EASL2020[AS095] 核苷酸类似物停产的前瞻性研究 非肝硬化HBeAg阴

StephenW

AS095
A prospective study of nucleot(s)ide analogue discontinuation in
non-cirrhotic HBeAg-negative chronic hepatitis B patients:
interimanalysis at week 48 demonstrates profound reductions of
HBsAg associated with ALT flare
Samuel Hall1, Gareth Burns1, Miriam Levy2, John Lubel3,
Amanda Nicoll3, Gail Matthews4, Paul Desmond1, William Sievert5,
Scott Bowden6, Stephen Locarnini6, Jacinta Holmes1,
Kumar Visvanathan1, Alexander Thompson1. 1St. Vincent’s Hospital
Melbourne, Gastroenterology, Fitzroy, Australia; 2Liverpool Hospital,
Gastroenterology, Liverpool, Australia; 3Eastern Health,
Gastroenterology, Box Hill, Australia; 4St Vincent’s Hospital Sydney,
Gastroenterology, Darlinghurst, Australia; 5Monash Medical Centre,
Gastroenterology, Clayton, Australia; 6Victorian Infectious Diseases
Reference Laboratory, Melbourne, Australia
Email: [email protected]
Background and Aims: Current guidelines recommend indefinite
Nucleot(s)ide Analogue (NA) therapy for patients with HBeAgnegative
CHB. However, sustained virological response (SVR) has
been described in patients after discontinuation of long-term NA
therapy, as well as HBsAg loss. The HBV-STOP study is a prospective
multi-centre 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.
Method: An interim narrative analysis of outcomes at week 48 post-
NA discontinuation was performed. The primary endpoint for the
study is outcomes at week 96. Inclusion criteria for the study were
HBeAg-negative, non-cirrhotic & virological suppression for ≥ 18
months on NA therapy uninterrupted for ≥ 2 years. Criteria for
recommencing NA therapy were HBV DNA >2000 IU/mL with either
ALT >5× ULN for ≥ 16 weeks or ALT >10× ULN for ≥ 8 weeks, INR ≥ 1.5,
Bilirubin >2× ULN, ascites, hepatic encephalopathy and investigator
discretion.
Results: The cohort is fully enrolled and data are currently available
for 90/111 patients. At baseline, median age was 55 yrs, 58% were
male, 83% were Asian. Median HBsAg level was 699 (250–1819) IU/
mL. All patients were non-cirrhotic. Virological reactivation occurred
in all, with median time to detection 8 (4–12)weeks. Atweek 48, four
(4%) patients have experienced HBsAg loss, 42 (47%) had DNA
<2,000 IU/mL, 13 (14%) had DNA >2,000 and ALT >2× ULN, and 10
(11%) had restarted treatment. Patients who achieved HBsAg loss had
low baseline HBsAg levels (HBsAg loss: median baseline HBsAg level
= 3.1 IU/ml in HBsAg loss vs. 776 IU/mL in patients with no HBsAg
loss). The overall median reduction in HBsAg was 68 IU/mL at week
48. 21 (23%) have experienced an ALT flare >10× ULN. ALT flare was
associated with reduction in HBsAg level. Median reduction of
HBsAg level from the flare time-point to week 48 was 2800(106–6090) IU/mL (vs 41.7 IU/mL in patients with peak ALT <10× ULN,
p-value =<0.001).
Conclusion: In this interim analysis, stopping NA therapy was
associated with virological relapse, but at week 48 only 11% had
restarted NA therapy. ALT flare >10xULNwas observed in 23% andwas
associated with profound reductions in HBsAg levels, suggesting that
immunological flare may be important for achieving HBsAg loss.
HBsAg loss itself was observed in a minority at week 48.

StephenW

AS095
核苷酸类似物停产的前瞻性研究
非肝硬化HBeAg阴性的慢性乙型肝炎患者：
第48周的中间分析表明，
HBsAg与ALT爆发有关
塞缪尔·霍尔（Samuel Hall）1，加雷斯·伯恩斯（Gareth Burns）1，米里亚姆·利维（Miriam Levy2），约翰·卢贝尔（John Lubel）3，
阿曼达·尼科尔（Amanda Nicoll）3，盖尔·马修斯（Gail Matthews）4，保罗·德斯蒙德（Paul Desmond）1，威廉·西维特（William Sievert）5，
Scott Bowden6，Stephen Locarnini6，Jacinta Holmes1，
库玛·维斯瓦纳坦（Kumar Visvanathan）1，亚历山大·汤普森（Alexander Thompson）1。 1st。文森特医院
墨尔本，胃肠病学，澳大利亚菲茨罗伊； 2利物浦医院
澳大利亚利物浦胃肠病学； 3Eastern Health，
澳大利亚博士山胃肠病学；悉尼第四圣文森特医院，
胃肠病学，澳大利亚达令赫斯特； 5蒙纳士医学中心
胃肠病学，澳大利亚克莱顿； 6维多利亚州传染病
澳大利亚墨尔本参考实验室
电子邮件：[email protected]
背景和目标：当前指南建议无限期
核苷类似物（NA）治疗HBe阴性患者
CHB。但是，持续病毒学应答（SVR）具有
长期NA停用后在患者中有描述
治疗以及HBsAg丢失。 HBV-STOP研究是一项前瞻性研究
患有NA的患者中止NA的多中心研究
在治疗上取得了长期的病毒学抑制。研究
描述治疗终止后的临床结果，
目的是确定SVR的决定因素。
方法：对术后48周的结局进行临时叙述性分析
进行了NA终止治疗。的主要终点
研究是第96周的结果。研究的纳入标准为
≥18的HBeAg阴性，非肝硬化和病毒学抑制
NA治疗连续2个月以上。准则
重新开始NA治疗的是HBV DNA> 2000 IU / mL或
ALT> 5×ULN≥16周或ALT> 10×ULN≥8周，INR≥1.5，
胆红素> 2倍正常值上限，腹水，肝性脑病和研究者
谨慎。
结果：该队列已完全注册，并且当前有可用数据
适用于90/111患者。在基线时，中位年龄为55岁，其中58％为
男性，亚洲人占83％。 HBsAg中位数为699（250-1819）IU /
毫升所有患者均为非肝硬化患者。发生病毒学激活
总的来说，平均检测时间为8（4-12）周。在第48周，四
（4％）患者经历了HBsAg丧失，其中42（47％）个人有DNA
<2,000 IU / mL，13（14％）的DNA> 2,000和ALT> 2×ULN，以及10
（11％）已重新开始治疗。 HBsAg丢失的患者有
基线HBsAg水平低（HBsAg丢失：基线HBsAg中位数
= HBsAg损失为3.1 IU / ml，而无HBsAg的患者为776 IU / mL
失利）。第一周HBsAg的总体中位数降低为68 IU / mL
48. 21（23％）的ALT眩光> 10倍ULN。原“ ALT耀斑”为
与HBsAg水平降低有关。中位数减少
从高峰期到第48周的HBsAg水平为2800（106-6090）IU / mL（相对于峰值ALT <10×ULN的患者为41.7 IU / mL，
p值= <0.001）。
结论：在此中期分析中，停止NA治疗是
与病毒学复发有关，但在第48周时只有11％
重新开始NA疗法。 ALT耀斑> 10xULN的发生率为23％
与HBsAg水平的大幅降低有关，这表明
免疫性耀斑对于实现HBsAg丢失可能很重要。
在第48周时，在少数人群中观察到HBsAg自身流失。