Hepatitis B Clinical Research Network

 描述（由申请人提供）：慢性B型肝炎病毒（HBV）影响全球超过3.5亿人和超过150万美国人，使他们处于发生肝硬化、肝功能衰竭和肝细胞癌的风险中。HBV的自然史是可变的，但往往遵循4个阶段：免疫耐受（IT），免疫活性（IA），非活性和清除。这些阶段取决于暴露年龄以及病毒和宿主特征。目前的指南建议仅对免疫活性疾病患者进行治疗。虽然大多数患者口服抗HBV治疗可以抑制病毒，但由于肝细胞中存在共价闭合环状DNA形式的持续病毒以及HBV DNA整合到人类基因组中，因此不可能“治愈”。B型肝炎研究网络（HBRN）成立于2008年，由21个成人和7个儿科站点、病毒学/血清学核心、免疫学中心和数据协调中心组成。在最初的资助期间，该网络建立了一个成人和儿童队列研究，成人IA研究，成人和儿童IT研究，以及几个辅助研究，重点关注各种临床场景的特定方面。在最初的供资周期中，HBRN已经招募了1869名成年人和368名儿童。生物样本库包含超过188，000份成人和7300份儿科血浆和血清样本，以及超过1479份成人和205份儿科全血DNA样本。HBRN在下一个资助周期的主要目标是在成人和儿童中进行慢性HBV的临床试验，前瞻性地量化数据库队列中的结果，并利用这些数据和先前收集的生物样本更好地了解疾病进展，并验证有临床意义的生物标志物。本研究的具体目的如下：1.成功完成在最初资助期间启动的研究。2.成功完成HBRN在初始资助期内批准的所有辅助研究。3.根据上一个资助期内收集的临床资料和样本，进行新的成人和儿童辅助研究。在初始资助期间，入组了几个新人群，这将使HBRN能够解决几个知识空白，例如（a）表征不确定HBV（既不是IA、IT，也不是非活动性）患者的组织学、病毒学和免疫学特征，（B）确定IT和IA试验之外患者停止抗病毒治疗的临床意义。(c)丁型肝炎病毒的治疗，和（d）评估替诺福韦对骨骼健康的长期影响。

 DESCRIPTION (provided by applicant): Chronic hepatitis B virus (HBV) affects over 350 million worldwide and over 1.5 million Americans, placing them at risk for developing cirrhosis, liver failure, and hepatocellular carcinoma. The natural history of HBV is variable but tends to follow 4 phases: immune tolerant (IT), immune active (IA), inactive, and clearance. These phases are dependent on age of exposure and both viral and host characteristics. Current guidelines recommend treatment only in those with immune active disease. Although viral suppression is achievable in most patients with oral anti-HBV therapy, "cure" is not possible because of persistent virus in hepatocytes in the form of covalently closed circular DNA and the integration of HBV DNA into the human genome. The Hepatitis B Research Network (HBRN), established in 2008, is composed of 21 adult and 7 pediatric sites, a Virology/Serology Core, an Immunology Center, and a Data Coordinating Center. During the initial funding period, the Network established an Adult and Pediatric Cohort study, an Adult IA study, an Adult and Pediatric IT study, and several Ancillary studies that focus on specific aspects of various clinica scenarios. Over the initial funding cycle, the HBRN has enrolled 1869 adults and 368 children. The bio-specimen repository contains over 188,000 adult and 7300 pediatric plasma and serum samples, and over 1479 adult and 205 pediatric whole blood DNA specimens. The primary goals of the HBRN over the course of the next funding cycle are to perform clinical trials on chronic HBV in adults and children, prospectively quantify outcomes in the database cohort, and leverage these data and previously collected bio-specimens to better understand disease progression, and validate clinically meaningful biomarkers. The specific aims of these studies are as follows: 1. To successfully complete the studies which have been initiated during the initial funding period. 2. To successfully complete all Ancillary Studies already approved by the HBRN during the initial funding period. 3. To undertake new Ancillary Studies in Adults and Children based on the clinical material and samples collected during the previous funding period. During the initial funding period, several novel populations were enrolled, which will allow the HBRN to address several gaps in knowledge such as (a) characterize histologic, virologic, and immunologic features of those with indeterminate HBV (neither IA, IT, or inactive), (b) determine the clinical implications of stopping anti-viral therapy in those outside of the IT ad IA trials. (c) treatment for hepatitis delta virus, and (d) assess the long-term effects of tenofovr on bone health.