Michael E. DeBakey Department of Surgery Baylor College of Medicine Houston, Texas

1. Liver Transplantation at SLEH/BCMJohn A. Goss, MDProfessor of Surgery Michael E. DeBakey Department of Surgery Baylor College of Medicine Houston, Texas

2. First attempt at kidney transplant with human kidney First pediatric living donor liver transplant First US adult living donor liver transplant First liver transplant 1902 1936 1954 1963 1983 1989 1994 1998 2002 First attempt at kidney transplant First successful kidney transplant Cyclosporine FDA approved Tacrolimus FDA approved MELD implemented History of Transplantation

3. Initial Kidney Transplant Attempts:

4. First Successful Kidney Transplant

5. Experimental Liver Transplantation

6. Initial Liver Transplant Attempts:1963-1964

7. Initial Liver Transplant Attempts:

8. First Liver Transplant • March 1, 1963: First attempted human liver transplant • July 23, 1967: First successful human liver transplant

9. Post-Moratorium Successes • anti-lymphocyte globulin (ALG) & the “triple cocktail” • improved organ preservation • definition of “brain death” Starzl TE. J Am Coll Surg 2002; 195:587.

10. 1968 Ad Hoc Committee of Harvard Medical School Published Criteria for Brain Death • 1968 Uniform Anatomical Gift Act • 1978 Uniform Brain Death Act • 1983 NIH Consensus Development Conference: • “…Liver Transplantation is a therapeutic modality for end stage liver disease that deserves broader application.” • 1984 National Organ Transplant Act: • Sale of organs prohibited • Development of UNOS

11. Indications for Liver Transplant • Life-threatening and progressive irreversible liver disease • Fulminant hepatic failure • Hepatopulmonary or hepatorenal syndrome • Worsening synthetic function • Ascites resistant to medical therapy • Hepatic encephalopathy • Variceal hemorrhage • Progressive malnutrition • Increasing fatigue that interferes with daily activities • Recurrent cholangitis • Development of hepatocellular carcinoma

12. Etiology of Liver Disease

13. Indication for Liver Transplantation Evaluation Process Hepatologist Transplant Surgeon Cardiologist Nurse Coordinator Social Worker Laboratory Studies Imaging (CT or MRI) List for Transplant • Absolute Contraindications • Uncontrolled systemic infection • Extra-hepatic malignancies • Ongoing drug or alcohol use • Inability to comply • with post-transplant therapy • Relative Contraindications • Portal vein thrombosis • Pulmonary hypertension • Cholangiocarcinoma • HIV Medical Management

14. Liver Waitlist

15. Timing of Transplant Organ Allocation 2002-present MELD (Model of End Stage Liver Disease) • Originally developed to evaluate mortality in patients undergoing elective TIPS procedures • Subsequently validated as predictive of survival in patients with end stage liver disease • 85% of time accurately predicts individuals survival • Only objective data used in calculation

16. MELD R= (0.957 x Loge(creatinine mg/dl) + 0.378 x Loge(total bilirubin mg/dl) + 1.120 x Loge(INR) + 0.643)) x 10

17. Liver Allocation • Status IA • Status IB • Local MELD/PELD • Regional MELD/PELD • National IA/IB • National MELD/PELD

19. Deceased Donor Technique

20. Recipient Technique: Liver

21. Recipient Technique: Liver

22. Immunosuppression

23. Improvement in Patient Survival Patient Survival % Time After Transplantation (years)

24. Improvementin Allograft Survival Survival % Time After Transplantation (years)

25. US Survival: Adult Liver

26. US Survival: Pediatric Liver

27. Liver Transplantation - • BCM initiated Recruitment in 1998 • 1 Hepatologist, 2 Surgeons, 1 Nurse Coordinator • 1 Social Worker, 1 Financial Coordinator, HLA Blood Bank, etc. • Development of Patient Care Protocols – ICU, Anesthesia, OR Nurse • Obtainment of UNOS Certification 6/98

28. Liver Transplantation - • Opened program 7/1/98 – combined with pediatric program at Texas Children’s Hospital • 1st resection 7/5/98 • 1st liver transplant 9/2/98 • 9 liver transplants in 1998 - All patients survived with 14 day length of stay

29. Liver Transplantation- • 17 Physicians - 9 Adult Hepatologists 6 Pediatric Hepatologists 2 Surgeons • 14 Nurse Coordinators • 5 Hepatology Nurses • 5 Medical Assistants • 2 Administrative Staff • 3 Transplant programs

30. SLEH/BCM Administration Margaret Van Bree, MHA, DrPH Paul Klotman, MD Todd Rosengart, MD Rachel Goldsmith, MPA Diesa Samp, BSN, RN, CCTC Physicians John Goss – BCM Blaine Hollinger-BCM Khozema Hussein-BCM Prasun Jalal-BCM SairaKhaderi-BCM Charles Phan-BCM Christine O’Mahony- BCM GaganSood, BCM Rise Stribling- BCM Norman Sussman-BCM John Vierling- BCM THI Anesthesiology C. David Collard, MD Cardiology SayeedFeghali, MD THI Pathology/Blood Bank/ Lab Med Rhonda Shannon, MD Psychiatry Jennifer Pate, M.D. Pulmonary, Nephrology, Infectious Diseases, GI THI Nurse Coordinators Claudette Campbell, RN Jeanette Cleveland, RN Shannon Cook, RN Norma Flores, RN Felicia Franco, RN Diana Gonzalez, RN Demetrice Gray, RN Yolanda Murray, RN Wanda Samuels, RN Tamara Stephens, RN Pharmacy Raymond Yau, PharmD Social Work Ann Holder, LCSW Robin Kremer, LCSW Dietary Amy Cook, RD Financial Deidra Lester Exercise Physiologist Fabian Nursing Staff: CVOR, CV Recovery, 8CB 12 & 7 Tower SLEH Liver Transplant Team

31. Diagnosis

32. Primary Payor 15% 33% 3% 48%

33. Transplant Totals 120 114 110 105 105 119 95 94 85 83 73 66 66 67 51 12

34. 2010: One Thousand Liver Transplants 2010 Adult Liver Transplant Team

35. Patient Survival

36. * * * *Statistically higher than expected Graft Survival

37. 2012 Summary • Unadjusted patient and graft survival: 98% • Median length of stay: 9 days • Operative time: 3 hours and 20 minutes • Number of blood transfusions: 1.7 units of PRBCs

38. Future Directions • Asian Liver Center • Outreach clinics • Improvement in length of stay • Improvement in survival • Telemedicine/ECHO

40. Liver Transplantation – Education/Research • Provide Clinical Environment for BCM 3rd Year Medical Student and BCM General Surgery Residents • TSMBE and ASTS Approved Liver Transplant Fellowship • AASLD Funded NP Fellowship • Trained Murat Kilic, MD – Chief of Liver Transplantation Izmir, Turkey • 108 Peer-reviewed publications • 102 National oral presentations • TSMBE/ACGME Hepatology Fellowship

41. Liver Transplant Division: Ongoing Research Projects Research Division Post-transplant Lymphoma Hepatocellular carcinoma Clinical Research

42. Status of Tissue Bank • >1400 tissue samples from 146 patients • Sanger Sequencing of HCC Samples • 300 amplicons over 30 genes • 89 HCC samples with matched non tumor tissue or blood • 33 HCV, 3 EtOH, 1 BA, 49 HBV, 3 with no underlying liver disease • 16 Hepatoblastoma with non tumor tissue • 4 Hepatic adenoma with non tumor tissue

43. Ongoing Projects • Epigenetics of HCC • Investigating differential methylation patterns in tumor and non tumor tissue • Gene expression profiling • Developing cDNA libraries from mRNA • Whole genome sequencing • Select patients to have entire genome sequenced • Testing new platforms • New Next Generation sequencers to be tested on HCC samples • Development of collaborative tissue exchange programs • Vanderbilt, Baylor Dallas, Harvard, and Mayo Clinic participating in the early stages of the development of an HCC consortium

44. Future Reduce Donor/Recipient Discrepancy • Donor awareness campaigns • Extended criteria/ asystolic donors • Split liver transplantation • Living-donor liver transplantation • Xenotransplantation

45. Future Bioartificial Liver Stem Cells

46. Future Tolerance

47. Future • Increase selectivity, decrease toxicity/side effects • Pediatric transplantation • Hepatitis C • Coinfection Personalized Immunosuppression

48. Future Pharmacogenetics and Pharmacogenomics

49. Future Primary Liver Tumors • Hepatocellular carcinoma that exceeds Milan Criteria • Down-staging • Presence of vascular invasion • Genetics • Choangiocarcinoma • Previously considered a contraindication to OLT • Mayo Protocol: multimodality neoadjuvant therapy • Genetics

50. Conclusion • Liver transplantation has produced a positive impact on patients with advanced liver disease • Spectacular improvement have occurred since the preliminary work of Dr. Starzl • The advances in liver transplantation have occurred in a short 45 years and provide a base for future advances