Department of Clinical Laboratory Medicine, Nagoya City University Hospital, Nagoya 467-8602, Japan.
Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
Genes (Basel). 2019 May 9;10(5):357. doi: 10.3390/genes10050357.
Hepatitis B virus (HBV) cannot be completely eliminated from infected hepatocytes due to the existence of intrahepatic covalently closed circular DNA (cccDNA). Serological biomarkers reflect intrahepatic viral replicative activity as non-invasive alternatives to liver biopsy. Hepatitis B core-related antigen (HBcrAg) is a novel biomarker that has an important role in chronic hepatitis B (CHB), because it correlates with serum HBV DNA and intrahepatic cccDNA. In clinical cases with undetectable serum HBV DNA or loss of HBsAg, HBcrAg still can be detected and the decrease in HBcrAg levels is significantly associated with promising outcomes for CHB patients. HBcrAg can predict spontaneous or treatment-induced hepatitis B envelope antigen (HBeAg) seroconversion, persistent responses before and after cessation of nucleos(t)ide analogues, potential HBV reactivation, HBV reinfection after liver transplantation, and risk of hepatocellular carcinoma progression or recurrence. In this review, the clinical applications of HBcrAg in CHB patients based on its virological features are described. Furthermore, new potential therapeutic anti-HBV agents that affect intrahepatic cccDNA are under development, and the monitoring of HBcrAg might be useful to judge therapeutic effects. In conclusion, HBcrAg might be a suitable surrogate marker beyond other HBV markers to predict the disease progression and treatment responses of CHB patients.
乙型肝炎病毒 (HBV) 由于肝内共价闭合环状 DNA (cccDNA) 的存在，无法从感染的肝细胞中完全清除。血清学标志物反映了肝内病毒复制活性，可作为肝活检的非侵入性替代方法。乙型肝炎核心相关抗原 (HBcrAg) 是一种新型的生物标志物，在慢性乙型肝炎 (CHB) 中具有重要作用，因为它与血清 HBV DNA 和肝内 cccDNA 相关。在血清 HBV DNA 不可检测或 HBsAg 丢失的临床病例中，仍可检测到 HBcrAg，HBcrAg 水平的降低与 CHB 患者的良好预后显著相关。HBcrAg 可预测自发性或治疗诱导的乙型肝炎表面抗原 (HBeAg) 血清学转换、核苷（酸）类似物停药前后的持续应答、潜在的 HBV 再激活、肝移植后 HBV 再感染以及肝细胞癌进展或复发的风险。在这篇综述中，根据其病毒学特征描述了 HBcrAg 在 CHB 患者中的临床应用。此外，正在开发新的潜在的抗 HBV 治疗药物，这些药物可影响肝内 cccDNA，HBcrAg 的监测可能有助于判断治疗效果。总之，HBcrAg 可能是一种替代其他 HBV 标志物的合适标志物，可预测 CHB 患者的疾病进展和治疗反应。
