慢性乙型肝炎患者共价关闭无法检测到核/潮类似物停止后HBV

StephenW

Rebound of HBV DNA After Cessation of Nucleos/Tide Analogues in Chronic Hepatitis B Patients With Undetectable Covalently Closed
Ching-Lung Lai  1   2 , Danny Ka-Ho Wong  1   2 , Gerald Tsz-Yau Wong  1 , Wai-Kay Seto  1   2 , James Fung  1   2 , Man-Fung Yuen  1   2
Affiliations
Affiliations

    1
    Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
    2
    State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong.

    PMID: 32462119 PMCID: PMC7242874 DOI: 10.1016/j.jhepr.2020.100112

Abstract

Background & aims: Nucleos(t)ide analogues (NUCs) effectively suppress serum HBV DNA. Previously, we have identified 21 patients with undetectable covalently closed circular DNA (cccDNA) upon long-term NUC therapy. This study investigated the effect of NUC withdrawal in patients with undetectable cccDNA.

Methods: Nineteen patients on long term NUCs (median 13.4 years) were recruited: 13 were randomized to discontinue NUCs; 6 to continue taking NUCs. All had undetectable cccDNA at the time of last liver biopsy (median time 2.9 years prior to randomization). Serum HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg), liver biochemistry, and serum HBV RNA were monitored.

Results: At the time of randomization, all patients had undetectable serum HBV DNA and HBV RNA. Twelve of the 13 patients had HBV DNA rebound to 100 IU/ml within 20 weeks of NUC discontinuation. The thirteenth patient had HBV DNA rebound at week 70. Three patients experienced biochemical flares after re-treatment which subsequently resolved. There was no significant association between the time of HBV DNA rebound and baseline HBsAg, HBcrAg and alanine aminotransferase, duration of treatment, and age at which treatment was stopped (all p >0.05). At the time of HBV DNA rebound, HBV DNA levels correlated with HBcrAg levels (p = 0.003), but not with HBsAg levels (p = 0.262).

Conclusions: In patients with undetectable intrahepatic cccDNA, virologic rebound still occurred after NUC cessation. At the rebound of HBV DNA, the kinetics of HBsAg production were independent of those of viral DNA replication. Additional studies are required to determine the factors that may predict virologic rebound and when NUCs can be discontinued in HBsAg-positive patients with chronic hepatitis B.

Lay summary: It has been shown that following long-term nucleos(t)ide analogue treatment for chronic hepatitis B, some patients have undetectable levels of viral DNA in their livers. We tested the results of withdrawing nucleos(t)ide analogue treatment in these patients and found that viral relapse could occur in patients with undetectable viral DNA. Further research is required to determine whether nucleos(t)ide analogue treatment can be discontinued in specific patients with chronic hepatitis B.

Keywords: ALT, alanine aminotransferase; CHB, chronic hepatitis B; Chronic hepatitis B; ETV, entecavir; HBcrAg, hepatitis B core-related antigen; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; LdT, telbivudine; NUCs, nucleos(t)ide analogues; TDF, tenofovir disoproxil fumarate; ULN, upper limit of normal; anti-HBe, antibody to HBeAg; antiviral therapy; cccDNA, covalently closed circular DNA; hepatitis B virus DNA rebound; stopping therapy.

© 2020 The Author(s).
Co

StephenW

慢性乙型肝炎患者共价关闭无法检测到核/潮类似物停止后HBV DNA反弹
赖静龙1 2，黄家豪1 2，黄子瑜1，怀威濑户1 2，詹姆斯冯1 2，袁文丰1 2
隶属关系
隶属关系

    1个
    香港大学玛丽医院香港大学医学系。
    2
    香港大学，肝脏研究国家重点实验室。

    PMID：32462119 PMCID：PMC7242874 DOI：10.1016 / j.jhepr.2020.100112

抽象

背景与目的：Nucleos（t）ide类似物（NUCs）有效抑制血清HBV DNA。以前，我们已经确定了21名长期NUC治疗后无法检测到的共价闭合环状DNA（cccDNA）患者。这项研究调查了cccDNA不可检测患者NUC戒断的影响。

方法：招募了19例长期NUC（中位13.4岁）患者：13例患者被随机分为NUCs组。 6继续服用NUC。在上次肝活检时（随机分组前中位时间为2.9年），所有患者的cccDNA均未检出。监测血清HBV DNA，乙型肝炎表面抗原（HBsAg），乙型肝炎核心相关抗原（HBcrAg），肝生物化学和血清HBV RNA。

结果：在随机分组时，所有患者的血清HBV DNA和HBV RNA均未检出。 13名患者中有12名在NUC停用后20周内HBV DNA反弹至100 IU / ml。第十三名患者在第70周出现HBV DNA反弹。三名患者在再次治疗后经历了生化反应，随后逐渐消退。 HBV DNA反弹时间与基线HBsAg，HBcrAg和丙氨酸转氨酶，治疗时间和停止治疗的年龄之间无显着相关性（所有p> 0.05）。在HBV DNA反弹时，HBV DNA水平与HBcrAg水平相关（p = 0.003），但与HBsAg水平无关（p = 0.262）。

结论：在无法检测到肝内cccDNA的患者中，NUC停止后仍会发生病毒学反弹。在HBV DNA反弹时，HBsAg产生的动力学独立于病毒DNA复制的动力学。需要进行进一步的研究来确定可预测病毒学反弹的因素以及何时可以在慢性乙型肝炎的HBsAg阳性患者中终止NUCs。

总结：已经证明，长期治疗慢性乙型肝炎的核苷酸类似物治疗后，一些患者的肝脏中病毒DNA水平检测不到。我们在这些患者中测试了退出核苷酸（t）类似物治疗的结果，发现病毒DNA不可检测的患者可能发生病毒复发。需要进一步的研究以确定在特定的慢性乙型肝炎患者中核苷酸（t）ide类似物治疗是否可以中断。

关键词：ALT，丙氨酸转氨酶； CHB，慢性乙型肝炎；慢性乙型肝炎； ETV，恩替卡韦； HBcrAg，乙肝核心相关抗原； HBeAg，乙型肝炎e抗原； HBsAg，乙肝表面抗原； LdT，替比夫定； NUCs，核苷（核苷酸）类似物； TDF，替诺福韦富马酸酯ULN，正常上限抗HBe，HBeAg抗体；抗病毒治疗； cccDNA，共价闭合的环状DNA；乙型肝炎病毒DNA反弹；停止治疗。

©2020作者。

StephenW

https://www.jhep-reports.eu/article/S2589-5559(20)30046-X/pdf

newchinabok

在无法检测到肝内cccDNA的患者中，NUC停止后仍会发生病毒学反弹。在HBV DNA反弹时，HBsAg产生的动力学独立于病毒DNA复制的动力学。需要进行进一步的研究来确定可预测病毒学反弹的因素

windu

cccdna为零还能反弹，估计表抗还是唯一的检验标准

乙肝人1949

狡猾狡猾的