1. Basics of PSC Christopher L. Bowlus, MD
Lena Valente Professor and Chief
Division of Gastroenterology and Hepatology
UC Davis School of Medicine

2. Questions What is Primary Sclerosing Cholangitis? Why did I get PSC?
How will PSC affect me?
What can I do about my PSC?
Will there ever be a cure for PSC?

3. What is PSC? Primary Sclerosing Cholangitis
Not secondary to another cause
Sclerosing
Stiffening with connective tissue (scarring)
Cholangitis
Inflammation of the bile ducts

4. What is PSC?

5. What is PSC?
Normal ERC
PSC MRC

6. What is PSC? Top 3 Facts about PSC: Men are affected more than women
Most PSC patients have colitis (IBD)
All PSCers should have a colonoscopy
Small duct PSC
Abnormal biopsy but normal ERC/MRC

7. Why did I get PSC? Genes and Environment Protection against PSC
Risk for PSC
Genes and Environment

8. Why did I get PSC? Smoking Female Asian IBD Male White/Black
Infection?

9. How will PSC affect me? The course of PSC is unpredictable
Varies from individual to individual
Varies over time in the same individual
Average time from diagnosis to liver transplant is years.

10. Liver-related Death/Liver Transplantation
NATURAL HISTORY OF PSC
Colitis
Biliary Inflammation
Elevated ALP
Biliary Fibrosis
Abnormal Cholangiogram
Portal Hypertension
Cirrhosis
Variceal Bleeding
Liver-related Death/Liver Transplantation
Pre-Clinical PSC
Competing Outcomes
Cholangiocarcinoma
Gallbladder cancer
Colon cancer
Hepatocellular carcinoma
Bacterial cholangitis
Colitis flare/Pouchitis
Diabetes/CVD

11. TRANSPLANT-FREE SURVIVAL IN PSC
Non-Liver Tx Centers
Liver Tx Centers

12. Transplant-Free Survival in PSC Partners Registry
811 self-identified PSC Patients
65.1% confirmed diagnosis
Mean age years
Mean age at diagnosis years
67.1% with IBD
Median transplant-free survival 21 years
95% CI 17.2 – 24.8 years
Kuo A, et al Clin Gastroenterol Hepatology 2018.

13. Factors Associated with Better Outcomes
Demographic
Female Sex
Young Age of Diagnosis
White Race
Clinical
Crohn’s Disease
Small duct PSC
Normal alkaline phosphatase
Weismuller TJ, et al. Gastroenterology. 2017;152:

14. PSC: Biochemical Response to Urso
Normal Alkaline Phosphatase Predicts Better Prognosis
Normalization can be spontaneous or from Urso
Lindstrom L, et al. Clinic Gastroenterol Hepatol

15. How will PSC affect me? THE LIVER Cirrhosis Bile duct obstruction
Need for liver transplant
Bile duct obstruction
Ascending Cholangitis
RUQ pain, fever, jaundice
Jaundice (yellowing of skin and eyes)

16. How will PSC affect me? CANCER Most PSCers do NOT get cancer
Risk of bile duct cancer (cholangiocarcinoma)
Risk of colon cancer with colitis
Yearly colonoscopy

17. How will PSC affect me? SYMPTOMS Abdominal Pain Fatigue Itching
Stress of the unknown

18. Most Common Symptoms Reported by 678 PSCP Registrants
Frequency 1
Fatigue
75% 2
Abdominal Pain
73% 3
Itching
64% 4
Diarrhea 5
Sleep Disturbances
54% 6
Depression
39% 7
Fever 8
Jaundice
35%
Kuo A, et al Clin Gastroenterol Hepatology 2018.

19. Fatigue in PSC and PBC
Liver International 35: ,2014

20. What tests should I have when I am first diagnosed?
Labs
CBC, CMP, INR
CA19-9
IgG4
Celiac test (?)
Vitamin A, D, E
Imaging
MRI
DEXA (?)
Procedures
Colonoscopy if no diagnosis of IBD

21. What tests should I have after I am diagnosed?
Labs at least every 6 months
CBC, CMP, INR
CA19-9 (?)
Vitamin A, D, E if previously low
Imaging
MRI or US every 6-12 months
Procedures
Colonoscopy every 1-2 years if IBD is present

22. What are the treatments for my PSC?
Urso (?)
ERCP and antibiotics for infected bile ducts
Diet and Nutrition
Treatment of symptoms/Coping Strategies
Liver Transplantation

23. Will there ever be a cure for PSC?
TREATMENT

24. Will there ever be a cure for PSC?
Old Drugs
Antibiotics
Sulfasalazine
“Probiotics”
New Drugs
FXR Agonists
Anti-fibrotics
Stem cells