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肝胆相照论坛 论坛 学术讨论& HBV English AASLD2020[729]HBsAg / ANTI-HBS免疫复合物持续存在 HBs ...
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AASLD2020[729]HBsAg / ANTI-HBS免疫复合物持续存在 HBsAg清除 [复制链接]

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发表于 2020-10-22 15:29 |只看该作者 |倒序浏览 |打印
729
HBsAg/ANTI-HBS IMMUNE COMPLEXES PERSIST AFTER
HBsAg CLEARANCE
Pir Ahmad Shah1, Satinder Pal Kaur2, Mark Anderson3,
Vera Holzmayer3, Jeffrey Gersch3, Gavin Cloherty3, Mary
Kuhns3 and Daryl Lau1, (1)Medicine, Beth Israel Deaconess
Medical Center, Harvard Medical School, (2)Division of
Gastroenterology and Hepatology, Beth Israel Deaconess
Medical Center, Harvard Medical School, (3)Abbott
Diagnostics, Abbott Park, IL, USA
Background: Functional cure with HBsAg clearance is a
desirable treatment endpoint HBsAg and anti-HBs can form
immune complexes (IC) during the course of HBV infection
With HBsAg seroconversion, there are detectable unbound
anti-HBs antibodies in addition to HBsAg loss We applied
an investigational IC assay to evaluate the dynamics of the
virological parameters leading to functional cure Patients
and Methods: 21 CHB patients with either spontaneous
(n=10) or nucleos(t)ide analog (NA)-induced (n=11) HBsAg
loss were included The Abbott ARCHITECT HBsAg NEXT
Qualitative (sensitivity 0 005 IU/ml), Architect quantitative
HBsAg (qHBsAg), anti-HBs, and IC assays were performed
on serial serum samples IC assay uses anti-HBs monoclonal
antibodies to capture the HBsAg complexed with patient-derived
anti-HBs (huIgG) After eliminating the unbound
huIgG, an acridinylated secondary mouse anti-huIgG
antibody binds to the huIgG on the IC A chemiluminescent
reaction is induced with the acridinium and the resulting light
signal is reported in Relative Light Units (RLUs) Results:
There were 16 (76%) males and 10 (48%) Asians in this
cohort They all had undetectable HBsAg by the ARCHITECT
HBsAg NEXT Qualitative assay 11 patients in the treatment
group had HBeAg (-) CHB and received NA between 0 5
and 16 years prior to HBsAg loss The 10 with spontaneous
HBsAg loss were monitored for 3 to 7 years prior to HBsAg
clearance Patients were subsequently monitored for up to
6 years 9 (43%) patients achieved HBsAg seroconversion
with persistently detectable anti-HBs; 6 of 9 were in the
treatment group Patients with anti-HBs (+) had a more rapid
reduction in quantitative HBsAg (qHBsAg) prior to HBsAg
loss compared to those without [2 2 vs 0 8 log IU/ml/year
(p=0 04)] Interestingly, regardless of the anti-HBs status, IC
was detectable in all the patients prior to and after HBsAg loss
The IC values were higher among the anti-HBs (+) patients at
the time of HBsAg clearance; this difference, however, was
not statistically significant. (Figure) IC remained detectable
for those with over 5-year follow-up after HBsAg clearance
Conclusion: In this cohort of patients with either spontaneous
or treatment-induced functional cure, HBsAg reduction was
faster among those who developed anti-HBs This likely
attributes to the role of humoral immunity in viral clearance
The persistence of HBsAg/ anti-HBs immune complexes after
HBsAg seroconversion suggests that HBsAg continues to be
present even with detectable unbound anti-HBs antibodies
The quantitation of IC may provide insight on the risk of
hepatitis B reactivation after HBsAg loss Longer term followup
will be necessary to determine the dynamics of the free
anti-HBs and the HBsAg/ anti-HBs immune complexes over
time.

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发表于 2020-10-22 15:30 |只看该作者
729
HBsAg / ANTI-HBS免疫复合物持续存在
HBsAg清除
皮尔·艾哈迈德·沙赫(Pir Ahmad Shah)1,萨特(Satinder)
Vera Holzmayer3,Jeffrey Gersch3,Gavin Cloherty3,Mary
Kuhns3和Daryl Lau1,(1)医学,贝丝·以色列女执事
哈佛医学院医学中心,(2)
贝丝·以色列女执事肠胃病和肝病
哈佛医学院医学中心,(3)阿博特
Diagnostics,美国伊利诺伊州雅培公园
背景:清除HBsAg的功能性治愈是一个
可以形成理想的治疗终点HBsAg和抗HBs
HBV感染过程中的免疫复合物(IC)
通过HBsAg血清转化,可以检测到未结合的
除HBsAg丢失外,还使用了抗HBs​​抗体
研究性IC分析以评估药物动力学
导致功能治愈的病毒学参数患者
方法:21名CHB患者自发
(n = 10)或核苷酸(t)ide类似物(NA)诱导(n = 11)HBsAg
损失包括在内雅培ARCHITECT HBsAg NEXT
定性(灵敏度0 005 IU / ml),建筑师定量
进行了HBsAg(qHBsAg),抗HBs和IC分析
连续血清样品的检测IC分析使用抗HBs单克隆抗体
抗体以捕获与患者来源复合的HBsAg
消除未结合的抗HBs(huIgG)
huIgG,一种腺苷酸化的次级小鼠抗huIgG
抗体结合IC A上的huIgG化学发光
cri啶诱导反应并产生光
信号以相对光单位(RLU)报告:
在这个地区,男性为16(76%),亚洲为10(48%)
他们都被ARCHITECT检测出HBsAg
HBsAg NEXT定性检测治疗中的11例患者
组患有HBeAg(-)CHB,0至5之间接受NA
HBsAg丢失前16年和10年自发
在HBsAg发生之前的3至7年内监测HBsAg的流失
清除率随后对患者进行监测,直至
6年9(43%)患者实现了HBsAg血清转化
具有可持久检测的抗HBs; 9人中有6人在
治疗组抗HBs(+)患者的病情较快
降低HBsAg之前的定量HBsAg(qHBsAg)
与没有[2 2 vs 0 8 log IU / ml /年
(p = 0 04)]有趣的是,无论抗HBs的状态如何,IC
HBsAg丢失前后所有患者中均可检测到
在2020年,抗HBs(+)患者的IC值较高
清除HBsAg的时间;但是,这种差异是
没有统计学意义。 (图)IC仍可检测
对于HBsAg清除后随访超过5年的患者
结论:在这组自发性患者中
或治疗引起的功能性治愈,HBsAg降低为
在开发抗HBs的人群中速度更快
归因于体液免疫在病毒清除中的作用
HBsAg /抗HBs免疫复合物持续存在
HBsAg血清转化表明HBsAg仍是
即使存在可检测的未结合抗HBs抗体
IC的定量分析可以提供有关
HBsAg丢失后乙肝再激活长期随访
将需要确定免费的动态
抗HBs和HBsAg /抗HBs免疫复合物
时间。
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