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.

项目概要 肝硬化（任何慢性肝损伤的终末期）患病率不断上升，是发病率的一个重要因素 和美国的死亡率。预防措施包括治疗潜在的肝脏疾病， 监测和筛查并发症并解决与疾病进展相关的危险因素 提高生存率的关键。随着肝硬化的进展，会出现肝衰竭和肝癌等并发症， 导致死亡。种族/族裔少数群体、患有药物滥用障碍、艾滋病毒感染者以及那些 由于合并症和治疗障碍，社会经济地位较低的人都面临着肝硬化并发症的高风险。 医疗保健服务。肝移植是终末期肝病唯一在医学上可行的选择，但考虑到 器官短缺，甚至更多的患者无法考虑肝脏 移植列表中，非常需要提高我们对潜在的促纤维化和抗纤维化的理解 过程和风险因素以及阻止疾病进展的潜在疗法。此外，评价 可能对不同国家的肝硬化负担产生不同影响的临床风险和健康社会决定因素的贡献 危险人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 预防肝硬化并发症是当务之急。越来越多的证据表明他汀类药物 降脂药，对肝硬化有预防作用。他汀类药物可改善门静脉压力并降低 流行病学研究和有限的临床试验中肝硬化的肝癌风险和死亡率。然而，大 需要在代偿性肝硬化患者中进行务实的随机对照试验来证实这些 观察。填补有关肝硬化的知识差距以及患者未满足的临床需求 患有这种疾病的加州大学旧金山分校 (UCSF) 内的两个地点及其多元化社区 这些链接将为肝硬化网络做出贡献，具体目标如下： 1. 建立一个纵向的 具有不同病因和肝硬化阶段的队列，得到综合临床措施和 生物样本库，以促进肝硬化的临床和转化研究； 2. 进行 随机对照双盲试验，测试瑞舒伐他汀与安慰剂的疗效和安全性 代偿性肝硬化患者。我们的短期目标是更好地描述临床风险和社会风险 与高危人群肝硬化并发症相关的健康决定因素，以评估 Hippo 途径 肝硬化进展的相关机制（YAP 评分），并评估瑞舒伐他汀在肝硬化进展中的作用 代偿性肝硬化和脂肪肝病（酒精性肝病和酒精性肝病）引起的具有临床意义的门静脉高压症 非酒精性）和慢性病毒性肝炎，适用于感染或未感染 HIV 的患者。预计结果将有 鉴于进行性纤维化不仅定义了肝脏的慢性损伤，而且基本上定义了所有疾病的慢性损伤，因此具有广泛的意义 上皮组织。