Liver Cirrhosis Network: Scientific and Data Coordination Center

项目摘要 肝硬化在美国（US）造成了重大的公共卫生负担，因为它与以下疾病相关： 严重的发病率、死亡率和成本。估计有三分之一的患者发生失代偿事件 如胃肠道静脉曲张出血、腹水、肝性脑病（HE）、黄疸和肾损害。 此外，这些不良结局也与肝细胞癌（HCC）的发生相关。 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， 对于肝硬化的治疗，由于缺乏可用的器官，患者通常不适合移植， 涉及额外风险。因此，患者和提供者经常关注对症治疗选择， 作为生活方式/营养改变，以启动减肥和优化蛋白质吸收，非选择性β- 阻断剂，以减少胃肠道出血的风险，治疗HE，以改善混乱。最近的一 荟萃分析表明，他汀类药物治疗肝硬化是一种有前途的治疗方法，因为他汀类药物倾向于减少氧化应激， 并增加内皮细胞功能，其下游效应包括减少 肝脏炎症、纤维化和血管张力。虽然这篇综述代表了超过12万名患者， 在随机对照试验（RCT）的背景下，真实的疗效数据目前仅限于来自以下的四项RCT： 在美国以外，代表不到300名肝硬化患者。 为了更好地了解疾病的自然史，并进一步评估他汀类药物在 肝硬化治疗，肝硬化网络（LCN），由多达10个临床中心（CC）和一个 科学和数据协调中心（SDCC）将负责开发（a）前瞻性队列， (b)一项评价他汀类药物在肝硬化患者中疗效的随机对照试验。西北大学数据分析和 协调中心（NUDACC）及其合作伙伴建议作为SDCC-中央科学和 LCN的领导核心--利用尖端资源协调所有业务和数据相关活动 用于研究设计、计划和实施、持续监测和统计分析。NUDACC联合了一个 具有广泛经验跨学科团队，包括协作和方法学生物统计学家， 肝病学家、数据管理员、项目经理和多名支持研究工作人员。我们共同提议 与LCN合作，领导设计、执行、协调、监督、管理、行政， LCN相关研究的分析和传播。

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.