乙型肝炎核心相关抗原：在慢性乙型肝炎患者中停止核（t）i

StephenW

Journal of Gastroenterology

January 2017, Volume 52, Issue 1, pp 127–128
Hepatitis B core-related antigen: a strong indicator for cessation of nucleos(t)ide analog therapy in patients with chronic hepatitis B

    Authors
   

      Akihiro Matsumoto        1 Email author

    1.Department of MedicineShinshu University School of MedicineMatsumotoJapan

Editorial

First Online:
    24 September 2016

DOI: 10.1007/s00535-016-1259-0

Cite this article as:
    Matsumoto, A. J Gastroenterol (2017) 52: 127. doi:10.1007/s00535-016-1259-0

    330 Downloads

With successful nucleos(t)ide analog therapy, serum hepatitis B virus (HBV) DNA titer decreases to below detection limit, alanine aminotransferase (ALT) normalizes, and fibrosis of the liver may become improved [1–4]. The incidence of hepatocellular carcinoma can be decreased as well [5–7].

However, withdrawal hepatitis frequently occurs after treatment cessation, even in patients with undetectable HBV DNA levels. As this complication is sometimes lethal [8–10], it is crucial to determine the optimal conditions for stopping nucleos(t)ide analog therapy, especially for young patients wishing to have children, the avoidance of hyper-resistant viral strains, and regulating medical expenses.

Knowledge of intrahepatic HBV replication status is the key to defining the safe conditions for nucleos(t)ide analog therapy cessation. cccDNA level is a suitable indicator for this aim, although frequent liver biopsies are needed. Serum HBV DNA was believed to be a good estimator of cccDNA. However, the correlation of HBV DNA and intrahepatic cccDNA levels is lost under the nucleos(t)ide analog treatment and cannot therefore be adopted [11]. Alternative, non-invasive markers are desired.

The possibility of discontinuation of nucleos(t)ide analogs is also affected by the clinical goal, such as no withdrawal hepatitis, no viral relapse, or long-term clinical response. The majority of patients experience viral recurrence during withdrawal, but some will not develop hepatitis or will achieve clinical remission after a hepatitis flare.

In this issue, Jung KS et al. [12] report on virological remission (i.e., HBV DNA ≤2000 IU/ml) over 1 year following cessation of nucleos(t)ide therapy in patients HBeAg-positive or HBeAg-negative at the start of treatment. The virological relapse rate of each group was 57.8 and 54.4 %, respectively. Significantly and independently related factors for virological relapse were age >40 years at the start of nucleos(t)ide therapy and basal HBV DNA level >20,000,000 IU/ml in the HBeAg-positive group, and age >40 years at the start of nucleos(t)ide analog therapy and HB core-related antigen (HBcrAg) level >3.7 log U/ml in the HBeAg-negative group.

HBcrAg is an established viral activity marker [13]. HBcrAg levels correlated closely with those of intrahepatic cccDNA, even when HBV DNA became undetectable, during nucleos(t)ide analog therapy [11]. Thus, HBcrAg may represent a non-invasive marker of cccDNA with or without nucleos(t)ide analog therapy. We have also reported that a combination of HBsAg and HBcrAg levels at the end of nucleos(t)ide analog therapy was useful to predict long-term clinical remission [14, 15].

According to APASL guidelines, the appropriate duration of nucleoside analog administration is unknown, although HBV DNA and HBsAg are suggested as estimators of treatment efficacy [16]. There are no precise criteria for the cessation of nucleos(t)ide analog therapy in the EASL guidelines as well [17]. In the AASLD guidelines, HBsAg loss is regarded as the best predictor of sustained remission off-treatment, but is also reported to be infrequent with current therapies [18].

In this issue, the authors present clear criteria for successful discontinuation of nucleos(t)ide analog therapy using HBcrAg, which is expected to contribute to the enhancement of chronic hepatitis B patient management. Their study also underscores the importance of measuring multiple HBV antigens in addition to HBV DNA to better estimate the behavior of HBV in the liver.

StephenW

胃肠病学杂志

2017年1月，第52卷，第1期，第127-128页
乙型肝炎核心相关抗原：在慢性乙型肝炎患者中停止核（t）ide类似物治疗的强指标

    作者
    作者和关系

    Akihiro松本电子作者

    Akihiro Matsumoto
        1电子邮件作者

    大学院医学部松本大学

社论

首先在线：
    2016年9月24日

DOI：10.1007 / s00535-016-1259-0

引用本文：
    Matsumoto，A.J Gastroenterol（2017）52：127。doi：10.1007 / s00535-016-1259-0

    330下载

随着成功的nucleos（t）ide模拟治疗，血清乙型肝炎病毒（HBV）DNA滴度降低到检测限以下，丙氨酸氨基转移酶（ALT）正常化，肝纤维化可能改善[1-4]。肝细胞癌的发病率也可以降低[5-7]。

然而，戒断性肝炎经常在治疗停止后发生，甚至在具有不可检测的HBV DNA水平的患者中。由于这种并发症有时是致死的[8-10]，确定停止核苷类似物治疗的最佳条件是至关重要的，特别是对于希望有孩子的年轻患者，避免高度耐药的病毒株和调节医疗费。

肝内HBV复制状态的知识是定义核苷类似物治疗停止的安全条件的关键。 cccDNA水平是这个目标的适当指标，虽然需要频繁的肝活检。血清HBV DNA被认为是cccDNA的良好估计。然而，HBV DNA和肝内cccDNA水平的相关性在核苷（t）ide模拟治疗下丢失，因此不能采用[11]。需要替代的，非侵入性标记物。

停止核苷（t）ide类似物的可能性也受临床目标的影响，例如无戒断性肝炎，无病毒复发或长期临床反应。大多数患者在戒断期间经历病毒性复发，但是一些患者不会发展为肝炎或在肝炎爆发后将实现临床缓解。

在这个问题上，Jung KS et al。 [12]报告了在治疗开始时HBeAg阳性或HBeAg阴性患者中核苷（t）ide治疗停止后1年内的病毒学缓解（即HBV DNA≤2000IU / ml）。每组的病毒学复发率分别为57.8％和54.4％。病毒学复发的显着和独立的相关因素在核苷（t）ide治疗开始时年龄> 40岁，HBeAg阳性组中基底HBV DNA水平> 20,000,000 IU / ml，核苷酸开始年龄> 40岁（t）ide模拟治疗和HB核心相关抗原（HBcrAg）水平> 3.7 log U / ml在HBeAg阴性组。

HBcrAg是一种已建立的病毒活性标记[13]。在核苷类似物治疗期间，HBcrAg水平与肝内cccDNA水平密切相关，甚至在HBV DNA变得不可检测时[11]。因此，HBcrAg可代表具有或不具有核苷酸类似物治疗的cccDNA的非侵入性标记。我们还报道，在核苷（t）ide类似物治疗结束时HBsAg和HBcrAg水平的组合可用于预测长期临床缓解[14,15]。

根据APASL指南，核苷类似物给药的适当持续时间是未知的，尽管建议HBV DNA和HBsAg作为治疗效力的估计量[16]。在EASL指南中也没有关于核苷（t）ide模拟治疗停止的精确标准[17]。在AASLD指南中，HBsAg丢失被认为是持续缓解脱离治疗的最佳预测因子，但据报道，目前的治疗并不常见[18]。

在这个问题中，作者提出了使用HBcrAg成功终止核苷类似物治疗的明确标准，预期这将有助于增强慢性乙型肝炎患者管理。他们的研究还强调了除HBV DNA外测量多种HBV抗原的重要性，以更好地估计HBV在肝脏中的行为。

TRUMPHILARY

对于HBsAg定量，HBeAg定量，HBcrAg定量，这三项指标
以前只是定性结论。比如乙肝5项的+和-，即阴和阳。
现在有条件定量，有具体数据高低衡量了。
自然可以研究一下。
应该能作为病情发展程度依据性指标。
一个重要意义，比如
同样是乙肝病毒携带者，为什么有的病人不用药而“自愈”，有的病人难治甚至在加重。
这在以前是解释不了的。
问题出在哪里？
我想，这两类病人的“HBsAg定量，HBeAg定量，HBcrAg定量”高低不同。
也许问题就出在这里。