Adult Living Donor Liver Transplantation Juan Guerrero, MD Clinical Assistant Professor Medicine Division of Gastroenterology

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1 Adult Living Donor Liver Transplantation Juan Guerrero, MD Clinical Assistant Professor Medicine Division of Gastroenterology

2 Overview Liver Transplantation Indications and contraindications Listing Process Organ Allocation Living Donor Liver Transplant (LDLT) LDLT Procedure LDLT Recipient LDLT Donor UTHSCSA cases and experience

3 Liver Transplantation End-stage liver disease is 12th leading cause of death Second most commonly transplanted organ Treatment of choice for symptomatic end-stage liver disease and some HCC Goals include prolonging life and quality of life

4 Liver Transplantation ~>120,000 liver transplants performed >6,000 living donor transplants ~ 17,000 patients waiting for liver transplant ~ 6,000 patients transplant annually ~ 2,000 patients die annually while on the waitlist 1 year patient survival ~85% 5 year patient survival ~75%

5 LI 1.1 Adult patients waiting for a liver transplant

6 LI 1.5 Liver transplant waiting list activity among adult patients

7 Indications for Liver Transplant

8 Trend in Liver Transplantations

9 Contraindications for Liver Transplant

10 When to refer for transplantation Cirrhotics with associated complications If a patient has well compensated cirrhosis without cirrhotic associated complications, 5-10yr survival without transplant ~90% Suspicion acute liver failure will lead to death Decision to proceed with transplant can be difficult All acute liver failure patients should consider transfer to transplant center Hepatocellular carcinoma and cirrhosis Significant compromise of quality of life

11 Transplant listing Routine evaluation at a liver transplant center Multidisciplinary approval for transplant candidacy Assigned a score based on the Model for End-Stage Liver Disease (MELD) MELD score= 0.957Xlog(creatinine mg/dl)+0.378xlog(bilirubin mg/dl)+1.120xloge(inr) ABO blood type and length of time at a particular MELD score contribute to priority Special situations include hepatocellular carcinoma, hepatopulmonary syndrome, portopulmonary hypertension, and other justifiable conditions.

12 Organ allocation United Network for Organ Sharing (UNOS) Divided nationally into 11 regions Regions divided into 59 Organ Procurement Organizations (OPOs) Typically donors within an OPO are matched to a suitable recipient within that OPO Status 1 candidates (prognosis is death within one week) matched within a region MELD 35 and above also get regional priority ~120 liver transplant centers across the US

13 UNOS Regions

14 Organ Procurement Organization (OPO) Texas Organ Sharing Alliance (TOSA)

15 LI 2.8 Cause of death among deceased liver donors

16 A Recipient to Donor Imbalance Continues to Worsen

17 Increasing Donor Availabiliy Increase number of cadaveric offers Increase acceptance of marginal donors Non-heart beating donors (DCD donors) Steatotic donors Older Donors HCV or HBV core + donors Split liver transplantation L Lobe to a child, R lobe to an adult Living Donor Liver Transplant (LDLT)

18 Living Donor Liver Transplant First attempted left lateral liver segment for a child in Brazil 1987 First successful live donor for a child in Australia same year First adult 1993 in Japan First U.S. adult 1998

19 Living Donor Liver Transplant Trend

20 Living Donor Liver Transplant Trend

21 LI 4.1 Total adult liver transplants

22 Liver Segments (Couinaud Classification)

23 Liver Segments (Couinaud Classification)

24 Right Lobe Living Donor Liver Transplant

25 Liver Regeneration After Hepatectomy

26 Liver Regeneration After Hepatectomy Greatest regeneration occurs in first week At 3 months liver volume approaches 100% expected in recipients, but only 80% in donors Felt higher portal flow and proliferogenic environment contributes to more efficient recipient regeneration IL-6, TNF alpha, and hepatocyte growth factor Portal venous inflow may contribute Hepatic arterial flow can autoregulate, venous cannot May contribute to small-for-size syndrome

27 Liver Volume Tolerance Residual volume following liver resection <30% associated with significant dysfunction Post Transplant felt higher volume required Initially felt 40-50% of standard liver volume Graft to recipient weight ratio (GRWR) >0.8% Graft wt/recepient wt X 100% Noncirrhotics and lower Child s score asscoiated with more tolerance of lower Graft to Recipient Weight ratio (GRWR) Different functional reserve of other organs

28 Liver Volume Tolerance Initially felt Graft-Recipient Weight Ratio (GRWR) <0.8% associated with delayed graft function and lower graft survival Reducing portal pressure to <15mmHg via splenectomy vs surgical shunting led to similar results with grafts of GRWR ~0.7% GRWR 0.8%= ~570cc graft in a 70kg recipient GRWR 0.7%= ~500cc graft in a 70kg recipient Ogura et al. Liver Transplant

29 LDLT Recipient Selection Need to qualify for OLT Need to insure a partial graft will be adequate Disease severity factor (MELD >30 and/or FHF) Lower limits of MELD score controversial Quality of life factor? HCV? HCC

30 LDLT Recipient Outcomes Whole liver cadaveric recipients have similar outcomes to living donor recipients Vascular and biliary complications greater in LDLT Right vs Common hepatic artery as anastomosis has greater thrombosis risk Debate on portal flow measurements/outcomes Biliary complications 15-60% (anastomotic narrowing, stricture,or leak from cut liver edge) Interventions limited based on biliary anastomosis ie: duct to duct vs roux-en-y hepaticojejunostomy

31 LDLT for Hepatitis C (HCV) Multicenter group actively collecting data LDLT (Adult to Adult Living Donor Liver Transplant Cohort) 3yr graft and patient survival in HCV 68% and 74% in LDLT vs 80% and 82% in OLT Lower graft and patient survival in first 20 LDLT at each center No difference in outcomes in patient and graft survival when considering LDLT after each centers first 20 LDLTs Olthoff et al. Liver Transplant

32 LDLT for HCC Transplanted within Milan Criteria similar outcomes to OLT (70-75% 5yr survival) No single lesion >5cm 3 lesions, not 1 >3cm Total tumor burden <9cms Those outside Milan 3 yr survival 50-60% Some suggestion outside Milan criteria may have better outcome based on tumor biology

33 Advantages of Live Donors Makes transplant semi elective optimizing timing Frees patients from waiting list priority HCC, cholestatic diseases, common blood types, refractory symptoms Live donors are healthy and ideal liver donors Minimal ischemic time Reduces burden on global pool of transplantable livers, allowing more patients to benefit

34 Disadvantages of Live Liver Donors Primum Non Nocere

35 LDLT Risks and Disadvantages Technically more complex than an OLT Require 2 highly trained surgical teams Mortality with left lobe donation 0.1% Right lobe donation mortality % Exact risks and morbidity probably underreported contributed by the absence of no international registry of liver donors Morbidity ~6-30% in largest reports Jaundice, bleeding, bile leak, infection

36 Documented Donor Mortality

37 Documented Donor Mortality in US

38 Living Liver Donor Selection Donor safety is paramount Noncoerced and autonomous decision for evaluation Throughout evaluation a medical out is available Healthy volunteers ages Blood type compatible Essentially no significant med/psych comorbidities and normal liver function BMI of favorably <30 <40% of donor evaluations lead to acceptable donor

39 Living Liver Donor Selection Surgeon Evaluation Hepatologist evaluation Independent (donor advocate) MD evaluation Social Work evaluation Laboratory evaluation Radiographic evaluation Cardiopulmonary evaluation Multidisciplinary conference

40 UTHSCSA Living Donor Liver Transplant 59yo ESLD ETOH (abstinent ~2yrs) complicated by small esophageal varices (no GIB) and massive refractory ascites requiring paracentesis every 2 weeks. No SBP. No admissions for PSE, but has significant minimal encephalopathy symptoms. PMH: CAD PSH: CABG 2004 SH: retired ICU nurse who ran a medical supply company c his wife FH: no liver disease, does have healthy 37yo daughter

41 UTHSCSA Living Donor Liver Transplant 37yo O blood type daughter found to be an acceptable living donor candidate Work up included CT Liver total volume 1486cc, L lobe 402cc ( L lobe GRWR= ~0.7% )

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43 UTHSCSA Living Donor Liver Transplant Uncomplicated L hepatic lobectomy, extubated day 0 and home day 4. Estimated EBL 100cc

44 UTHSCSA Living Donor Liver Transplant Recipient went for LDLT and CDJ Intraop found with portal vein- IVC gradient of >20, thus a porto systemic shunt performed (R PV to vena cava graft) now with gradient <10mm Hg and subsequent less congestion of the transplanted graft Initially did well postop, extubated POD 1 POD 2&3 some mild confusion, Hct slowly trending down, JPs looked serosanguinous but thin, T bili running ~6-8, ALT peaked at 340, NH3~100

45 UTHSCSA Living Donor Liver Transplant POD 4 had large bloody BM and hypotension. Taken back emergently to OR for repair and revision of CDJ anastomosis NH3 and lactate profoundly increased (1215 & 13.9) Developed status epilepticus Started on CRRT, multiple vasopressor support with failure to improve Anoxic brain injury and brain herniation eventually found on CT brain Care withdrawn and pt expired POD 7

46 UTHSCSA Living Donor Liver Transplant 59yo with end-stage liver disease from primary sclerosing cholangitis on OLT list for 3 years Multiple GI bleeds from varices s/p TIPS 1yr ago MELD score at time of hemorrhage >30, following TIPS ranged from No more bleeding s/p TIPS, but refractory low grade encephalopathy symptoms PMH & PSH: None No substance abuse

47 UTHSCSA Living Donor Liver Transplant Social History: Extremely supportive family, married with three adult children, numerous family members offered LDLT Brother initially evaluated and found to have coronary artery disease 26yo nephew, O blood type, evaluated and found to be an ideal LDLT candidate with no coercion and altruistic intent LDLT candidate s right lobe volume= 1466cc, left lobe= 829cc (L lobe GRWR= 1.2% )

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57 Case #2 Patients outcomes Donor blood loss: ~ 200cc Donor OR time: ~ 3 hours Recipient OR time: 4.5 hours Donor hospital stay: 5d Recipient hospital stay: 7d Donor basically normal & doing well Recipient hospitalized with fever 2d after d/c, now alive and well almost 4 years out

58 UTHSCSA Data Over 1,400 liver transplant since 1992 One year overall OLT survival ~89% 25 living liver donor transplants (4 pediatric) from 1999 to present 3 recipient deaths within first year (~1 wk (X2) and 7 months post transplant) No donor deaths Zero need for donor takeback to the OR Zero need for donor blood product transfusion

59 UTHSCSA Data

60 LDLT Summary Living donor liver transplant is an attractive option for some liver transplant candidates. Lots of symptoms moderate MELD score Safety to the donor is paramount. Evolving surgical techniques should make the procedure more safe for both donor and recipient.

61 Questions???