停止慢性乙型肝炎患者核苷（酸）类似物后的有限持续反应

StephenW

Gut. 2019 Aug 28. pii: gutjnl-2019-318981. doi: 10.1136/gutjnl-2019-318981. [Epub ahead of print]
Limited sustained response after stopping nucleos(t)ide analogues in patients with chronic hepatitis B: results from a randomised controlled trial (Toronto STOP study).
Liem KS1,2, Fung S1, Wong DK1, Yim C1, Noureldin S1, Chen J1, Feld JJ1,3, Hansen BE1,4, Janssen HLA5.
Author information

1
    Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
2
    Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
3
    Sandra Rotman Centre for Global Health, Toronto, Ontario, Canada.
4
    Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.
5
    Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada [email protected].

Abstract
OBJECTIVE:

Although most patients with chronic hepatitis B (CHB) reach effective virological suppression with long-term nucleos(t)ide analogues (NA) therapy, some might not need to continue treatment for life. In this randomised, controlled, phase IV trial, we evaluated off-therapy outcomes in patients after discontinuing long-term NA therapy.
DESIGN:

Patients who had received NA therapy for ≥1 year and achieved virological suppression (hepatitis B e antigen (HBeAg) seroconversion combined with undetectable hepatitis B virus (HBV) DNA ≥12 months in HBeAg-positive patients or undetectable HBV DNA ≥36 months in HBeAg-negative patients) were randomised 2:1 to stop or continue NA therapy for 72 weeks. Sustained disease remission (HBeAg negative, HBV DNA <2000 IU/mL and normal alanine aminotransferase (ALT)) was evaluated at 72 weeks after stopping NA therapy.
RESULTS:

Among 67 enrolled patients, sustained disease remission was observed in 13/45 (29%) stop versus 18/22 (82%) continue patients. Hepatitis B surface antigen (HBsAg) loss occurred in two patients (one in each group). The median HBsAg decline from randomisation to week 72 was similar in both groups (0.2 (0.0-0.4) vs 0.1 (0.0-0.2) log IU/mL in stop vs continue patients; p=0.04). Among patients who stopped, 15/45 (33%) had virological or biochemical relapse and 17/45 (38%) were retreated according to predefined criteria. A total of 11/18 (61%) pretreatment HBeAg-positive versus 6/27 (22%) HBeAg-negative patients required retreatment (p=0.01). Fourteen (31%) patients developed ALT >10× upper limit of normal (ULN) and another 7 (16%) had ALT >5× ULN. No patients experienced liver decompensation or died.
CONCLUSION:

The findings of this prospective study suggest limited benefit of stopping NA therapy in chronic hepatitis B.
TRIAL REGISTRATION NUMBER:

NCT01911156.

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
KEYWORDS:

HBeAg negative; discontinuation; nucleos(t)ide analogue; viral hepatitis

PMID:
    31462554
DOI:
    10.1136/gutjnl-2019-318981

StephenW

肠道。 2019年8月28日.pii：gutjnl-2019-318981。 doi：10.1136 / gutjnl-2019-318981。 [印刷前的电子版]
停止慢性乙型肝炎患者核苷（酸）类似物后的有限持续反应：来自随机对照试验的结果（多伦多STOP研究）。
Liem KS1,2，Fung S1，Wong DK1，Yim C1，Noureldin S1，Chen J1，Feld JJ1,3，Hansen BE1,4，Janssen HLA5。
作者信息

1
多伦多综合医院多伦多肝病中心，大学健康网络，多伦多，安大略省，加拿大。
2
荷兰鹿特丹鹿特丹伊拉斯姆斯大学医学中心胃肠病学和肝病学系。
3
Sandra Rotman全球健康中心，加拿大安大略省多伦多市。
4
加拿大安大略省多伦多市多伦多大学卫生政策，管理和评估研究所。
五
多伦多综合医院多伦多肝病中心，加拿大安大略省多伦多大学健康网络[email protected]。

抽象
目的：

虽然大多数慢性乙型肝炎（CHB）患者通过长期核苷（酸）类似物（NA）治疗达到有效的病毒学抑制，但有些人可能不需要继续终身治疗。在这项随机，对照，IV期试验中，我们评估了停止长期NA治疗后患者的治疗后结果。
设计：

接受NA治疗≥1年并且病毒学抑制（乙型肝炎e抗原（HBeAg）血清转换与HBeAg阳性患者检测不到乙型肝炎病毒（HBV）DNA≥12个月或HBeAg检测不到HBVDNA≥36个月的患者） - 阴性患者）以2：1随机化以停止或继续NA治疗72周。在停止NA治疗后72周评估持续的疾病缓解（HBeAg阴性，HBV DNA <2000 IU / mL和正常丙氨酸氨基转移酶（ALT））。
结果：

在67名入选患者中，在13/45（29％）停止与18/22（82％）继续患者中观察到持续的疾病缓解。两名患者（每组一名）发生乙型肝炎表面抗原（HBsAg）丢失。从随机分组到第72周的中位数HBsAg下降在两组中相似（0.2（0.0-0.4）vs 0.1（0.0-0.2）log IU / mL，停止与继续患者; p = 0.04）。在停止的患者中，15/45（33％）患有病毒学或生化复发，17/45（38％）根据预定标准进行复治。总共11/18（61％）治疗前HBeAg阳性与6/27（22％）HBeAg阴性患者需要再治疗（p = 0.01）。 14名（31％）患者发生ALT> 10×正常上限（ULN），另外7名（16％）ALT> 5×ULN。没有患者出现肝脏失代偿或死亡。
结论：

这项前瞻性研究的结果表明，在慢性乙型肝炎中停止NA治疗的效果有限。
试用注册号码：

NCT01911156。

©作者（或其雇主）2019。无商业再利用。请参阅权限。由BMJ发布。
关键词：

HBeAg阴性;停药;核苷（酸）类似物;

结论：
31462554
DOI：
10.1136 / gutjnl-2019-318981