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Meta-Analysis
. 2025 Jun 30;17(7):929.
doi: 10.3390/v17070929.

Predictive Value of Hepatitis B Core-Related Antigen for Multiple Recurrence Outcomes After Treatment Cessation in Chronic Hepatitis B: A Meta-Analysis Study

Guoyang Yu  1 , Meiqi Cheng  1 , Yuxin Duan  1 , Minrong Kang  1 , Ning Jiang  1 , Wei Yan  1 , Jianhua Yin  2
Affiliations
Meta-Analysis

Predictive Value of Hepatitis B Core-Related Antigen for Multiple Recurrence Outcomes After Treatment Cessation in Chronic Hepatitis B: A Meta-Analysis Study

Guoyang Yu et al. Viruses. .

Abstract

Background: Hepatitis B core-related antigen (HBcrAg), a novel serum biomarker reflecting the activity of intrahepatic covalently closed circular DNA (cccDNA), has generated conflicting evidence regarding its clinical utility for predicting post-antiviral therapy relapse in chronic hepatitis B (CHB) patients.

Methods: We systematically analyzed 13 studies (15 cohorts, n = 1529 patients) from PubMed, Web of Science, Wanfang, and CNKI (through April 2025). A bivariate model evaluated HBcrAg's predictive performance for relapse outcomes, including virological relapse, clinical relapse, and hepatitis flares.

Results: HBcrAg demonstrated a pooled sensitivity of 0.81 (95% CI: 0.75-0.86) and specificity of 0.72 (95% CI: 0.67-0.76) for relapse prediction, with a diagnostic odds ratio of 10.66 (95% CI: 7.36-15.42) and summary AUC of 0.83 (95% CI: 0.80-0.86). Subgroup analysis identified threshold effects as the primary source of heterogeneity, which resolved (I2 < 13%) after excluding studies with outlier cutoff values. Meta-regression established that HBcrAg's predictive value was unaffected by age, sex, hepatitis B e antigen status, or detection methods (p > 0.05).

Conclusions: HBcrAg is validated as a robust non-invasive biomarker to optimize treatment cessation strategies, with high sensitivity providing strong negative predictive value in CHB populations. Future research should prioritize multi-marker models to enhance prediction accuracy.

Keywords: CHB patients; HBcrAg; meta-analysis; treatment cessation strategy; viral relapse prediction.

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Conflict of interest statement

The authors have declared that they have no conflicts of interest.

Figures

Figure 1
Figure 1
PRISMA flowchart of the study selection process.
Figure 2
Figure 2
Deeks’ funnel plot asymmetry test.
Figure 3
Figure 3
Subgroup analysis based on different cutoff value levels. (a) Subgroup analysis based on different cutoff value levels before exclusion. (b) Subgroup analysis after exclusion of outlier studies [16,17,18,19,20,21,22,23,24,25,26,27,28].
Figure 4
Figure 4
Integrated sensitivity, specificity, PLR, NLR, and DOR after exclusion. (a) Forest plot depicting the pooled sensitivity estimate and individual study contributions. (b) Forest plot depicting the pooled specificity estimate and individual study contributions. (c) Forest plot depicting the pooled PLR estimate and individual study contributions. (d) Forest plot depicting the pooled NLR estimate and individual study contributions [17,18,19,20,21,22,25,26,27,28].
Figure 5
Figure 5
DOR and SROC after exclusion of studies. (a) Forest plot depicting the pooled DOR estimate and individual study contributions after exclusion. (b) SROC curve post-exclusion with fitted curve, summary operating point (red lozenge), and 95% confidence region (ellipsoid shading) [17,18,19,20,21,22,25,26,27,28].
Figure 6
Figure 6
Sensitivity analysis with effect size measured by DOR [17,18,19,20,21,22,25,26,27,28].
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