1. Risё Stribling, MD Medical Director of Liver Transplant St Luke’s Medical Center Associate Professor of Surgery Baylor College of Medicine

2. Liver Transplant Evaluation: The Process Risё Stribling, MD Medical Director of Liver Transplant St Luke’s Medical Center Associate Professor of Surgery Baylor College of Medicine

3. Liver Transplant Clinical Indications Decompensated cirrhosis- all causes Hepatocellular carcinoma- defined criteria Acute liver failure Hepatopulmonary Syndrome Portopulmonary Hypertension Metabolic disorders

4. Liver Transplant  Extrahepatic malignancy  Active infection  Active substance abuse  Cholangiocarcinoma-relative  Significant non-hepatic co- morbidity  Significant portal/SMV thrombosis  Extrahepatic malignancy  Active infection  Active substance abuse  Cholangiocarcinoma-relative  Significant non-hepatic co- morbidity  Significant portal/SMV thrombosis Contraindications LIVER TRANSPLANT – INDICATIONS AND CONTRAINDICATIONS

5. Cirrhosis Normal Liver Cirrhosis Histopathologic Result of Chronic Liver Diseases

6. Etiology of Liver Disease

7. Cirrhosis  End stage of any chronic liver disease  Characterized histologically by regenerative nodules surrounded by fibrous tissue  Clinically there are two types of cirrhosis:  Compensated  Decompensated  End stage of any chronic liver disease  Characterized histologically by regenerative nodules surrounded by fibrous tissue  Clinically there are two types of cirrhosis:  Compensated  Decompensated DEFINITION OF CIRRHOSIS

8. Compensated cirrhosis Compensated cirrhosis Decompensated cirrhosis Decompensated cirrhosis Death Chronic liver disease Natural History of Chronic Liver Disease Development of complications:  Variceal hemorrhage  Ascites  Encephalopathy  Jaundice  Variceal hemorrhage  Ascites  Encephalopathy  Jaundice NATURAL HISTORY OF CHRONIC LIVER DISEASE

9. Development of Complications in Compensated Cirrhosis Ascites Jaundice Encephalopathy GI hemorrhage Probability of developing event 0 0 20 60 80 100 0 0 60 40 20 40 80 100 120 140 160 Months Gines et. al., Hepatology 1987; 7:122 NATURAL HISTORY OF CIRRHOSIS

10. 60 40 80 100 120 140 160 0 0 40 60 80 20 0 0 100 Months Probability of survival All patients with cirrhosis Decompensated cirrhosis 180 Decompensation Shortens Survival Gines et. al., Hepatology 1987;7:122 Median survival ~ 9 years Median survival ~ 1.6 years SURVIVAL TIMES IN CIRRHOSIS

11. Liver Transplant  Cirrhosis - all causes (hepatitis C most common indication)  Intrahepatic malignancy  Acute liver failure  Metabolic disease  Cirrhosis - all causes (hepatitis C most common indication)  Intrahepatic malignancy  Acute liver failure  Metabolic disease  Extrahepatic malignancy  Active infection  Active substance abuse  Cholangiocarcinoma  Non hepatic co-morbidity  Extrahepatic malignancy  Active infection  Active substance abuse  Cholangiocarcinoma  Non hepatic co-morbidity Indications Contraindications LIVER TRANSPLANT – INDICATIONS AND CONTRAINDICATIONS

12. Cirrhosis and Decompensation Compensated cirrhosis patients may be followed for years but once decompensation occurs, liver transplant referral should be done promptly.

13. Liver Transplant Referral The initial step of the liver transplant referral process is financial clearance. This step requires the designated center to attain financial clearance to begin the evaluation process. It is important to note that neither the patient or the physicians may obtain this clearance. This step may take any where from a few hours up to a few weeks depending on the insurance company.

14. The Liver Transplant Evaluation Process Once financial clearance is obtained, the liver transplant coordinator will begin communication with the patient. The transplant coordinator is there to review the records, place the orders for the tests, imaging, and consultations needed. This evaluation is usually completed over several days

15. The Liver Transplant Evaluation Process The patient will have consultations with the following team members during the evaluation: 1. Transplant Financial Counselor 2. Liver Transplant Surgeon 3. Transplant Hepatologist 4. Transplant Social Worker 5. Transplant Dietician 6. Transplant Coordinator 7. Transplant Cardiologist- as needed 8. Other consultants are based on medical indications such as Anesthesia, Pulmonary, Nephrology, Hematolgy/Oncology

16. Social Worker Evaluation Full assessment of the social support for a patient Development of a suitable 24 hour care plan Evaluation of patient’s financial status to determine if the out of pocket expenses are within the patient’s financial means Assessment of the home including pets: reptiles, birds, cats, chicks/ducklings, exotic pets such as monkeys Alcohol and substance use history including any co-existing psychiatric issues Recommendations for psychiatric evaluation of substance abuse treatment/relapse prevention Functional status of the patient Assess the level of commitment to the transplant process, follow up and compliance Assess for the medical power of attorney, directives to physicians

17. Medical Review Board The case is then taken to a Medical Review Board It is at this time that the case is fully reviewed with presentations by the primary team members including surgery, hepatology, social worker, dietician, financial counselor. Recommendations from the MRB are made on the needed labs, imaging, and additional consultations are made at this stage

18. Medical Review Board Patients who appear to be at risk from a financial standpoint will be asked to come up with a financial plan to pay for transplant medications Patients will also be asked to have a 24 hour care plan The social worker evaluation recommendations are reviewed with follow up plans assessed

19. Liver Transplant Listing Once full clearance is obtained from the medical review board, the patient is then listed for liver transplant using the MELD score determination

20. MELD Model of End Stage Liver Disease Formula based on bilirubin, INR, creatinine – no subjective component Predicts mortality at 90 days Adopted for liver allocation in Feb 2002 Sickest get transplanted first Avoids certain problems with CTP Accurate in about 80% of patients – requires certain exceptions

21. MELD Formula 6.3 + ([0.957 x log creat] + [0.378 x log bili] + [1.12 x log INR] + 0.643) x 10 Renewed based on score >25 – every 7 days 19-24 – every 30 days 11-18 – every 90 days <10 – every year Exceptions: tumors, biliary sepsis, lung diseases, metabolic diseases, bleeding

22. MELD – Prognostic Significance MELD Score3-Month Mortality (%) <102-8 10-196-29 20-2950-76 30-3962-83 >40100

23. 60 0 0 80 40 20 0 0 2 2 4 4 6 6 8 8 10 Months from listing Probability of survival (%) Probability of survival (%) 12 MELD and Survival on Transplant Waiting List MELD AND SURVIVAL ON TRANSPLANT WAITING LIST 33.8% > 30 66.0% 90.7% 92.3% 20-29 15-20 < 15

24. Share 35 Program This is the newest organ allocation policy. This program requires regional sharing of organs in all patients whose MELD is greater than 35. This program has made a dramatic difference in our abilities to get organs for the sickest patients.

25. United Network for Organ Sharing (UNOS) Regions 2 2 9 9 1 1 11 3 3 10 7 7 8 8 4 4 5 5 6 6 UNOS REGIONS

26. SUMMARY Cirrhosis decompensation such as ascites, encephalopathy, GIB, jaundice should all prompt referral to a liver transplant center Liver transplant assessment is commonly done by the transplant hepatologist with a full evaluation recommended once the MELD score is >15 or if there is a suspected HCC which is within the specified criteria The liver transplant referral process may take days to weeks to complete in the outpatient setting. Urgent inpatient evaluations can be done in 1-2 days. Patients are listed in UNOS based on their MELD scores

27. Question 1 Which of the following is the most common cause of cirrhosis prompting liver transplant in the U.S.? 1. Alcohol abuse 2. Hepatitis B 3. Hepatitis C 4. Acute Tylenol overdose

28. Question 2 At what time should a liver transplant evaluation be considered? 1. When the patient first receives the diagnosis of cirrhosis 2. Once the patient deteriorates and is in the ICU 3. When there is evidence of decompensation of the cirrhosis 4. When the crash cart arrives to the bedside

29. Question 3 When following cirrhosis patients, calculation of the MELD score helps to assess the time at which liver transplant referral should be done. What MELD score has been shown to be the time for transplant referral? 1. MELD < 15 2. MELD >25 3. MELD >15