1. History of PSC Care Doctor, What’s Gonna Happen to Me?
PSC Partners Seeking a Cure 2019 Conference
Nicholas F. LaRusso, M.D.
Charles H. Weinman Endowed Professor of Medicine and
Biochemistry/Molecular Biology
Distinguished Investigator of the Mayo Foundation

2. What is Primary Sclerosing Cholangitis (PSC)?
Normal
PSC
Lazaridis, LaRusso, 2016
Rare chronic disease of the bile ducts
Unknown cause
Diagnosed by blood tests and imaging studies
Associated with inflammatory bowel disease
No effective pharmacologic treatment
Liver transplantation for late stage disease is life saving
What is Primary Sclerosing Cholangitis (PSC)?
PSC
Normal

4. Publications on Primary Sclerosing Cholangitis
# of Publications
40 Years (1978 – 2018)
PubMed.gov

5. Historical Overview Clinical, Pathological and Radiological Features
Natural History
Complications
Management/Clinical Trials
Pathogenesis

6. Clinical, Pathological and Radiological Features

7. Natural History

8. Complications

9. Management/Clinical Trials

10. Pathogenesis

11. Now
We know a lot about the characteristics, natural history, complications, and management
There is more scientific interest in PSC than ever before - - thus, we are making progress on understanding the causation and identifying molecular targets for drug treatment
Huge increase in clinical trials
Increased federal support … BUT WE NEED MORE!!

12. Federal Grants on PSC 2018-2019 Total = 24 NIDDK (17) VA (4) NCI (1)
NIBIB (1)
NCATS (1)
Grants.gov

13. Clinical Trials on PSC (2003 to 2018)12 10 8
# of
Clinical
Trials 6 4 2
Year
Clinical Trials.gov

14. The NOW is better
and
the future looks
BRIGHT!!!

15. Why did I get PSC?
Is my family at risk for PSC?
What are the complications of
PSC?
Will I need a liver transplant?
How should I handle my diet
and medications??
What can you do to help me?
What can I do to help me?

16. Why did I get PSC ?
The cause(s) of PSC are not known; a heterogeneous disease!
Genes, immune system problems, microbes, and environmental exposures likely play roles in the development of the disease
N Engl J Med 2016
Lazaridis, LaRusso

17. Is my family at risk for PSC ?
Having family members with PSC and/or IBD may increase a person's risk for developing PSC
However, the increased risk is minimal and we do not recommend family screening for first degree relatives of patients with PSC

18. What are the complications of PSC ?
PSC can lead to various complications:
- Deficiencies of vitamins A, D, E, and K
- Infections of the bile ducts
- Cirrhosis (scarring of the liver)
- Liver failure
- Bile duct cancer
N Engl J Med 2016;
Lazaridis, LaRusso

19. Will I need a liver transplant ?
Most patients with PSC will NOT need a liver transplant
Outcomes for most patients who do need a liver transplant are excellent
Appropriate monitoring will determine if and when you might need a liver transplant
Recurrence of PSC after liver transplant can often be managed effectively
N Engl J Med 2016;
Lazaridis, LaRusso

20. How should I handle my diet and medications?
No specific food or supplement has been shown to impact PSC
If advanced disease, avoid raw seafood and modify protein and salt intake
Avoid NSAIDS and opioids - - Tylenol safest pain medication
Avoid regular alcohol consumption

21. Doctor, what can you do to help me?
Remain accessible and engaged in your care
Provide expert, compassionate advice regarding:
- Overall management
- Monitoring
- Timing of liver transplant
Participation in clinical trials

22. Doctor, what can I do to help me?
Establish relationships with
A knowledgeable physician
Center of Excellence
- Other patients with PSC
Lead a healthy life style
BE OPTIMISTIC!!!!!

23. Is my family at risk for PSC? What are the complications of PSC?
Why did I get PSC?
Is my family at risk for PSC?
What are the complications of
PSC?
Will I need a liver transplant?
How should I handle my diet
and medications??
What can you do to help me?
What can I do to help me?
A long & healthy lifestyle

24. “Predictions are always dangerous - - especially those about the future”
Yogi Berra
Circa 1960

25. Future Personalized forecast of individual patient prognosis
Management based on better understanding of the heterogeneous nature of the disease(s)
Clinical trials become the norm
Pharmacologic agent(s) that inhibit progression
Continued progress in clarifying causation
DISCOVERY TRANSLATION APPLICATION

26. Email: larusso.nicholas@mayo.edu
Thank you