USC Cirrhosis Clinical Center

南加州大学肝硬化临床中心

基本信息

批准号：
10704580
负责人：
ANDREW Abba STOLZ
金额：
$ 52.43万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-22 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10704580
关键词：
3-hydroxy-3-methylglutaryl-coenzyme A Acculturation Address Adherence Adult Affect Age Alcohol consumption Alcoholic Liver Diseases Alcohols Ancillary Study Antiviral Therapy Ascites Asian Asian population Attention Behavior Biological Black Populations 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 Compensation 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 Hispanic Populations 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 Phospholipase Physical activity Placebo Control Placebos Population Population Heterogeneity Populations at Risk Portal Hypertension Poverty Primary carcinoma of the liver cells Process Prospective cohort Proteins Public Health Questionnaires Radiology Specialty Randomized Randomized, Controlled Trials Risk Risk Reduction Role Safety Specimen Standardization Subgroup Therapeutic Therapeutic Intervention Underrepresented Minority United States Universities Varicosity Venous Pressure level Viral hepatitis Virus Diseases alcohol abstinence biobank chronic liver disease clinical center clinically significant cohort community setting contextual factors dietary drug induced liver injury effective therapy efficacy evaluation ethnic diversity experience follow-up genetic variant health literacy improved improved outcome inflammatory modulation inhibitor 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 diversity racial population response rosuvastatin safety net sarcopenia secondary endpoint social social determinants social health determinants sociodemographic factors targeted treatment translational study transplant centers treatment duration trend

项目摘要

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 大死因，且其发病率正在上升。主要原因肝硬化包括慢性病毒感染（乙型和丙型肝炎）、酒精相关性肝硬化（ALD）和非酒精性肝硬化。酒精性脂肪肝炎（NASH）。稳定的代偿性肝硬化提供了干预预防的机会进展到失代偿，从而减少与肝脏相关的死亡。代偿性肝硬化的两个阶段被认可； 2 期通过存在临床显着的门脉高压（CSPH，由肝静脉压力梯度为 10 mmHg 或更高定义）。他汀类药物是一类新型药物考虑治疗肝硬化，因为初步数据显示门脉高压和提高了生存率，并为第二阶段代偿性肝硬化的治疗干预提供了希望。这多中心研究将建立一个由 2000 名代偿性肝硬化和 CSPH 患者组成的前瞻性队列，用于治疗对临床、生活方式、实验室和影像学特征的变化进行纵向随访，并结合为未来的转化研究提供丰富的生物样本收藏。遗传变异，尤其是 patatin 样的作用含磷脂酶结构域的蛋白 3 (PNPLA-3) 在肝硬化进展和对他汀类药物治疗的反应中的作用。该纵向队列的主要目标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的风险状况进展。此外，健康的社会决定因素及其对医疗保健参与和的影响将检查促进健康的肝脏生活方式，并进一步探讨这些因素如何影响肝脏相关结果。最后，一项关于瑞舒伐他汀的随机、安慰剂对照 3 期研究将在 200 名因接受乙型或丙型肝炎、ALD 或 NASH 治疗而出现代偿性肝硬化和 CSPH 的患者。这治疗持续时间为 96 周，主要终点是无失代偿的生存期。中学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，包括肝毒性和肌肉毒性。安吉利斯市肝硬化临床中心 (CACC)，位于位于洛杉矶的南加州大学拥有独特的、种族多元化的人口，代表肝硬化发病率上升的人群。通过这个协作网络，CACC 将有助于：1）增强以患者为中心的护理模式； 2）建立丰富的生物样本库来支持辅助和转化研究，以提高我们对肝硬化进展病理学的理解和回归； 3) 进行严格的临床试验来明确他汀类药物的作用，特别要注意 PNPLA3 基因变异对疗效的作用。最终，这些研究的目标是改善代偿性肝硬化患者的临床结果，尤其是来自代表性不足的患者少数民族。