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标题: EASL2019 THU-222 新型HBV pgRNA检测在预测HBeAg中的应用 长期核苷( [打印本页]

作者: StephenW    时间: 2019-4-7 12:21     标题: EASL2019 THU-222 新型HBV pgRNA检测在预测HBeAg中的应用 长期核苷(

本帖最后由 StephenW 于 2019-4-7 12:27 编辑

THU-222
The application of novel HBV pgRNA assay to predict HBeAg
Clearance on long-term nucleos (t)ide analogues
Pir Ahmad Shah1, Idriss Rajab1, Saad Choudhry1, Jeffrey Gersch2,
Vijayram Malladi1, Rizwan Ishtiaq1, Mary Kuhns2, Gavin Cloherty2,
Daryl Lau1. 1Beth Israel Deaconess Medical Center, Gastroenterology,
Medicine, Boston, United States; 2Abbott, Infectious disease research,
Chicago, IL, United States
Email: [email protected]
Background and aims: Nucleos (t)ide analogues (NAs) are associated
With HBeAg loss in only approximately 40-50% of patients with
Prolonged therapy. The aim of the study is to identify the virologicalprofiles of patients who are unlikely to clear HBeAg with long term
NA treatment so alternative therapy can be considered.
Method: HBeAg positive patients with baseline HBV DNA ≥ 5 log10
IU/ml on NAs for at least 20 months with available stored serial sera
Were included. HBV pgRNAwas measured using the Abbott research
Assay [Sensitivity is 1.65 log10 U/ml with linearity from 2.5 to 7.5 log10
IU/ml (R2 = 0.99)]. Clinical and virological parameterswere
Between patients with and without HBeAg clearance on prolonged
Therapy.
Results: This predominantly Asian (86%) cohort included 17 and 11
Patients with and without NA treatment-related HBeAg loss
The duration of therapy, baseline HBV DNA, ALT levels
Were similar between the 2 groups [Table]. Patients with and without
HBeAg loss achieved HBV DNA < 20 IU/ml at similar time line from
Start of therapy. Those with HBeAg loss, however, had significantly
Lower HBV pgRNA levels when HBV DNA became suppressed to < 20
IU/ml. With long term therapy more than 5 years, HBV RNA levels
Silent > 4 log10 IU/ml among those without HBeAg loss. Five of 17
(29%) patients with HBeAg loss had hepatitis flare (ALT > 100 U/L)
Associated with HBV RNA reduction (Mean 1.68 log) preceding HBeAg
Clearance. Their HBV pgRNA levels became <1.65 log10 IU/ml shortly
After HBeAg loss. In contrast, 12 of 17 patients without hepatitis flare
Prior to HBeAg loss had significant higher HBV pgRNA level
(Average 3.12 log10 IU/ml) at time of HBeAg clearance. At last followup,
The HBV pgRNA level was significant lower among those with
HBeAg loss [Table]. Ten of 17 (59%) patients with HBeAg clearance
Achieved HBV pgRNA < 1.65 log10 IU/ml.
[Mean, range]       HBeAg Loss(N = 17)   Without HBeAg Loss (N = 10)            P Value
Duration of therapy:
Months
                           75 (22, 168)              84 (27, 184)                                      0.30
Baseline HBV DNA
(log10 IU/ml)
                           7.2 (5.2, 8.2)            7.5 (5, 8.2)                                         0.28
Baseline ALT (U/L) 107 (18, 260)           84 (14, 268)                                     0.20
Time to HBV DNA <20
IU/ml (Months)
                          38.6 (10.6, 141)        46.9 (6, 159)                                      0.29
HBV pgRNA (log10
IU/ml) when HBV
DNA <20 IU/ml
                          2.5 (*UD, 5.32)            5.6 (3.83, 6.72)                             <0.00002
HBV pgRNA at last
Follow-up (log10
IU/ml)
                          1.62 (*UD,3.33)           4.68 (3.29,5.77)                             <0.00001
*UD = undetectable
Conclusion: In this cohort, HBV pgRNA kinetics on therapy
Differentiated patients with and without HBeAg clearance on long
Term NA treatment. Those HBV pgRNA remaining > 5.6 log10 IU/ml
When HBV DNA was suppressed tended to have very gradual HBV
pgRNA decline over prolonged therapy and were impossible to achieve
HBeAg loss. Hepatitis flare with ALT > 100 U/L was often associated
With significant HBV pgRNA reduction and subsequent HBeAg
Clearance. These observations need to be carefully validated in a
Larger cohort of patients.
作者: StephenW    时间: 2019-4-7 12:22

THU-222
新型HBV pgRNA检测在预测HBeAg中的应用
长期核苷(t)ide类似物的清除率
Pir Ahmad Shah1,Idriss Rajab1,Saad Choudhry1,Jeffrey Gersch2,
Vijayram Malladi1,Rizwan Ishtiaq1,Mary Kuhns2,Gavin Cloherty2,
Daryl Lau1。 1B以色列女执事医疗中心,消化内科,
医学,波士顿,美国; 2Abbott,传染病研究,
芝加哥,伊利诺伊州,美国
电子邮件:[email protected]
背景和目的:Nucleos(t)ide类似物(NA)是相关的
由于HBeAg仅在约40-50%的患者中丧失
延长治疗时间。该研究的目的是确定不太可能长期清除HBeAg的患者的病毒学特征
NA治疗可以考虑替代疗法。
方法:HBeAg阳性患者基线HBVDNA≥5log10
使用可存储的系列血清,在NA上IU / ml至少20个月
包括在内。使用Abbott研究测量HBV pgRNA
分析[灵敏度为1.65 log10 U / ml,线性范围为2.5至7.5 log10
IU / ml(R2 = 0.99)]。临床和病毒学参数
有和没有HBeAg清除的患者之间延长
治疗。
结果:这一主要是亚洲人(86%)的队列包括17和11
有和没有NA治疗相关的HBeAg丢失的患者
治疗持续时间,基线HBV DNA,ALT水平
两组之间相似[表]。患者有无
HBeAg损失在相似的时间线上达到HBV DNA <20 IU / ml
开始治疗。然而,那些HBeAg丢失的患者有显着性
当HBV DNA被抑制到<20时,HBV pgRNA水平降低
国际单位/毫升。长期治疗超过5年,HBV RNA水平
在没有HBeAg损失的人群中,沉默> 4 log10 IU / ml。 17中的5个
(29%)HBeAg丢失患者发生肝炎(ALT> 100 U / L)
与HBeAg之前的HBV RNA减少(平均1.68对数)相关
间隙。他们的HBV pgRNA水平很快变为<1.65 log10 IU / ml
HBeAg丢失后。相比之下,17名患者中有12名没有肝炎发作
在HBeAg丢失之前,HBV pgRNA水平显着升高
(HBeAg清除时的平均值为3.12 log10 IU / ml)。最后的跟进,
HBV pgRNA水平显着降低
HBeAg丢失[表]。 17例(59%)HBeAg清除患者中有10例
实现HBV pgRNA <1.65 log10 IU / ml。
[平均值,范围]
HBeAg损失
(N = 17)
没有
HBeAg损失
(N = 10)P值
治疗持续时间:

75(22,168)84(27,184)0.30
基线HBV DNA
(log10 IU / ml)
7.2(5.2,8.2)7.5(5,8.2)0.28
基线ALT(U / L)107(18,260)84(14,268)0.20
HBV DNA的时间<20
IU / ml(月)
38.6(10.6,
141)
46.9(6,159)0.29
HBV pgRNA(log10
IU / ml)当HBV时
DNA <20 IU / ml
2.5(* UD,5.32)5.6(3.83,6.72)<0.00002
最后HBV pgRNA
后续行动(log10
IU / ml)的
1.62(* UD,
3.33)
4.68(3.29,
5.77)
<0.00001
* UD =无法检测到
结论:在这个队列中,HBV pgRNA动力学治疗
有和没有HBeAg清除的分化患者
术语NA治疗。那些HBV pgRNA保持> 5.6 log10 IU / ml
当HBV DNA被抑制时,往往具有非常缓慢的HBV
pgRNA在长期治疗后下降并且无法实现
HBeAg丢失。通常伴有ALT> 100 U / L的肝炎
具有显着的HBV pgRNA减少和随后的HBeAg
间隙。这些观察结果需要在a中仔细验证
更大的患者队列。




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