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标题: EASL2019 PS-055 HBV转录活性标志物HBcrAg和前基因组 核苷酸(t)id [打印本页]

作者: StephenW    时间: 2019-3-30 15:29     标题: EASL2019 PS-055 HBV转录活性标志物HBcrAg和前基因组 核苷酸(t)id

PS-055
The markers of HBV transcriptional activity-HBcrAg and pregenomic
HBV DNA during antiviral therapy with nucleos (t)ide
analogue help to predict optimal timing of therapy withdrawal
Ivana Carey1, Jeffrey Gersch2, Matthew Bruce1, Christiana Moigboi1,
Bo Wang1, Mary Kuhns2, Gavin Cloherty2, Geoffrey Dusheiko1,
Kosh Agarwal1. 1Institute of Liver Studies, King’s College Hospital,
London, United Kingdom; 2Department of Infectious Diseases, Abbott
Diagnostics, Chicago, United Kingdom
Email: [email protected]
Background and aims: Nucelos (t)ide analogue (NA) withdrawal is a
potential therapeutic strategy in long-term supressed HBeAgnegative
non-cirrhotic chronic hepatitis B (CHB) patients. We
previously demonstrated in 15 patients that 20% patients had
severe post-withdrawal ALT flare (> 10 UNL) and required to restart
NA therapy. At time of NA withdrawal all patients with
significant flare after stopping NA had detectable HBcrAg and pregenomic
(pg)HBV RNA, both markers of cccDNA transcriptional
activity. Data regarding changes of HBV serological/virological
markers during NA therapy prior to NA withdrawal are lacking and
might provide valuable information about the timing of NA
withdrawal. We aimed to compare the levels of HBV DNA, HBsAg,
HBcrAg and pgHBV RNA and their kinetics during long-term NA
therapy prior to NA withdrawal to evaluate whether on-treatment
markers can help with timing of successful NA withdrawal.
Methods: We studied 25 CHB non-cirrhotic patients (64%males,
median age 48yrs) were treated for a median duration 6.9 yrs (3.2-
11.2) with tenofovir (TDF) and had undetectable HBV DNA for at least
3 years. TDF was stopped and patients were followed for at least 52
weeks (median 78, range 52-78). Based on type of ALT flare post NA
withdrawal, patientswere divided into 3 groups: no flare (n = 9), mild
ALT flare (> 2 < 5 UNL and > 2 fromNA stop baseline, n = 11) and 5 with
severe flare (> 10UNL withHBVDNA> 100, 000IU/ml). Serum samples
from NA therapy at baseline, years 1, 2 and 3 on therapy and at time
of withdrawal were tested for HBV DNA and HBsAg levels, HBcrAg
concentrations (by were CLEIA Fujirebio assay [LLDQ 2 log10U/ml])
and pgHBV RNA (using a real-time PCR research assay Abbott
Diagnostics [LLDQ 1.65 log10U/ml]). The markers were compared
between patients according to post withdrawal ALT flare status.
Results: At time of startingNA therapy patients with severe flares had
significantly higher levels of HBV DNA, HBcrAg and pgHBV RNA, but
quantitative HBsAg, ALT and degree of liver damage were similar. All
serological/virological markers declines did not differ across the
groups. By year 1 only HBcrAg and pgHBV RNA levels were higher in
patients with subsequent severe flares and this remained the case
until NA withdrawal (Figure 1). The proportions of patients withdetectable HBcrAg and pgHBV RNA reduced during NA therapy
(Figure 1); only patients who developed severe flares had detectable
HBcrAg and pgHBV RNA at time of withdrawal.
Conclusion: During NA treatment of HBeAg negative patients, serum
levels of HBcrAg and pgHBV RNA, ostensibly markers of transcriptional
cccDNA activity were strong predictors of subsequent
significant ALT flares after NA withdrawal and their monitoring on
NA therapy might assist with appropriate timing of NAwithdrawal to
avoid relapse and related disease after NA withdrawal
作者: StephenW    时间: 2019-3-30 15:29

PS-055
HBV转录活性标志物HBcrAg和前基因组
核苷酸(t)ide抗病毒治疗期间的HBV DNA
类比有助于预测治疗退出的最佳时机
Ivana Carey1,Jeffrey Gersch2,Matthew Bruce1,Christiana Moigboi1,
Bo Wang,Mary Kuhns2,Gavin Cloherty2,Geoffrey Dusheiko1,
Kosh Agarwal1。 1国王学院医院肝脏研究所,
伦敦,英国; 2雅培传染病科
诊断,芝加哥,英国
电子邮件:[email protected]
背景和目的:Nucelos(t)ide模拟(NA)退出是一种
长期抑制HBeAg阴性的潜在治疗策略
非肝硬化慢性乙型肝炎(CHB)患者。我们
此前在15名患者中证实了20%的患者
严重的戒断后ALT突发(> 10 UNL)并需要重新启动
NA疗法。在NA停止时所有患者均有
停止NA后显着的眩光可检测到HBcrAg和pregenomic
(pg)HBV RNA,均为cccDNA转录的标志物
活动。关于HBV血清学/病毒学变化的数据
NA戒断前NA治疗期间的标志物缺乏和
可能会提供有关NA时间的宝贵信息
退出。我们的目的是比较HBV DNA,HBsAg,
HBcrAg和pgHBV RNA及其长期NA动力学
在NA停药前进行治疗以评估是否接受治疗
标记可以帮助成功停止NA。
方法:我们研究了25例CHB非肝硬化患者(64%男性,
中位年龄48岁)治疗中位时间为6。9年(3.2-
11.2)使用替诺福韦(TDF)并至少检测不到HBV DNA
3年。 TDF停止,患者随访至少52
周(中位数78,范围52-78)。基于NA的ALT耀斑类型
停药后,患者分为3组:无眩光(n = 9),轻度
ALT突发(> 2 <5 UNL和> 2来自NA停止基线,n = 11)和5
严重眩光(> 10UNL,HBVDNA> 100,000IU / ml)。血清样本
来自NA治疗的基线,第1,2和3年的治疗和时间
对HBV DNA和HBsAg水平HBcrAg进行了检查
浓度(按CLEIA Fujirebio分析[LLDQ 2 log10U / ml])
和pgHBV RNA(使用实时PCR研究分析Abbott
诊断[LLDQ 1.65 log10U / ml])。比较标记
患者之间根据戒断后ALT突发状态。
结果:在开始治疗时,严重发作的患者有
显着更高水平的HBV DNA,HBcrAg和pgHBV RNA,但是
定量HBsAg,ALT和肝脏损害程度相似。所有
血清学/病毒学标记物的下降并没有差异
组。到第1年,只有HBcrAg和pgHBV RNA水平较高
随后严重发作的患者仍然如此
直到NA退出(图1)。在NA治疗期间,可检测到的HBcrAg和pgHBV RNA患者的比例降低
(图1);只有发生严重发作的患者才有可检测到
停药时HBcrAg和pgHBV RNA。
结论:NA治疗HBeAg阴性患者,血清
HBcrAg和pgHBV RNA的水平,表面上是转录的标志物
cccDNA活性是后续的强有力预测因子
NA停药后及其监测的显着ALT突发
NA治疗可能有助于适当的NA退出时间
戒断NA后避免复发和相关疾病




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