Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.
State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, Hong Kong.
Aliment Pharmacol Ther. 2018 Jan;47(1):43-54. doi: 10.1111/apt.14376. Epub 2017 Oct 16.
Chronic hepatitis B (CHB) cannot be completely eradicated due to the presence of covalently closed circular DNA (cccDNA) in the nuclei of infected hepatocytes. While quantification of intrahepatic cccDNA requires liver biopsies, serological markers can be non-invasive alternatives to reflect intrahepatic viral replicative activity. Recently, hepatitis B core-related antigen (HBcrAg) has been advocated as a novel serum marker for disease monitoring and prognostication of CHB.
To examine the virological aspect and clinical application of HBcrAg with respect to the natural history and treatment of CHB.
We reviewed all papers published in the PubMed journal list and abstracts from major international meetings that included the keyword "HBcrAg" or "hepatitis B core-related antigen" until March 2017. Selected studies were compared and summarised on the basis of existing theories, as well as the authors' experience.
HBcrAg exhibited good correlation with intrahepatic (ih) cccDNA, ih total hepatitis B virus (HBV) DNA, serum HBV DNA and to a lesser extent HBV surface antigen (HBsAg). In situations where serum HBV DNA levels become undetectable or HBsAg loss is achieved, HBcrAg can still be detectable. This marker is helpful in differentiation of HBeAg-negative chronic hepatitis from HBeAg-negative chronic infection, predicting spontaneous or treatment-induced HBeAg seroconversion, sustained response to nucleos(t)ide analogue (NA), risk of HBV reactivation in occult HBV infection under immunosuppressive therapies, and risk of hepatocellular carcinoma (HCC) development as well as post-operative HCC recurrence.
HBcrAg is a potential surrogate marker of cccDNA. It may soon become a useful marker for disease monitoring, predicting treatment response and disease outcome of chronic hepatitis B.
由于感染肝细胞内的共价闭合环状 DNA（cccDNA）的存在，慢性乙型肝炎（CHB）无法被完全清除。虽然肝内 cccDNA 的定量需要肝活检，但血清标志物可以作为反映肝内病毒复制活性的非侵入性替代方法。最近，乙型肝炎核心相关抗原（HBcrAg）被认为是一种新型血清标志物，可用于监测 CHB 疾病和预测其预后。
检查 HBcrAg 在 CHB 的自然史和治疗方面的病毒学方面和临床应用。
我们在 PubMed 期刊列表中检索了截至 2017 年 3 月发表的所有包含关键字“HBcrAg”或“肝炎 B 核心相关抗原”的文献，并查看了主要国际会议的摘要。在现有理论和作者经验的基础上，对选定的研究进行了比较和总结。
HBcrAg 与肝内（ih）cccDNA、ih 总乙型肝炎病毒（HBV）DNA、血清 HBV DNA 以及在较小程度上与 HBV 表面抗原（HBsAg）具有良好的相关性。在血清 HBV DNA 水平变得不可检测或 HBsAg 丢失的情况下，仍可检测到 HBcrAg。该标志物有助于区分 HBeAg 阴性慢性乙型肝炎和 HBeAg 阴性慢性感染，预测自发性或治疗诱导的 HBeAg 血清学转换，核苷（酸）类似物（NA）持续应答，免疫抑制治疗下隐匿性 HBV 感染的 HBV 再激活风险，以及肝细胞癌（HCC）发展和术后 HCC 复发的风险。
HBcrAg 是 cccDNA 的潜在替代标志物。它可能很快成为慢性乙型肝炎疾病监测、预测治疗反应和疾病结局的有用标志物。
