The purpose of this research study is to determine whether a low dose of ATRA will improve laboratory tests of liver and bile duct inflammation in patients with PSC. The investigators will also look for changes to other blood tests which are related to inflammation, scarring, and the immune system.
Inclusion Criteria: * Males and females ages 18-80 * Diagnosis of large-duct PSC based on ERCP or MRCP, or liver biopsy findings without alternative explanation for findings, for at least 6 months. * Serum ALP levels persistently more than 1.5 x upper limit of normal over the past 6 months. * Ursodeoxycholic acid therapy must be discontinued for at least 3 months. * At least 2 forms of barrier protection for males and females of child-bearing age. Exclusion Criteria: * Small duct PSC, overlap with autoimmune hepatitis, IgG4 disease or secondary sclerosing cholangitis. * Any malignancy, presently or within the past 5 years, except adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix or in situ prostate cancer. * Viral hepatitis including hepatitis A, B, C, D, E. * Decompensated cirrhosis, or planned liver transplantation. * Recent diagnostic or therapeutic biliary manipulation (endoscopic, radiologic) within the past 3 months. * Ascending Cholangitis requiring antibiotics within the past 3 months. * Uncontrolled IBD, or IBD requiring the use of steroids. * Acute or Chronic Kidney Disease with serum creatinine \> 2 mg/dL. * Allergy to ATRA or vitamin A compounds.