s 458D
Association of Circulating Hepatitis B Virus
(HBV) Biomarkers with HBsAg Loss and
Absence of Re-Treatment after Discontinuation
of Long Term Treatment with Tenofovir (DF) in
HBeAg Negative Patients in the Finite Study
Florian van Bömmel1, Alena Van Bömmel2, Danilo Deichsel1,
Maria Pfefferkorn1, Christin Felkel1, Janett Fischer1, Sandra
Krohn1, Karen Rother1, Jessica Wacker3, Martin Brehm3,
Rainer Dannenberg3, Anuj Gaggar4, William E. Delaney5,
Andrea Cathcart4 and Thomas Berg1, (1)Department of
Gastroenterology and Rheumatology, Section of Hepatology,
University Hospital Leipzig, (2)Max Planck Institute for
Molecular Genetics, (3)Mvz Labor Dessau Gmbh, (4)
Gilead Sciences, Inc, Foster City, California, USA, (5)Gilead
Sciences, Inc.
Background: Following > 4 years of treatment with tenofovir
disoproxil fumarate (TDF), 42 patients were randomized (1:1)
to either continue or discontinue TDF and followed for 144
weeks (FINITE study). In the discontinue arm, HBsAg loss had
occurred in 4/21 patients and 8 patients required re-treatment.
We aimed at investigating the association of circulating HBV
biomarkers with HBsAg loss and need for re-treatment after
TDF discontinuation. Methods: A total of 210 serum samples
stored at -20°C collected from 42 patients at weeks 12, 24,
36 and 48 after TDF discontinuation was analyzed. Levels
of HBV DNA, HBsAg, components of HBsAg, HBV RNA and
HBcrAg and were quantified by either real time PCR (Roche,
LOD 6IU/mL), ELISA (Abbott Architect, LOD 0.5 IU/mL),
ELISA (LHBs, LOD=0.03ng/mL; MHBs, LOD=0.47ng/mL;
SHBs/total HBsAg, LOD=0.08ng/mL; HBsAg 6.0, Enzgnost,
Siemens), specific real-time PCR (LOD 800 copies/mL) or
ELISA (Fujirebio, LOD 2 log10IU/mL), respectively. End points
were HBsAg loss or re-treatment with TDF by week 144.
Results: Absence of re-treatment was associated with lower
mean HBcrAg levels at baseline (3.2±1.4 (3-3.9) vs. 3.7±1.6
(3-7.5) log10 U/mL; p=0.019), higher ratios of SHBs (83 (79-88)
vs. 92 (82-100);p=0.007), lower increases in mean HBV DNA
(2.4±0.9 (1.3-4.2) vs. 4.7±1.7 (2.5-7.8) log10 IU/mL; p=0.003)
and HBV RNA (1.2±1.3 (0-1.3) vs. 2.7±2.6 (0-6.3) log10 c/mL;
p=0.005) at week 12. Patients with HBsAg loss showed a lower
increase in mean HBV DNA at weeks 12 (1.7±0.4 (1.3-2.2)
vs. 3.7±1.6 (1.3-7.8); p=0.008) and 24 (1.8±0.6 (1.3-2.6) vs.
3.3±1.1 (2-5.1); p=0.011) and lower mean HBsAg at baseline
(3.7±0.7 (2.7-4.2) vs. 4.5±0.6 (2.7-5.3); p=0.019), weeks 12
(3.0±0.8 (2.1-3.6) versus 4.6±0.7 (2.1-3.6); p=0.0082) and
24 (1.8±1.2 (0.2-3.2) versus 4.4±0.7 (2.7-5.3) log10 IU/mL;
p=0.0034) and there was a trend towards lower MHBs ratios
at all time points. HBV RNA was undetectable by week 12
in all patients with and in 8/17 patients without HBsAg loss
(p=0.031). Patients who continued TDF treatment showed no
changes in HBV biomarkers at all time points. Conclusion:
Lower levels of HBcrAg before TDF discontinuation as well
as the kinetics of, HBV DNA, HBV RNA and SHBs were
associated with treatment free follow up and HBsAg levels
at baseline and during follow up as well as HBV DNA kinetics
with subsequent HBsAg loss. Interestingly, HBV DNA and
HBV RNA relapses following TDF discontinuation were
significantly greater in those patients without response. Our
findings need to be validated in larger cohorts作者: StephenW 时间: 2018-10-23 15:33
s 458D
循环乙型肝炎病毒协会
（HBV）HBsAg丧失和生长标志物的生物标志物
停产后无再治疗
替诺福韦（DF）长期治疗
HBeAg阴性患者的有限研究
FlorianvanBömmel1，AlenaVanBömmel2，Danilo Deichsel1，
Maria Pfefferkorn1，Christin Felkel1，Janett Fischer1，Sandra
Krohn1，Karen Rother1，Jessica Wacker3，Martin Brehm3，
Rainer Dannenberg3，Anuj Gaggar4，William E. Delaney5，
Andrea Cathcart4和Thomas Berg1，（1）部门
胃肠病学和风湿病学，肝病学科，
莱比锡大学医院，（2）马克斯普朗克研究所
Molecular Genetics，（3）Mvz Labor Dessau Gmbh，（4）
Gilead Sciences，Inc，Foster City，California，USA，（5）Gilead
科学公司
背景：使用替诺福韦治疗> 4年
disoproxil fumarate（TDF），42例患者随机分组（1：1）
继续或停止TDF，然后是144
周（有限研究）。在停药组中，HBsAg丢失了
发生在4/21例患者中，8例患者需要再次治疗。
我们的目的是调查循环HBV的关联
HBsAg丢失的生物标志物，需要再次治疗
TDF中止。方法：共210份血清样本
储存于-20°C，在第12周，第24周收集42名患者，
分析TDF中断后的36和48。水平
HBV DNA，HBsAg，HBsAg成分，HBV RNA和HBV
HBcrAg并通过实时PCR（Roche，
LOD 6IU / mL），ELISA（Abbott Architect，LOD 0.5 IU / mL），
ELISA（LHBs，LOD = 0.03ng / mL; MHBs，LOD = 0.47ng / mL;
SHB /总HBsAg，LOD = 0.08ng / mL; HBsAg 6.0，Enzgnost，
西门子），具体的实时PCR（LOD 800拷贝/ mL）或
ELISA（Fujirebio，LOD 2 log10IU / mL）分别为。终点
到第144周时，HBsAg丢失或再次使用TDF治疗。
结果：没有再治疗与较低的相关
基线时的平均HBcrAg水平（3.2±1.4（3-3.9）对3.7±1.6
（3-7.5）log10 U / mL; p = 0.019），SHB比例较高（83（79-88））
与92（82-100）; p = 0.007），平均HBV DNA增加较低
（2.4±0.9（1.3-4.2）对4.7±1.7（2.5-7.8）log10 IU / mL; p = 0.003）
和HBV RNA（1.2±1.3（0-1.3）vs。2.7±2.6（0-6.3）log10 c / mL;
p = 0.005）在第12周.HBsAg丢失的患者显示较低
第12周平均HBV DNA增加（1.7±0.4（1.3-2.2）
vs. 3.7±1.6（1.3-7.8）; p = 0.008）和24（1.8±0.6（1.3-2.6）vs.
3.3±1.1（2-5.1）; p = 0.011）并且在基线时降低平均HBsAg
（3.7±0.7（2.7-4.2）对4.5±0.6（2.7-5.3）; p = 0.019），第12周
（3.0±0.8（2.1-3.6）对4.6±0.7（2.1-3.6）; p = 0.0082）和
24（1.8±1.2（0.2-3.2）对比4.4±0.7（2.7-5.3）log10 IU / mL;
p = 0.0034）并且存在降低MHB比率的趋势
在所有时间点。到第12周时HBV RNA检测不到
所有患者和8/17例患者均无HBsAg丢失
（p值= 0.031）。持续TDF治疗的患者没有
在所有时间点HBV生物标志物的变化。结论：
在TDF中止之前，HBcrAg水平也较低
作为HBV DNA，HBV RNA和SHBs的动力学
与无治疗随访和HBsAg水平相关
在基线和随访期间以及HBV DNA动力学
随后HBsAg丢失。有趣的是，HBV DNA和
TDF停药后HBV RNA复发率为
没有反应的患者显着增加。我们的
研究结果需要在更大的队列中得到验证