Yu Guoyang, Cheng Meiqi, Duan Yuxin, Kang Minrong, Jiang Ning, Yan Wei, Yin Jianhua
Department of Laboratory Medicine, Naval Medical Centre, Naval Medical University, Shanghai 200052, China.
Department of Epidemiology, Naval Medical University, Shanghai 200433, China.
Viruses. 2025 Jun 30;17(7):929. doi: 10.3390/v17070929.
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.
We systematically analyzed 13 studies (15 cohorts, = 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.
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 (I < 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 ( > 0.05).
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.
乙肝核心相关抗原（HBcrAg）是一种反映肝内共价闭合环状DNA（cccDNA）活性的新型血清生物标志物，但其在预测慢性乙型肝炎（CHB）患者抗病毒治疗后复发的临床应用方面存在相互矛盾的证据。
我们系统分析了来自PubMed、Web of Science、万方和知网（截至2025年4月）的13项研究（15个队列，n = 1529例患者）。采用双变量模型评估HBcrAg对复发结局的预测性能，包括病毒学复发、临床复发和肝炎发作。
HBcrAg对复发预测的合并敏感性为0.81（95%CI：0.75 - 0.86），特异性为0.72（95%CI：0.67 - 0.76），诊断比值比为10.66（95%CI：7.36 - 15.42），汇总AUC为0.83（95%CI：0.80 - 0.86）。亚组分析确定阈值效应是异质性的主要来源，排除具有异常临界值的研究后异质性得到解决（I² < 13%）。Meta回归表明，HBcrAg的预测价值不受年龄、性别、乙肝e抗原状态或检测方法的影响（P > 0.05）。
HBcrAg被验证为一种可靠的非侵入性生物标志物，可优化治疗停药策略，其高敏感性在CHB人群中提供了强大的阴性预测价值。未来的研究应优先考虑多标志物模型以提高预测准确性。
