Vancomycin for Primary Sclerosing Cholangitis

Inclusion Criteria: 1. Male or female subject age 18-76 years 2. Diagnosis of PSC consistent with the guidelines published by the American Association for the Study of Liver Diseases (AASLD).39 All subjects must have an elevated serum ALP of at least 1.5 times upper limit of normal at baseline plus cholangiographic evidence of PSC, as demonstrated by magnetic resonance imaging, endoscopic retrograde cholangiography, direct cholangiography, or liver biopsy. 3. Total bilirubin at screening must be ≤ 2 times upper limit of normal 4. An ultrasound (or equivalent imaging modality) that excludes biliary obstruction and malignancy within 6 months of study entry, 5. If a patient is on any of the following medications and/or supplements, he or she is expected to remain on the same daily dose through the treatment period: UDCA, azathioprine, prednisone (or an equivalent steroid compound), methotrexate, a 5-aminosalicylic acid, biologic therapy, and/or a probiotic. 6. If a patient has been on obeticholic acid or other experimental therapies for PSC, they must complete a 3 month washout period before study entry 7. PSC with or without inflammatory bowel disease, such as ulcerative colitis or Crohn's disease 8. Must agree to comply with the study protocol and provide informed consent. Exclusion Criteria: 1. Administration of an antibiotic within 3 months prior to the study, 2. Pregnancy or attempting to become pregnant or breastfeeding, 3. Presence of any of the following: i. Hepatitis B infection ii. Hepatitis C infection (antibody positive); patients with a history of hepatitis C infection will be eligible for this study if they have undetectable levels of HCV RNA iii. Other cholestatic liver diseases such as primary biliary cholangitis and cholestatic diseases of pregnancy iv. Metabolic liver diseases such as Wilson's disease and hemochromatosis v. Inherited diseases of the liver such as α-1 antitrypsin deficiency vi. Immunoglobulin G4-related cholangitis vii. PSC with concomitant autoimmune hepatitis (AIH) and/or primary biliary cholangitis (previously known as primary biliary cirrhosis) viii. Secondary sclerosing cholangitis (SSC), ix. Active acute ascending cholangitis requiring antibiotics x. CCA (malignant biliary stricture, neoplasm, and cytology/histopathology or positive fluorescence in situ hybridization (FISH) consistent with adenocarcinoma of the bile duct) xi. A liver biopsy, if one has been previously obtained, which showed non-alcoholic steatohepatitis (NASH). Patients with suspected fatty liver by imaging will not be excluded xii. Presence of decompensated cirrhosis such as hepatic encephalopathy, hepato-renal syndrome and hepato-pulmonary syndrome, xiii. History of liver transplantation, anticipated need for liver transplantation within 12 months from randomization, or a Model of End Stage Liver Disease (MELD) score of ≥15 xiv. Ongoing alcohol abuse (\>4 drinks per day for men, and \>2 drinks per day for women) xv. History of allergic reaction to vancomycin, xvi. Moderate-to-severe renal impairment with a calculated creatinine clearance of \< 60mL/min xvii. HIV/AIDS, xviii. Any other conditions or abnormalities that, in the opinion of the investigator, may compromise the safety of the subject or interfere with the subject participating in or completing the study.