AASLD2018[419]48周前44名患者的结果 在HBV-STOP研究中，一项前瞻

StephenW

419
Outcomes of the First 44 Patients at 48 Weeks
in the HBV-STOP Study, a Prospective Study
of Nucleot(s)Ide Analogue Discontinuation
in Non-Cirrhotic Hbeag-Negative Chronic
Hepatitis B Patients Who Have Achieved Long
Term Virological Suppression
Samuel Hall1, Gareth Burns1, Miriam T. Levy2, John S.
Lubel3, Amanda Nicoll3, Gail Matthews4, Paul V. Desmond1,
William Sievert5, Scott Bowden6, Stephen Locarnini7, Kumar
Visvanathan1 and Alexander Thompson8, (1)Gastroenterology,
St Vincent’s Hospital Melbourne, (2)University of New South
Wales, (3)Department of Gastroenterology, Eastern Health,
(4)The Kirby Institute, (5)Monash Medical Centre, (6)Victorian
Infectious Diseases Reference Laboratory, (7)Victorian
Infectious Disease Reference Laboratory, (8)Department of
Gastroenterology, St Vincent’s Hospital Melbourne
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 longterm
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 posttreatment
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 HBeAgnegative,
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

419
48周前44名患者的结果
在HBV-STOP研究中，一项前瞻性研究
Nucleot（s）Ide Analogue Discontinuation
在非肝硬化的Hbeag-Negative慢性病
已经实现长期的乙型肝炎患者
术语病毒学抑制
Samuel Hall1，Gareth Burns1，Miriam T. Levy2，John S.
Lubel3，Amanda Nicoll3，Gail Matthews4，Paul V. Desmond1，
William Sievert5，Scott Bowden6，Stephen Locarnini7，Kumar
Visvanathan1和Alexander Thompson8，（1）胃肠病学，
墨尔本圣文森特医院，（2）新南威尔士大学
威尔士，（3）东部卫生消化内科，
（4）柯比研究所，（5）蒙纳士医疗中心，（6）维多利亚时代
传染病参考实验室，（7）维多利亚时代
传染病参考实验室，（8）
墨尔本圣文森特医院消化内科
背景：目前的指导方针建议无限期
Nucleot（s）ide长期治疗患者的类似物（NA）疗法
基于观察到的高复发率，感染HBV
停止短期治疗后。然而，
最近持续的病毒学应答（SVR）
约50％的患者在长期停药后描述
NA疗法。 HBV-STOP研究是一项前瞻性研究
NA中断的多中心平行队列研究
已经实现长期病毒学抑制的患者
在治疗上。该研究描述了治疗后的临床结果
停止，目的是识别
SVR的决定因素。方法：叙事分析
招募到48周观察的前44名参与者是
进行。该研究的纳入标准是HBeAgnegative，
非肝硬化（Fibroscan≤9.6kPa或Metavir F0-
F3），NA治疗后病毒学抑制≥18个月
不间断≥2年。所有患者都被跟踪
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。在这
分析，我们评估了48周的临床结果
到目前为止的队列，重点是HBV DNA抑制，ALT
耀斑，HBsAg下降/丢失，安全性和重新启动NA的需要
治疗。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。
所有患者在停止后都经历了病毒学再激活
NA。在第48周，24名（55％）处于免疫控制阶段
（表格1）。一名（2％）患者出现HBsAg损失，25
（57％）HBsAg水平降低> 1 log10
14（32％）经历过ALT耀斑> 5 x ULN。六（14％）
患者已重新开始NA治疗。没有临床发作
虽然胆红素（BR）> 2 x，但已发生失代偿
在肝炎的背景下，在3名患者中观察到ULN
眩光 - LFT在重新开始NA治疗后正常化。招聘
正在继续结论：停止NA治疗是相关的
随着HBV DNA的再激活，但在第48周，大部分是HBV DNA
患者处于免疫控制阶段，只有14％患者
重新开始NA治疗。观察到HBsAg降低> 1log
在48周时占57％。该研究正在进行中。