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发表于 2018-6-30 16:25 |只看该作者 |倒序浏览 |打印

Hepatology
Original article
Multiple HBV transfusion transmissions from undetected occult infections: revising the minimal infectious dose

    Daniel Candotti1, Sonny Michael Assennato2, Syria Laperche1, Jean-Pierre Allain2, Snezna Levicnik-Stezinar3

Author affiliations

    Department of Blood Transmitted Agents, National Institute of Blood Transfusion, Paris, France
    Department of Haematology, University of Cambridge, Cambridge, UK
    Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia

    Correspondence to Dr Daniel Candotti, Department of Blood Transmitted Agents, National Institute of Blood Transfusion, 75015 Paris, France; [email protected]

Abstract

Objective HBV infection by blood components is currently prevented in most developed countries by combining sensitive HBV surface antigen (HBsAg) assays, nucleic acid testing (NAT) and in a few of them antibodies against the HBV core antigen (anti-HBc) screening. HBV transmissions by blood components from three repeat donors tested negative for HBsAg and HBV DNA with a highly sensitive screening test (limit of detection (LOD): 3.4 IU/mL) were investigated.

Design 30 of the 47 recipients of components produced from these three donors were examined. Transfusion transmission was confirmed by phylogenetic analysis of viral sequences obtained from recipients and donors following viral particle concentration.

Results 9 of 31 (29%) recipients were infected: 7 infections were related to 200 mL of fresh frozen plasma and 2 infections to red blood cells containing 20 mL plasma. Transfusion transmission was confirmed by >99% identity of donor/recipient sequences in five cases, probable in three and possible in one. HBV active infection remained unsuspected for 24–57 months in three recipients. Five non-infected recipients carried anti-HBs when transfused. Six patients transfused with platelet concentrates treated with a pathogen reduction method were not infected. These data enabled to revise previous estimate of the minimal infectious dose from approximately 100 to 16 copies (or 3 IU) of HBV DNA.

Conclusions HBV transfusion transmission from occult HBV infection carrying extremely low viral loads is related to plasma volume transfused and possibly prevented by anti-HBs. HBV blood safety could be further improved by either anti-HBc screening, HBV DNA NAT with a LOD of 0.8 copies/mL (0.15 IU/mL) or pathogen reduction of blood components.

http://dx.doi.org/10.1136/gutjnl-2018-316490

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Footnotes

    Contributors DC designed the study, performed molecular investigations, analysed data and wrote manuscript. SMA performed molecular experiments, contributed to data analysis, reviewed manuscript. SL contributed to experiment design, data analysis and manuscript writing. J-PA contributed to study design, data analysis and manuscript writing. SL-S designed the study, identified and collected samples, analysed data and wrote manuscript.

    Funding This work was supported by a Grifols Diagnostics research grant to DC.

    Competing interests None declared.

    Patient consent Not required.

    Provenance and peer review Not commissioned; externally peer reviewed.

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发表于 2018-6-30 16:25 |只看该作者
肝病
来源文章
未发现隐匿性感染的多次HBV输血传播:修改最小感染剂量

    Daniel Candotti1,Sonny Michael Assennato2,叙利亚Laperche1,Jean-Pierre Allain2,Snezna Levicnik-Stezinar3

作者从属关系

    法国巴黎国立输血研究所血液传播代理处
    英国剑桥大学血液学系
    斯洛文尼亚的输血中心,斯洛文尼亚卢布尔雅那

    对应于法国巴黎75015国立输血研究所血液传播代理部Daniel Candotti博士; [email protected]

抽象

通过结合敏感的HBV表面抗原(HBsAg)检测,核酸检测(NAT)以及其中一些针对HBV核心抗原(抗-HBc)筛选的抗体,大多数发达国家目前都可以防止血液成分感染HBV。通过高度敏感的筛选试验(检测限(LOD):3.4IU / mL),来自三个重复供体的血液成分的HBV传递测试为HBsAg和HBV DNA阴性。

对这三名捐助者生产的47个组件中的30个设计进行了检查。通过系统发育分析病毒颗粒浓度后从受体和供体获得的病毒序列确认输血传播。

结果31例(29%)接受者中有9例感染:7例感染与200 mL新鲜冷冻血浆有关,2例感染含有20 mL血浆的红细胞。输血传播通过5例供体/受体序列> 99%的同一性证实,三例可能,一例可能。在三名接受者中,HBV活动性感染在24-57个月内未受到怀疑。五名未感染者在输血时携带抗-HBs。用病原体还原法治疗的6名输注血小板浓缩物的患者未被感染。这些数据能够修改以前估计的最低感染剂量,大约为100到16个拷贝(或3 IU)的HBV DNA。

结论携带极低病毒载量的隐匿性HBV感染的HBV输血传播与输注血浆容量有关,并可能被抗-HBs阻止。通过抗-HBc筛选,HBV DNA NAT,LOD为0.8拷贝/ mL(0.15 IU / mL)或血液成分的病原体减少,可以进一步改善HBV血液安全性。

http://dx.doi.org/10.1136/gutjnl-2018-316490

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脚注

    撰稿人DC设计了这项研究,进行了分子检查,分析了数据并撰写了手稿。 SMA进行分子实验,为数据分析做出贡献,审查手稿。 SL有助于实验设计,数据分析和手稿撰写。 J-PA致力于研究设计,数据分析和手稿撰写。 SL-S设计了这项研究,确定并收集了样本,分析了数据并撰写了手稿。

    资助这项工作得到了Grifols Diagnostics研究基金的支持。

    竞争利益无声明。

    患者同意不需要。

    出处和同行评审未委托;外部同行评审。
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