The Risk of Transfusion Transmission of Hepatitis E Virus

摘要/总结 戊型肝炎病毒（HEV）是世界范围内公认的人类肝炎的重要原因， 它被证明是20年前亚洲水传播疾病爆发的原因。目前已知该病毒 在美国，欧洲和其他国家引起临床和亚临床肝炎的人畜共患病 猪和其他动物的寄生虫。由于HEV感染通常会导致成年人的隐性感染， 通过输血传播，从渐近捐助者。然而，尽管有一些案例报告， 欧洲和日本的血浆池中检测到HEV RNA， 美国和其他地方是未知的。免疫功能低下患者、孕妇和 肝病患者可能具有严重的发病率或死亡率。在这项研究中，我们将估计 通过对三个人群的研究，探讨了血液制品输注对戊型肝炎病毒传播的影响。我们会研究 5,000名献血员血清抗-HEVIgM和HEVRNA的流行病学调查 未感染B和C型肝炎的肝酶升高患者。其次，我们将测量 在NHLBI资助的FACTS研究中招募的11，532名患者样本中的血清转换率 90年代初。在这项研究中，9，294名患者输注了来自120，000多名献血者的血液制品 另2,238名相似的受试者不输血，作为对照。第三，我们将衡量 RADAR研究中3,575例HEV输血传播。雷达研究是一个相关的 捐助者-受援者储存库。我们将检测与任何在其感染后发生血清转化的患者相关的供体。 输血以证明活动性HEV感染，即HEV RNA和抗HEV IgM。戊型肝炎病毒株 在可能的情况下，将对捐赠者和接受者进行测序。我们还将测试100个含有50个血浆的小型池， 从雷达储存库中提取5,000个样本，即5,000个单独样本，这些样本与接收者没有联系。积极 将按顺序重新检测样本池，以确定单个供体的感染性。这三个相互关联的 研究将使我们能够估计通过输血传播HEV的风险水平。如果 如果这种风险得到证实，我们的数据可用于制定筛选供体的政策，以防止最近的 记录了高风险患者中HEV感染的严重临床后果。

ABSTRACT/SUMMARY Hepatitis E virus (HEV) has been recognized as an important cause of human hepatitis worldwide, since it was shown to be responsible for water-born outbreaks in Asia two decades ago. The virus is now known to cause clinical and subclinical hepatitis in the United States, Europe and other countries from a zoonotic reservoir in pigs and other animals. Since HEV infection typically causes silent infection in adults, it can also be transmitted by blood transfusion from asymptotic donors. However, despite a few case reports from Europe and Japan and the detection of HEV RNA in plasma pools, the risk of transfusion transmission in the US and elsewhere is unknown. HEV infection in immunocompromised patients, pregnant women and patients with liver disease can have serious morbidity or mortality. In this study we will estimate the risk of transmission of HEV by blood product transfusion by studying three populations. We will study the prevalence of anti-HEV IgM and HEV RNA in a serum repository obtained from 5,000 Chinese blood donors with elevated liver enzymes who were not infected with hepatitis B and C. Secondly, we will measure the rate of sero-conversion among a sample of 11,532 patients enrolled in the NHLBI-funded FACTS study in the early 1990's. In this study, 9,294 patients were transfused with blood products from over 120,000 donors and 2,238 similar subjects were not transfused, who will serve as controls. Third, we will measure the risk of transfusion transmission of HEV in 3,575 patients with RADAR study. The RADAR study is a linked donor-recipient repository. We will test the donors linked to any patients who have sero-converted after their transfusion for evidence of active HEV infection, i.e. HEV RNA and anti-HEV IgM. Strains of HEV from donors and recipients will be sequenced when possible. We will also test 100 mini-pools of 50 plasma samples, i.e. 5,000 individual samples, from the RADAR repository that are unlinked to a recipient. Positive pools will be re-tested sequentially to resolve infectivity of an individual donor. These three inter-related studies will allow us to estimate the level of risk of transmission of HEV by transfusion of blood products. If this risk is confirmed, our data can be used to develop policies for screening donors to prevent the recent documented serious clinical consequences of HEV infection among high risk patients.