Bay Area Hepatitis C Cooperative Research Center

描述（由申请人提供）：丙型肝炎病毒（HCV）感染是美国肝脏相关发病率和死亡率的主要原因。尽管一些感染者能够自发清除病毒，目前的治疗方案也能在其他感染者中产生持续的病毒学反应，但治疗失败的频率仍然高得令人无法接受。为了更好地了解免疫反应对病毒清除的贡献，我们建议建立湾区丙型肝炎合作研究中心。本中心的目标是定义慢性感染HCV的先天和适应性免疫反应的生物学，了解这些反应是如何通过治疗调节的，并辨别免疫反应的哪些参数与治疗的有效抗病毒反应相关（并可能预测）。该中心将在旧金山湾区的多个地点组建一支强大的多学科团队，由免疫学家和临床研究人员组成，包括与加州大学旧金山分校（旧金山总医院、加州大学医疗中心和旧金山退伍军人事务医疗中心）以及加州太平洋医疗中心、血液系统研究所、以及北加州的凯撒医疗机构（Kaiser Permanente）。临床流行病学核心(由dr。KP研究部的Michele Manos和UCSF的Norah Terrault将开发和管理(a)一个由200名对标准治疗有反应或无反应的受试者组成的回顾性病例对照队列，以及(b)一个未经治疗的受试者的前瞻性队列，他们将在治疗开始前后进行随访。在项目1中(由dr。UCSF的James Ryan和Lewis Lanier)，将研究先天免疫对治疗反应的贡献。同时，使用同一组患者样本。项目2(由dr。加州大学旧金山分校的Dennis Hartigan- O'Connor和Joseph McCune将分析适应性T细胞和B细胞对HCV的作用。对这两个项目中获得的数据进行协调分析，将允许对说明先天系统和适应系统之间相互作用的离散假设进行检验。该中心的活动将通过一个行政核心组织，由PI （mcune博士）指导。我们期待该中心的努力将提供数据，可以在短期内为治疗决策提供信息，并有助于长期开发更好、更普遍适用的慢性HCV疾病治疗方法。

DESCRIPTION (provided by applicant): Hepatitis C virus (HCV) infection is the leading cause of liver-related morbidity and mortality in the United States. Although spontaneous clearance of virus occurs in some who are infected and current treatment regimens result in sustained virologic response in others, there remains an unacceptably high frequency of treatment failure. To better understand the contribution of the immune response to viral clearance, we propose the creation of a Bay Area Hepatitis C Cooperative Research Center. The goals of this Center are to define the biology of the innate and adaptive immune responses to HCV in the setting of chronic infection, to understand how these responses are modulated by treatment, and to discern which parameters of the immune response are associated with (and possibly predictive of) an effective antiviral response to therapy. The Center will assemble a strong multidisciplinary team comprised of immunologists and clinical investigators at multiple sites in the San Francisco Bay Area, including three different sites associated with the University of California at San Francisco (UCSF) (San Francisco General Hospital, UC Medical Center, and the San Francisco Veterans Affairs Medical Center) as well as with the California Pacific Medical Center, the Blood Systems Research Institute, and Kaiser Permanente (KP) of Northern California. A Clinical Epidemiology Core (led by Drs. Michele Manos of KP Division of Research and Norah Terrault of UCSF) will develop and manage (a) a retrospective case-control cohort of 200 subjects who did or did not respond to standard-of-care therapy, and (b) a prospective cohort of treatment-naive subjects who will be followed before and after the initiation of therapy. In Project 1 (led by Drs. James Ryan and Lewis Lanier of UCSF), the contribution of innate immunity to treatment response will be studied. Concomitantly, and using the same set of patient samples. Project 2 (led by Drs. Dennis Hartigan- O'Connor and Joseph McCune of UCSF) will analyze the role of adaptive T and B cell responses against HCV. Coordinated analyses of data obtained in both Projects will permit tests of discrete hypotheses that speak to interactions between the innate and adaptive systems. The activities of the Center will be organized through an Administrative Core, directed by the PI (Dr. McCune). We anticipate that the efforts of this Center will provide data that can inform treatment decisions in the short term and contribute to development of better and more generally applicable therapies for chronic HCV disease in the longer term.