PROJECT SUMMARY
The rising prevalence of cirrhosis, the end-stage of any chronic liver injury, is a significant contributor to morbidity
and mortality in the United States. Preventative measures including treatment of underlying liver disease,
monitoring and screening for complications and addressing risk factors associated with disease progression are
key to improved survival. As cirrhosis progresses, complications such as liver failure and liver cancer develop,
resulting in death. Racial/ethnic minorities, individuals with substance use disorders, HIV infection, and those
with low socioeconomic status are all at high risk for cirrhosis complications due to comorbidities and barriers to
healthcare access. Liver transplantation is the only medically viable option in end stage liver disease but given
the shortage of organs and even more numerous patients who are unable to be considered for liver
transplantation listing, there is a significant need to improve our understanding of underlying pro- and anti-fibrotic
processes and risk factors along with potential therapies to halt disease progression. In addition, evaluation of
contribution of clinical risk and social determinants of health that may differentially impact cirrhosis burden in at
risk populations is critical to addressing disparities in cirrhosis burden in this country. Thus, effective strategies
for prevention of cirrhosis complications is a high-priority need. Accumulating evidence suggests that statin, a
lipid lowering drug, has a preventative role in cirrhosis. Statins improve portal venous pressure and decrease
liver cancer risk and mortality in cirrhosis in epidemiologic studies and limited clinical trials. However, large
pragmatic randomized controlled trials in patients with compensated cirrhosis are required to confirm these
observations. To address these gaps in knowledge about cirrhosis as well as the unmet clinical needs of patients
with the disease, two sites within the University of California, San Francisco (UCSF) and their diverse community
links will contribute to the Liver Cirrhosis Network with the following specific aims: 1. To assemble a longitudinal
cohort with diverse etiology and stage of cirrhosis supported by comprehensive clinical measures and a
biospecimen repository in order to promote clinical and translational research in cirrhosis; 2. To conduct a
randomized controlled double-blind trial testing the efficacy and safety of a rosuvastatin versus placebo in
patients with compensated cirrhosis. Our short-term goals are to better characterize clinical risks and social
determinants of health associated with cirrhosis complications in at risk populations, to evaluate a Hippo pathway
related mechanism for cirrhosis progression (the YAP score), and to assess the role of rosuvastatin in
compensated cirrhosis and clinically significant portal hypertension from fatty liver disease (alcoholic and
nonalcoholic) and chronic viral hepatitis in those with or without HIV infection. The results are expected to have
broad implications, given that progressive fibrosis defines chronic injury not only in the liver but in essentially all
epithelial tissues.