乙型肝炎e抗原阴性患者中核苷类似物的撤出：亚洲的观点

StephenW

Withdrawal of Nucleos(t)ide Analogues in Hepatitis B e Antigen–Negative Patients: An Asian Perspective
Tung‐Hung Su M.D., Ph.D.
Jia‐Horng Kao M.D., Ph.D., F.A.A.S.L.D.
First published: 13 January 2021
https://doi.org/10.1002/cld.950

Correspondence

Jia‐Horng Kao, M.D., Ph.D., F.A.A.S.L.D., Chair Professor, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 1 Chang‐Te Street, Taipei 10048, Taiwan. E‐mail: [email protected]
This work was supported by grants from the Ministry of Science and Technology, Taiwan (grant MOST 107‐2628‐B‐002‐005), National Taiwan University Hospital (grant VN108‐05), and the Liver Disease Prevention & Treatment Research Foundation, Taiwan.
Potential conflict of interest: Nothing to report.
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Abbreviations

AASLD
    American Association for the Study of Liver Diseases
ALT
    alanine aminotransferase
APASL
    Asian Pacific Association for the Study of the Liver
cccDNA
    covalently closed circular DNA
CHB
    chronic hepatitis B
CR
    clinical (biochemical) relapse
EASL
    European Association for the Study of the Liver
ETV
    entecavir
HBeAg
    hepatitis B e antigen
HBsAg
    hepatitis B surface antigen
HBV
    hepatitis B virus
HCC
    hepatocellular carcinoma
N/A
    not available
NA
    nucleos(t)ide analogue
TDF
    tenofovir disoproxil fumarate
ULN
    upper limit of normal
VR
    virological relapse

Chronic hepatitis B virus (HBV) infection is currently incurable. Long‐term treatment with potent and safe nucleos(t)ide analogues (NAs) can reduce hepatocellular carcinoma (HCC), cirrhotic complications, and liver‐related mortality through substantial viral suppression.1 However, long‐term therapy raises several crucial issues with pros and cons. Because hepatitis B surface antigen (HBsAg) seroclearance or functional cure is not easily achievable, a finite therapy may provide an opportunity to facilitate HBsAg seroclearance by the rejuvenation of exhausted immune cells. However, the virological relapse (VR) or surge of alanine aminotransferase (ALT) levels may increase the risk for adverse outcomes (e.g., decompensation, fibrosis progression, HCC, or liver‐related mortality) before HBsAg seroclearance, which are the safety concerns of finite therapy. Little is known about whether repeated therapeutic interruption will increase the chance of drug resistance, whereas the reduction of renal function and bone mineral density are the safety issues of infinite therapy. Lastly, the practice of “to stop” or “to continue” therapy should also consider the accessibility and affordability of the health care system. Patients who stop therapy need to be monitored closely with frequent virological and biochemical tests in the first year, especially if they experience a VR or clinical (biochemical) relapse (CR) (Table 1). About 40% of patients who stop NA therapy eventually receive retreatment.2 The cost‐effective analysis should thus be performed on the basis of individual regions.

StephenW

乙型肝炎e抗原阴性患者中核苷类似物的撤出：亚洲的观点
苏东雄博士
高家宏博士，F.A.A.S.L.D.
首次发布：2021年1月13日
https://doi.org/10.1002/cld.950

对应

高嘉or，博士，法学博士，国立台湾大学医学院临床医学研究所研究生教授，台湾台北市长德街1号，10048。电子邮件：[email protected]
该工作得到了台湾科学技术部的资助（MOST 107‐2628‐B‐002‐005），台湾大学医院（资助的VN108‐05）和肝病预防与治疗研究基金会的资助，台湾。
潜在的利益冲突：无可报告。
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缩略语

协会
    美国肝病研究协会
ALT
    丙氨酸转氨酶
阿帕斯
    亚太肝病研究协会
基因
    共价闭合的环状DNA
CHB
    慢性乙型肝炎
CR
    临床（生化）复发
EASL
    欧洲肝脏研究协会
电子电视
    恩替卡韦
乙肝抗原
    乙型肝炎e抗原
乙肝表面抗原
    乙肝表面抗原
乙肝病毒
    乙型肝炎病毒
肝癌
    肝细胞癌
不适用
    无法使用
不适用
    核苷酸（t）类似物
TDF
    替诺福韦酯富马酸
超净值
    正常上限
虚拟现实
    病毒学复发

慢性乙型肝炎病毒（HBV）感染目前无法治愈。通过有效的病毒抑制，长期有效和安全的核苷酸类似物（NAs）长期治疗可降低肝细胞癌（HCC），肝硬化并发症和与肝脏相关的死亡率。1然而，长期治疗引起了以下几个关键问题：利弊。由于不容易实现乙肝表面抗原（HBsAg）血清清除或功能性治愈，因此有限的疗法可能会通过使疲惫的免疫细胞恢复活力来提供促进HBsAg血清清除的机会。但是，HBsAg血清清除之前的病毒学复发（VR）或丙氨酸氨基转移酶（ALT）水平升高可能会增加不良后果（例如代偿失调，纤维化进展，HCC或肝相关死亡率）的风险，这是有限疗法。关于反复治疗中断是否会增加耐药性的知之甚少，而肾功能和骨矿物质密度的降低是无限治疗的安全性问题。最后，“停止”或“继续”治疗的做法还应考虑卫生保健系统的可及性和可负担性。停止治疗的患者在第一年需要经常进行病毒学和生化测试，尤其是如果他们经历了VR或临床（生化）复发（CR）时，应密切监测其病情（表1）。约有40％停止NA治疗的患者最终接受了再治疗。2因此，应根据具体地区进行具有成本效益的分析。

StephenW

https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/cld.950