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.
|Journal||Clinical Gastroenterology and Hepatology|
|Publication status||Published - 2021 Jan|
Bibliographical noteFunding Information:
Conflicts of interest These authors disclose the following: Maurizia R. Brunetto has received grants and personal fees from AbbVie and Gilead, grants from BMS, and research support from Fujirebio; Maria Buti has received grants and personal fees from Gilead; Gian Paolo Caviglia has received grants from Fujirebio Europe; Markus Cornberg has received personal fees from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen-Cilag, Roche , Merck , MSD, Biogen, Falk Foundation, Boehringer Ingelheim, Siemens, and Spring Bank, and grants from Roche; Christoph Höner Zu Siederdissen has received grants from Novartis Pharma and Gilead Sciences; Harry L. A. Janssen has received grants and personal fees from AbbVie, Bristol Myers Squibb, Gilead Sciences, Janssen, MedImmune, Merck, and Roche, and personal fees from Benitec, Arbutus, and Vir Biotechnology, Inc; Benjamin Maasoumy has received grants from Fujirebio, Roche Diagnostics, Abbott Diagnostics, Fujirebio Europe, and Altona Diagnostics, personal fees from Abbott Diagnostics, Merck/MSD, AbbVie, Falk Foundation, and Astellas, and research support from Merck/MSD, Gilead, and AbbVie; Hidenori Toyoda has received personal fees from AbbVie and MSD; Margo J. H. van Campenhout has received personal fees from Fujirebio Europe; and Yasuhito Tanaka has received grants and personal fees from Fujirebio. The remaining authors disclose no conflicts.
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