Determinants of Liver Injury in Chronic Hepatitis C Virus Infection

慢性丙型肝炎病毒感染肝损伤的决定因素

基本信息

  • 批准号:
    7575792
  • 负责人:
  • 金额:
    $ 55.81万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2005
  • 资助国家:
    美国
  • 起止时间:
    2005-09-01 至 2010-11-28
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The majority of persons acutely infected with hepatitis C virus (HCV) will develop chronic infection, but not all subjects go on to develop the complications of chronic infection such as hepatic fibrosis or steatosis. Current antiviral treatments are neither effective nor available for most persons with chronic HCV infection, and thus chronic infection remains a significant health problem. The natural history of HCV liver disease combined with the epidemiology of this infection has resulted in an increasing prevalence of persons with chronic HCV, and rising rates of hepatic decomposition and hepatocellular carcinoma. However, our understanding of the host and viral determinants of liver disease progression are poorly understood. This program project will address the determinants of liver injury in chronic HCV infection, using cohorts with rapid disease progression and controls to better understand the factors that distinguish a relatively benign course of HCV from one with progression to cirrhosis. This will be accomplished in three integrated projects: The first Project will test the hypothesis that failure of the CD4 response results in an inappropriate CD8+ cytotoxic T lymphocyte (CTL) and natural killer T (NKT) response that serves to drive fibrosis and viral evolution. The second Project will characterize the role of oxidative stress in chronic HCV and the mechanisms of hepatic steatosis. The third Project will determine which viral and host factors drive hepatic stellate cell activation as a key step in fibrosis. The projects will be supported by a clinical core, which will maintain a repository of clinical samples derived from cohorts with rapid progression (transplant, HIV/HCV co-infection and Schistosoma mansoni co-infection) as well as more slowly progressive disease. This joint use of common clinical material will facilitate maximal integration of results. Through this unique cooperative approach, we will determine which viral and host factors contribute to fibrosis, the major complication of chronic HCV infection, which might suggest new therapeutic strategies to prevent liver disease progression.
描述(由申请人提供):大多数急性感染丙型肝炎病毒(HCV)的患者将发展为慢性感染,但并非所有受试者都会发展为慢性感染的并发症,如肝纤维化或脂肪变性。 目前的抗病毒治疗对大多数慢性HCV感染者既不有效也不可用,因此慢性感染仍然是一个重大的健康问题。HCV肝病的自然史与这种感染的流行病学相结合,导致慢性HCV患者的患病率增加,肝分解和肝细胞癌的发病率上升。然而,我们对肝病进展的宿主和病毒决定因素的了解还很有限。该计划项目将解决慢性HCV感染中肝损伤的决定因素,使用具有快速疾病进展和对照的队列,以更好地了解区分相对良性的HCV过程与进展为肝硬化的因素。这将在三个综合项目中完成:第一个项目将测试CD 4应答失败导致不适当的CD 8+细胞毒性T淋巴细胞(CTL)和自然杀伤T(NKT)应答的假设,这些应答将驱动纤维化和病毒进化。 第二个项目将描述氧化应激在慢性HCV中的作用和肝脂肪变性的机制。第三个项目将确定哪些病毒和宿主因素驱动肝星状细胞活化作为纤维化的关键步骤。这些项目将得到一个临床核心的支持,该核心将维持一个来自快速进展(移植、艾滋病毒/丙型肝炎病毒合并感染和曼氏血吸虫合并感染)以及进展较慢的疾病队列的临床样本库。共同使用临床材料将有助于最大限度地整合结果。通过这种独特的合作方法,我们将确定哪些病毒和宿主因素有助于纤维化,慢性HCV感染的主要并发症,这可能会提出新的治疗策略,以防止肝脏疾病的进展。

项目成果

期刊论文数量(11)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Anti-fibrotic therapy: Lost in translation?
  • DOI:
    10.1016/s0168-8278(12)60008-7
  • 发表时间:
    2012-01-01
  • 期刊:
  • 影响因子:
    25.7
  • 作者:
    Schuppan, Detlef;Pinzani, Massimo
  • 通讯作者:
    Pinzani, Massimo
Pharmacological inhibition of integrin alphavbeta3 aggravates experimental liver fibrosis and suppresses hepatic angiogenesis.
  • DOI:
    10.1002/hep.23144
  • 发表时间:
    2009-11
  • 期刊:
  • 影响因子:
    13.5
  • 作者:
    Patsenker, Eleonora;Popov, Yury;Stickel, Felix;Schneider, Vreni;Ledermann, Monika;Saegesser, Hans;Niedobitek, Gerald;Goodman, Simon L.;Schuppan, Detlef
  • 通讯作者:
    Schuppan, Detlef
Specific hepatic delivery of procollagen α1(I) small interfering RNA in lipid-like nanoparticles resolves liver fibrosis.
  • DOI:
    10.1002/hep.27936
  • 发表时间:
    2015-10
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Jiménez Calvente C;Sehgal A;Popov Y;Kim YO;Zevallos V;Sahin U;Diken M;Schuppan D
  • 通讯作者:
    Schuppan D
IL28B genotype is associated with differential expression of intrahepatic interferon-stimulated genes in patients with chronic hepatitis C.
  • DOI:
    10.1002/hep.23912
  • 发表时间:
    2010-12
  • 期刊:
  • 影响因子:
    13.5
  • 作者:
    Urban, Thomas J.;Thompson, Alexander J.;Bradrick, Shelton S.;Fellay, Jacques;Schuppan, Detlef;Cronin, Kenneth D.;Hong, Linda;McKenzie, Alexander;Patel, Keyur;Shianna, Kevin V.;McHutchison, John G.;Goldstein, David B.;Afdhal, Nezam
  • 通讯作者:
    Afdhal, Nezam
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DETLEF SCHUPPAN其他文献

DETLEF SCHUPPAN的其他文献

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{{ truncateString('DETLEF SCHUPPAN', 18)}}的其他基金

Fibrolytic Activation of Hepatic Stellate Cells by T Cell Derived Microparticles
T 细胞衍生微粒对肝星状细胞的纤维溶解激活
  • 批准号:
    7386870
  • 财政年份:
    2009
  • 资助金额:
    $ 55.81万
  • 项目类别:
Viral, T Cell, and Cytokine Determinants of Hepatic Stellate Cell Activation
肝星状细胞激活的病毒、T 细胞和细胞因子决定因素
  • 批准号:
    7575790
  • 财政年份:
    2008
  • 资助金额:
    $ 55.81万
  • 项目类别:
Characterization of Innate immune receptors
先天免疫受体的表征
  • 批准号:
    7686836
  • 财政年份:
    2008
  • 资助金额:
    $ 55.81万
  • 项目类别:
Characterization of Innate immune receptors
先天免疫受体的表征
  • 批准号:
    7451469
  • 财政年份:
    2008
  • 资助金额:
    $ 55.81万
  • 项目类别:
Identification of Serum Markers of Liver Fibrogenesis/ Fibrolysis by Proteomics
通过蛋白质组学鉴定肝纤维发生/纤维溶解的血清标志物
  • 批准号:
    7313389
  • 财政年份:
    2007
  • 资助金额:
    $ 55.81万
  • 项目类别:
Identification of Serum Markers of Liver Fibrogenesis/ Fibrolysis by Proteomics
通过蛋白质组学鉴定肝纤维发生/纤维溶解的血清标志物
  • 批准号:
    7493091
  • 财政年份:
    2007
  • 资助金额:
    $ 55.81万
  • 项目类别:
Mouse Models for Celiac Disease
乳糜泻小鼠模型
  • 批准号:
    7017340
  • 财政年份:
    2006
  • 资助金额:
    $ 55.81万
  • 项目类别:
Mouse Models for Celiac Disease
乳糜泻小鼠模型
  • 批准号:
    7229848
  • 财政年份:
    2006
  • 资助金额:
    $ 55.81万
  • 项目类别:
Viral, T Cell, & Cytokine Determinants of Stellate Cell
病毒、T 细胞、
  • 批准号:
    7013913
  • 财政年份:
    2005
  • 资助金额:
    $ 55.81万
  • 项目类别:
Determinants of Liver Injury in Chronic Hepatitis C Virus Infection
慢性丙型肝炎病毒感染肝损伤的决定因素
  • 批准号:
    7385107
  • 财政年份:
    2005
  • 资助金额:
    $ 55.81万
  • 项目类别:

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肝受体类似物(Liver Receptor Homolog 1, LRH 1)在雌鼠生殖过程中的作用及其机制
  • 批准号:
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中性粒细胞特异性NOX2在酒精性肝损伤中的作用
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非编码 RNA 生物标志物可预测癌症治疗期间的肝损伤
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