Hepatitis B Core-Related Antigen to Indicate High Viral Load: Systematic Review and Meta-Analysis of 10,397 Individual Participants.


Journal

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
ISSN: 1542-7714
Titre abrégé: Clin Gastroenterol Hepatol
Pays: United States
ID NLM: 101160775

Informations de publication

Date de publication:
01 2021
Historique:
received: 26 03 2020
accepted: 10 04 2020
pubmed: 4 5 2020
medline: 19 8 2021
entrez: 4 5 2020
Statut: ppublish

Résumé

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. 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. 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. HBcrAg might be a useful serologic marker to indicate clinically important high viremia in treatment-naïve, HBV-infected patients.

Sections du résumé

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.

Identifiants

pubmed: 32360825
pii: S1542-3565(20)30590-5
doi: 10.1016/j.cgh.2020.04.045
pii:
doi:

Substances chimiques

DNA, Viral 0
Hepatitis B Core Antigens 0
Hepatitis B Surface Antigens 0

Types de publication

Journal Article Meta-Analysis Systematic Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

46-60.e8

Informations de copyright

Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.

Auteurs

Kyoko Yoshida (K)

Department of Surgery and Cancer, Liver Unit, Imperial College London, Paddington, London, United Kingdom.

Alice Desbiolles (A)

Unité d'Épidémiologie des Maladies Émergentes, Institut Pasteur, Paris, France.

Sarah F Feldman (SF)

Unité d'Épidémiologie des Maladies Émergentes, Institut Pasteur, Paris, France.

Sang Hoon Ahn (SH)

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Enagnon K Alidjinou (EK)

Laboratoire de Virologie, Centre de Biologie Pathologie, Centre Hospitalier Universitaire de Lille, Lille, France.

Masanori Atsukawa (M)

Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan.

Laurence Bocket (L)

Laboratoire de Virologie, Centre de Biologie Pathologie, Centre Hospitalier Universitaire de Lille, Lille, France.

Maurizia R Brunetto (MR)

Hepatology Unit, Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, University Hospital of Pisa, Pisa PI, Italy.

Maria Buti (M)

Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

Ivana Carey (I)

Institute of Liver Studies, King's College Hospital, London, United Kingdom.

Gian Paolo Caviglia (GP)

Department of Medical Sciences, University of Turin, Turin, Italy.

En-Qiang Chen (EQ)

Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.

Markus Cornberg (M)

Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.

Masaru Enomoto (M)

Department of Hepatology, Graduate School of Medicine, Osaka City University Medical School, Osaka, Japan.

Masao Honda (M)

Department of Gastroenterology, Department of Advanced Medical Technology, Kanazawa University Graduate School of Health Medicine, Ishikawa, Japan.

Christoph Höner Zu Siederdissen (CH)

Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.

Masatoshi Ishigami (M)

Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Harry L A Janssen (HLA)

Toronto Centre for Liver Disease, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.

Benjamin Maasoumy (B)

Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.

Takeshi Matsui (T)

Center for Gastroenterology, Teine-Keijinkai Hospital, Hokkaido, Japan.

Akihiro Matsumoto (A)

Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.

Shuhei Nishiguchi (S)

Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.

Mar Riveiro-Barciela (M)

Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

Akinobu Takaki (A)

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Pisit Tangkijvanich (P)

Center of Excellence in Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Hidenori Toyoda (H)

Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan.

Margo J H van Campenhout (MJH)

Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, GD Rotterdam, The Netherlands.

Bo Wang (B)

Institute of Liver Studies, King's College Hospital, London, United Kingdom.

Lai Wei (L)

Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University People's Hospital, Beijing, China.

Hwai-I Yang (HI)

Genomics Research Center, Academia Sinica, Taipei, Taiwan.

Yoshihiko Yano (Y)

Center for Infectious Diseases, Department of Gastroenterology, Kobe University Graduate School of Medicine, Kobe, Japan.

Hiroshi Yatsuhashi (H)

Clinical Research Center, National Hospital Organization, Nagasaki Medical Center, Nagasaki, Japan.

Man-Fung Yuen (MF)

Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.

Eiji Tanaka (E)

Department for the Promotion of Regional Medicine, Shinshu University School of Medicine, Matsumoto, Japan.

Maud Lemoine (M)

Department of Surgery and Cancer, Liver Unit, Imperial College London, Paddington, London, United Kingdom.

Yasuhito Tanaka (Y)

Department of Virology and Liver Unit, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Yusuke Shimakawa (Y)

Unité d'Épidémiologie des Maladies Émergentes, Institut Pasteur, Paris, France. Electronic address: yusuke.shimakawa@gmail.com.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH