长期抑制病毒，HBeAg阴性慢性乙型肝炎后停药替诺福韦可以HBs

StephenW

J Clin Virol. 2015 Jul;68:61-8. doi: 10.1016/j.jcv.2015.05.002. Epub  2015 May 8.
Tenofovir discontinuation after long-term viral suppression in HBeAg negative chronic hepatitis B. Can HBsAg levels be useful?Buti M1, Casillas R2, Riveiro-Barciela M2, Homs M3, Tabernero D3, Salcedo MT4, Rodriguez-Frias F3, Esteban R5.
Author information

• 1Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: [email protected].
• 2Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona, Barcelona, Spain.
• 3Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Liver Pathology Unit, Departments of Biochemistry and Microbiology (Virology Unit) Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona, Barcelona, Spain.
• 4Pathology Department, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona, Barcelona 08035, Spain.
• 5Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona, Barcelona, Spain.
  

AbstractBACKGROUND: Recent studies have shown that antiviral treatment discontinuation is safe and associated with virologic remission in HBeAg-negative patients. However, the period of viral suppression and follow-up in these studies was relatively short.
OBJECTIVES: To investigate whether continuous viral suppression with tenofovir disoproxil fumarate for more than 7 years is associated with HBsAg loss and sustained response after treatment discontinuation and receiving a full course of hepatitis B vaccination.
STUDY DESIGN: Patients with HBeAg-negative chronic HBV infection and more than 7 years of persistent viral suppression with tenofovir therapy were selected for treatment discontinuation and HBV vaccination. Follow-up with monthly ALT, HBV-DNA, and HBsAg determinations lasted 72 weeks. In patients with viral relapse, the viral quasispecies in the overlapping reverse transcriptase and small surface protein regions was analysed by ultra-deep pyrosequencing.
RESULTS: Eight of 17 HBeAg-negative patients accepted tenofovir discontinuation: 5 patients achieved sustained response (persistent HBV-DNA levels <2000IU/mL and normal ALT) despite an initial virologic relapse, one lost HBsAg, and two needed re-treatment. All patients with an on-treatment HBsAg level decline >5000IU/mL achieved sustained response. Patients with HBsAg level <100IU/mL during an ALT flare after antiviral discontinuation achieved sustained response. Significant changes were seen in the composition of the HBV quasispecies, and half the patients showed changes in HBV genotype.
CONCLUSIONS: Even though the majority of patients presented an initial relapse with selection of HBV variants, most achieved sustained response. Changes in HBsAg levels on and off treatment may be useful for predicting the likelihood of virologic remission.
Copyright © 2015 Elsevier B.V. All rights reserved.


KEYWORDS: HBeAg chronic hepatitis B; HBsAg levels; HBsAg loss; Sustained response; TDF discontinuation

StephenW

Ĵ临床病毒学杂志。 2015年七月; 68：61-8。 DOI：10.1016 / j.jcv.2015.05.002。 EPUB 5月8日2015年。
长期抑制病毒，HBeAg阴性慢性乙型肝炎后停药替诺福韦可以HBsAg水平是有用的？
布提M1，卡西利亚斯R2，Riveiro-M2巴尔谢拉，霍姆斯M3，Tabernero D3，萨尔塞多MT4，罗德里格斯·弗里亚斯F3，埃斯特万R5。
作者信息

    1Centro德InvestigaciónBIOMEDICA恩红日EnfermedadesHepáticasÿDigestivas（CIBERehd），德研究所Salud的卡洛斯三世，马德里，西班牙;肝单位，内科，医院Universitari瓦勒d'Hebron城和巴塞罗那自治大学，巴塞罗那，西班牙系。电子地址：[email protected]。
    2Liver单位，内科，医院Universitari瓦勒d'Hebron城和巴塞罗那自治大学，巴塞罗那，西班牙。
    3Centro德InvestigaciónBIOMEDICA恩红日EnfermedadesHepáticasÿDigestivas（CIBERehd），德研究所Salud的卡洛斯三世，马德里，西班牙;肝脏病理单位，生物化学部门和微生物学（病毒学单位）医院Universitari瓦勒d'Hebron城和巴塞罗那自治大学，巴塞罗那，西班牙。
    4Pathology署，医院Universitari瓦勒d'Hebron城和巴塞罗那自治大学，巴塞罗那08035，西班牙。
    5Centro德InvestigaciónBIOMEDICA恩红日EnfermedadesHepáticasÿDigestivas（CIBERehd），德研究所Salud的卡洛斯三世，马德里，西班牙;肝单位，内科，医院Universitari瓦勒d'Hebron城和巴塞罗那自治大学，巴塞罗那，西班牙系。

抽象
背景：

最近的研究表明，抗病毒治疗停药是安全的，并与HBeAg阴性患者病毒学缓解有关。然而，抑制病毒和后续的这些研究期间相对较短。
目的：

探讨持续的病毒抑制与富马酸替诺福韦酯为7年以上是否与HBsAg消失和停药后持久的反应和接受乙肝疫苗接种全过程相关联。
研究设计：

例HBeAg阴性慢性HBV感染者和超过7年持续的病毒抑制替诺福韦治疗被选定为治疗中断和乙肝疫苗。后续每月ALT，HBV-DNA，与HBsAg持续确定72周。病毒性肝炎患者复发，在重叠逆转录酶和小的表面蛋白区域的病毒准种的超深焦磷酸测序分析。
结果：

17 HBeAg阴性患者接受八停用替诺福韦：5例患者尽管一开始病毒学复发实现了持续应答（持续HBV-DNA水平<2000IU / mL和ALT正常），一个失去了乙肝表面抗原和两个所需的再处理。所有患者的一间治疗乙肝表面抗原水平下降> 5000IU / mL的取得持续的反应。患者的HBsAg水平<100IU /毫升时抗病毒停药后ALT耀斑取得持续的反应。显著变化主要出现在HBV准种的组成，一半患者表现改变HBV基因型。
结论：

尽管多数患者提出了一个初步的复发与选择的HBV变异，大多数取得了持续的反应。改变HBsAg水平上落治疗可能是预测病毒学缓解的可能性非常有用。

版权所有©2015年爱思唯尔BV保留所有权利。
关键词：

大三阳慢性乙型肝炎; HBsAg水平; HBsAg消失;持续应答; TDF停药

咬牙硬挺

感谢分享

682256

and half patiences showed changes in HBV genotype.一半病人HBV基因种类改变了。

682256

西班牙学者得出了替诺变异的结论？

高高山顶立

变异是坑定的，在长期的替诺筛选下。不知变异了的病毒毒性是增强了还是减弱了，免疫系统是更容易识别还是更不容易。

StephenW

682256 发表于 2015-6-24 19:34
西班牙学者得出了替诺变异的结论？

"changes in HBV genotype" -
http://www.sciencedirect.com/sci ... i/S1201971210024239
"Due to the lack of proof-reading activity of DNA- and RNA-dependent DNA polymerase, mis-incorporations of nucleotides occur during viral replication. The rate of nucleotide substitution per site is estimated to be 1.4–3.2 × 10^(−5) per year.[7] and [8] This has led to the emergence of HBV genotypes and subgenotypes. At least eight different genotypes (A–H) have been identified that differ in more than 8% of the genome, while subgenotypes differ by at least 4%."

在我看来，病毒基因组时刻都在变化. 这些患者, 病毒基因组变化没有导致泰诺物药.