Pisit Tangkijvanich20, Hidenori Toyoda21, Margo J H van Campenhout22, Bo Wang8, Lai Wei23, Hwai-I Yang24, Yoshihiko Yano25, Hiroshi Yatsuhashi26, Man-Fung Yuen27, Eiji Tanaka28, Maud Lemoine1, Yasuhito Tanaka29, Yusuke Shimakawa30. 1. Department of Surgery and Cancer, Liver Unit, Imperial College London, Paddington, London, United Kingdom. 2. Unité d'Épidémiologie des Maladies Émergentes, Institut Pasteur, Paris, France. 3. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. 4. Laboratoire de Virologie, Centre de Biologie Pathologie, Centre Hospitalier Universitaire de Lille, Lille, France. 5. Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan. 6. Hepatology Unit, Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, University Hospital of Pisa, Pisa PI, Italy. 7. Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. 8. Institute of Liver Studies, King's College Hospital, London, United Kingdom. 9. Department of Medical Sciences, University of Turin, Turin, Italy. 10. Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China. 11. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. 12. Department of Hepatology, Graduate School of Medicine, Osaka City University Medical School, Osaka, Japan. 13. Department of Gastroenterology, Department of Advanced Medical Technology, Kanazawa University Graduate School of Health Medicine, Ishikawa, Japan. 14. Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan. 15. Toronto Centre for Liver Disease, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada. 16. Center for Gastroenterology, Teine-Keijinkai Hospital, Hokkaido, Japan. 17. Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan. 18. Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan. 19. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. 20. Center of Excellence in Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 21. Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan. 22. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, GD Rotterdam, The Netherlands. 23. Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University People's Hospital, Beijing, China. 24. Genomics Research Center, Academia Sinica, Taipei, Taiwan. 25. Center for Infectious Diseases, Department of Gastroenterology, Kobe University Graduate School of Medicine, Kobe, Japan. 26. Clinical Research Center, National Hospital Organization, Nagasaki Medical Center, Nagasaki, Japan. 27. Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China. 28. Department for the Promotion of Regional Medicine, Shinshu University School of Medicine, Matsumoto, Japan. 29. Department of Virology and Liver Unit, Nagoya University Graduate School of Medicine, Nagoya, Japan. 30. Unité d'Épidémiologie des Maladies Émergentes, Institut Pasteur, Paris, France. Electronic address: yusuke.shimakawa@gmail.com.
Abstract
BACKGROUND & AIMS: To eliminate hepatitis B virus (HBV) infection, scale-up of testing and treatment in resource-limited countries is crucial. However, access to nucleic acid testing to quantify HBV DNA, an essential test to examine treatment eligibility, remains severely limited. We assessed the performance of a novel immunoassay, HBV core-related antigen (HBcrAg), as a low-cost (less than US $15/assay) alternative to nucleic acid testing to indicate clinically important high viremia in chronic HBV patients infected with different genotypes. METHODS: We searched Medline, Embase, Scopus, and Web of Science databases through June 27, 2018. Three reviewers independently selected studies measuring HBV DNA and HBcrAg in the same blood samples. We contacted authors to provide individual participant data (IPD). We randomly allocated each IPD to a derivation or validation cohort. We applied optimal HBcrAg cut-off values derived from the derivation set to the validation set to estimate sensitivity/specificity. RESULTS: Of 74 eligible studies, IPD were obtained successfully for 60 studies (81%). Meta-analysis included 5591 IPD without antiviral therapy and 4806 treated with antivirals. In untreated patients, the pooled area under the receiver operating characteristic curve and optimal cut-off values were as follows: 0.88 (95% CI, 0.83-0.94) and 3.6 log U/mL to diagnose HBV DNA level of 2000 IU/mL or greater; and 0.96 (95% CI, 0.94-0.98) and 5.3 log U/mL for 200,000 IU/mL or greater, respectively. In the validation set, the sensitivity and specificity were 85.2% and 84.7% to diagnose HBV DNA level of 2000 IU/mL or greater, and 91.8% and 90.5% for 200,000 IU/mL or greater, respectively. The performance did not vary by HBV genotypes. In patients treated with anti-HBV therapy the correlation between HBcrAg and HBV DNA was poor. CONCLUSIONS: HBcrAg might be a useful serologic marker to indicate clinically important high viremia in treatment-naïve, HBV-infected patients.
BACKGROUND & AIMS: To eliminate hepatitis B virus (HBV) infection, scale-up of testing and treatment in resource-limited countries is crucial. However, access to nucleic acid testing to quantify HBV DNA, an essential test to examine treatment eligibility, remains severely limited. We assessed the performance of a novel immunoassay, HBV core-related antigen (HBcrAg), as a low-cost (less than US $15/assay) alternative to nucleic acid testing to indicate clinically important high viremia in chronic HBVpatientsinfected with different genotypes. METHODS: We searched Medline, Embase, Scopus, and Web of Science databases through June 27, 2018. Three reviewers independently selected studies measuring HBV DNA and HBcrAg in the same blood samples. We contacted authors to provide individual participant data (IPD). We randomly allocated each IPD to a derivation or validation cohort. We applied optimal HBcrAg cut-off values derived from the derivation set to the validation set to estimate sensitivity/specificity. RESULTS: Of 74 eligible studies, IPD were obtained successfully for 60 studies (81%). Meta-analysis included 5591 IPD without antiviral therapy and 4806 treated with antivirals. In untreated patients, the pooled area under the receiver operating characteristic curve and optimal cut-off values were as follows: 0.88 (95% CI, 0.83-0.94) and 3.6 log U/mL to diagnose HBV DNA level of 2000 IU/mL or greater; and 0.96 (95% CI, 0.94-0.98) and 5.3 log U/mL for 200,000 IU/mL or greater, respectively. In the validation set, the sensitivity and specificity were 85.2% and 84.7% to diagnose HBV DNA level of 2000 IU/mL or greater, and 91.8% and 90.5% for 200,000 IU/mL or greater, respectively. The performance did not vary by HBV genotypes. In patients treated with anti-HBV therapy the correlation between HBcrAg and HBV DNA was poor. CONCLUSIONS: HBcrAg might be a useful serologic marker to indicate clinically important high viremia in treatment-naïve, HBV-infectedpatients.
Authors: Gian Paolo Caviglia; Antonella Zorzi; Mario Rizzetto; Massimo Mirandola; Antonella Olivero; Giada Carolo Journal: Diagnostics (Basel) Date: 2021-11-24