PSC is a liver disease that has no medical cure. Patients with PSC are at a greatly increased risk of cancer and infection. Additionally, many patients require a liver transplant. Progress towards a cure has been severely limited by an incomplete understanding of why patients develop PSC. The investigators aim to close this gap by conducting a pilot human study in patients with PSC, using statin therapy as a model

Database studies have suggested that use of statins is associated with lower mortality in patients with PSC. Statins are also safe, widely used medications for the treatment of high cholesterol. This track record of safety makes repurposing statins for use in PSC an attractive option.

This study will evaluate the impact of bile acid profile and the microbiome. Rosuvastatin induced changes in cell signaling pathways in the body, as well as its impact of bacterial gene expression in the microbiome will be evaluated. The investigators anticipate that this study will provide key insights into the biologic basis of PSC, which may aid in the development of drugs for the treatment of PSC.

This research study will enroll patients with PSC. The study will be conducted in 3 phases: baseline measurements, study period (treatment with rosuvastatin), and follow-up (follow-up after completing statin treatment). All patients will receive the study drug, and no patients will receive placebo treatment. Rosuvastatin is FDA approved for treatment of high cholesterol, but its use in this trial is off label.

Inclusion Criteria:

• Males and females, greater than or equal to 18 years of age
• Established diagnosis of PSC, defined by either appropriate cholangiographic findings or supportive liver biopsy plus an established diagnosis of inflammatory bowel disease (IBD - Crohn's disease or ulcerative colitis) per American College of Gastroenterology (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 bacterial cholangitis, recurrent pyogenic cholangitis, ischemic cholangiopathy, surgical biliary 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 5 times 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 calcineurin inhibitor, 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

Individual participant data will not be shared