In the current protocol, we propose the assessment of potential beneficial effects of the antibiotic Xifaxan on liver biochemistries, liver related symptoms and Mayo risk score in 15 adult and 5 pediatric patients with PSC. Adult patients will receive Xifaxan, 550 mg twice daily over a 12-week period. Pediatric patients with PSC whose weight is greater than or equal to 40 kg will receive Xifaxan, 550 mg twice daily.

Inclusion criteria:

• Diagnosis of PSC established by all of the following criteria:

  • Alkaline phosphatase >1.5 times upper limit of normal for at least 6 months duration
  • Gamma-glutamyl transferase (GGT) >1.5 times upper limit of normal in pediatric patients
  • Cholangiography demonstrating intrahepatic and/or extrahepatic biliary obstruction, beading, or narrowing consistent with PSC
  • Liver histology in the past (if available for review) with features consistent with or diagnostic of PSC

• Both genders

• Adults: Ages 18-75 years.

• Pediatric: Weight > 40 kg

• Patient's informed consent for study participation

Exclusion criteria:

• Treatment with systematic antibiotics, Azulfidine, ursodeoxycholic acid, corticosteroids, colchicine, methotrexate, azathioprine, cyclosporine, chlorambucil, budesonide, pentoxifylline, tacrolimus, vitamin E or prednisone in the preceding three months
• Active drug or alcohol use
• Prior history of allergic reaction to the antibiotics which will be used in the study
• Any condition that, in the opinion of the investigator, would interfere with the patient's ability to complete the study safely or successfully
• Evidence of decompensated liver disease such as recurrent variceal bleeding, refractory ascites or spontaneous hepatic encephalopathy
• Anticipated need for transplantation in one year (Mayo survival model <80% one-year survival without transplant)
• Findings highly suggestive of liver disease of other etiology such as chronic alcoholic liver disease, chronic hepatitis B or C infection, hemochromatosis, Wilson's disease, 1-antitrypsin deficiency, non-alcoholic steatohepatitis, primary biliary cirrhosis or secondary sclerosing cholangitis
• Treatment with any study medications in the preceding three months
• Pregnancy or current lactation; subjects becoming pregnant during the study despite all the precautions will be withdrawn and referred to their primary physicians