Long Term Atorvastatin for Hepatocellular Carcinoma Risk Reduction in Patients with Advanced Liver Fibrosis

Inclusion Criteria

• Willing and able to provide informed consent
• Male or female age > 18 years at time of consent
• Clinically or histologically diagnosed advanced liver fibrosis or cirrhosis, as defined by one or more of the following: * Liver biopsy demonstrating advanced fibrosis or cirrhosis meta-analysis of histological data in viral hepatitis (METAVIR 3-4) * Fibroscan or magnetic resonance (MR) elastography consistent with advanced fibrosis or cirrhosis * Imaging showing cirrhotic-appearing liver with signs of portal hypertension * Advanced fibrosis or cirrhosis documented clinically by a treating physician
• High-risk for HCC at screening according to the Fibrosis-4 (FIB-4) index. Patients with Fontan Associated Liver Disease (FALD) will be considered for eligibility utilizing the FonLiver risk score derived severe fibrosis risk score chart in place of the FIB-4 index
• PLSec score ≥ 3 measured in screening blood samples from the FIB-4-high individuals
• Liver imaging within 6 months of day 1 is required in cirrhotic subjects only, to exclude HCC
• Female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
• Willing and able to undergo protocol blood sampling
• Subject must be able to comply with dosing instructions for study drug administration and able to complete study schedule of assessments

Exclusion Criteria

• Diagnosis of any of the following forms of chronic liver disease: * Alpha-1-antitrypsin (A1AT) deficiency, Wilson disease, hemochromatosis, iron overload, prior known or suspected drug-induced liver injury (DILI) * Patients with primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), or stable hemochromatosis may be included if their liver disease etiology overlaps with that of steatotic liver disease (SLD)
• Current or prior history of any of the following: * Clinically significant illness or any other major medical disorder that in the opinion of the investigator, may interfere with subject treatment, assessment or compliance with the protocol
• Known positivity for human immunodeficiency virus (HIV) infection
• Active, untreated hepatitis C virus (HCV) infection * Patients with prior history of HCV who achieved sustained virologic response (SVR) > 12 months from day 1 may be included in the study
• Uncontrolled chronic hepatitis B virus (HBV) * Patients with well controlled disease with > 12 months of stable medication use (or no medication use, in those persons for whom anti-HBV therapy is not indicated)
• Clinical hepatic decompensation, defined as Child’s Pugh class B or C cirrhosis
• Patients with Child’s Pugh score of 7, class B, may be included in the study
• History of biliary diversion
• Solid organ transplant
• Malignancy within the 5 years prior to screening, with the exception of specific cancers that have been cured by surgical resection (basal cell skin cancer, etc). Subjects under evaluation for possible malignancy are not eligible
• Pregnant or nursing females (a negative serum pregnancy test is required at screening for women of childbearing potential [WOCBP])
• Life threatening serious adverse event (SAE) during the screening period
• Alanine aminotransferase (ALT) > 10 x upper limit of normal (ULN) (at screening)
• Aspartate aminotransferase (AST) > 10 x ULN (at screening)
• Hemoglobin < 8.5 g/d (at screening)
• Serum creatinine > 2.0 mg/dL (at screening)
• Creatine kinase (CK) > 3 x ULN (at screening)
• Females who may wish to become pregnant and/or plan to undergo egg harvesting during the study and up to 30 days of the last dose of study drug
• WOCBP must abstain from breastfeeding and be willing to use effective birth control during through the week 4 post treatment follow-up visit
• Clinically relevant alcohol or drug abuse within 12 months of screening
• Use of any prohibited concomitant medications
• Use of a statin medication within 90 days of day 1 visit * Subjects who are on a current statin at time of consent must be willing to undergo a 90-day washout period prior to randomization
• Known hypersensitivity to atorvastatin
• Current or planned participation in an investigational new drug (IND) trial from 30-days prior to randomization through the week 4 post treatment follow-up visit