Principles of LIVER TRANSPLANTATION.pptx

This is a presentation of principles of Liver transplantation. I discussed the aetiology of liver failure, indication and contraindication to liver transplantation. Then, I went further to discuss the peri-operative principles including preoperative, intraoperative and postoperative principles. the intraoperative principles further looked at the salient surgical technique of dissection and anastomosis. Furthermore, I went ahead to look at the post-operative complications and how to address them. Finally, I discussed the training opportunity for Fellowships in HPB surgery, Liver transplantation and abdominal organ transplantation across the globe.

1. LIVER TRANSPLANTATION Olayinka L. Adewunmi Division of General Surgery UMTH 30 th January, 2023

2. Outline Introduction Definition Historical perspective Epidemiology- Nigeria, Africa and Global Immunology of liver transplantation Indications Contraindications Source of organ Perioperative approach pre-op, Intra-op and post-op Complications Training opportunities and liver transplant societies/membership Summary References 1/30/2023 2 Liver transplantation

3. Introduction- Definition Liver transplantation is defined as the replacement of a non-functioning liver with a functioning one. Liver transplantation is a form of orthotopic transplant, i.e. the diseased organ is removed and replaced with a functioning one at the same site. OLTx - Orthotopic Liver transplantation 1/30/2023 3 Liver transplantation

4. Introduction- Historical perspective 1952- Vittorio Staudacher described what looks like liver transplant today 1955- C. Stuart Welch liver transplant in Dog 1956- Jack Cannon liver transplant in Dog 1963- Thomas Starzl started the first human liver transplant, but a series of deaths led to a voluntary moratorium for 3.5 years 1/30/2023 4 Liver transplantation

5. Introduction- Epidemiology No Liver transplant services in Nigeria. In Africa, only 2 country has Liver transplant services: South Africa (SA) and Egypt. Sudan just commenced Liver transplant services about 5month ago In SA, the first programme was established in 1988 at Groóte Schuur Hospital in Cape Town and the second programme in 2004 at Wits Donald Gordon Medical Centre (WDGMC) in Johannesburg . 1/30/2023 Liver transplantation 5

6. Introduction- Epidemiology Living donor liver transplant (LDLT) was first performed in Egypt in 1991 by the surgical team at the National Liver Institute (NLI), Menoufeya University, with the help of Prof. Habib. The longest recipient survival was 11 months There are thirteen LDLT centers in Egypt, including six university centers, two military centers, three private centers and two centers in the ministry of health hospitals. By the end of June 2014, the total number of cases reached 2,406 . 1/30/2023 Liver transplantation 6

7. Introduction- Epidemiology In 2021, there were just over 9,200 liver transplant carried out in the USA. Most liver transplants in the U.S. are among adults aged 50 to 64 years, with this age group accounting for around 45 percent of all liver transplants in 2021. California had the highest number of liver transplants performed among all U.S. states. That year, there were just over 1,000 liver transplants performed in California. The state with the second highest number of liver transplants was Texas. Liver transplants are the second most common transplant in the United States behind kidney transplants. 1/30/2023 Liver transplantation 7

8. Immunology of liver transplantation Histocompatibility complex/protein Human leucocyte antigen (HLA)- 6q 2 types Major- MHC- important in organ rejection minor- miH HLA 2 types Class I- HLA A, B and C- present in all antigen Class II- HLA DP, DQ, DR- present in APCs 1/30/2023 Liver transplantation 8

9. Immunology of liver transplantation A two-signal model , T-cell activation begins with the engagement of the T-cell receptor (TCR)/CD3 complex with the foreign molecule- signal 1. An additional costimulatory signal is required . Two well-characterized costimulatory interactions are the CD40/CD154 and B7/CD28 pathways- signal 2 1/30/2023 Liver transplantation 9

10. Indications for OLTx End stage liver disease (ESLD)- decompensated liver failure Chronic non-Cholestatic liver disorders Chronic hepatitis B (HBV) Chronic hepatitis C (HCV) Autoimmune hepatitis Alcoholic liver disease 1/30/2023 10 Liver transplantation

11. Indications for OLTx Cholestatic Liver disease Primary biliary cirrhosis Primary sclerosing cholangitis Congenital/Paediatric patients Biliary atresia Cystic fibrosis Alagille syndrome 1/30/2023 11 Liver transplantation

12. Indications for OLTx Metabolic disorders causing cirrhosis Alpha-1-antitrypsin deficiency Wilson’s disease Hereditary hemochromatosis Non-alcoholic fatty liver disease (NAFLD) Glycogen storage disease type IV Acute fulminant hepatic failure- King’s college criteria 1/30/2023 12 Liver transplantation

13. Indications for OLTx Primary liver malignancy Hepatocellular carcinoma (HCC)- Milan criteria Hepatoblastoma Hemangioendothelioma Miscellaneous Budd-Chiari syndrome Polycystic disease Metastatic NETs 1/30/2023 13 Liver transplantation

14. Indications for OLTx Complications of End stage Liver Disease (ESLD) Recurrent variceal hemorrhage Intractable ascites Spontaneous bacterial peritonitis Refractory encephalopathy Severe jaundice Fulminant hepatic failure Hepatorenal syndrome 1/30/2023 14 Liver transplantation

15. Contraindication Absolute Advanced Cardiopulmonary disease Active sepsis/SBP Extensive portal/visceral venous thromboses metastatic malignancy active drug/alcohol abuse untreated psychiatric illness Relative AIDS Advanced age (global variation) absent social support inadequate insurance for post-op medications 1/30/2023 15 Liver transplantation

16. Liver transplantation: Overview First- establish a diagnosis End stage Liver disease (ESLD ) Second- to exclude any absolute or relative contraindication for Liver transplant Mandatory consultations/clearances Organ Procurement Transplant Network (OPTN ) Listing of candidates 1/30/2023 16 Liver transplantation

17. Liver transplantation: Approach First- establish a diagnosis End stage Liver disease (ESLD ) History Examination: Ascites, Jaundice, Investigations Laboratory- LFT, Total protein/albumin, Clotting profile, a-fetoprotein, viral screening Imaging: USS, CT, MRI, Angiography, PET scan Biopsy: cirrhosis/chronic liver disease 1/30/2023 17 Liver transplantation

18. Imaging USS 1/30/2023 Liver transplantation 18

19. Imaging: CT 1/30/2023 Liver transplantation 19

20. Liver transplantation: Approach Second- to exclude any absolute or relative contraindication for Liver transplant Test for cardiopulmonary reserve: CXR, FEV1, spirometry ECG, ECHO, PAC Tissue typing: HLA typing other test as required 1/30/2023 20 Liver transplantation

21. Liver transplantation: Approach Mandatory consultations/clearances cardiopulmonary clearance- chest physician psychiatry and social worker consultation clearance Financial/insurance clearance Nephrologist, infectious dx clearance 1/30/2023 21 Liver transplantation

22. Liver transplantation: Approach Liver allocation list by Organ Procurement Transplant Network (OPTN) M odel for End stage Liver D isease (MELD) score >12ys Paediatric End stage L iver Disease (PELD) score <12yrs 1/30/2023 22 Liver transplantation

23. Liver transplantation: Approach MELD score: 3 biochemical parameter MELD Score = 10 * ((0.957 * ln(Creatinine)) + (0.378 * ln(Bilirubin)) + (1.12 * ln(INR))) + 6.43 Cr=4mg/dl in a patient who underwent HD in the last 7 days any value less than 1, is given a value of 1 1/30/2023 23 Liver transplantation

24. Liver transplantation: Approach MELD Score No of patients Mortality rate (%) Death or removal from list because of illness <9 124 1.9 2.9 10-19 1800 6 7.7 20-29 1098 19.6 23.5 30-39 295 52.6 60.2 ≥40 120 71.3 79.3 1/30/2023 24 Liver transplantation

25. Liver transplantation: Approach PELD score: 3 clinical and 3 biochemical variables PELD Score = 10 * ((0.480 * ln(Bilirubin)) + (1.857 * ln(INR)) - (0.687 * ln(Albumin)) + 0.436(if the child is <1yr old) + 0.667(if the child has growth failure[<2 SD]) 1/30/2023 25 Liver transplantation

26. Source of organ donation Deceased donors Brain death- consent from relatives cardiac death- consent before death Living donors OLTx Split liver donors- left lobe, left lateral segment/section 1/30/2023 26 Liver transplantation

27. Liver transplantation: Approach Living donor evaluation laboratory: FBC, EUC, LFT, clotting profile, a-fetoprotein, work up for metabolic dx. HLA typing Imaging: Duplex USS CECT/MRI A ngiography 1/30/2023 27 Liver transplantation

28. Liver transplantation: Approach Donor surgery Deceased donor follow the conventional organ procurement method Living donor: left lobe or left lateral segment piggyback donor method After harvest, organ is perfused with preservation solution within the acceptable Ischaemic time for liver tissue. 1/30/2023 Liver transplantation 28

29. Organ procurement for deceased donor 1/30/2023 Liver transplantation 29

30. Organ procurement for deceased donor 1/30/2023 Liver transplantation 30

31. Organ Package and Transportation in Liver Graft 1/30/2023 Liver transplantation 31 The liver is inspected in the basin. The first sterile bag is filled with the liver graft and 700–1,000 mL of HTK solution (4°C), and the bag is secured with a tie. It is then placed into the second sterile bag filled with 1 L of cold normal saline or slush ice and tied. The second bag is placed into the third bag and tied. The liver in the three-layered bag is then placed in the heat preservation container box filled with ice blocks for transportation.

32. Preservatives University of Wisconsin solution Histidine-Tryptophan-Ketoglutarate Celsior solution Collins solution Eurocollins solution 1/30/2023 Liver transplantation 32

33. Organ procurement for LDLT Three different types of donor hepatectomies are used for living donor liver transplantation (LDLT) , as follows: Left lateral hepatectomy, in which the graft consists of segments II and III, with or without segment I Left hepatectomy, in which the graft consists of the whole left lobe, segments I, II, III, and IV Right hepatectomy, in which the graft consists of the right lobe, segments V, VI, VII, and VIII 1/30/2023 Liver transplantation 33

34. Liver transplantation: Approach Recipient hepatectomy B ilateral subcoastal + midline extension (Mercedes-Benz incision) all ligaments are mobilized supra and infra hepatic vena cava is transected hilar dissection: portal vein, HA and hepatic veins (with supra-hepatic vena cava) and bile duct veno -venous cannula passed from the femoral/portal to the subclavian for those who are hemodynamically unstable hepatectomy completed 1/30/2023 34 Liver transplantation

35. Liver transplantation: Approach Recipient graft transplantation IVC: suprahepatic IVC, then Infrahepatic IVC portal vein anastomosis: end-to-end Hepatic artery: end-to-end Bile ducts: end-to-side or roux- en -Y anastomosis 1/30/2023 35 Liver transplantation

36. Liver transplantation: Approach 1/30/2023 36 Liver transplantation

37. Liver transplantation: Approach-Piggyback technique IVC is not removed hepatic veins are divided at their confluence before entering the IVC. bypass may not be required or partial bypass Adv: ↓hemodynamic instability, good renal perfusion Disadv : ↑ hepatectomy time, ↑ blood loss 1/30/2023 Liver transplantation 37

38. Liver transplantation: Approach- LDLT Donor and recipient procedure for living donor liver transplant into a pediatric recipient 1/30/2023 Liver transplantation 38

39. Liver transplantation: Approach- LDLT A . Hepatic transection completed for removal of left lateral segments (S2 and S3). Bile ducts to segments 2 and 3 divided; vascular structures still intact. B . Implantation of the donor left lobe. 1/30/2023 Liver transplantation 39

40. Liver transplantation: Approach- LDLT Hepatic transection completed for right lobe removal Implantation of the donor right lobe with the MHV 1/30/2023 Liver transplantation 40

41. Post-op care ICU monitoring until hemodynamic stability Serial liver function test: transaminases Duplex scan to check HA, portal vein, bile flow, bleeding Platelet sequestration by the graft but later normalizes 1/30/2023 41 Liver transplantation

42. Immunosuppressive medications Induction steroid + polyclonal/monoclonal antibody Maintenance steroid, cyclosporine/tacrolimus and MMF/ azathiopine 1/30/2023 Liver transplantation 42

43. Immunosuppressive medications 1/30/2023 Liver transplantation 43

44. Complications Peri-operative (first 30 days) complications Early (first 6 month) complications Late complications (>6month) 1/30/2023 44 Liver transplantation

45. Complications- first 30 days Primary non function or Primary poor function (1-7%) Hepatic artery thrombosis (2.9%) Portal vein thrombosis (<2%) Preservation/reperfusion injury Haemorrhage Biliary complications (10-35%) bile leak benign strictures 1/30/2023 45 Liver transplantation

46. Complications- first 6months Biliary strictures Acute graft rejection Infections 1/30/2023 46 Liver transplantation

47. Complications- >6month Malignancy: PTLD, Kaposi sarcoma, lymphoma, etc Incisional hernia Biliary strictures Vascular complications- aneurysm of HA, late thrombosis Chronic rejection 1/30/2023 47 Liver transplantation

48. Founder of Dr Rela Institute and Medical centre in Chennei , India President, International Liver transplant Society (ILTS) Former President, Liver Transplant society of India (LTSI) www.ilts.com and become a member Guinness book of records Done over 1/30/2023 Liver transplantation 48

49. Liver Transplant fellowship (with HPB surgery) https ://www.ihpba.org/fellowship/?group=Asia+% 2F+Pacific https:// www.ihpba.org/27_HPB-Fellowship-Registry.html https://www.ihpba.org/fellowship/?group=Europe%2C+Africa+% 26+Middle+East 1/30/2023 Liver transplantation 49

50. Liver transplant society International Liver transplantation Society President- Prof Mohamed Rela - Owner of Rela institute & medical centre in Chennei , India. 1/30/2023 Liver transplantation 50

51. Summary Liver transplantation has seen r apid development and growth from the pioneering days of Starzl and Calne Today, liver transplant recipients enjoy excellent patient and graft survival and the procedure has become routine in many centres Living donor LT has emerged as a viable option for patients with ESLD Advances in surgical technique, immunosuppression, perioperative care have not only reduced operative morbidity/mortality, but have also significantly improved the quality of life for the recipients 1/30/2023 51 Liver transplantation

52. References Charles F. Brunicardi: Schwartz’s principles of Surgery, 10 th edition Chapters 33 https://www.statista.com/statistics/954207/us-liver-transplants-by-state/ O. James Garden and Simon Peterson-Brown: Hepatobiliary and pancreatic surgery, a companion to specialist surgical practice, 5 th edition, chapter 15 Norman, S. W., Christopher J.K.B., and P.Ronan O’ Connell (2008). Bailey and Love principles and practice of Surgery , 25 th edition, chapter 61, 63 and 64 Michael J Zinner and Stanley W Ashley: Maingot’s abdominal operations, 12 th edition. Chapter 59 1/30/2023 52 Liver transplantation

53. John L. R. Forsythe: Transplantation, a companion to specialist surgical practice, 5 th edition, chapter 8 1/30/2023 53 Liver transplantation

54. THANK YOU FOR YOUR ATTENTION 1/30/2023 54 Liver transplantation