The Risk of Transfusion Transmission of Hepatitis E Virus

描述(申请人提供)：戊型肝炎病毒(HEV)自20年前被证明是亚洲水生疫情的罪魁祸首以来，已被公认为全球人类肝炎的重要原因。目前已知，在美国、欧洲和其他国家，这种病毒会通过猪和其他动物的人畜共患宿主引起临床和亚临床型肝炎。由于HEV感染通常会在成年人中引起静默感染，它也可以通过输血传播。然而，尽管来自欧洲和日本的一些病例报告以及在血浆池中检测到HEV RNA，但在美国和其他地方输血传播的风险尚不清楚。免疫功能低下的患者、孕妇和肝病患者感染HEV可能会有严重的发病率或死亡率。在这项研究中，我们将通过研究三个人群来估计通过输血传播HEV的风险。我们将研究从5,000名肝酶升高且未感染乙肝和丙型肝炎的中国献血者的血清库中抗-HEVIgM和HEVRNA的流行率。其次，我们将测量上世纪90年代初在国家卫生研究院资助的FACTS研究中登记的11,532名患者的血清转换率。在这项研究中，9,294名患者接受了来自120,000多名献血者的血液产品输血，2,238名类似的受试者没有输血作为对照。第三，我们将通过雷达研究来测量3575名患者输血传播HEV的风险。雷达研究是一个关联的捐赠者和接受者储存库。我们将对与输血后血清转换的患者有关联的献血者进行HEV活动性感染的证据检测，即HEV RNA和抗HEV IgM。如有可能，将对来自捐赠者和接受者的HEV毒株进行测序。我们还将测试100个迷你库中的50个血浆样本，即5,000个独立样本，这些样本来自雷达存储库，与接收者脱钩。阳性池将按顺序重新检测，以解决个别门的传染性。这三项相互关联的研究将使我们能够估计通过输血产品传播HE的风险水平。如果这一风险得到证实，我们的数据可以用来制定筛查捐赠者的政策，以防止最近在高危患者中记录的HEV感染的严重临床后果。

DESCRIPTION (provided by applicant): 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 door. These three inter-related studies will allow us to estimate the level of risk of transmission of HE 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.