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.