HBsAg降低至<1 IU / mL期间的转氨酶耀斑与 基于NAP的联合治疗

StephenW

Oral Abstract O3
Transaminase flares during HBsAg reduction to < 1 IU/mL are correlated with the
establishment of functional cure of HBV following NAP-based combination therapy
Andrew Vaillant,
Replicor Inc, Montreal Canada
(on behalf of the REP 301-LTF and REP 401 study authors)
Background: Nucleic acid polymers (NAPs) inhibit the assembly and secretion of HBV subviral
particles and interact with small and large forms of the hepatitis delta antigen. An analysis of all
52 participants in the REP 301 and REP 401 studies was conducted to examine the correlation
between HBsAg clearance, transaminase flares and therapeutic outcome for HBV (rebound,
virologic control or functional cure) reported for these studies.
Methods: All 52 participants from the REP 301 (NCT02233075, currently in extended follow-up
in the REP 301-LTF study, NCT02876419) and REP 401 (NCT02565719) were included.
Variables analyzed included on therapy HBsAg and anti-HBs response, maxima and area under
the curve (AUC) for ALT, AST and GGT, baseline characteristics, and therapeutic outcomes
(based on 48-week follow-up in the REP 401 study and 2-year follow-up in the REP 301-LTF
study). Virologic control of HBV is defined as HBV DNA ≤ 2000 IU/mL with normal ALT ≥ 24
weeks off therapy. Functional cure of HBV is defined as HBV DNA target not detected, HBsAg
< LLOQ and normal ALT ≥ 24 weeks off therapy.
Results: Outcomes were balanced between rebound, virologic control and functional cure
(p=0.750) and independent of baseline characteristics (p≥0.274). Transaminase flares occurred
in 96% of participants, were otherwise asymptomatic with unaltered liver function throughout
(normal bilirubin, INR and albumin) and normalized during follow-up in 81% of participants.
The incidence (p=0.733) and magnitude (p≥0.189) of flares were similar between outcomes and
independent from baseline characteristics or anti-HBs titers during therapy. Transaminase
maxima or AUC during therapy were significantly correlated with HBsAg reductions > 3 log
10 from baseline (p<0.05)
Transaminase elevations (maxima and AUC) during different thresholds of HBsAg clearance (<
1000, < 100, < 10 and < 1 IU/mL) were analyzed and were significantly greater in the virologic
control and functional cure groups (p<0.05) at all thresholds. However, the prevalence of flares
in virologic control and rebound outcome groups declined at lower HBsAg thresholds and the
presence of flares while HBsAg was < 1 IU/mL was significantly more selective for functional
cure (see table below).
Conclusions: Transaminase flares during NAP therapy occur regardless of outcome and are
well tolerated, with intensity correlated with HBsAg decline > 3 log10 from baseline. Increased
strength of transaminase flare activity, and its occurrence during HBsAg declines to < 1 IU/mL
may be important for the establishment of functional cure of HBV.

StephenW

口语摘要O3
HBsAg降低至<1 IU / mL期间的转氨酶耀斑与
基于NAP的联合治疗后建立HBV的功能性治疗
安德鲁·威兰特
Replicor Inc，加拿大蒙特利尔
（代表REP 301-LTF和REP 401研究作者）
背景：核酸聚合物（NAP）抑制HBV亚病毒的装配和分泌
颗粒与肝炎三角洲抗原的大小型相互作用。全部分析
进行了REP 301和REP 401研究的52名参与者以检验其相关性
HBsAg清除率，转氨酶耀斑与HBV治疗结果之间的关系（反弹，
病毒学控制或功能性治疗）报告用于这些研究。
方法：REP 301（NCT02233075）的全部52名参与者，目前正在进行进一步随访
在REP 301-LTF研究中，NCT02876419）和REP 401（NCT02565719）也包括在内。
分析的变量包括治疗HBsAg和抗HBs反应，最大和下面积
ALT，AST和GGT，基线特征和治疗结果的曲线（AUC）
（基于REP 401研究中的48周随访和REP 301-LTF中的2年随访
研究）。 HBV的病毒学控制定义为ALT≥24且HBV DNA≤2000 IU / mL
休假治疗。 HBV的功能性治愈定义为未检测到HBV DNA靶标HBsAg
<LLOQ和正常ALT≥24周停药治疗。
结果：结果在反弹，病毒学控制和功能治愈之间取得平衡
（p = 0.750），并且与基线特征无关（p≥0.274）。发生转氨酶耀斑
96％的参与者在整个过程中均无症状，肝功能未改变
（正常的胆红素，INR和白蛋白），并在随访期间将81％的参与者恢复正常。
结果和结果之间，耀斑的发生率（p = 0.733）和强度（p≥0.189）相似。
在治疗期间不受基线特征或抗HBs效价的影响。转氨酶
治疗期间的最大值或AUC与HBsAg降低> 3 log显着相关
距基线10（p <0.05）
在不同的HBsAg清除阈值下，转氨酶升高（最大值和AUC）（<
分别分析了1000，<100，<10和<1 IU / mL的病毒学指标
所有阈值的对照组和功能治愈组（p <0.05）。但是，耀斑的流行
在HBsAg阈值较低时，病毒控制和反弹结果组的患者下降，
在HBsAg <1 IU / mL时出现耀斑对功能的选择性更高
治愈（见下表）。
结论：NAP治疗期间转氨酶耀斑的发生与结果无关，且
耐受性良好，其强度与HBsAg下降相对于基线下降> 3 log10有关。增加
转氨酶耀斑活性的强度及其在HBsAg中的发生率降至<1 IU / mL
对于建立HBV的功能性治疗可能很重要。

乙肝人1949

马上今年就收官了，看了这个消息，反倒不知说什么，唯一不想说的就是对这药的希望

乙肝人1949

马上今年就收官了，看了这个消息，反倒不知说什么，唯一不想说的就是对这药的希望，其实关心恩替卡韦和替诺降价更有意义

平凡之路123

REP这个药都十几年了，跑到孟加拉做实验，整天说效果多么好，有在FDA报备过吗？没有。
这么好的药，除了初始的投资者，有其他公司投资吗？没有。资本市场都是瞎子？傻子？

平凡之路123

箭头的药为什么被强生收购？因为效果好。
丙肝的药为什么被吉利德收购？因为效果好。
REP为什么没人收购，也没人合作？它这水平可以吊打任何一个新药。

newchinabok

阿弥陀佛，rep

平凡之路123

整天拿着似是而非的数据忽悠人，还是有一大堆战友指着它脱离苦海。
对，没有理由没有条件的相信。
创造理由创造条件的相信。
都知道赌博传销是骗人的，还是有那么多人愿意信。
穷是原罪，病是原罪。