Bay Area Hepatitis C Cooperative Research Center

湾区丙型肝炎合作研究中心

• 批准号: 8282820
• 负责人: JOSEPH M MCCUNE
• 金额: $ 71.73万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-15 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8282820
• 关键词: Accounting; Acute; Acute Hepatitis C; Address; Aftercare; Antibodies; Antigen-Presenting Cells; Antigens; Antiviral Agents; Antiviral Response; Applications Grants; Area; B-Lymphocytes; Biological; Biology; Blood; CCR5 gene; CD94 Antigen; California; Caring; Case-Control Studies; Cell physiology; Cells; Cessation of life; Chronic; Chronic Disease; Chronic Hepatitis C; Cirrhosis; Clinic; Clinical; Clinical Investigator; Clinical Research; Clinical Sciences; Clinical Trials; Combined Modality Therapy; Complex; Computerized Medical Record; Consult; Cytokine Network Pathway; Data; Data Analyses; Data Set; Databases; Dendritic Cells; Development; Enrollment; Ensure; Epidemiology; Ethnic group; Family; Frequencies; General Hospitals; General Population; Genetic Polymorphism; Genotype; Goals; HLA Antigens; Hepatitis C; Hepatitis C Antibodies; Hepatitis C virus; Hispanics; Histocompatibility Antigens Class II; Immune response; Immune system; Immunity; Immunologist; Individual; Infection; Inflammatory; Institutes; Interferon-alpha; Interferons; Laboratories; Lead; Learning; Ligands; Literature; Liver; Macrophage Activation; Malignant neoplasm of liver; Mediating; Medical center; Memory; Morbidity - disease rate; NK Cell Activation; Natural Immunity; Natural Killer Cells; Outcome; Patients; Phenotype; Plasma; Play; Population; Process; Prospective Studies; Recruitment Activity; Regimen; Registries; Research; Research Infrastructure; Research Institute; Resources; Ribavirin; Role; Sampling; San Francisco; Services; Site; Source; Specimen; System; T-Lymphocyte; Testing; Time; Translational Research; Treatment Failure; Treatment Protocols; United States; Universities; Up-Regulation; Veterans; Viral; Viral Load result; Viral hepatitis; Virus; Virus Diseases; Work; adaptive immunity; arm; base; case control; cell motility; chemokine receptor; clinical epidemiology; cohort; cytokine; cytotoxic; cytotoxicity; data management; data sharing; experience; immunoglobulin receptor; improved; insight; liver biopsy; memory acquisition; monocyte; mortality; multidisciplinary; neutralizing antibody; novel; peripheral blood; prospective; racial and ethnic; receptor; research study; response; standard of care; systems research; treatment response

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.

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。尽管一些感染者会自发清除病毒，并且目前的治疗方案会导致其他感染者出现持续的病毒学反应，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，我们建议创建湾区丙型肝炎合作研究中心。该中心的目标是定义慢性感染情况下对 HCV 的先天性和适应性免疫反应的生物学，了解这些反应如何通过治疗进行调节，并辨别免疫反应的哪些参数与（和）相关。可能预测）对治疗的有效抗病毒反应。该中心将组建一支强大的多学科团队，由旧金山湾区多个地点的免疫学家和临床研究人员组成，其中包括与加州大学旧金山分校 (UCSF) 相关的三个不同地点（旧金山综合医院、加州大学医学中心、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、血液系统研究所和北加州凯撒医疗机构 (KP)。临床流行病学核心（由 KP 研究部的 Michele Manos 博士和加州大学旧金山分校的 Norah Terrault 博士领导）将开发和管理 (a) 由 200 名对标准护理有反应或没有反应的受试者组成的回顾性病例对照队列治疗，以及（b）未接受过治疗的受试者的前瞻性队列，他们将在治疗开始之前和之后进行随访。在项目 1（由加州大学旧金山分校的 James Ryan 和 Lewis Lanier 博士领导）中，将研究先天免疫对治疗反应的贡献。同时并使用同一组患者样本。项目 2（由 UCSF 的 Dennis Hartigan-O'Connor 和 Joseph McCune 博士领导）将分析适应性 T 和 B 细胞针对 HCV 的反应的作用。对两个项目中获得的数据进行协调分析将允许对有关先天系统和适应性系统之间相互作用的离散假设进行测试。该中心的活动将通过一个由 PI（McCune 博士）领导的行政核心组织。我们预计该中心的努力将提供可为短期治疗决策提供信息的数据，并有助于开发更好、更普遍适用的长期慢性丙型肝炎疗法。