1. LIVER HEALTH an integral part of CF gastrointestinal care Zachary M Sellers, MD, PhD Fellow Pediatric Gastroenterology, Hepatology, and Nutrition Stanford University, Palo Alto, CA 2016 Stanford CF Education Day

2. Who I am… I am not a pulmonologist I am a Pediatric Gastroenterology and Hepatology Fellow…which means I am receiving specialized training in Pediatric GI and Liver Diseases My focus is on GI and liver problems in CF and I coordinate care for CF patients in our GI division I perform research related to gastrointestinal and liver problems in CF

3. “Doc, what does my liver have to do with my CF?” “I don’t know anything about the liver.” “No one ever mentioned anything about their liver.” “What does the liver do?” “How do I know their liver is OK?” “What do we do to keep the liver healthy?”

4. Objectives Review the function of the liver Why good liver function is important in CF What we know about how liver disease develops What happens when liver disease develops What we are doing to detect CF liver disease Trying to keep your liver healthy and managing complications from liver disease

5. Liver 101 – Where it is and what it does Location: right upper part of abdomen, under diaphragm Function: –Detoxifies –Processes drugs –Produces proteins and blood clotting factors –Bile Fat absorption Bicarbonate secretion contributes to intestinal pH

6. Liver Health Intestinal pH Fat Absorption Proteins and Clotting factors Pancreatic Enzyme Efficacy

7. CF Liver Disease The majority of individuals with CF will have some degree of hepatic steatosis (fat in liver) by the time they are adults 5-10% of children with CF develop liver cirrhosis with its associated complications –Does not correlate with liver enzyme levels. ~50% of CF children will have elevation in AST/ALT Colds and drugs are common causes of transient elevations in AST and ALT –Those with “severe” mutations are at risk Clin Gastroenterol Hepatol 2013, 11:333-342

8. Current theories of what goes wrong Inspissated Bile Hypothesis A newer theory… Does an altered intestinal microbiome lead to signals to the liver that causes liver inflammation?

10. Liver Cirrhosis and its Complications Impaired liver function –Loss of proteins, clotting factors, impaired clearance of drugs Shunting of blood flow –Portal hypertension: enlarged spleen (consumption of platelets), esophageal and gastric varices (GI bleed risk) –Hepatopulmonary syndrome: decreased oxygenation to lungs –Hepatorenal syndrome: kidney dysfunction

12. Detection of Liver Disease Traditional screening –AST, ALT, GGT, platelets with yearly labs Newly implemented Screening for CF Liver Disease at Stanford Pediatric CF Center –For everyone: AST, ALT, GGT, Platelets Predictive calculators of fibrosis and portal hypertension –6 years-old and pancreatic insufficient, or abnormal labs US with elastography –If concern on screening  referral to GI

13. Detailed Evaluation by GI Are there any other reasons for liver abnormalities beyond CF? –E.g. viral hepatitis, alpha-1-antitrypsin, autoimmune Advanced evaluation for determination of liver disease and resultant sequelae –Serum markers of fibrosis –Magnetic resonance imaging –Endoscopy

14. Interventions Halting progression of liver disease –Treat non-CF causes –Ursodiol: increases bile flow Managing complications –Surveillance –Endoscopy treatment of varices –Surgical shunts –Liver transplantation

15. Summary Liver health is important to decreasing morbidity and mortality in CF Some individuals may develop serious liver disease, which may lead to life threatening complications Traditional screening programs are insufficient to identify early CF liver disease, but we are working to change this Working closely with your pulmonologists and gastroenterologists, you can keep your liver as healthy as possible Remember…it takes a village. And we are proud to be a part of that village with you.

16. This is a Team Effort Pediatric Pulmonologists Screening Patients and Families Monitoring Health Pediatric Gastroenterologists Evaluate and Monitor Liver Health Provide Medical and Endoscopic Therapies Transplant Surgeons Provide Surgical Therapies Pediatric Radiologists Assist with Evaluating and Monitoring Liver Health

17. Thank you Questions?