Hepatitis B Clinical Research Network Clinical Center: Michigan - Hawaii Consortium

 描述（由申请人提供）：B肝炎病毒（HBV）感染仍然是美国（US）的主要公共卫生问题，估计有多达220万人慢性感染。B型肝炎研究网络（HBRN）成立于2008年，旨在解决2008年NIH B型肝炎共识会议上确定的研究重点。HBRN由美国和加拿大多伦多的13个临床联盟（21个成人和7个儿科临床中心）、一个数据协调中心和一个免疫学中心组成。在HBRN的初始资助周期中，研究人员开发并实施了一项观察性队列研究，一项针对免疫耐受期患者的临床试验和一项针对HBV感染免疫活跃期患者的临床试验。本临床中心申请包括2个研究中心：密歇根大学（安阿伯）（PI：Lok博士）和夏威夷大学/皇后医学中心（檀香山）（PI：Tsai博士）。夏威夷-里根（MI-HI）团队通过招募和保留患者以及收集数据和生物标本为HBRN研究做出了重要贡献。此外，我们在设计研究方案和数据表格、担任HBRN委员会主席以及起草和编辑摘要和手稿方面发挥了关键作用。作为HBRN指导委员会和执行委员会的主席，Lok博士在科学研究的设计和执行、制定HBRN政策以及与行业合作伙伴建立合作方面发挥了领导作用。在HBRN的下一个资助周期中，MI-HI联盟的具体目标是：1）继续招募患者参加HBRN研究，并跟踪那些已经招募的患者完成研究; 2）利用收集的数据和生物标本促进新研究提案的发展，以进一步了解B型肝炎的流行病学、自然史、发病机制和治疗; 3）参与数据分析 并通过抽象的演示文稿和手稿传播。我们提出的辅助研究旨在确定：1）HBsAg和抗- HBs共存的患病率; 2）相关流行病学因素; 3）临床意义; 4）定量HBsAg水平及其与抗-HBs水平的相关性; 5）免疫逃逸变异体和混合HBV基因型/血清型的患病率;（6）HBsAg和抗-HBs共存的HBRN参与者（成人和儿童）循环抗-HBs的表位识别和中和能力。

 DESCRIPTION (provided by applicant): Hepatitis B virus (HBV) infection remains a major public health problem in the United States (US) with an estimate of up to 2.2 million persons chronically infected. The Hepatitis B Research Network (HBRN) was established in 2008 to address the research priorities identified at the 2008 NIH Consensus Conference on Hepatitis B. The HBRN comprises 13 clinical consortia (21 adult and 7 pediatric clinical centers) in the US and in Toronto, Canada, a data coordinating center, and an immunology center. During the initial funding cycle of HBRN, the investigators developed and implemented an observational cohort study, a clinical trial for patients in the immune tolerant phase and a clinical trial for patients in the immune active phase of HBV infection. This Clinical Center application comprises 2 sites: University of Michigan in Ann Arbor (PI: Dr. Lok) and University of Hawaii/Queen's Medical Center in Honolulu (PI: Dr. Tsai). The Michigan-Hawaii (MI-HI) team has made important contributions to the HBRN studies through enrollment and retention of patients, and data and biospecimen collection. Furthermore, we have played a key role in designing the study protocols and data forms, serving and chairing on HBRN committees, and drafting and editing abstracts and manuscripts. As Chair of the HBRN Steering Committee and Executive Committee since its inception, Dr. Lok has provided leadership in the design and execution of scientific studies, establishing policies for HBRN, and setting up collaboration with industry partners. The specific aims of the MI-HI consortium in the next funding cycle of HBRN are: 1) to continue to enroll patients into HBRN studies and to follow those who have been enrolled to study completion; 2) to contribute to the development of new study proposals making use of data and biospecimens that are collected to further our understanding of the epidemiology, natural history, pathogenesis, and treatment of hepatitis B; and 3) to participate in data analyses and dissemination through abstract presentations and manuscripts. The ancillary study we propose aims to determine: 1) prevalence of co-existent HBsAg and anti- HBs; 2) associating epidemiologic factors; 3) clinical significance; 4) quantitative HBsAg levels and correlation with anti-HBs levels; 5) prevalence of immune escape variants and mixed HBV genotypes/serotypes; and 6) epitope recognition and neutralizing ability of circulating anti-HBs in HBRN participants (adults and children) with co-existent HBsAg and anti-HBs.