Hepatitis E in HIV-Infected Patients

 描述(由申请人提供)： 戊型肝炎病毒(HEV)是一种RNA病毒，可导致艾滋病毒携带者或实体器官移植后的急性肝炎和慢性肝病。HIV实体器官移植研究(HIVTR)是一项针对接受肝和/或肾移植的HIV感染者的多中心队列研究。HCVRES和HEPRO是NIH队列研究，收集了艾滋病毒-丙型肝炎病毒感染患者和丙型肝炎病毒对照的数据和样本。将对总共589名艾滋病毒感染患者和非艾滋病毒对照患者进行HEV感染评估。HIVTR队列的初步数据显示，在移植之前，超过20%的受试者有既往感染的血清学证据，近2%的候选肝脏患者最近有急性感染。这项建议旨在确定美国HIV感染者中HEV的流行率、发病率和临床意义。此外，我们将评估免疫学和病毒学与慢性化的相关性以及与肝损伤的相关性。我们建议使用一种有效的检测方法对HEV血清进行纵向评估，并通过实时聚合酶链式反应(Real-Time-PCR)对HEV RNA进行表征。我们实验室开发的一种灵敏的HEV ELISPOT试验将用于评估血清阴性病例及其与既往感染、发病和慢性化风险的关系。使用队列数据库，我们将评估HEV感染持久性和清除性的临床相关性。此外，还将确定慢性感染者的自然病史，包括进展为肝硬变的风险、对其他复发病毒感染(乙肝病毒和丙型肝炎病毒)的影响，以及在移植队列中，移植物丢失的风险。这个 预期结果将为今后艾滋病毒感染者的监测工作提供信息。

 DESCRIPTION (provided by applicant): Hepatitis E Virus (HEV) is an RNA virus associated that can cause both acute hepatitis and chronic liver disease in those with HIV or following solid organ transplantation. The HIV Solid Organ Transplant Study (HIVTR) is a multicenter cohort study of HIV-infected adults who received liver and/or kidney transplantation. HCVRES and HEPRO are NIH Cohort Studies that collected data and samples on HIV-HCV infected patients and HCV controls. A total of 589 HIV infected patients plus non-HIV controls will be evaluated for HEV infection. Preliminary data in the HIVTR cohort demonstrates that prior to transplant over 20% of subjects had serologic evidence of prior infection and nearly 2% of liver candidates had recent acute infection. This proposal is designed to determine the prevalence, incidence and clinical significance of HEV in the HIV infected persons in the U.S.. Furthermore, we will evaluate immunologic and virologic correlates of chronicity and the association with liver injury. We propose to perform longitudinal evaluation of HEV serologies using a validated assay methodology as well as HEV RNA characterization by real-time PCR. A sensitive HEV ELISPOT assay developed in our laboratory will be employed to evaluate seronegative cases and the relationship to prior infection, incident disease and risk of chronicity. Using the cohort databases we will assess the clinical correlates of HEV infection persistence and clearance. Additionally, the natural history of those with chronic infection will be determined, including risk of progression to cirrhosis, effect on other recurrent viral infections (HBV and HCV), and in the transplant cohort, the risk of graft loss. The anticipated results will inform future surveillance practices in HIV-infected persons.