Central Biorepository Subproject for SP0065429

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.