Liver Cirrhosis Network Rosuvastatin Efficacy and Safety for Cirrhosis in the United States

This is a double-blind, phase 2 study to evaluate safety and efficacy of rosuvastatin in comparison to placebo after 2 years in patients with compensated cirrhosis.

Inclusion Criteria 1. Age 18-75 years 2. Cirrhosis due to NAFLD, ALD, or chronic viral hepatitis (treated HBV or HCV) 3. Clinical diagnosis of cirrhosis as defined by investigator confirmation and the following: a. At least one liver biopsy within 5 years prior to consent showing either: Metavir stage 4 fibrosis; Ishak Stage 5-6 fibrosis, OR b. At least 2 of the following: i. Evidence on imaging: Nodular liver with either splenomegaly or recanalized umbilical vein within the past 48 weeks ii. Liver stiffness: VCTE within 48 weeks prior to consent or during Screening ≥15.0 kPa or MRE within 48 weeks prior to consent or during Screening ≥5 kPa iii. Evidence of varices demonstrated on imaging or endoscopy within 3 years prior to consent or during Screening iv. Either: FIB-4\>2.67 or platelets \ 1. Currently on a statin or any statin exposure within 24 weeks prior to consent. 2. Known indication for statin therapy, defined as: 1. Prior peripheral vascular, cardiovascular or cerebrovascular event for which statins are indicated for secondary prevention, OR 2. Documented familial hypercholesterolemia, heterozygous familial hypercholesterolemia, OR 3. Fasting LDL-C ≥ 190 mg/dL 3. Myocardial infarction, Unstable angina, transient ischemic events, or stroke within 24 weeks of screening. 4. Alcohol Use Disorder Identification Test (AUDIT) total score of ≥8 at screening. 5. Patients with limitations in attending study visits. 6. Prisoners. 7. Known prior or current hepatocellular carcinoma (HCC) or cholangiocarcinoma. 8. Known transjugular intrahepatic portosystemic shunt (TIPS), balloon retrograde transvenous obliteration (BRTO) or porto-systemic shunt surgery regardless of time of occurrence. 9. Current (in past 24 weeks prior to consenting) use of medications known to cause hepatic fibrogenesis or confound endpoint assessment, defined as: 1. amiodarone 2. methotrexate 3. warfarin 10. Current (in past 24 weeks prior to consenting) use of medications which may increase risk for rosuvastatin-related myositis or DILI, defined as: 1. fenofibrate 2. erythromycin 3. gemfibrozil 4. niacin (500 mg or more) 5. HIV protease inhibitors (darunivar, indinavir, nelfinavir, amprenavir) 6. colchicine 7. cyclosporin 8. Additional medications that will be excluded: atazanavir/ritonavir capmatinib darolutamide dasabuvir/ombitasvir/paritaprevir/ritonavir ledipasvir/sofosbuvir elbasvir/grazoprevir erythromycin lopinavir/ritonavir regorafenib ritonavir, in any combination simeprevir sofbuvir/velpatasvir/voxilaprevir sofosbuvir/velpatasvir tafamidis tamoxifen teriflunomide \*If exposure was for 7 or less days for one of these medications can consider enrollment after 28 days from final dose. 11. Presence of portal or hepatic vein thrombosis 12. Diagnosis of untreated hypothyroidism or on unstable treatment regimen for hypothyroidism 13. Receiving an elemental diet or parenteral nutrition 14. Chronic pancreatitis or pancreatic insufficiency 15. Etiology of cirrhosis other than ALD, NAFLD, or viral hepatitis (excluded diagnoses include cryptogenic immune-mediated such as AIH, PSC and PBC, cardiac cirrhosis or Fontan-associated liver disease, A1AT, Wilson's disease, etc.) 16. Conditions which may confound study outcome: a. Unstable or active inflammatory bowel disease b. Active infection c. Any malignant disease (other than squamous or basal cell carcinoma of the skin) within previous 3 years d. Prior solid organ or hematopoietic cell transplant e. Bariatric surgery in the last 24 weeks prior to consent or planned bariatric surgery within the next 96 weeks f. Current liver-unrelated end-stage organ failures such as end-stage renal disease on dialysis, stage 3-4 congestive heart failure (CHF), current chronic obstructive pulmonary disease (COPD) on home oxygen. 17. Known current medical or psychiatric conditions which, in the opinion of the investigator, would make the participant unsuitable for the study for safety reasons or interfere with or prevent adherence to the protocol. 18. The following laboratory abnormalities within 90 days of screening: a. Hemoglobin \