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

Eligibility Criteria

• 1. Age 18-75 years
• 2. Cirrhosis due to nonalcoholic steatohepatitis, alcohol-associated liver disease, or chronic viral hepatitis (treated hepatitis B virus or hepatitis C virus), or cryptogenic cirrhosis
• 3. Clinical diagnosis of cirrhosis as defined investigator confirmation and the following:
• 1. At least one liver biopsy within 5 years prior to consent showing either: Metavir stage 4 fibrosis; Ishak Stage 5-6 fibrosis, OR
• 2. At least 2 of the following:
• 4. Two measures of vibration-controlled transient elastography: one at screening and one at the randomization study visit, meeting the following criteria:
• 1. The first measure must be ≥ 12.5 kilopascal.
• 2. The two measures must be at least 1 day apart and no more than 60 days apart from one another.
• 3. The mean of two measurements must be ≥ 12.5 kilopascal.
• 5. Compensated defined by:
• 1. Absence of ascites/hydrothorax, hepatic encephalopathy or variceal bleeding currently or in the last 48 weeks, as determined clinically by investigator.
• 2. If prior history of decompensation, must be without current symptoms of decompensation and no longer requiring treatment of complications for the last 48 weeks, including the use of diuretics for the treatment of ascites, and/or rifaximin or lactulose for the treatment of hepatic encephalopathy. Use of non-selective beta blockers will be allowed.
• 3. Child-Pugh score \<8
• 6. Provision of written informed consent.
• 1. Currently on a statin or any statin exposure within 48 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
• 4. Myocardial infarction, Unstable angina, transient ischemic events, or stroke within 24 weeks of screening.
• 3. Alcohol Use Disorder Identification Test (AUDIT) score of ≥8. 4. Patients with limitations in attending study visits. 5. Prisoners. 6. Known prior or current hepatocellular carcinoma (HCC) or cholangiocarcinoma. 7. Known transjugular intrahepatic portosystemic shunt (TIPS), balloon retrograde transvenous obliteration (BRTO) or porto-systemic shunt surgery regardless of time of occurrence.
• 8. 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 9. Current (in past 24 weeks prior to consenting) use of medications which may increase risk for rosuvastatin-related myositis or drug-induced liver injury, defined as:
• 15. 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.
• 16. The following laboratory abnormalities within 90 days of screening:
• 1. Absolute neutrophil count \<1.0 x 109 / L
• 2. Hemoglobin \<10 g/dL
• 3. Albumin \<3.0 g/dL
• 4. Prolonged international normalized ratio (INR) \>1.5
• 5. Total bilirubin ≥ 2.0 mg/dl (unless due to Gilbert's syndrome or hemolysis as denoted by normal direct bilirubin fraction)
• 6. Uncontrolled diabetes (HbA1c ≥ 9.0%) within past 24 weeks 17. Kidney function abnormalities including:
• 1. Hepatitis C virus eligible for enrollment if hepatitis C virus RNA negative and after sustained virologic response at 24 weeks
• 2. Hepatitis B virus eligible if Hepatitis B virus DNA \<100 IU/mL and on treatment 20. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 200 U/L within the past 24 weeks 21. Documented history of intolerance to statins 22. Serious co-morbid medical disease which in the investigator's opinion renders a life-expectancy less than 96 weeks 23. Active illicit substance abuse, including inhaled or injected drugs, in the 48 weeks prior to screening 24. Pregnancy, planned pregnancy or breast-feeding 25. Current participation in active medication treatment trials (within 24 weeks prior to randomization) or planned participation in active medication treatment trials simultaneous to participation in present trial.
• 26. Significant existing muscle pain or tenderness as determined by a site physician.
• 27. Failure or inability to provide informed consent.