HBeAg阴性慢性乙型肝炎患者停用长期核苷酸（类似物）类似物

StephenW

Limited sustained response and lack of HBsAg decline after stopping long-term nucleos(t)ide analogue therapy in HBeAg negative patients with chronic hepatitis B:

Results of the prospective, randomized, open-label phase IV

STOP study





Reported by Jules Levin

AASLD 2018 Nov 9-13 SF

Kin Seng Liem­1,2, Scott Fung1, David K. Wong1, Colina Yim1, Seham Noureldin1, Feng Fei Huang1, Hemant Shah1, Jordan J. Feld1,3, Bettina E. Hansen1,2,4, Harry L.A. Janssen1

1 Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada.

2 Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.

3 McLaughlin-Rotman Centre for Global Health, Toronto, Canada.

4 Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada

program abstract

Background: Current guidelines recommend indefinite Nucleot(s)ide Analogue (NA) therapy for patients chronically infected with HBV, based on the high relapse rates observed following discontinuation of short-term therapy. However, sustained virological response (SVR) has recently been described in ~50% of patients after discontinuation of long-term NA therapy. The HBV-STOP study is a prospective multi-centre parallel cohort study of NA discontinuation in patients who have achieved long-term virological suppression on treatment. The study describes clinical outcomes post-treatment discontinuation, with the aim of identifying determinants of SVR.

Methods: A narrative analysis of the first 44 participants recruited to 48 weeks observation was undertaken. Inclusion criteria for the study were HBeAg-negative, non-cirrhotic (Fibroscan ≤ 9.6kPa or Metavir F0-F3), virological suppression for ≥ 18 months on NA therapy uninterrupted for ≥ 2 years. All patients are being followed for 2 years. Criteria for recommencing NA therapy were HBV DNA > 2000IU/mL with either ALT > 5 x ULN for ≥ 16 weeks or ALT > 10 x ULN for ≥ 8 weeks, INR ≥ 1.5, Bilirubin > 2 x ULN, ascites, hepatic encephalopathy and investigator discretion. ULN was defined as the ULN at the site’s laboratory. In this analysis, we have evaluated clinical outcomes to 48 weeks for the cohort to date, with a focus on HBV DNA suppression, ALT flare, HBsAg decline/loss, safety and need for restarting NA therapy.

Results: Baseline characteristics included mean age of 55 years, 71% were male, and 89% were Asian. Median HBsAg level was 2135 IU/mL. All patients were non-cirrhotic. All patients experienced virological reactivation after stopping NA. At week 48, 24 (55%) are in the immune control phase (Table 1). One (2%) patient has experienced HBsAg loss, 25 (57%) have achieved > 1 log10 reduction in HBsAg level and 14 (32%) have experienced an ALT flare > 5 x ULN. Six (14%) patients have restarted NA therapy. No episodes of clinical decompensation have occurred, although bilirubin (BR) > 2 x ULN was observed in 3 patients in the context of a hepatitis flare – LFTs normalised on restarting NA therapy. Recruitment is continuing.

Conclusion: Stopping NA therapy is associated with reactivation of HBV DNA but at week 48 the majority of patients are in the immune control phase and only 14% have restarted NA therapy. HBsAg reduction >1 log was observed in 57% at 48 weeks. The study is ongoing.

StephenW

HBeAg阴性慢性乙型肝炎患者停用长期核苷酸（类似物）类似物治疗后，持续反应有限，HBsAg缺乏下降：

前瞻性，随机，开放标记IV期的结果

停止学习





Jules Levin报道

AASLD 2018年11月9日至13日SF

Kin Seng Liem1,2，Scott Fung1，David K. Wong1，Colina Yim1，Seham Noureldin1，Feng Fei Huang1，Hemant Shah1，Jordan J. Feld1,3，Bettina E. Hansen1,2,4，Harry L.A.Janssen1

1多伦多肝病中心，多伦多综合医院，加拿大多伦多大学健康网络。

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 McLaughlin-Rotman全球健康中心，加拿大多伦多。

4加拿大多伦多大学卫生政策，管理和评估研究所

程序摘要

背景：根据短期治疗中断后观察到的高复发率，目前的指南建议对慢性HBV感染的患者进行无限期核苷酸类似物（NA）治疗。然而，最近在长期NA治疗中断后约50％的患者中描述了持续病毒学应答（SVR）。 HBV-STOP研究是一项前瞻性多中心平行队列研究，对在治疗中实现长期病毒学抑制的患者进行NA中止治疗。该研究描述了治疗后停药的临床结果，目的是确定SVR的决定因素。

方法：对招募到48周观察的前44名参与者进行叙述性分析。该研究的纳入标准为HBeAg阴性，非肝硬化（Fibroscan≤9.6kPa或Metavir F0-F3），NA治疗的病毒学抑制≥18个月，不间断≥2年。所有患者均被随访2年。重新开始NA治疗的标准是HBV DNA> 2000IU / mL，ALT> 5 x ULN≥16周或ALT> 10 x ULN≥8周，INR≥1.5，胆红素> 2 x ULN，腹水，肝性脑病和研究者自由裁量权。 ULN被定义为现场实验室的ULN。在该分析中，我们评估了迄今为止48周的临床结果，重点是HBV DNA抑制，ALT突发，HBsAg下降/丢失，安全性以及重新开始NA治疗的需要。

结果：基线特征包括平均年龄55岁，71％是男性，89％是亚洲人。中位数HBsAg水平为2135 IU / mL。所有患者均为非肝硬化。所有患者在停止NA后都经历了病毒学再激活。在第48周，24（55％）处于免疫控制阶段（表1）。一名（2％）患者出现HBsAg损失，25名（57％）患者HBsAg水平降低> 1 log10,14名（32％）患者ALT眩光> 5 x ULN。六名（14％）患者重新开始NA治疗。没有发生临床失代偿发作，尽管在肝炎突发情况下3例患者中观察到胆红素（BR）> 2 x ULN - LFT在重新开始NA治疗后正常化。招聘工作仍在继续。

结论：停止NA治疗与HBV DNA的再激活有关，但在第48周，大多数患者处于免疫控制阶段，只有14％的患者重新开始NA治疗。在48周时观察到HBsAg减少> 1log，57％。该研究正在进行中。

SK蜗牛

抗病毒停药后，表抗开始减少，难道再次激活了免疫系统？今年有好几偏相类似的研究报道了

Hepbest

这个效果还是不错的。 这次把重新开始NA治疗的标准更清晰化啦。
停药后，肯定会激活免疫系统。表抗低于100的可以试试看

重新开始NA治疗的标准是HBV DNA> 2000IU / mL，ALT> 5 x ULN≥16周

方法：对招募到48周观察的前44名参与者进行叙述性分析。该研究的纳入标准为HBeAg阴性，非肝硬化（Fibroscan≤9.6kPa或Metavir F0-F3），NA治疗的病毒学抑制≥18个月，不间断≥2年。
所有患者均被随访2年。
重新开始NA治疗的标准是HBV DNA> 2000IU / mL，ALT> 5 x ULN≥16周
或ALT> 10 x ULN≥8周，INR≥1.5，胆红素> 2 x ULN，腹水，肝性脑病和研究者自由裁量权。 ULN被定义为现场实验室的ULN。
在该分析中，我们评估了迄今为止48周的临床结果，重点是HBV DNA抑制，ALT突发，HBsAg下降/丢失，安全性以及重新开始NA治疗的需要。

Hepbest

回复 StephenW 的帖子

这个有原文链接吗？谢谢

StephenW

回复 Hepbest 的帖子

http://hbvhbv.info/forum/thread-1712028-1-1.html

Hepbest

回复 StephenW 的帖子

感谢！