Adult-to-adult living donor liver transplantation Triumphs and challenges

Transcription

1 Falk Symposium No. 163 on Chronic Inflammation of Liver and Gut Adult-to-adult living donor liver transplantation Triumphs and challenges ST Fan, MS, MD, PhD, DSc Professor Sun CY Chair of Hepatobiliary Surgery The University of Hong Kong Hong Kong

2 Pioneers of adult-to-child LDLT Raia S Brazil 1989 Strong R Australia 1989 Nagasue N Japan 1989 Ozawa K Japan 199 Broelsch C USA 199

3 Mother-to-child living donor liver transplantation

4 Left lobe donation from large body size donor to small body size recipient

5 The first 6 right liver LDLT recipients in the world. All of their right liver grafts contain the MHV. All except one are surviving in good condition.

6 Right liver donation from small body size donor to large body size recipient Right liver graft (MHV) expands applicability of LDLT

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8 Right liver LDLT override body-size mismatch Number Donor BW > Recipient BW Donor BW = Recipient BW Donor BW < Recipient BW 62 (21.6 %) 14 (4.9%) 211 (73.5%)

9 Publications on LDLT since inception (1989) Left liver Right liver Year

10 Left liver graft with middle hepatic vein Left liver graft with caudate lobe Right liver graft without middle hepatic vein Right liver graft with middle hepatic vein Right lateral sector graft The available graft types for adult-to-adult LDLT. The shaded area represent the graft portion of the liver.

11 Adult-to-adult living donor liver transplantation using dual grafts Lateral segment Left lobe Left lobe Left lobe Right lobe Left lobe Posterior segment Lateral segment Lee SG, Asian J Surg, 23

12 Year Number Right liver living donor liver transplant in Queen Mary Hospital, Hong Kong MELD score (median) Recipient hospital mortality ICU stay (days) (median) Blood transfusion unit (median) University of HK Recipient with no blood transfusion (4.5%) 11 consecutive patients without hospital mortality (34.5%) 4 (14.3%) 13 (31%) 6 (18.8%) 15 (45.5%) 1 (29.4%)

13 Comparison between living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) Patient survival at Queen Mary Hospital University of HK Cumulative survival (%) LDLT (n = 124) DDLT (n = 56) P = Survival time (months)

14 Results of right liver LDLT (including MHV) at Queen Mary Hospital, University of Hong Kong University of HK No. of transplant MELD score Graft wt to ESLW (%) Graft wt to recipient body wt (%) Hospital mortality Cirrhosis (7 41) (4.3%) ( ) ( ) Cirrhosis with acute deterioration (15 59) 47.5 ( ).89 ( ) 3 (6.8%) CAH acute flare (23 52) 49.7 ( ).93 ( ) 3 (7.7%) Fulminant hepatic failure 2 36 (27 5) 55 ( ).98 ( ) 1 (5.%)

15 Cumulative survival (%) 1 Graft survival of adult recipients with cirrhosis R lobe LDLT (n=11) Survival time (years) DDLT (n=92) P= Graft survival of adult patients with liver cirrhosis with acute deterioration Cumulative survival (%) DDLT (n=19) 3 R lobe LDLT (n=38) 4 Survival time (years) 5 6 P= University of HK Cumulative survival (%) Graft survival of adult patients with chronic hepatitis B with acute flare DDLT (n=5) R lobe LDLT (n=29) 5 Survival time (years) P= Cumulative survival (%) Graft survival of adult recipients with fulminant hepatic failure DDLT (n=5) R lobe LDLT (n=18) 9 P= Survival time (years)

16 Relative risk of dying after liver transplantation Graft type Live donor Standard criteria deceased donor Extended criteria donor Donation after cardiac death donor Relative risk Emond J, 27

17 Disease-free survival of HCC recipients 1 9 DDLT (n=21) University of HK Cumulative survival (%) LDLT (n=59) P= Survival time (years) Lo CM et al, Br J Surg, 27

18 Probability of freedom from HCC recurrence by time since LDLT or DDLT Freedom from Recurrence (%) DDLT (n=34) LDLT (n=58) P=.2 Year from transplant Fisher RA et al, Am J Transplant, 27

19 Possible reasons for higher incidence of HCC recurrence after LDLT HCC with aggressive biological behavior are transplanted early Less lymph node removal More liver manipulation More acute phase injury in small graft Rapid liver regeneration stimulates HCC growth More immunosuppression relative to liver graft size

20 Tumor growth in small graft (nude mice model) Whole graft Small graft Day 2 Day 4

21 Acute phase injury and late phase tumor recurrence Liver transplantation using small liver graft Shear stress Liver regeneration Hepatic sinusoidal injury Microvascular barrier dysfunction Liver parenchyma damage Favorable environment for tumor growth and metastasis Inflammatory cascades Cell adhesion, migration and invasion (ROCK, RAC, Pyk2 ) Angiogenesis (VEGF, HSC activation ) Tumor cell proliferation (Ki67 ) Invasive tumor growth in small-for-size liver graft Man K, Liver Transpl, in press

22 Is the living donor graft to be blamed for higher HCC recurrence? Risk factors for recurrence of HCC by multivariate analysis Transplant year (pre MELD) AFP level Recipient age Centre experience Fisher RA et al, Am J Transpl, 27 Salvage transplant Pathological stage beyond UCSF criteria CM Lo et al, Br J Surg, 27

23 Possible reasons for loss of small-for-size graft Hyperdynamic portal flow Endothelial cell damage Adhesion molecule upregulation Cytokine release Liver regeneration Mediator release e.g. VEGF Macrophage activation and infiltration Enhanced alloantigen presentation Generation of reactive oxygen species Exacerbated acute rejection Initiation of apoptotic pathway Exacerbation of inflammation Loss of small-for-size graft

24 Inter-relationship of variables contributing to small-for-size graft injury portal inflow impaired venous outflow suboptimal graft quality graft size Fan ST, Transplantation, 26

25 Small-for-size graft injury Measures to improve graft outcome portal inflow porta-systemic shunt FK49 splenic artery ligation impaired venous outflow inclusion of MHV in the graft venoplasty graft size >35% ESLW suboptimal graft quality ischemia time avoid fatty graft avoid elderly graft FTY72 HO-1 transfer Fan ST, Transplantation, 26

26 Known donor mortalities Author Country Type of graft Remarks Akabayashi Japan Rt liver (w/ MHV) Nonalcoholic steatohepatitis - India Not known Suspected pulmonary embolism Boillot France Rt liver (w/o MHV) Right pleural effusion, multiple organ failure Broering Germany Left lateral segment Massive pulmonary embolism Brown United States Rt liver (w/o MHV) Pancreatitis - United States Not known Not known Malago Germany Rt liver (w/o MHV) Congenital lipodystrophy Malago Germany Lt liver Pulmonary embolism Miller United States Rt liver (w/o MHV) Gas gangrene of stomach Wiederkehr Brazil Rt liver (w/o MHV) Cerebral hemorrhage Chan Hong Kong Rt liver (w/mhv) Duodeno-caval fistula complicating chronic duodenal ulcer

27 Known donor mortalities Author Country Type of graft Remarks Polido Singapore Rt liver Heart attack - Korea Rt liver Liver failure, steatosis Coelho Brazil Rt liver Cardiac arrhythmia - India Rt liver Cardiac arrest, unknown cause - France Rt liver Multiple mycloma Abofetouh Egypt Rt liver Sepsis, bile leakage

28 Donor operation Principle A donor receives an operation for a disease that he does not have To protect the donor and to prevent unnecessary morbidity and mortality, vigilant evaluation and perioperative care is necessary

29 Donor evaluation Principle Healthy donor is a completely healthy person Any volunteer with concomitant medical disease should not be allowed to donate No compromise in donor evaluation and acceptance criteria

30 Pre-requisite for successful donor hepatectomy Experience and skill in liver transection Knowledge of liver anatomy Protection of remnant liver Meticulous post-operative care

31 Living donor liver transplantation Major stride in liver transplantation Donor mortality and morbidity are major concerns Further strategies to improve outcome small for size graft injury HCC recurrence Minimize donor morbidity