Unraveling the Mechanisms Underlying Primary Sclerosing Cholangitis Through a Multidisciplinary, Integrative Research Approach

• PSC SUBJECTS:

INCLUSION CRITERIA

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or nonpregnant female, greater than or equal to 18 years of age
• Evidence of PSC established by biochemical testing and either MRCP or ERCP. Participant must have evidence of large duct disease on imaging.
• Agreement to adhere to Lifestyle Considerations throughout study duration.

EXCLUSION CRITERIA

An individual who meets any of the following criteria will be excluded from participation in this study:

• Pregnant or lactating women or females of child-bearing age not taking measures to prevent pregnancy during the period of study.
• History of clinical, serologic, or histopathologic evidence supporting etiologies of chronic liver disease other than PSC
• History of liver transplantation
• Diagnosis consistent with secondary sclerosing cholangitis (cholelithiasis, bile duct strictures secondary to ischemia, HIV cholangiopathy, etc.).
• Current or past clinical evidence of decompensated liver disease (e.g. ascites, bleeding esophageal varices, spontaneous bacterial peritonitis, encephalopathy, etc.).
• History of liver or bile duct lesions concerning for malignancy.
• Ca-19-9 >130 U/microL
• Alpha-fetoprotein level greater than 200 ng/microL.
• Patients with active bacterial, viral, or fungal, systemic or localized infection.
• Unwillingness to refrain from ingesting probiotics during study.
• History of systemic disease not related to PSC that is poorly controlled or associated with declining functional status. Examples include but are not limited to: poorly controlled diabetes mellitus, chronic renal failure with eGFR is \<60 microl/min/1.73m\^2, chronic

symptomatic heart failure or severe COPD.

• Patients with history of any gastrointestinal malignancy in the last 3 years prior to enrollment will be excluded. Patients with history of any malignancy in the last 3 years prior to enrollment other than those individuals who had undergone curative surgical therapy and deemed as low risk for recurrence by her/his treating physician would be excluded.
• History of portal vein thrombosis
• Patients with severe allergic reactions to iodine or other contrast, which cannot be controlled by premedication with antihistamines or steroids.
• History of gastric and/or proximal small bowel surgery including bariatric surgery such as Roux-en-Y gastric bypass
• Contraindication to monitored anesthesia care and/or medications that are commonly used for conscious sedation during GI Endoscopy
• Use of anti-coagulant and anti-platelet agents excluding aspirin and NSAIDs
• Contraindications to completing MRCP or MRI
• Absolute neutrophil count below 1000/mm\^3
• Hemoglobin level below 10.0 g/dl
• Platelet count lower than 50,000/mm\^3.
• INR greater than or equal to 1.5, PTT greater thna or equal to 1.3 times control and/or any known history of disease associated with

increased bleeding diathesis.

• Inability to provide informed consent

CONTROLS

INCLUSION CRITERIA

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• Male or female greater than or equal to 18 years of age
• Any individual who is either a parent, sibling or child of a PSC patient enrolled to the study, or an unrelated person who has been living with the patient for at least 3 consecutive months before study enrollment

EXCLUSION CRITERIA

An individual who meets any of the following criteria will be excluded from participation in this study:

• History suggestive of PSC
• History of chronic liver disease (except for steatosis)
• Patients with history of any malignancy in the 3 years prior to enrollment other than those individuals who had undergone curative surgical therapy and deemed as low risk for recurrence by her/his treating physician would be excluded.
• History of Inflammatory Bowel Disease
• Antibiotic use within the last 6 weeks
• Pregnancy
• Inability to provide informed consent