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: 10690118
• 负责人: Bilal Hameed
• 金额: $ 20.53万
• 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: 2021-09-15 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10690118
• 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; Fibrosis; Genetic Variation; Goals; HIV Infections; Health; Hepatic; Hepatic Stellate Cell; Image; 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; end stage liver disease; epidemiology study; ethnic minority population; fatty liver disease; 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.

项目总结 作为慢性肝损伤的终末期，肝硬变患病率的上升是发病率的一个重要因素。 以及美国的死亡率。预防措施，包括治疗潜在的肝病， 监测和筛查并发症并处理与疾病进展相关的风险因素 提高存活率的关键。随着肝硬变的进展，肝功能衰竭和肝癌等并发症也会增加， 导致死亡。种族/少数民族、有药物使用障碍的个人、艾滋病毒感染以及 社会经济地位低的人都有很高的肝硬变并发症风险，这是由于他们的并存和障碍 医疗保健服务。肝移植是治疗终末期肝病的唯一可行的医学选择，但 器官的短缺和更多无法考虑肝脏的患者 移植清单，有必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治疗方法。此外，还评估了 临床风险和健康的社会决定因素可能不同地影响AT患者的肝硬变负担 危险人群对于解决这个国家在肝硬变负担方面的差异至关重要。因此，有效的战略 预防肝硬变并发症是当务之急。越来越多的证据表明，他汀类药物 降脂药，对肝硬变有预防作用。他汀类药物改善门静脉压力并降低 在流行病学研究和有限的临床试验中的肝硬变的肝癌风险和死亡率。然而，大型 需要在代偿性肝硬变患者中进行实用的随机对照试验来证实这些 观察。为了解决这些关于肝硬变的知识差距以及患者未得到满足的临床需求 有了这种疾病，加州大学旧金山分校(UCSF)的两个地点及其不同的社区 LINKS将为肝硬变网络做出贡献，具体目标如下：1.建立纵向的 不同病因和不同分期的肝硬变的队列研究 Biospecimen资料库，以促进肝硬变的临床和翻译研究；2.开展 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 代偿性肝硬变患者。我们的短期目标是更好地描述临床风险和社会风险 评估河马途径的高危人群中与肝硬变并发症相关的健康决定因素 肝硬变进展的相关机制(YAP评分)，并评估瑞舒伐他汀在 脂肪肝病(酒精性和酒精性)所致的代偿性肝硬变和临床显著门脉高压症 非酒精性肝炎)和慢性病毒性肝炎患者中感染或不感染艾滋病毒。预计结果将有 广泛的含义，因为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 上皮组织。