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, espe...