USC Cirrhosis Clinical Center

南加州大学肝硬化临床中心

• 批准号: 10310993
• 负责人: ANDREW Abba STOLZ
• 金额: $ 32.29万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-22 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10310993
• 关键词: Acculturation; Address; Adherence; Adult; Affect; Age; Alcohol consumption; Alcohols; Ancillary Study; Antiviral Therapy; Ascites; Asians; Attention; Behavior; Biological; Body Weight decreased; California; Cardiovascular system; Caring; Cause of Death; Cessation of life; Characteristics; Child; Chronic; Cirrhosis; Cities; Clinical; Clinical Research; Clinical Trials; Cohort Studies; Collection; County; Data; Development; Diabetes Mellitus; Educational Status; Endothelium; Etiology; Evaluation; Event; Fibrosis; Future; Goals; Health; Health Resources; Healthcare; Hemorrhage; Hepatic; Hepatic Encephalopathy; Hepatitis; Hepatitis B; Hepatitis C; Hepatotoxicity; Heterogeneity; Hispanics; Human; Image; Incidence; Injury; Intervention Studies; Laboratories; Language; Life Style; Link; Liver; Liver diseases; Longitudinal cohort; Los Angeles; Measures; Minority Groups; Modeling; Morbidity - disease rate; Multicenter Studies; National Institute of Diabetes and Digestive and Kidney Diseases; Natural History; Nature; Neighborhoods; Outcome; Participant; Pathway interactions; Patient-Centered Care; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Phospholipase; Physical activity; Placebos; Population; Population Heterogeneity; Portal Hypertension; Poverty; Primary carcinoma of the liver cells; Process; Prospective cohort; Proteins; Public Health; Questionnaires; Radiology Specialty; Randomized; Randomized Controlled Trials; Risk; Role; Safety; Specimen; Standardization; Subgroup; Therapeutic; Therapeutic Intervention; Transplantation; Underrepresented Minority; United States; Universities; Varicosity; Venous Pressure level; Viral hepatitis; Virus Diseases; biobank; chronic liver disease; clinical center; clinically significant; cohort; community setting; contextual factors; dietary; effective therapy; efficacy evaluation; ethnic diversity; experience; follow-up; genetic variant; glutaryl coA; health literacy; improved; improved outcome; inflammatory modulation; inhibitor/antagonist; liver injury; mortality; multilevel analysis; non-alcoholic fatty liver disease; nonalcoholic steatohepatitis; novel drug class; patient oriented; phase 3 study; prevent; primary endpoint; prospective; racial and ethnic; response; rosuvastatin; safety net; secondary endpoint; social; social determinants; social health determinants; sociodemographic factors; targeted treatment; translational study; treatment duration; trend

Cirrhosis is the 11th leading cause of death in the United States and its incidence is rising. Major causes of cirrhosis include chronic viral infections (hepatitis B and C), alcohol-associated cirrhosis (ALD) and non- alcoholic steatohepatitis (NASH). Stable compensated cirrhosis offers an opportunity to intervene to prevent progression to decompensation and thereby reduce liver-related deaths. Two stages of compensated cirrhosis are recognized; with stage 2 identified by the presence of clinically significant portal hypertension (CSPH, defined by hepatic venous pressure gradient of 10 mmHg or higher). Statins are a novel drug class for consideration in treatment of cirrhosis as preliminary data show reductions in both portal hypertension and improved survival and offer promise as a therapeutic intervention in stage 2 compensated cirrhosis. This multicenter study will establish a prospective cohort of 2000 patients with compensated cirrhosis and CSPH for longitudinal follow-up of changes in clinical, lifestyle, laboratory, and imaging characteristics combined with a rich biospecimen collection for future translational studies. Genetic variants, especially the role of patatin-like phospholipase domain-containing protein 3 (PNPLA-3), in cirrhosis progression and response to statin therapy. The primary goal of this longitudinal cohort is to characterize that natural history of compensated cirrhosis in a representative and contemporary population, and to refine the risk profiles for progression versus non- progression. Additionally, social determinants of health and their influence on healthcare engagement and promotion of healthy liver lifestyle will be examined, with further exploration of how these factors affects liver- related outcomes. Finally, a randomized, placebo-controlled phase 3 study of rosuvastatin will be conducted in 200 patients with compensated cirrhosis and CSPH due to treated hepatitis B or C, ALD or NASH. The treatment duration is 96 weeks with the primary endpoint being survival without decompensation. Secondary endpoints include liver-related mortality, cardiovascular events, diabetes and statin safety, including rates of hepatotoxicity and myotoxicity. The City of Angeles Clinical Center for Cirrhosis (CACC), located at the University of Southern California in Los Angeles, has a unique, ethnically diverse population, that well- represents the population experiencing rising rates of cirrhosis. Through this collaborative network, CACC will contribute to an: 1) enhanced patient-centered model of care; 2) build a rich biorepository to support ancillary and translational studies to improve our understanding of the pathobiology of cirrhosis progression and regression; and 3) conduct a rigorous clinical trial to define the role of statins, with particular attention to the role of PNPLA3 genetic variants on efficacy. Ultimately, the goal of these studies is to improve the clinical outcomes of patients with compensated cirrhosis, especially those from underrepresented minorities.

肝硬化是美国第11大死亡原因，其发病率正在上升。的主要原因 肝硬化包括慢性病毒感染（乙型和丙型肝炎B）、酒精相关肝硬化（ALD）和非酒精性肝硬化。 酒精性脂肪性肝炎（NASH）。稳定的代偿性肝硬化提供了一个干预的机会，以防止 进展到失代偿，从而减少肝脏相关死亡。代偿性肝硬化的两个阶段 是公认的;第2阶段通过存在临床上显著的门静脉高压（CSPH， 定义为肝静脉压力梯度为10 mmHg或更高）。他汀类药物是一种新型药物， 考虑肝硬化的治疗，因为初步数据显示门静脉高压和 提高生存率，并有望作为2期代偿性肝硬化的治疗干预。这 一项多中心研究将建立2000例代偿性肝硬化和CSPH患者的前瞻性队列， 对临床、生活方式、实验室和影像学特征的变化进行纵向随访， 丰富的生物标本收集，用于未来的转化研究。遗传变异，特别是马铃薯蛋白样的作用 含磷脂酶结构域蛋白3（PNPLA-3）在肝硬化进展和对他汀类药物治疗反应中的作用。 这个纵向队列的主要目的是描述代偿性肝硬化的自然史， 代表性和当代人群，并完善进展与非进展 进展此外，健康的社会决定因素及其对医疗保健参与和 促进健康的肝脏生活方式将被检查，进一步探索这些因素如何影响肝脏- 相关成果。最后，一项随机、安慰剂对照的瑞舒伐他汀III期研究将在 200例因治疗过的B或C型肝炎、ALD或NASH而患有代偿性肝硬化和CSPH的患者。的 治疗持续时间为96周，主要终点为无失代偿的存活。二次 终点包括肝脏相关死亡率、心血管事件、糖尿病和他汀类药物安全性，包括 肝毒性和肌毒性。洛杉矶市肝硬化临床中心（CACC），位于 位于洛杉矶的南加州大学拥有独特的、种族多样的人口， 代表肝硬化发病率上升的人群。通过这一合作网络，CACC将 有助于：1）加强以患者为中心的护理模式; 2）建立丰富的生物储存库，以支持 辅助和转化研究，以提高我们对肝硬化进展的病理生物学的理解 和回归; 3）进行严格的临床试验，以确定他汀类药物的作用，特别注意 PNPLA 3基因变异体对疗效的作用。最终，这些研究的目标是改善 代偿性肝硬化患者的临床结局，特别是那些代表性不足的患者 少数群体