HEGAZY SURGERY

1. Liver Transplantation: An Update
Mahmoud El-Meteini, MD
General Secretary of PALTS
Professor of HPB & Liver Transplant Surgery, Ain Shams University.
Director of Ain-Shams Center for Organ Transplant (ASCOT)
Ain Shams University, Cairo - Egypt

2. History of Orthotopic Liver Transplantation (OLTx)
• 1963: 1st Unsuccessful attempt (Denver)
• 1967: 1st Long term survivor
• 1970’s: 1 year pt Survival: 35%
• 1980’s: 5 year pt Survival: 70%
• 1984: Reduced Liver Tx
• 1989: Split Liver Tx
• 1989/1990: 1st successful LDLT (Brazil/ Australia)
• 1994: 1st AALDLT (Japan)
• 1993: 1st Unsuccessful LDLT (Egypt)
• 1996: Undisciplined trial OLT (Egypt)
• 2001: 1st Real LDLT Program (Egypt)

3. 3
Patient survival after liver transplantation
has shown continued improvement
• The last 10 yrs have seen steady
improvements in pt survival in
Europe, the US, Australia & New
Zealand1–3
– 1-year post-transplant
survival of ≈ 90%
– These improvements are due
to advances in peri-operative
care, perfection of surgical
technique, introduction of
potent immunosuppressants,
antibiotics & antiviral drugs4
1. European Liver Transplant Registry, ELTR. 2010. Available at: http://www.eltr.org/spip.php?article152, accessed 28 October 2011. 2.
US Organ Procurement and Transplantation Network, OPTN. 2008. Available at:
http://optn.transplant.hrsa.gov/ar2008/Preface_Contributors.htm?cp=1, accessed 28 October 2011; 3. Lynch SV, Balderson GA. ANZLTR
Registry Report. Australia and New Zealand Liver Transplant Registry. Available at: http://www.anzltr.org/thisYear/report.pdf, 28
October 2011.4. Braun F et al. Transplant Proc 2009;41:2564-66
European patient survival (%) following liver
transplantation has improved over the past 25 years1
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10
18
46
56
61
66
79
22
34
64
81
85
86
52
65
1995–99: 18162
<1985: 519 1985–89: 4129 1990–94: 12007
2000–2004: 22945 >2004: 18786
Time Post-transplant (years)
PercentageSurvival(%)

4. Indications/ Contraindications for LTX

6. Indications: East versus West

8. 8
In Egypt: HCV & HCC are the main indications
65%
30%
5%
HCV
HCC
Other

9. 200 Million People Infected With HCV Worldwide
2.5%–10%
>10%
1%–2.5%
Prevalence of infection
Global Burden of HCV Working Group. J Clin Pharmacol. 2004;4420-4429.
WHO. Wkly Epidemiol Rec. 2002;77:41-48.
Not available

10. Global Incidence of Hepatocellular carcinoma
• HCC is the 3rd cancer related mortalitiy worldwide.³
• Its the 5th common malignancey in males, the 9th among females.²
• Main cause of mortalitiy in cirrhotic patients.4
• Its annual incidence is 560,000, and annual mortality of 550,000.5
1. Perz JF, et al. J Hepatol. 2006;45:529-38. 2. Jelic S. Ann Oncol. 2009;Suppl 4:iv41-5.
3. Garcia M, et al. American Cancer Society. 2007. www.cancer.org. Accessed Jan 2010.
4. Llovet J, J Hepatol. 2000;33:423-9. 5. Marrero CR, Marrero JA. Arch Med Res. 2007;38:612-20.

11. Survival of the 3 Leading Indications for
LTx (01/1988 - 06/2002)
Cirrhosis : 24227
Cancers : 4608
63
66
71
75
82
4144
49
58
74
55
56
5961
65
0
20
40
60
80
100
1 2 3 4 5 6 7 8 9 10
(%)
Yrs
p Log Rank :
Acute Hepatic Failure vs Cirrhosis : 0.0001
Cancers vs Cirrhosis : 0.0001
Acute Hepatic Failure vs Cancers : 0.0001 (Wilcoxon test)

12. 12
1197 1018 984 1070
638
5124
121 14 29 23 192
0
1000
2000
3000
4000
5000
6000
Brazil Germany Italy Spain UK USA
Numberoflivertransplantations
Whole liver (deceased donor) Liver (living donor)
More than 20,000 liver transplants are now
performed annually worldwide
1. US Organ Procurement and Transplantation Network, OPTN. 2008. Available at:
http://srtr.org/annual_reports/current/905_li.htm, accessed 28 October 2011; 2. European Liver Transplant Registry, ELTR.
2010. Available at: http://eltr.org, accessed 28 October 2011; 3. Van Gelder F et al. Organs,Tissues & Cells 2010;13:5-8.
NA
In the US, the incidence of liver transplantation was 21.6 ppm in 20071
In Europe, there were 6120 transplants during 2007, compared with only 531 in 19862
IRODaT 2009 preliminary data3

13. Cadaveric Donors/ million population

14. WL: Problems/ Management
• OLTx is the only treatment that improves Survival rate in pts. with
ESLD.
• OLTx is the only treatment with potential for cure in pts. with HCC in
Cirrhotic liver.
• Globally, 1.4 million deaths occur annually as a result of chronic liver
diseases.
• UNOS Waiting List:as of April 27th,2011
Liver 16,171
<30 days 854
30 to < 90 days 1,439
90 to 6 months 1,539
Total 3832
(23.6%)

15. Liver Tx Waiting List is growing
& Waiting times are now longer
0
2,000
4,000
6,000
8,000
10,000
12,000
The liver waiting list has grown by
23% since 1998
0
2
4
6
8
10
12
14
Medianmonthstotransplant
Time on the liver transplant
waiting list has increased by 54%
since 2005
Numberofpatients
US Organ Procurement and Transplantation Network and Scientific Registry of Transplant Recipients Annual Report 2011,
Available at: http://srtr.transplant.hrsa.gov/annual_reports/2011/default.aspx. Accessed February 2013.

16. Gap between supply and demand
1000
1500
2000
2500
3000
2007 2008 2009 2010 2011
Numberofpatients
Number of donors Patients active on waiting list
In the UK, about 14% of all waiting list patients die or become too sick to undergo the
transplant procedure2
Eurotransplant International Foundation Annual Report 2012, Figure 6.5, Available at: http://statistics.eurotransplant.org/.
Accessed April 2013; 2. van der Meulen JH, et al. Transplantation 2007;84:572–579.

19. 19
In the face of donor organ shortage, Organ
Allocation is determined by MELD score
• MELD scale provides a predictive measure of short-term mortality risk &
prognosis in patients with ESLD1,2
– MELD score is based on laboratory indicators of renal dysfunction (serum
creatinine), liver disease (serum bilirubin) and bleeding risk (INR for
prothrombin time)
• The higher the MELD score, the higher the priority for a liver transplant
• In the MELD era, patients with ESLD and poor renal function have
become increasingly common candidates for liver
transplantation3
• Allocation of donor livers is based on MELD scores in most countries
ESLD, end stage liver disease; MELD, Model for End-stage Liver Disease; INR, international normalized ratio
1. Malinchoc M et al. Hepatology 2000;31:864-871;
2. Kamath PS et al. Hepatology 2001;33:464-470;
3. Sharma P et al. Liver Tranpl 2009;15:1142-48

20. MELD score: 6- 40
• Serum , serum Creatinine & INR to predict survival
• Patients twice within the last 7 days, value for serum
creatinine should be 4.0
Hepatology, 2001

21. BenefitBenefit
BenefitBenefit
Benefit
Benefit

22. • T1  no extra MELD points
• T2 (within Milan)  MELD 22
Freeman RB, et al. Am J Transplant. 2006;6:1416-21.
Freeman RB, et al. Liver Transpl. 2004;10:7-15.
The 2004 MELD for HCC in USA

23. Extended Criteria Donors (ECD)
Marginal Donors
• Ideal Donor: Age<40, trauma as cause of death, donation after
brain death (DBD), haemodynamic stability at time of procurement,
no steatosis or any underlying liver disease & no transmissible
diseases (infectious/ malignant).
• ECD: Any donor who does not fit these criteria
SRTR Data: increased utilization of elderly donors, DCD
& donors with positive markers of HBV & HCV
• Implications:
1ry graft nonfunctioning 
Early graft poor function 
Transmission of donor derived disease
Death or need for re-transplantation

24. Donor after Cardiac Death (DCD)
• Def. Organ procurement after a standoff period of 5 min.
after death is certified
• Implications: variable period of warm ischemia time
that may result in early poor function, non-function of the
graft or diffuse cholangiopathy
• Measures to halt deleterious effects on graft function:
judicious donor selection (age<40, no steatosis), use of
heparinized perfusate, use of extracorporeal oxygenation,
short WIT (<15 min) & short CIT (<10 hrs)
Deshpande R, Heaton N: J.Hepatology 2006; 45: 499

26. Donor Assessment
• Age 18-50
• BMI < 30
• No Co-morbid disease
• Phase I: ABO blood group compatibility & Blood
chemistry (CBC, Liver and Kidney function)
• Phase II: Virology markers (e.g. Anti HCV antibodies,
Anti HBV antibodies, etc)
• Phase III: CT scan anatomy & Volumetry.
• Phase IV: Liver biopsy, Medical consultation (e.g.
Cardiac , Chest & Psychiatric consultation)

27. Donor Assessment
Volume of harvested
lobe should be ≥ 1% of
the recipient weight:
GRWR ≥ 0.8%

28. Recipient Assessment
• History
– Etiology of liver disease
– Previous liver transplantation
– GIT hemorrhage
– Ascites
– History of SBP
– History of encephalopathy
– Surgical history
– Medical history eg, diabetes, hypertension,
ischemic heart disease
• Child-Pugh & MELD score

29. Recipient Assessment
 CVS assessment:
› Clinical examination
› ECG
› Echocardiography (pulmonary hypertension; cardiomyopathy, etc)
› Dobutamine Stress echo
 Respiratory assessment
› Clinical examination
› Chest x-ray
› Pulmonary function tests
 Renal assessment
› Urea and serum creatinine &Creatinine clearance
 ENT and dental examination
› Exclude septic foci
 Imaging and laboratory investigation

30. Surgical Team

31. Technique
• Cadaveric full size • Split

32. • Partial liver graft Tx was
initially suggested by Smith in
1969.
•Reduced liver graft was
reported by Bismuth &
Houssin 1984.
•Pichlamyr & Bismuth
reported successful split liver
transplant 1989

33. Technical Aspects of LDLT

35. Interrelationship for Technically Successful LDLT

36. Surgical procedures
• The two surgical techniques are performed simultaneously;
the donor procedure last 6-8 hrs while the recipient
procedure 10-12 hrs
• The donor spend the first 24- 48 hrs post-op in the ICU & an 6-
10 days in hospital
• The two half-livers (both in donor and recipient) grow back to
80% of their size in 3-4 weeks

37. 0
10
20
30
40
50
60
70
80
90
100
Kidney-CD Kidney-LD Pancreas SPK Liver Heart
%Graftsurvival
1 year 5 years 10 years
Excellent short-term but poor long-term
survival
CD, cadaver donor; LD, living donor; SPK, simultaneous pancreas and kidney transplant.
Levy, GA, Lake, JR, Holt, DW, Wallemacq P. Current Trends in Transplantation: Drug Therapy and Monitoring, Abbott
Laboratories, Abbott Park, USA, 1–157 (2009). Published in July 2009 37
Organ type

38. Infections, malignancies and CVD are leading causes
of death among liver transplant patients
CVD, cardiovascular disease
US Organ Procurement and Transplantation Network and Scientific Registry of Transplant Recipients Annual Report 2008;
Available at: http://optn.transplant.hrsa.gov/ar2008/Preface_Contributors.htm?cp=1, accessed 28 September 2012 38
0
50
100
150
200
4 12 20 28 36 44 52 60 68 76 84 92
Infection
Malignancy
CVD
Other
Unknown
Deathsper100patient-yearswith
afunctioninggraft
Time posttransplant, months

39. 39
LTx pts had the 2nd-highest Cumulative
Incidence of “chronic renal failure” at 5 yrs
Ojo AO et al. N Engl J Med 2003;349:931-40
Incidence of CRF in a study of >60,000 non-renal organ transplant recipients
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
0 12 24 36 48 60 72 84 96 108 120
Cumulativeincidenceof
chronicrenalfailure
Months since Transplantation
Intestine
Liver
Lung
Heart
Heart-lung

40. 40
Liver transplant recipients are becoming;
Older with Higher MELD scores
MELD, Model for End-stage Liver Disease ;CRF, chronic renal failure
1. US Organ Procurement and Transplantation Network and Scientific Registry of Transplant Recipients Annual Report 2008; Available at:
http://optn.transplant.hrsa.gov/ar2008/Preface_Contributors.htm?cp=1, accessed 28 October 2011;
2. Sharma P et al. Liver Transpl 2009;15:1142-8
0
2
4
6
8
10
12
Deceased donor transplant
Living donor transplant
Patients(%)
0
5
10
15
20
25
30
Deceased donor transplant
Living donor transplant
Age >65 years1 MELD score 21–301
US data show that 24% of recipients of deceased donor transplants have MELD score
>20, compared with 9% of recipients of living donor transplants1

41. 41
HCV recurrence post-transplant is a key
unmet need in HCV patients
HCV, hepatitis C virus; CNI, calcineurin inhibitor
1. Berenguer M et al. Hepatology 2002;36:202-10; 2. Prieto M et al. Hepatology 1999;29:250-256; 3. Berenguer M et al. J Hepatol 2001;35:666-
78; 4. Berenguer M et al. J Hepatol 2000;32:673-684. 5. Firpi RJ et al. Liver Transpl 2009;15:1063-71; 6. Bhat I, Mukherjee S. Panminerva Med
2009;51:235-47
Liver transplant
Recurrence of infection: >98%
Acute hepatitis: 25–45%
• HCV-related chronic hepatitis: 80–100%
• HCV-related graft cirrhosis: 8–30%
• Cholestatic hepatitis: 2–8%
Follow-up: 3.5 months
(1–13 months)
Follow-up: 5 years
• HCV reinfection is “Universal”1–5
• Early & aggressive HCV recurrence
significantly accelerates the progression of
the disease, compared with HCV in the non-
transplant population1–5
• HCV Recurrence after LTx is associated with
– Accelerated fibrosis progression
– Accelerated graft cirrhosis
– Reduced graft survival
– Reduced pt survival
• Reducing the use of CNIs & Steroids
appears to slow the progression of
HCV6

42. 42
HCV recurrence is associated with
Reduced Patient Survival
HCV, hepatitis C virus.
Berenguer M et al. Hepatology. 2002;36:202-10
Log-rank p=0.0001
HCV–
HCV+
0.0
Time post-transplant (years)
1 2 3 4 5 6 7 8 9
20
40
60
80
100
0
Patientsurvival(%)
HCV+
77
65
61
55
HCV–
87
83
76
70
Year
1
3
5
7
Patient survival (%)
Prospective, single-centre study of 522 pts who underwent liver transplant
between 1991 and 2000

43. Portal pressure/
bilirubin
HCC
PEI/RFA Sorafenib
Stage 0
PST 0, Child–Pugh A
Very early stage (0)
1 HCC < 2 cm
Carcinoma in situ
Early stage (A)
1 HCC or 3 nodules
< 3 cm, PST 0
End stage (D)
Liver transplantation TACEResection Symptomatic
treatment (20%)
Survival < 3 months
Curative treatments (30%)
5-year survival (40–70%)
Palliative treatments (50%)
Median survival 11–20 months
Associated diseases
YesNo
3 nodules ≤ 3 cm
Increased
Normal
1 HCC
Stage D
PST > 2, Child–Pugh C
Intermediate stage (B)
Multinodular,
PST 0
Advanced stage (C)
Portal invasion,
N1, M1, PST 1–2
Stage A–C
PST 0–2, Child–Pugh A–B
Adapted from Bruix J, Sherman M. Hepatology. 2010.
AASLD = American Association for the Study of Liver Diseases;
PEI = percutaneous ethanol injection; PST = Performance
Status test; RFA = radiofrequency ablation;
TACE = transarterial chemoembolization.
BCLC Staging System Treatment Strategy
(AASLD guidelines updated 2010)

44. Treatment options in Intermediate HCC

46. Bhoori S, et al. Transplant International. 2010;23:712-22.
Proposals of Expansion of Conventional
Criteria in Liver Tx for HCC
Author (year), centre Expanded criteria
5-yr specific survival for
exceeding Milan criteria
Yao et al. (2001), San Francisco
1 HCC  6.5 cm or  3 HCC  4.5 cm with
cumulated diameter  8 cm
73%
Herrero et al. (2001), Pamplona 1 HCC  6 cm or  3 HCC  5 cm 73%
Onaca et al. (2007), Dallas 1 HCC  6 cm or  4 HCC  5 cm N/A
*Kwon (2007), Seoul
HCC  5 cm, no number restriction AFP 
400 ng/mL
80% (including Milan)
*Jonas et al. (2007), Berlin
Any number, each  6 cm with cumulated
diameter  15 cm
62% at 3 years
*Takada et al. (2007), Kyoto
 10 HCC, each  5 cm PIVKA-II < 400
mAU/mL
67%
*Soejima et al. (2007), Fukuoka Any number, each  5 cm 74%
*Sugawara et al. (2007), Tokyo  5 HCC  5cm 70% (at 3 years)
Zheng et al. (2008), Hangzhou
Total tumor diameter  8cm or HCC grade
I/II and AFP  400 ng/mL
72.3%
*Lee et al. (2008), Asan  6 HCC  5 cm 76.3%
Silva et al. (2008), Valencia
 3 HCC  5 cm with cumulated diameter
 10 cm
67%
Toso et al. (2008), Edmonton TTV  115 cm3 72%
Mazzaferro et al. (2009), Milan
Number of HCC nodules  maximum
diameter (cm)  7
71% (if microvascular
invasion absent)
*LDLT = living donor liver transplantation.
AFP = alpha-fetoprotein; PIVKA-II = protein-induced by vitamin K

47. Contour plot of 5-yr survival according to size & number of tumors
Mazzaferro V, et al. Lancet Oncology. 2009;10:35-43.
Size of largest tumor in mm
*1,112 patients exceed Milan criteria.
Liver Transplantation: 5-yr survival in
an Exploratory Analysis of 1,556* HCC pts
Numberoftumors

48. Mazzaferro V, et al. Lancet Oncology. 2009;10:35-43.
Patients beyond Milan criteria &
exceeding “up-to-7”criteria have
a poor overall survival of < 50%
Liver Transplantation: Overall Survival in an
Exploratory Analysis of 1,556 HCC patients
• 444 patients within Milan criteria .
• 283 patients beyond Milan criteria and within “up-to-7” criteria.
• 829 patients beyond Milan criteria and exceeding “up-to-7” criteria
• More HCC pts could be candidates for transplant if precise survival estimation using
individual tumor characteristics and “up-to-7” criteria is employed
0.8
0.6
0.4
0.2
0.0
0 12 24 36 48 60 72
Months
Survival
probability
1.0
Exceeding “up-to-7” criteria (N = 829)
Beyond Milan – “up-to-7” criteria (N = 283)
Milano IN (N = 444)
73%
71%
48%

49. Are Neo-Adjuvant Locoregional Treatment
Indicated in pts listed for LT ?
• Bridge Therapy: No recommendation could
be made on bridging therapy in pts with
UNOS T1 HCC .
• A cost-effective analysis based on Markov
model & the review of cohort studies indicate
a benefit for bridging therapies if the
waiting time is expected to be > 6 months
to avoid TP.

50. Definitions of Down-staging before
transplantation
Toso C, et al. J Hepatology. 2010;52:930-6.
Neo-adjuvant
treatment
Down-staging
To decrease tumor progression
and hence dropout from the
waiting list
To improve long-term results To select pts with good
long-term outcomes among
poor risks pts.
(Response to ttt & observation time
used as a surrogate markers for
favorable biology)
To bring patient whose tumor
burden is outside accepted
criteria for Tx to within acceptable
criteria.
Before transplantation

51. Which is the best neo-adjuvant treatment in Pts
considered for LT?
Locoregional
therapy Indications Risks Benefits
RFA Small HCC (usually  3 cm),
away from the liver surface,
away from major vessels
HCC seeding (1–2%)
liver rupture (small)
• OK even in case of
decreased liver function
• Only one session usually
required
• Complete necrosis in 
90% of cases
TACE Any HCC size preserved liver
function (Child–Pugh A-B)
uptake of contrast
Liver failure
arterial injury (2%)
• OK even for large HCCs
TARE Any HCC preserved liver
function (Child–Pugh A-B),
absence of intra-hepatic
shunt, uptake of contrast
Off-target embolization
arterial injury
• OK even for large HCCs
(up to 10 cm?)
• OK even in case of portal
vein thrombosis more
efficient than TACE (to be
confirmed)
• Shorter time to response
(to be confirmed)
Toso C, et al. J Hepatology. 2010;52:930-6.

52. Response to therapy is a potentially effective tool for prioritizing HCC patients for
liver transplantation
Vitale A, et al. Ann Surg Oncol. 2010;17:2290-302.
Siegel AB, et al. Hepatology. 2010;52:360-9.
Response to therapy as a criterion for awarding priority
to patients with HCC awaiting liver transplantation
Months post-liver transplantation
Intention-to-treat survival
1.0
0.8
0.6
0.4
0.2
0 12 24 36 48 60
Responder (n = 85)
Non-responder (n = 62)
p < 0.01
Months
Freedomfromrecurrence

53. Increased HCC recurrence & lower survival
are linked to Several Factors
Higher exposure to CNIs1
Portal vein thrombus3 Pretransplant
AFP levels1,3
Vascular invasion1
TNM staging3Tumor biology1,2
AFP, alpha fetoprotein; CNI, calcineurin inhibitor; HCC, hepatocellular carcinoma; TNM, tumor node metastasis.
1. Vivarelli M, et al. Ann Surg. 2008;248:857862; 2. Vakili K, et al. Liver Transpl. 2009;15:18611866;
3. Wang ZX, et al. Clin Transplant. 2010;24:752757. 53

54. 54
100
75
50
25
0
HCC Recurrence post transplantation is a key
unmet need in HCC pts
HCC, hepatocellular carcinoma; OLT, orthotopic liver transplant
1. Valdivieso A et al. Transplant Proc 2010;42:660-2; 2. Lee KK et al. J Surg Oncol. 2010;101:47-53
Cumulative post-transplant survival for patients with and without HCC recurrence1
SurvivalafterOLT(%)
0 1 2 5 10
No HCC recurrence (n=159)
HCC recurrence (n=23)
Years
p<0.001
3 4
HCC recurrence following transplantation ranges from 10–35%1,2
Pts with HCC recurrence have a poorer prognosis

55. Drinking coffee cuts liver cancer risk ??
Drinking three cups of coffee daily can reduce the risk of
developing liver cancer by more than 50 per cent, a new
study has claimed.

56. EVEROLIMUS in LTx

57. The incidence of acute transplant
rejection is declining. . .
0%
10%
20%
30%
40%
50%
60%
US Organ Procurement and Transplantation Network and Scientific Registry of Transplant Recipients Annual Reports 2003 &
2005, Available at: http://www.srtr.org/annual_Reports/default.aspx. Accessed March 2013.
Acuterejection[%]
Percentage of liver transplant patients who received antirejection
medication by 1-year posttransplant from 1992–2003

58. CNI minimization in liver transplant patients
…… but High level exposure to CNIs is a well-recognized risk
factor for chronic kidney disease in liver transplant recipients1
Attempts to withdraw CNI have
lead to increased risk of
acute rejection2,3
CNI minimization can help tip the
balance between adequate
immunosuppression and
exposure to CNIs2
CNI, calcineurin inhibitor.
1. Kong Y, et al. PLoS One. 2011;6:e24387; 2. De Simone P, et al. Am J Transplant. 2012;12:3008–3020;
3. Schlitt HJ, et al. Lancet. 2001;357:587591. 58

59. 59
Everolimus + low Tac demonstrated a Comparable Safety
profile with standard Tac
aThe incidence of clinically relevant proteinuria above 3 g/day in the everolimus + low Tac group was
comparable to that in the standard Tac group. Patients with proteinuria ≥0.5 g/24 hrs at one month post-
transplant had no progression to more severe proteinuria with everolimus + low Tac.
Incidence rates of selected adverse
events
Everolimus +
low Tac (n=245)
Standard Tac
(n=241)
Hyperlipidemia 23.7% 9.5%
Hypertension 17.1% 15.8%
New Onset DM 19.6% 16.6%
Proteinuriaa
17.6% 0.8%
Peripheral edema 2.9% 10.8%
Stomatitis, Mouth Ulceration 9.4% 1.2%
Tremor 9.4% 12.0%
Wound Healing Complications 11% 7.9%
Tac, Tac, tacrolimus
DeSimone P et al. Am J Transpl. 2012

62. Both Sirolimus (P≤ 0.05) & Anti-CD25 Antibody induction
(P≤ 0.01) demonstrated significantly improved survivals
after LTx for HCC.

63. HR (95% CI) to compare Risk of Mortality after LTx using diff. immunosuppress. protocols.
Results corrected for MELD, Tx year, Primary Liver Disease (non-HCC), Age at Tx
& when applicable: TTV, AFP & PreTx HCC ttt.
*Significant variables

64. Use of Everolimus as a Rescue
Immunosuppressive therapy in Liver
Transplant Patients with Neoplasms
Gomez-Camarero J et al, Transplantation 2007;84: 786–791

65. Father of Modern Transplantation
Thomas Starzl
First successful human liver
transplant in 1967 (Denver,
U.S.A.)
No sense of accomplishment
can exceed that of seeing a
robust LT recipient who, a
few weeks earlier, was
seemingly near death from
ESLD.

66. Summary
• Successful LTx requires optimal patient selection and timing of Tx.
• Indications across most centers are similar, however, a regional
difference exists with HCC & metabolic reasons being on the rise.
• To date, MELD score is the most accurate to predict early outcome
of LTx & to prioritize organ allocation including that for HCC
patients.
• Organ shortage is currently tackled by: ECD & Surgical innovation.
• Current unmet needs following LTx include: minimizing CNI toxicity,
CKD, HCV & HCC recurrence.
• Introduction of new immunosuppressant with less severe AEs and
equivalent anti-rejection efficacy are urgently needed with mTORi
emerging as a new player in this context.