Watanabe Takehisa, Inoue Takako, Tanaka Yasuhito
Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
Department of Clinical Laboratory Medicine, Nagoya City University Hospital, Nagoya 467-8602, Japan.
Microorganisms. 2021 Oct 2;9(10):2083. doi: 10.3390/microorganisms9102083.
The hepatitis B core-related antigen (HBcrAg) is an unprecedented novel HBV biomarker that plays an essential role in reflecting covalently closed circular DNA (cccDNA) in chronic hepatitis B (CHB) because its levels correlate with intrahepatic cccDNA and serum HBV DNA. In this review, we describe the clinical application of serum HBcrAg in CHB patients, with a particular focus on new therapies targeting intrahepatic HBV replication. (1) HBcrAg can be detected in clinical cases where serum HBV DNA is undetectable during anti-HBV therapy. (2) A highly sensitive HBcrAg assay (iTACT-HBcrAg) may be useful for monitoring HBV reactivation, as an alternative to HBV DNA. (3) Decreased HBcrAg levels have been significantly associated with promising outcomes in CHB patients, reducing the risk of progression or recurrence of hepatocellular carcinoma. Additionally, we focus on and discuss several drugs in development that target HBV replication, and monitoring HBcrAg may be useful for determining the therapeutic efficacies of such novel drugs. In conclusion, HBcrAg, especially when measured by the recently developed iTACT-HBcrAg assay, may be the most appropriate surrogate marker, over other HBV biomarkers, to predict disease progression and treatment response in CHB patients.
乙肝核心相关抗原（HBcrAg）是一种前所未有的新型乙肝病毒生物标志物，在反映慢性乙型肝炎（CHB）中的共价闭合环状DNA（cccDNA）方面发挥着重要作用，因为其水平与肝内cccDNA和血清乙肝病毒DNA相关。在本综述中，我们描述了血清HBcrAg在CHB患者中的临床应用，特别关注针对肝内乙肝病毒复制的新疗法。（1）在抗乙肝病毒治疗期间血清乙肝病毒DNA检测不到的临床病例中可以检测到HBcrAg。（2）一种高灵敏度的HBcrAg检测方法（iTACT-HBcrAg）可能有助于监测乙肝病毒再激活，可作为乙肝病毒DNA的替代方法。（3）HBcrAg水平降低与CHB患者的良好预后显著相关，降低了肝细胞癌进展或复发的风险。此外，我们关注并讨论了几种正在研发的针对乙肝病毒复制的药物，监测HBcrAg可能有助于确定此类新药的治疗效果。总之，HBcrAg，尤其是通过最近开发的iTACT-HBcrAg检测方法测量时，可能是预测CHB患者疾病进展和治疗反应的最合适替代标志物，优于其他乙肝病毒生物标志物。
