Statin Therapy in Primary Sclerosing Cholangitis (PSC): a Multi-omics Study

Inclusion Criteria:

• Males and females, greater than or equal to 18 years of age

• Established diagnosis of PSC, defined by either appropriate cholangiographicfindings or supportive liver biopsy plus an established diagnosis of inflammatorybowel disease (IBD - Crohn's disease or ulcerative colitis) per American College ofGastroenterology (ACG) guidelines for the PSC-IBD arm

• Hypercholesterolemia with BMI < 25.0 for the comparison arm

Exclusion Criteria:

• Diagnosis of PSC-autoimmune hepatitis overlap syndrome

• Woman who are pregnant, nursing, or expect to be pregnant

• The presence of any comorbidity known to cause secondary sclerosing cholangitis,including: immunoglobulin G-4 (IgG4), associated cholangitis, recurrent bacterialcholangitis, recurrent pyogenic cholangitis, ischemic cholangiopathy, surgicalbiliary trauma, cholangiocarcinoma, and portal hypertensive biliopathy

• Diagnosis of a serious medical condition (unless approved in writing by a physician)

• Patients taking statin therapy prior to study initiation

• Patients with known clinically allergy to statin therapy

• aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 5times the upper limit of normal

• Bilirubin greater than 3.0 mg/dL

• Recent use of antibiotics (within the last 90 days)

• Concurrent use of any immunosuppressive medications (such as any calcineurininhibitor, steroids at a dose greater than 10 mg of prednisone-equivalents per day)

• Actively using a fibrate drug

• Actively using a ritonavir containing drug

• Familial hypercholesterolemia or other inherited disorder of lipid metabolism

• Recent myocardial infarction or cerebrovascular accident

• Body mass index > 25.0 for the comparison arm

• Chronic kidney disease stage 5 or end-stage renal disease