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

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

Publications on Primary Sclerosing Cholangitis # of Publications 78 80 82 84 86 88 90 92 94 96 98 00 02 04 06 08 10 12 14 16 18 40 Years (1978 – 2018) PubMed.gov

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

Clinical, Pathological and Radiological Features

Natural History

Complications

Management/Clinical Trials

Pathogenesis

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!!

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

Clinical Trials on PSC (2003 to 2018) 12 10 8 # of Clinical Trials 6 4 2 03 04 05 06 07 08 09 10 11 12 13 14 15 16 17 18 Year Clinical Trials.gov

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

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?

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

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

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

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 www.unos.org N Engl J Med 2016; Lazaridis, LaRusso

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

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

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!!!!!

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

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

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

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