Liver Cirrhosis Network: Longitudinal and Clinical Trial Studies

肝硬化网络：纵向和临床试验研究

• 批准号: 10310199
• 负责人: Bilal Hameed
• 金额: $ 39.3万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-06 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10310199
• 关键词: Address; Anti-Inflammatory Agents; Antiinflammatory Effect; Biological Markers; Biological Specimen Banks; California; Cause of Death; Cessation of life; Cholesterol; Chronic; Chronic viral hepatitis; Cirrhosis; Clinical; Clinical Research; Clinical Trials; Communities; Complication; Conduct Clinical Trials; Country; Data; Diagnostic; Disease; Disease Progression; Double-blind trial; Epithelial; Etiology; Evaluation; Failure; Fatty Liver; Fibrosis; Genetic Variation; Goals; HIV Infections; Health; Hepatic; Hepatic Stellate Cell; Image; Individual; Injury; Intervention; Knowledge; Link; Lipids; Liver; Liver Cirrhosis; Liver Failure; Liver Fibrosis; Liver diseases; Longitudinal cohort; Malignant neoplasm of liver; Measurement; Measures; Medical; Monitor; Morbidity - disease rate; Myofibroblast; Obesity; Observational Study; Organ; Outcome; Pathogenesis; Pathway interactions; Patient Care; Patients; Pharmaceutical Preparations; Placebos; Play; Population; Population Heterogeneity; Populations at Risk; Portal Hypertension; Prevalence; Prevention; Prevention strategy; Preventive measure; Primary carcinoma of the liver cells; Process; Proteins; Quality of life; Randomized; Randomized Controlled Trials; Risk; Risk Factors; Role; Safety; San Francisco; Serology; Signal Pathway; Signal Transduction; Site; Substance Use Disorder; Testing; Therapeutic; Tissues; Transcription Coactivator; Transcriptional Coactivator with PDZ-Binding Motif; Translating; Translational Research; United States; United States National Institutes of Health; Universities; Venous Pressure level; adverse outcome; barrier to care; cancer risk; chronic liver disease; chronic liver injury; clinical efficacy; clinical risk; clinically significant; cohort; comorbidity; double-blind placebo controlled trial; efficacy testing; epidemiology study; ethnic minority population; fibrogenesis; genetic signature; health care availability; high risk; improved; liver biopsy; liver injury; liver transplantation; low socioeconomic status; mortality; non-alcoholic; novel; oxidized low density lipoprotein; prevent; problem drinker; prognostic; prospective; public health relevance; racial and ethnic; response; rosuvastatin; safety testing; screening; social health determinants

PROJECT SUMMARY The rising prevalence of cirrhosis, the end-stage of any chronic liver injury, is a significant contributor to morbidity and mortality in the United States. Preventative measures including treatment of underlying liver disease, monitoring and screening for complications and addressing risk factors associated with disease progression are key to improved survival. As cirrhosis progresses, complications such as liver failure and liver cancer develop, resulting in death. Racial/ethnic minorities, individuals with substance use disorders, HIV infection, and those with low socioeconomic status are all at high risk for cirrhosis complications due to comorbidities and barriers to healthcare access. Liver transplantation is the only medically viable option in end stage liver disease but given the shortage of organs and even more numerous patients who are unable to be considered for liver transplantation listing, there is a significant need to improve our understanding of underlying pro- and anti-fibrotic processes and risk factors along with potential therapies to halt disease progression. In addition, evaluation of contribution of clinical risk and social determinants of health that may differentially impact cirrhosis burden in at risk populations is critical to addressing disparities in cirrhosis burden in this country. Thus, effective strategies for prevention of cirrhosis complications is a high-priority need. Accumulating evidence suggests that statin, a lipid lowering drug, has a preventative role in cirrhosis. Statins improve portal venous pressure and decrease liver cancer risk and mortality in cirrhosis in epidemiologic studies and limited clinical trials. However, large pragmatic randomized controlled trials in patients with compensated cirrhosis are required to confirm these observations. To address these gaps in knowledge about cirrhosis as well as the unmet clinical needs of patients with the disease, two sites within the University of California, San Francisco (UCSF) and their diverse community links will contribute to the Liver Cirrhosis Network with the following specific aims: 1. To assemble a longitudinal cohort with diverse etiology and stage of cirrhosis supported by comprehensive clinical measures and a biospecimen repository in order to promote clinical and translational research in cirrhosis; 2. To conduct a randomized controlled double-blind trial testing the efficacy and safety of a rosuvastatin versus placebo in patients with compensated cirrhosis. Our short-term goals are to better characterize clinical risks and social determinants of health associated with cirrhosis complications in at risk populations, to evaluate a Hippo pathway related mechanism for cirrhosis progression (the YAP score), and to assess the role of rosuvastatin in compensated cirrhosis and clinically significant portal hypertension from fatty liver disease (alcoholic and nonalcoholic) and chronic viral hepatitis in those with or without HIV infection. The results are expected to have broad implications, given that progressive fibrosis defines chronic injury not only in the liver but in essentially all epithelial tissues.

项目摘要 肝硬化的发生率上升，即任何慢性肝损伤的终阶段，是发病率的重要原因 和在美国的死亡率。预防措施，包括治疗潜在的肝病， 监测和筛查并发症并解决与疾病进展相关的危险因素是 改善生存的关键。随着肝硬化的进展，肝癌和肝癌等并发症的发展， 导致死亡。种族/族裔少数群体，患有药物使用障碍的人，艾滋病毒感染以及那些 由于合并症和障碍，具有低社会经济状况的肝硬化并发症的高风险 医疗保健访问。肝移植是末期肝病中唯一可行的医学选择，但给予 器官的短缺以及更多无法考虑肝脏的患者 移植清单，非常需要提高我们对潜在促纤维化和抗纤维化的理解 过程和危险因素以及阻止疾病进展的潜在疗法。另外，评估 临床风险和健康决定因素的贡献可能会差异地影响肝硬化负担 风险种群对于解决该国肝硬化负担的差异至关重要。因此，有效的策略 为了预防肝硬化并发症是一种很高的需求。积累的证据表明他汀类药物，一个 脂质降低药物在肝硬化中具有预防作用。他汀类药物可以提高门户静脉压力并降低 流行病学研究和临床试验有限的肝硬化中的肝癌风险和死亡率。但是，很大 需要补偿肝硬化患者的务实随机对照试验以确认这些试验 观察。解决有关肝硬化的知识以及患者未满足的临床需求的这些差距 有了这种疾病，加利福尼亚大学，旧金山大学（UCSF）及其多元化社区的两个地点 链接将以以下特定目的有助于肝硬化网络：1。组装纵向 与全面的临床措施支持的不同病因和肝硬化的各个阶段 为了促进肝硬化的临床和转化研究，生物循环库； 2。进行 随机对照双盲试验测试瑞士瓦抗蛋白与安慰剂的功效和安全性 肝硬化的患者。我们的短期目标是更好地描述临床风险和社会 与肝硬化并发症相关的健康决定因素，以评估河马途径 肝硬化进展的相关机制（YAP评分），并评估瑞士伐他汀在 脂肪肝病（酒精和 患有或没有HIV感染的患者中的非酒精性）和慢性病毒肝炎。结果预计将有 鉴于进行性纤维化不仅定义了慢性损伤，而且在所有基本上都定义了慢性损伤 上皮组织。