Liver Cirrhosis Network: Scientific and Data Coordination Center

肝硬化网络：科学和数据协调中心

• 批准号: 10309196
• 负责人: Jody D. Ciolino
• 金额: $ 239万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-28 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10309196
• 关键词: Adrenergic beta-Antagonists; Alcohol dependence; Ascites; Biometry; Blood Vessels; Body Weight decreased; Budgets; Case Report Form; Cause of Death; Cell physiology; Charge; Chronic Hepatitis C; Cirrhosis; Clinical; Clinical Trials Design; Cohort Studies; Communication; Confusion; Data; Data Analyses; Data Coordinating Center; Development; Disease; Disease Progression; Endothelial Cells; Enzymes; Event; Faculty; Fatigue; Fibrosis; Gastrointestinal Hemorrhage; Hemorrhage; Hepatic; Hepatic Encephalopathy; Human Resources; Icterus; Image; Impairment; Inflammation; Institutional Review Boards; Intervention; Investigation; Kidney; Laboratories; Lead; Leadership; Left; Life Style; Link; Liver; Liver Cirrhosis; Liver diseases; Longitudinal cohort; Malignant Neoplasms; Manuals; Medical; Meta-Analysis; Methodology; Modification; Monitor; Morbidity - disease rate; Multi-site clinical study; Multicenter Studies; National Institute of Diabetes and Digestive and Kidney Diseases; Obesity; Operative Surgical Procedures; Organ; Outcome; Oxidative Stress; Oxidoreductase; Patients; Positioning Attribute; Preventive Medicine; Primary carcinoma of the liver cells; Prognosis; Prospective cohort; Proteins; Protocols documentation; Provider; Public Health; Randomized; Randomized Controlled Trials; Reporting; Reproducibility; Research; Research Design; Research Personnel; Resources; Risk; Role; Safety; Sampling; Site; Social Sciences; Statistical Data Interpretation; Symptoms; Training; Transplantation; United States; Universities; Work; absorption; central database; clinical center; cost; curative treatments; data quality; design; disease natural history; double-blind placebo controlled trial; experience; gastrointestinal; improved; infection risk; innovation; liver transplantation; member; method development; mid-career faculty; mortality; multiple data types; nonalcoholic steatohepatitis; novel; nutrition; operation; prevent; professor; prospective; quality assurance; symptom treatment; transplant centers; treatment strategy

PROJECT SUMMARY Liver cirrhosis poses a significant public health burden in the United States (US) as it is associated with substantial morbidity, mortality and cost. An estimated one-third of patients develop decompensating events such as gastrointestinal variceal bleeding, ascites, hepatic encephalopathy (HE), jaundice, and renal impairment. Further, these poor outcomes are also associated with development of hepatocellular carcinoma (HCC) in the cirrhotic liver, the ninth leading cause of death among cancers within the US. While transplantation is a curative treatment for cirrhosis, patients are often ineligible for transplantation due to lack of available organs and additional risks involved. Thus, patients and providers frequently focus on symptomatic treatment options such as lifestyle/nutrition modifications to initiate weight loss and optimize protein absorption, nonselective beta- blockers to reduce the risk of gastrointestinal bleeding, and treatment for HE to improve confusion. A recent meta-analysis suggests statin therapy as a promising treatment for cirrhosis as statins tend to decrease oxidative stress and inflammation and increase endothelial cell function, with downstream effects including reduction of hepatic inflammation, fibrosis, and vascular tone. Although this review represents over 120 thousand patients, true efficacy data in the setting of a randomized controlled trial (RCT) are presently limited to just four RCTs from outside of the US, representing less than 300 patients with cirrhosis. To better understand the natural history of the disease and also to further evaluate the use of statins in the treatment of cirrhosis, the Liver Cirrhosis Network (LCN), consisting of up to 10 clinical centers (CCs) and one Scientific and Data Coordination Center (SDCC) will be charged with developing (a) a prospective cohort and (b) an RCT to evaluate statin efficacy in patients with cirrhosis. Northwestern University Data Analysis and Coordinating Center (NUDACC) and its partners propose to serve as the SDCC--the central scientific and leadership core for the LCN--coordinating all operational and data-related activities using cutting-edge resources for study design, planning and conduct, ongoing monitoring, and statistical analyses. NUDACC unites an interdisciplinary team with wide-ranging experience including collaborative and methodologic biostatisticians, hepatologists, data managers, project managers, and multiple supporting study staff. Together we propose to collaborate with the LCN to lead the design, conduct, coordination, oversight, management, administration, analyses, and dissemination for the LCN-related studies.

项目概要 肝硬化在美国构成了重大的公共卫生负担，因为它与 巨大的发病率、死亡率和费用。估计三分之一的患者出现失代偿事件 例如胃肠道静脉曲张出血、腹水、肝性脑病（HE）、黄疸和肾功能损害。 此外，这些不良结果还与肝细胞癌（HCC）的发生有关。 肝硬化是美国癌症死亡的第九大原因。虽然移植是一种治疗方法 在治疗肝硬化时，患者往往因缺乏可用器官而没有资格进行移植 涉及的额外风险。因此，患者和提供者经常关注对症治疗选择，例如 作为生活方式/营养的改变，以开始减肥和优化蛋白质吸收，非选择性β- 阻滞剂可降低胃肠道出血的风险，治疗 HE 可改善意识混乱。最近的一个 荟萃分析表明他汀类药物治疗是一种有前途的肝硬化治疗方法，因为他汀类药物往往会减少氧化 应激和炎症并增加内皮细胞功能，具有下游效应，包括减少 肝脏炎症、纤维化和血管张力。尽管本次审查代表了超过 12 万名患者， 随机对照试验（RCT）中的真实疗效数据目前仅限于来自 美国以外的地区有不到 300 名肝硬化患者。 为了更好地了解该疾病的自然史，并进一步评估他汀类药物在治疗中的使用 肝硬化治疗网络 (LCN)，由多达 10 个临床中心 (CC) 和 1 个中心组成 科学和数据协调中心 (SDCC) 将负责开发 (a) 一个前瞻性队列和 (b) 评估他汀类药物对肝硬化患者疗效的随机对照试验。西北大学数据分析与 协调中心 (NUDACC) 及其合作伙伴提议充当 SDCC——中央科学和技术中心 LCN的领导核心——利用尖端资源协调所有运营和数据相关活动 用于研究设计、规划和实施、持续监测和统计分析。 NUDACC 联合 具有广泛经验的跨学科团队，包括协作和方法生物统计学家， 肝病专家、数据经理、项目经理和多名支持研究人员。我们共同提议 与 LCN 合作，领导设计、实施、协调、监督、管理、行政、 LCN 相关研究的分析和传播。