Statin Therapy for patients with compensated Cirrhosis

项目摘要 肝硬化是一种高度病态和资源密集型的病症，其折磨越来越多的个体， 美方然而，肝硬化的流行病学正在发生变化，随着人口统计学的变化和增加， 代谢和酒精相关肝病的患病率。我们缺乏足够的风险分层工具， 肝硬化患者人群的变化，作为我们目前代偿性肝硬化的预后模型 缺乏足够的歧视。此外，肝硬化患者有症状和生活质量缺陷 这些问题在临床实践中没有得到常规解决。患者报告的结局（PRO）可纳入 风险模型具有良好的预后判别力。肝硬化患者有致命并发症的风险 例如肝代偿失调或肝细胞癌，然而我们缺乏疾病调节剂， 可以预防这些并发症的发展。一些流行病学研究表明，他汀类药物可能是 与肝硬化相关失代偿风险降低相关，但是我们缺乏前瞻性数据， 支持其用于该适应症。在本提案的目标1中，作为多中心联盟的一部分，我们的目标是 从我们的肝病学中招募一个大型的当代代偿性肝硬化患者纵向队列 密歇根大学的实践，纵向跟踪了1,900多名肝硬化患者。我们将 对临床、肝纤维化、PRO、功能和实验室参数进行连续测量， 学习期间。作为PRO测量的一部分，将在 电子医疗记录，以提醒供应商酒精使用障碍的患者参加了队列。在目标2中， 我们将开发和验证多维风险模型，并将测量的纵向参数纳入其中 在目标1中，为了预测结局，包括生存期、肝功能失代偿、心血管事件和 残疾。在目标3中，我们将进行一项他汀类药物在代偿性心力衰竭患者中的随机安慰剂对照试验。 肝硬化主要结局为总生存期，次要结局为肝脏 失代偿/肝细胞癌发展和心血管事件。我们将提供额外的 探索性分析，以确定他汀类药物对纤维化进展的影响。该提案将提供 这些关键信息将对肝硬化患者的管理产生深远的临床影响。我们 鉴于我们的肝病学和临床研究基础设施，我们完全有能力进行这项研究。

Project Abstract Cirrhosis is a highly morbid and resource intensive condition that afflicts an increasing number of individuals in the US. The epidemiology of cirrhosis, however is changing, with demographic shifts and increasing prevalence of metabolic and alcohol associated liver disease. We lack sufficient tools for risk stratification of the changing population of patients with cirrhosis, as our current prognostic models for compensated cirrhosis lack adequate discrimination. Furthermore, patients with cirrhosis have symptoms and quality of life deficits that are not routinely addressed in clinical practice. Patient reported outcomes (PROs) can be incorporated into risk models with excellent prognostic discrimination. Patients with cirrhosis have a risk of deadly complications such as hepatic decompensation or hepatocellular carcinoma, however we lack disease modifying agents that can forestall the development of these complication. Several epidemiological studies suggest statins may be associated with a decreased risk of cirrhosis related decompensation, however we lack prospective data to support its use for this indication. In Aim 1 of this proposal, as part of a multicenter consortium, we aim to recruit a large contemporary longitudinal cohort of patients with compensated cirrhosis from our Hepatology practice at the University of Michigan, which follows over 1,900 patients with cirrhosis longitudinally. We will perform serial measurements of clinical, liver fibrosis, PRO, functional, and laboratory parameters over the study period. As part of the PRO measurement, will develop automated alerts with care pathways within the electronic medical record to alert providers for alcohol use disorder in patients enrolled in the cohort. In Aim 2, we will develop and validate multidimensional risk models, incorporating the longitudinal parameters measured in Aim 1, in order to predict outcomes, including survival, hepatic decompensation, cardiovascular events, and disability. In Aim 3 we will perform a randomized placebo control trial of statins in patients with compensated cirrhosis. The primary outcome will be overall survival, with secondary outcomes of hepatic decompensation/hepatocellular carcinoma development and cardiovascular events. We will perform additional exploratory analyses to determine the impact of statins on fibrosis progression. This proposal will provide critical information that will have profound clinical impact on the management of patients with cirrhosis. We are well positioned to conduct this study given our Hepatology and clinical research infrastructure.