Australian National Liver Transplantation Unit...There are several key issues to report. 1. A number of new heights were reached in 2015. These were: 98 orthotopic liver transplant

Australian National Liver Transplantation Unit

© copyright ANLTU Data to 31 December 2015

0

10

20

30

40

50

60

70

80

90

100

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

2015

Child (n = 306)Adult (n = 1256)

Data to 31 December 2015

Celebrating 30 years of Liver Transplantation

Data to 31/12/2015 © copyright ANLTU

Contents Preface ......................................................................................................................................... i Summary ..................................................................................................................................... ii ASSESSMENT INFORMATION ............................................................................................................................. 1 Allocation of Assessed Adults/Children ...................................................................................... 2 Patients Considered Unsuitable for Transplantation (Adults) .................................................... 2 Comparison Over Time Of Patients Assessed ............................................................................. 3 Waiting List Activity ..................................................................................................................... 4 Urgent Listings ............................................................................................................................ 5 Age and Waiting Time of Transplant Recipients (Primary Grafts) .............................................. 6 DONOR INFORMATION ...................................................................................................................................... 9 Deceased Donor Offers ............................................................................................................. 10 DBD Donor Offers...................................................................................................................... 14 DCD Donor Offers ...................................................................................................................... 14 Allocation of Accepted and Utilised Deceased Donor Offer Livers 2013 ................................. 15 Living Donor Procedures – Paediatric & Adult .......................................................................... 15 Deceased Donor Age by Era (Median) ...................................................................................... 16 Donors over 50 years ................................................................................................................ 16 Deceased Donor Cause of Death .............................................................................................. 17 RECIPIENT DEMOGRAPHICS ............................................................................................................................ 19 Patient Age at Transplant.......................................................................................................... 20 Primary Hepatic Disease ........................................................................................................... 20 Chronic Viral and Auto-Immune Hepatitis ................................................................................ 22 Fulminant Hepatic Failure as Primary Indication Treated by Liver Transplantation ................ 23 HCC and Associated Disease ..................................................................................................... 24 NASH/NAFLD by Era .................................................................................................................. 25 Indication For Secondary Transplantation ................................................................................ 26 PERIOPERATIVE DATA ...................................................................................................................................... 27 Mean/Median Hospital Stay ..................................................................................................... 28 Red Cell Usage ........................................................................................................................... 28 Graft Ischaemic Time, Operation Duration and Red Cell Utilisation ........................................ 28 OUTCOME DATA .............................................................................................................................................. 29 Patient Survival ......................................................................................................................... 30 Children ..................................................................................................................................... 32 Primary Disease and Outcome .................................................................................................. 34 Status at Transplant vs Patient Outcome ................................................................................. 35 Chronic HBV Outcomes ............................................................................................................. 36 Chronic HCV Outcomes ............................................................................................................. 37 Donor Age vs Primary Graft Outcome ...................................................................................... 40 Steatosis vs Graft Outcome (Adults) ......................................................................................... 41 Graft Survival ............................................................................................................................. 42 Split vs Reduced vs Whole Grafts ............................................................................................. 45 Cause of Death .......................................................................................................................... 47 Cause of Graft Failure ............................................................................................................... 52 CANCER AND TRANSPLANTATION ................................................................................................................... 57 Malignancy at Transplantation ................................................................................................. 58 De Novo Non Skin Cancer Post Transplant ............................................................................... 61 Pre Transplant Liver Disease and De Novo Non Skin Cancer .................................................... 62 Cumulative Risk of Diagnosis of Cancer .................................................................................... 64

Data to 31 December 2015 © copyright ANLTU

Data to 31 December 2015 © copyright ANLTU i

Preface

In 2015, 93 new, 4 secondary and 1 tertiary orthotopic liver transplant procedures were performed within the ANLTU (20 – The Children’s Hospital at Westmead; 78 – Royal Prince Alfred Hospital). This included the ongoing usage of split liver allografts and the use of extended criteria donor liver allografts, which maximise the limited donor resources available. The staff within the ANLTU would like to thank the members of the departments within Royal Prince Alfred Hospital and Sydney Local Health Network who have helped contribute to the success of the program in the past year. This includes Haematology, Biochemistry, other Laboratory services, Blood Bank, Department of Pathology, Department of Renal Medicine, Intensive Care Unit, Operating Room, Department of Psychiatry, Department of Cardiology, Department of Respiratory Medicine, Dietetic Department, Department of Social work, Department of Anaesthesia, the Casemix unit and all the other people who have not been specifically mentioned. We would also like to thank the other departments within the Children’s Hospital at Westmead, who have helped contribute to the success of the paediatric programme. These include the membership of Department of Anaesthesia, the Intensive Care Unit, Laboratory services staff, Department of Social Work, Department of Nutrition and other medical departments. The staff of the Australian Red Cross Blood Service are also acknowledged for their assistance during the year. Finally, without the generosity of the deceased organ donors and their families, liver transplantation would not be able to proceed at this level. Hence we give our thanks to them as well as to the team at Donate Life NSW, Kogarah. Professor Geoff McCaughan Dr Deborah Verran Dr Michael Crawford Pamela Dilworth Gavin Lackey

Data to 31 December 2015 © copyright ANLTU ii

Data to 31 December 2015 © copyright ANLTU iii

Summary

Summary There are several key issues to report.

1. A number of new heights were reached in 2015. These were:

98 orthotopic liver transplant procedures 122 new listings on the Waiting List 68 patients on the Waiting List at the end of the year 8 Donations after Circulatory Death 10 Paediatric Donors

2. In 2015, 93 new, 4 secondary and 1 tertiary orthotopic liver transplant procedures were performed, 20 of which were Paediatric and 78 were Adult.

3. Between January 1986 to December 2015, 1562 liver transplants were performed on 1444 patients, of which 1179 and 265 recipients were adults and children, respectively.

4. The number of transplants per year continues to be related to the deceased donor rate.

5. In 2015, 19 patients (10%) on the waiting list were subsequently withdrawn due to advanced and/or extra-hepatic disease. One patient improved whilst on the waiting list.

6. The movement of patients on and off the waiting list continues to be dynamic.

7. The average waiting time for adults in all blood groups remains variable depending on blood group.

8. The median deceased donor age has increased from 29 years (1986 – 1995) to 44 years (2006 – 2016). In 2015 there were ten deceased donors over the age of 70 years. This is the highest number of donors from this age group whose livers have been used for transplant.

9. The median age for adult recipients has increased from 45.7 years (1986 – 1995) to now stand at 49.5 years. The median age for child recipients has decreased from 4.1 years (1986 – 1995) and now stands at 2.2 years.

10. HCV infection has been an increasing primary and secondary indication for liver transplantation in adults. In the period 1986 – 1995 11% of adults had this diagnosis compared to 37% in 2006 – 2015.

11. Hepatocellular carcinoma has also become an increasingly common primary and secondary indication for liver transplantation, with 28% of the adult recipients having a diagnosis of HCC in the five year period 2011 – 2015.

12. The overall patient survival rate over the past 2 years was 93% at one year.

Data to 31 December 2015 © copyright ANLTU

Data to 31 December 2015 © copyright ANLTU 1

ASSESSMENT INFORMATION


Assessment Information

Allocation of Assessed Adults/Children


Allocation of Patients Accepted for Assessment

Accepted67%

Deferred11%

Unsuitable20% Died Pre-

List2%

Adults (n = 2375)

Accepted88%

Deferred5%

Unsuitable7%

Children (n = 350)

Patients Considered Unsuitable for Transplantation (Adults)


Patients Considered Unsuitable for Transplantation2375 Adults have been assessed since 1985

Reason Adults

Too Advanced + extra-hepatic disease 173 37%

Tumour Progression + Tumour (extra-hepatic spread) 76 16%

Good prognosis 64 14%

Psychological 59 13%

Alcohol 57 12%

Patient’s wish 24 5%

Alternative therapy 7 1%

Age 5 1%

Condition improved 2 <1%

Logistics 1 <1%

Total 468 100%



Comparison Over Time Of Patients Assessed

Comparison Over Time of Patients Assessed


1985 - 1995

Accepted48%

Deferred18%

Unsuitable34% Died

Pre-List

0.2%

Adults (n = 657)

Accepted72%

Deferred11%

Unsuitable17%

Children (n = 120)


1996 - 2005

Accepted62%

Deferred16%

Unsuitable20%

Died Pre-List2%

Adults (n = 918)

Accepted94%

Deferred3%

Unsuitable3%

Children (n = 112)


2006 - 2015

Accepted89%

Deferred1%

Unsuitable7%Died Pre-

List3%

Adults (n = 800)

Accepted98%

Unsuitable2%

Children (n = 118)

Adult patient acceptance rate has increased from 48% in the period of 1985 – 1995 to 89% in 2006 – 2016. Child patient acceptance rate has increased from 72% in the period of 1985 – 1995 to 98% in 2006 – 2015.



Waiting List Activity


Waiting List Activity

YearListed at Start of

Year

New Listings Total Tx Died

Pre Tx

Withdrawn Total Withdrawn/

MortalityImproved Listed at

End of YearTumour Progressed Other

2006n 38 83 121 55 6 3 0 9 6 46

% 45 5 2.5 0 7.4 5

2007n 46 95 141 54 19 2 2 23 2 63

% 38 13 1 1 16 1

2008n 63 76 139 59 25 2 5 32 5 43

% 42 18 1 3.5 23 3.5

2009n 43 97 140 59 11 3 5 19 8 54

% 42 8 2 3.5 13.6 5.7

2010n 54 98 152 77 6 4 2 12 2 61

% 51 4 3 1 8 1

2011n 61 82 143 71 9 5 2 16 4 52

% 50 6 3 1 11 3

2012n 52 104 156 75 15 2 9 26 2 53

% 48 10 1.3 6 17 1.3

2013n 53 113 166 80 15 5 11 31 3 52

% 48 9 3 7 19 2

2014n 52 112 164 76 5 1 14 20 4 64

% 46 3 0.6 9 12 2

2015n 64 122 186 98 3 3 13 19 1 68

% 53 2 2 7 10 .5


46

63

43

54

61

52

53

52

64

68

0 10 20 30 40 50 60 70 80

2006

2007

2008

2009

2010

2011

2012

2013

2014

2015

Patients on Waiting List at the end of Calendar Year




7.4

16

23

14

811

1719

1210

5

1

3.5

6

1

3

1

2

2

0.5

0

5

10

15

20

25

30

2006 2007 2008 2009 2010 2011 2012 2013 2014 2015

Improved

Withdrawn/Mortality

% Patients Withdrawn from Waiting List

Urgent Listings


Urgent Listings 2015

Number of Patients Listed as Urgent Cat 1 Cat 2 Total

Transplanted 6 6 12

Delisted 0 0 0

Total 6 6 12



Age and Waiting Time of Transplant Recipients (Primary Grafts)


2030

4050

6070

Age

at T

rans

plan

t - Y

ears

1986 - 1995 1996 - 2005 2006 - 2015

05

1015

Age

at T

rans

plan

t - Y

ears

1986 - 1995 1996 - 2005 2006 - 2015

Age of Transplant Recipients (Primary Grafts)

n 63 89 113

Median 4.1 2.4 1.4

Mean 5.6 4.3 3.4

Children

n 265

Median 2.2 years

Mean 4.2 years

Range 0.1 – 15.6 years

n 244 397 538

Median 45.7 50.5 54.2

Mean 44.0 49.1 52.3

Adults

n 1179

Median 51.9 years

Mean 49.5 years



Waiting Time of Transplant Recipients (Primary Grafts)Children

Median 2.33 months

Mean 5.15 months

Max 76.49 months

Adults

Median 2.39 months

Mean 5.52 months

Max 95.48 months

Median 1.54 3.11 2.33

Mean 2.91 6.48 5.48

Max 14.49 48.10 76.49

Median 0.79 2.16 4.30

Mean 1.27 4.46 7.91

Max 7.84 69.25 95.48

05

1015

2025

Mon

ths

Wai

ting

1986 - 1995 1996 - 2005 2006 - 2015

05

1015

20M

onth

s W

aitin

g

1986 - 1995 1996 - 2005 2006 - 2015




5.5

98.6

3.6

1.5

4

9.7

12.7

6.9

11.7

6.67.3

0

2

4

6

8

10

12

14

2007 - 2009 2010 - 2012 2013 - 2015

AABBO

Adult Mean Months WaitingPrimary Liver Transplantation vs ABO (2007 – 2015)


2007– 2009 2010 – 2012 2013 – 2015 Overall

A 5.5 9 8.6 8.2

AB 3.6 1.5 4.0 3.2

B 9.7 12.7 6.9 9.6

O 11.7 6.6 7.3 8.3

Mean 8.7 8.4 7.6 8.2

Adult Mean Months WaitingPrimary Liver Transplantation vs ABO (2007 – 2015)




DONOR INFORMATION


Donor Information

Deceased Donor Offers


53

46

52 51

66

61

69

74

69

79

14

2 3 4 42 2 2

10

1 2 3 4 52 3

58

0

10

20

30

40

50

60

70

80

90

2006 2007 2008 2009 2010 2011 2012 2013 2014 2015

Adult DBD Paediatric DBD Adult DCD

Deceased Adult and Paediatric Donor Organs Used By Year

Since 2000, 93.7% of liver donors were adults (>=15yrs) and 6.3% were paediatric donors.


Deceased Donor Offers to NSW 2007 - 2015Donor Type State 2007 - 2009 2010 - 2012 2013 2014 2015 Total

DBD

ACT 12 20 5 9 10 56

NSW 147 194 88 63 89 581

NT 3 2 1 1 1 8

NZ 9 10 1 5 6 31

QLD 23 18 5 7 12 65

SA 15 9 7 5 9 45

TAS 4 1 1 1 7

VIC 19 32 7 3 10 71

WA 8 15 6 8 4 41

Total BDD Offers 240 303 121 102 141 907

BDD Used 137 186 68 66 83 540

DCD

ACT 6 6 1 3 16

NSW 41 66 15 15 19 156

NT 1 1

NZ 1 1

QLD 1 1 2

SA 1 1

VIC 1 7 1 3 2 14

WA 1 1

Total DCD Offers 48 81 17 20 26 192

DCD Used 7 15 3 5 8 38

Total Offers 288 384 138 122 167 1099

Total Used 144 201 71 71 92 579


Donor Information


DBD Donor Offers Declined 201558/143 (40.6%)

Declined at Offer

Declined at Hepatectomy

Abnormal LFTs 3

Cirrhosis 1

Consent withdrawn/relatives refused consent 1

Donor Age 1

Donor history * 5

Donor malignancy - extrahepatic 1

High risk donor for tumour or infection 5 2

Impaired perfusion/ischaemia 2

Interstate donor not suitable for directed recipient (Urgent Case) 7

Liver fibrosis 2

Logistics ** 1

No suitable ABO compatible recipient/No suitable recipient 7

Offer waived for urgent Tx elsewhere/Offer waived *** 6 1

Positive virology 1

Steatosis 6

Trauma to liver/Vascular issues 1 1

Other **** 1 3

TOTAL 40 18


DBD Donor Offers Declined 201558/143 (40.6%)

* Donor history 1 Alpha 1 anti-trypsin. No patients with high enough MELD to accept risk of transmission.

Declined all states

2 Heavy ETOH/Tumour Risk (underweight/heavy smoker/hx coughing up blood/strong FHxcolorectal cancer)/Infections inadequately treated.

3 Likely fatty liver in combination with high strength inotropes, elevated INR, abnormal LFTs and high risk of infection transmission.

4 Multiple reasons: age, obesity, diabetes. Hypertension, smoker

5 Vascular disease, age, obesity (BMI 41), prostate ca

** Logisitcs 1 Long CIT from WA, already cross clamped.

*** Offer waived 1 Accepted for a Cat 1 pt, however local donor became available at same time. Hepatectomy

proceeded and sent to another interstate urgent listing.

**** Other 1 Biliary abnormality on cholangiogram. Unable to split..

2 Gangrenous gallbladder extending into hilum.

3 Liver & kidneys retrieved however heparin not given. Team decided not to proceed. No other organs retrieved.

4 Offer revoked. Local team accepted offer. Were enquiring if we were interested if NAT positive


Donor Information


DCD Donor Offers Declined 201518/26 (69.2%)

Declined at Offer

Declined at Hepatectomy

Abnormal LFTs 1

DCD did not proceed to hepatectomy 10

Donor history * 1

Impaired perfusion/ischaemia 2

Interstate donor not suitable for directed recipient (Urgent case) 1

Offer waived for urgent Tx elsewhere 1

Steatosis 1

Unstable

Other ** 1

TOTAL 5 13

* Donor history 1 Obese in a DCD, Hx Prader Willi Syndrome. Attempted kidney retrieval - did not die in time frame.

** Other 1 Long CIT in DCD


Donor Information


Enquiries Declined 2015

Declined at Enquiry

Abnormal LFTs 1

Consent withdraw/relatives refused consent 3

Donor age 7

Donor arrest prior to retrieval 1

Donor history * 8

High risk donor for tumour or infection 10

Interstate donor not suitable for directed recipient (Urgent Case) 3

Known liver disease ** 2

Logistics 1

No suitable recipient 3

No suitable ABO compatible recipient 7

Outside DCD acceptance criteria 4

Other *** 5

TOTAL 55


Enquiries Declined 2015* Donor

history 1 ? Cause of encephalitis.

2 DCD, downtime, ?hepatorenal, ECMO, CVVHD, DIC, metabolic acidosis, diabetes, cardiovascdisease, bili 235.

3 DCD, unstable donor, complicated admission, extensive medical hx, HCV, ? Current IVDU.

4 Donor Age, comorbidities, poor vessels, smoker, inotropes.

5 ESRF, dialysis, CAGS, bilat common iliac artery stents, BMI 42, hx deranged LFT's.

6 Extensive peripheral vascular disease.

7 Infective Endocarditis. Extensive cardiovascular hx, on dialysis. Will be a DCD.

8 Long cardiac downtime with abnormal INR, likely ischaemic damage. Requiring high dose inotropes, unable to be supported

** Known liver disease 1 Cirrhosis, extensive vascular disease, endovascular stent leak.

2 DCD, HCV, chronic liver disease, IVDU, bili 573, abnormal blood results. Extensive medical issues this admission.

*** Other 1 Asked DonateLife to pursue donor. Later informed that treatment had been withdrawn.

2 Did not proceed to formal offer. Deemed NMS as organ donor as no COD determined

3 Hx of ETOH abuse, drug use. Accepted enquiry however did not proceed to formal offer. Pt died before offer

4 Never proceeded to formal offer

5 Said to pursue donor. Never progressed to full referral


Donor Information

DBD Donor Offers


42

47 48

6062

6468

66

83

911

912 11

20

25

1618

21

30

2325 26

23

28

20

40

0

10

20

30

40

50

60

70

80

90

2007 2008 2009 2010 2011 2012 2013 2014 2015

Used Declined at Hepatectomy Declined at Offer

DBD Donor Offers to NSW

DCD Donor Offers


1

2

4

8

5

2

3

5

8

6

8

10

5

9

7

8

13

5

8

11

18

9

15

7

6

5

0

2

4

6

8

10

12

14

16

18

20

2007 2008 2009 2010 2011 2012 2013 2014 2015

Used Declined at Hepatectomy Declined at Offer

DCD Donor Offers to NSW


Donor Information

Allocation of Accepted and Utilised Deceased Donor Offer Livers 2013


Allocation of Accepted and Utilised Deceased Donor Livers

1st Recipient Allocation Total

DBD

Highest prioritised patient suitable for this type of graft 69

Size of graft not suitable for higher priority patient(s) 6

Higher priority patient(s) medically unfit 2

Higher priority patient(s) has HCV and older donor 1

Logistical reasons not suitable for higher priority patients 1

No prioritised patient in this ABO suitable 1

No prioritised patient in this ABO suitable for Split Graft 1

Positive donor virology 1

Other * 2

DCDHighest prioritised patient suitable for this type of graft 7

High risk donor on history for virus or tumour 1

Total 92

2nd Recipient Allocation

DBD Highest prioritised patient suitable for this type of graft 5

Total 5

* Other Required combined liver/lung tx

Suitable graft for this patient

Living Donor Procedures – Paediatric & Adult


Living Donor Procedures – Paediatric and Adult

* The Living Unrelated Donor Procedures in 2003 and 2013 were adult domino transplants.

** The Living Unrelated Donor Procedure in 2011 was adult to adult.

Year 1990 2002 2003 2004 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Total

TypeLRD LRD LUD

*LRD LRD LRD LRD LRD LRD LUD

**LRD LUD

*LRD

Total 1 1 1 1 2 3 3 2 3 1 2 1 0 1 22


Donor Information

Deceased Donor Age by Era (Median)


020

4060

80D

onor

Age

- Ye

ars

1986 - 1995 1996 - 2005 2006 - 2015

Deceased Donor Age by Era

n 336 518 686

Median 29 42 44

Mean 31.1 38.7 43.2

n = 1540

Median 40 years

Mean 39.1 years


The donor age ranged from 0 to 87 years, with a mean value of 40 years.

Donors over 50 years


1 2 1 15

810

3 4 57

9 96

84

7

18

118 8

14

9 1012

17

10

1517

1

4

3

13 1

3

86

32

4

4

6

8

5 5

7

9 7

13

13

11

9

14

2

22

3

5

2

51

26

4

3

7

8

7

1

1

21

3

0

5

10

15

20

25

30

35

40

45

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

2015

> 80 (n = 8)71 - 80 (n = 59)61 - 70 (n = 150)51 - 60 (n = 239)

Deceased Donors Over 50 Years(n = 456)


Donor Information

Deceased Donor Cause of Death


Hypoxia/Anoxia15%

Cerebrovascular Accident

49%

Tumour1%

Road Trauma23%

Other Trauma9%

Other2% Suicide

1%

Hypoxia/AnoxiaCerebrovascular AccidentTumourRoad TraumaOther TraumaOtherSuicide

Deceased Donor Cause of Death(n = 1540)

754 (49%) donors died due to cerebral haemorrhage, 495 (32%) died due to trauma.


32

46

151

147

282

325

4

6

5

115

137

106

36

35

66

1

5

6

1

7

27

0 50 100 150 200 250 300 350

1986 - 1995

1996 - 2005

2006 - 2015

OtherSuicideOther TraumaRoad TraumaTumourCerebrovascular AccidentHypoxia/Anoxia

Deceased Donor Cause of Death by Era

Deaths due to trauma were 45% (1986 – 1995), 42% (1996 – 2005) and 25% (2006 – 2015). In these same time periods, deaths due to cerebral causes were 44%, 54% and 47%.


Donor Information


16

7

2321

33

46

40

48

40

52

20 20

17

1315

1112 12

21

18

23

6

10

56

3 32

46

2

7

21 1 1

0

5

10

15

20

25

30

35

40

45

50

55

2006 2007 2008 2009 2010 2011 2012 2013 2014 2015

S0 (n = 326) S1 (n = 159)S2 (n = 40)S3 (n = 24)

Adult Graft Steatosis 2006 - 2015

Steatosis Scoring: S0 less than 5% steatosis in biopsy (either macro or micro) S1 Ma/Mi 5 – 29% Macrovesicular steatosis on biopsy combined with varying degrees of Micro S2 Ma/Mi 30 < 60% Macrovesicular steatosis on biopsy combined with varying degrees of Micro S3 Ma/Mi 60 +% Macrovesicular steatosis on biopsy combined with varying degrees of Micro Since 2006 there are 18 cases (3.2%) where post reperfusion biopsy was not performed.


RECIPIENT DEMOGRAPHICS


Recipient Demographics

Patient Age at Transplant


79 71

109

213

292

490

149

41

0

50

100

150

200

250

300

350

400

450

500

< 1 1 - 3 4 - 15 16 - 40 41 - 50 51 - 60 61 - 65 > 65

Breakdown of Patient Age at Primary Transplant(n = 1444)

The modal group was in the age range 51 – 60 years (33.9%).

Primary Hepatic Disease


Biliary Atresia11%

Malignancy9%

HCV19%Metabolic

9%

Fulminant10%

ALD10%

CC2%

PSC8%

PBC5%

Other4%

AIH4%

HBV6%

B,C1%

NASH/NAFLD2%

Primary Disease – All Patients(n = 1444)

The most common primary indications for transplantation are Chronic Hepatitis C (270, 19%), Biliary Atresia (154, 11%), Alcoholic Disease (146, 10%) and Fulminant Liver Failure (143, 10%).




Biliary Atresia1%

Malignancy11%

HCV23%

Metabolic6%

Fulminant10%

ALD12%

CC2%

PSC10%

PBC6%

Other4%

AIH4% HBV

7%B,C1% NASH/NAFLD

3%

Primary Disease – Adults(n = 1179)

Hepatitis C was the most common indication of transplantation in adults (270, 23%), followed by Alcoholic Liver Disease (ALD 146, 12%), Malignancy (129, 11%), Primary Sclerosing Cholangitis (PSC 119, 10%), Fulminant Hepatic Failure (114, 10%), and Hepatitis B (83, 7%).


Biliary Atresia54%

Malignancy3%

Metabolic23%

Fulminant11% CC

1%CAH2%

Other7%

Primary Disease – Children(n = 265)

The most common indication for transplantation in children was Biliary Atresia (143, 54%), followed by Metabolic disease (60, 23%) and Fulminant Hepatic Failure (29, 11%).



Chronic Viral and Auto-Immune Hepatitis


Chronic Viral and Auto-Immune HepatitisPrimary and Secondary

n = 549 (46.6% of all Adults)

AIH9% B, C

2%

HCV63%

HBV23%

HDV3%

Viral91%

Auto-Immune Hepatitis (AIH) comprised 9% of cases, the remainder (91%) being viral in origin (CVH). Of the cases of viral hepatitis, the most common is Hepatitis C (HCV, 63%), followed by Hepatitis B (HBV, 23%) HDV (3%) and HBV/HCV co-infection (2%).


Chronic Viral (Primary and Secondary)Adults by Era

11%11%

78%

1986 - 1995

9%

37%54%

2006 - 2015

HBV (n = 128)

HCV (n = 345)

Non Viral (n = 706)

14%

30%56%

1996 - 2005

The number of patients requiring transplantation due to HCV has steadily increased over the three time periods, whereas the number of patients requiring transplantation for HBV has now decreased.




0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1986 - 1995 1996 - 2005 2006 - 2013 2014 2015

Non Viral (n = 706) HBV (n = 128) HCV (n = 345)

% Adults with Chronic HBV or HCV(Primary and Secondary)

Chronic HCV infection comprises 22.9% of adults transplanted.

Fulminant Hepatic Failure as Primary Indication Treated by Liver Transplantation


Fulminant Hepatic Failure As Primary Indication Treated by Liver Transplantation

Aetiology No of Patients No of TxOutcome

Alive Dead

Idiopathic 53 58 34 19

Drug Induced 22 24 14 8

Wilson’s Disease 14 16 12 2

Viral Hepatitis

Hep B 32 33 19 13

Hep C 1 1 1 0

Hep A 3 3 0 3

Hep E 1 1 0 1

Autoimmune Hepatitis 5 6 3 2

Budd-Chiari 1 1 0 1

Other 11 12 9 2

Totals 143 155 92 (64% pts) 51 (36% pts)



HCC and Associated Disease


HCC AND Associated DiseaseAdults by Era

HBV34%

HCV33%

Other33%

1986 - 1995

* HCV includes 1 case of HBV,HCV

NASH/NAFLD

7%

HBV40%

HCV *37%

Alcholic Cirrhosis

13%

Other10%

1996 - 2005

* HCV includes 2 case of HBV,HCV


HCC and Associated DiseaseAdults by Era

NASH/NAFLD

6%

HBV *22%

HCV50%

Alcoholic Cirrhosis

20%

Other4%

2006 - 2010

* HBV includes 1 case of HDV

HCC Only1%

NASH/NAFLD

7%

HBV *12%

HCV **42%

Alcholic Cirrhosis

28%

Other10%

2011 - 2015

* HBV includes 2 cases of HDV** HCV includes 1 case of HBV,HCV



NASH/NAFLD by Era


NASH/NAFLD (Primary and Secondary)Adults by Era

NASH/NAFLD

2%

Other98%

1996 - 2005

NASH/NAFLD

0%

Other100%

1986 - 1995


NASH/NAFLD (Primary and Secondary)Adults by Era

NASH/NAFLD

5%

Other

2006 - 2010

NASH/NAFLD

10%

Other

2011 - 2015



Indication For Secondary Transplantation


1

7

13

37

21

5

3

5

511

15

21

2

5

81

4

4

11

1 1

2

4

0

5

10

15

20

25

30

35

0 - 7 days 8 - 30 days 1 - 6 months 6 months - 1 year

1 - 5 years > 5 years

Time to Secondary Transplant

OtherBiliary StricturesViral RecurrencePNFRejectionVascular

Indication for Secondary Transplantation(n = 125)

Primary non function (PNF) is the major indication for re-transplantation in the first 7 days. Rejection and vascular indications are prominent indications for re-transplantation in all other time periods.


57.1%

48.6% 48.5%51.0%

60.4%

55.6%

0%

10%

20%

30%

40%

50%

60%

70%

1986 - 1990 1991 - 1995 1996 - 2000 2001 - 2005 2006 - 2010 2011 - 2015

Percentage of Children Transplanted for Biliary Atresia(n = 143; 54.0% of all Children)


PERIOPERATIVE DATA


Perioperative Data

Mean/Median Hospital Stay


9

5 56

53

43 3

5 5

23 3 3

4 4 46

4

86

46

76

8

5 56

36

32

44

49

42

32

38

24 24

40

26

32

42

25 2526

24

21

18

23

20

15

1918

1618

17

13

16

12

0

5

10

15

20

25

30

35

40

45

50

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

2015

ICU (Mean)Ward (Mean)ICU (Median)Ward (Median)

Hospital Stay (Mean & Median Days)Adults Only

Red Cell Usage


133 133

58

1611

4

0

20

40

60

80

100

120

140

1986 - 1995 1996 - 2005 2006 - 2015

Red Cell Usage (Max)

Red Cell Usage (Median)

Red Cell Usage(Units of Packed Cells)

Graft Ischaemic Time, Operation Duration and Red Cell Utilisation


Graft Ischaemic Time, Operation DurationAnd Red Cell Utilisation

1986 – 1995 1996 – 2005 2006 – 2015

Mean Graft Ischaemic Time 9 hr 18 min 9 hr 11 min 8 hr 20 min

Mean Operation Time 7 hr 43 min 7 hr 23 min 7 hr 13 min

No. Of Packed Cells Utilised1 – 133

Mean = 20.8; Median = 16

0 – 133 Mean = 14.6;Median = 11

0 – 58 Mean = 6.3;Median = 4


OUTCOME DATA


Outcome Data

Patient Survival


025

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0 5 10 15 20 25Years Post Transplant

Overall Patient Survival 1986 - 2015Adults and Children

1yr 5yr 10yr 15yr 20yr 25yr

No at risk 1181 817 528 285 139 44

Actuarial Survival % 88 79 70 61 52 45

n = 1444


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0 6 1812 24Months Post Transplant

Patient Survival 2014 - 2015Adults and Children

6m 12m 18m

No at risk 114 67 30

Actuarial Survival % 97 93 92

n = 166


Outcome Data


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Patient Survival 1986 – 2015Adults vs Children


ChildNo at risk 218 173 118 67 40 16


Adult No at risk 963 644 410 218 99 28


Child (n = 265)

Adult (n = 1179)

p < .01


025

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0 6 12 18 24Months Post Transplant

Patient Survival 2014 - 2015Adults vs Children

6m 12m 18m

ChildNo at risk 22 11 8


AdultNo at risk 92 56 27


Child (n = 30)

Adult (n = 136)

p = ns


Outcome Data

Children


025

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Children – Weight vs OutcomePrimary Grafts


<10kg No at risk 95 72 40 20 11 5


>10kgNo at risk 123 101 78 47 29 11


<10kg (n = 119)

>10kg (n = 146)

p = ns


025

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Children – Type of Transplant vs OutcomePrimary Grafts


Split (n = 103)

No at risk 87 56 25


Whole(n = 70)

No at risk 61 54 46 33 17 7


Reduced(n = 92)

No at risk 70 63 47 34 23 9


Split (n = 103)

Whole (n = 70)

Reduced (n = 92)

p < .01


Outcome Data


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Children – Donor TypePrimary Grafts


Split(n = 102)

No at risk 86 55 24


Whole(n = 70)

No at risk 61 54 46 33 17 7


Live(n = 15)

No at risk 15 11 3


Reduced(n = 78)

No at risk 59 53 46 34 23 9


Split (n = 102)

Whole (n = 70)

Live (n = 15)

Reduced (n = 78)

p < .01


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Fulminant Disease vs OutcomeAdults vs Children


ChildNo at risk 25 18 13 8 5 2


AdultNo at risk 81 61 41 25 15 4


Child (n = 29)

Adult (n = 114)

p < .05


Outcome Data

Primary Disease and Outcome


025

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Primary Disease vs OutcomeAdults

Malignancy (n = 129)

PBC (n = 71)

Metabolic (n = 73)

PSC (n = 119)

Alcoholic (n = 146)

CC (n = 27)

p < . 05


025

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Primary Disease vs OutcomeChildren

CC (n = 3)

BA (n = 143)

FHF (n = 29)

CAH (n = 5)

Metabolic (n = 60)

Malignancy (n = 7)

p = ns


Outcome Data

Status at Transplant vs Patient Outcome


025

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Status vs OutcomeAdults and Children – Primary Grafts


ICUNo at risk 102 69 44 26 18 6


At HomeNo at risk 549 362 234 116 46 16


Hosp. BoundNo at risk 184 119 67 46 23 7


Oc. InpatientNo at risk 346 267 183 101 52 15


ICU (n = 142)

At home (n = 642)

Hosp. Bound

(n = 239)

Oc. Inpatient

(n = 421)

p < .01


025

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Chronic Viral, Autoimmune Disease vs OutcomePrimary Grafts


B, CNo at risk 9 9 9 7 3 0


AINo at risk 45 36 27 22 15 3


HBVNo at risk 61 47 40 27 10 3


HCVNo at risk 225 126 73 28 6 2


B, C (n = 9)

AI (n = 54)

HBV (n = 83)

HCV (n = 270)

p = ns


Outcome Data

Chronic HBV Outcomes


025

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Chronic HBV Before and After Prophylaxis Protocol*Primary and Secondary Indication

* Oral nucleos(t)ide therapy + low dose monthly IMI HBIG


Post23/2/1996

No at risk 89 64 44 21

Actuarial Survival % 90 81 77 64

Pre 23/2/1996

No at risk 23 20 19 17 15 3


Post 23/2/1996

(n = 108)

Pre 23/2/1996

(n = 32)

p = ns


025

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Chronic HBV (Primary and Secondary) vs Era


2006 – 2015No at risk 36 18

Actuarial Survival % 93 88

1996 – 2005No at risk 54 48 45 22


1986 – 1995No at risk 22 19 18 16 15 3


2006 – 2015 (n = 48)

1996 – 2005 (n = 61)

1986 – 1995 (n = 31)

p < .05


Outcome Data

Chronic HCV Outcomes


025

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Chronic HCV (Primary and Secondary) vs Era


2006 – 2015No at risk 169 55


1996 – 2005No at risk 111 94 79 23


1986 – 1995No at risk 30 26 20 16 12 2


2006 – 2015 (n = 204)

1996 – 2005 (n = 126)

1986 – 1995 (n = 30)

p = ns


025

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Chronic HCV Primary vs Secondary IndicationPrimary Graft Survival


SecondaryNo at risk 69 36 17 9 3

Actuarial Survival % 92 75 57 54 54

PrimaryNo at risk 234 135 81 33 9 2


Secondary (n = 78)

Primary (n = 279)

p = ns


Outcome Data


025

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100

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HCV vs Donor Age vs Primary Graft OutcomeAdults (n = 360)

> 60 (n = 54)

<30 (n = 86)

50 - 60 (n = 80)

30 - 50 (n = 140)

p = ns


HCV vs Donor Age vs Primary Graft OutcomeAdults (n = 360)


>60(n = 54)

No at risk 41 22 12 4 1


<30(n = 86)

No at risk 74 48 62 17 5 2


50 - 60(n = 80)

No at risk 68 39 9 4 4


30 - 50(n = 140)

No at risk 114 68 36 13 4



Outcome Data


025

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Non HCV vs Donor Age vs Primary Graft OutcomeAdults (n = 819)

> 60 (n = 143)

< 30 (n = 241)

30 - 50 (n = 266)

50 - 60 (n = 169)

p = ns


Non HCV vs Donor Age vs Primary Graft OutcomeAdults (n = 819)


>60(n = 169)

No at risk 125 65 27 13 4


<30(n = 241)

No at risk 188 153 110 76 43 15


30 - 50(n = 266)

No at risk 214 157 106 58 22 9


50 - 60(n = 143)

No at risk 107 76 51 24 11



Outcome Data

Donor Age vs Primary Graft Outcome


025

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> 80 (n = 8)

< 30 (n = 516)

61 - 70 (n = 140)

31 – 50 (n = 494)

51 – 60 (n = 230)

71 – 80 (n = 56)

p < .05




> 80(n = 8)

No at risk 5 1


<30(n = 516)

No at risk 408 311 219 140 74 28


61 – 70(n = 140)

No at risk 106 58 28 11 4


31 - 50(n = 494)

No at risk 397 275 171 84 32 11


51 - 60(n = 230)

No at risk 180 108 58 28 14 1


71 - 80(n = 56)

No at risk 41 21 8 3



Outcome Data

Steatosis vs Graft Outcome (Adults)


025

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Macro Steatosis vs Primary Graft Outcome (Adults)2001 - 2015

1yr 5yr 10yr

S1 Ma/MiNo at risk 45 13




S0No at risk 291 113 34




S1 Ma/Mi (n = 63)

S2 Ma/Mi (n = 22)

S0 (n = 375)

S3 Ma/Mi (n = 6)

p = .05


025

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Micro Steatosis vs Primary Graft Outcome (Adults)2001 - 2015

1yr 5yr 10yr

S3 MiNo at risk 30 26 11






S0No at risk 291 113 34


S3 Mi (n = 30)

S1 Mi (n = 89)

S2 Mi (n = 28)

S0 (n = 375)

p = ns


Outcome Data

Graft Survival


025

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100

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Graft Survival by Graft NoAdults and Children

Tertiary (n = 15)

Primary (n = 1444)

Secondary (n = 103)

p < .01


Graft Survival by Graft NoAdults and Children


Tertiary(n = 15)

No at risk 15 9 3 2 1


Primary(n = 1444)

No at risk 1137 774 484 266 124 40


Secondary(n = 103)

No at risk 66 44 23 13 6 4



Outcome Data


025

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Graft Survival by Graft NoAdults and Children 2014 – 2015

6m 12m 18m

TertiaryNo at risk 1

Actuarial Survival % 100

PrimaryNo at risk 113 65 29


SecondaryNo at risk 4 2 1


Tertiary (n = 1)

Primary (n = 166)

Secondary (n = 7)

p = ns


025

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Graft SurvivalAdults vs Children 2014 - 2015

6m 12m 18m

ChildNo at risk 23 11 8


AdultNo at risk 94 56 27


Child (n = 32)

Adult (n = 142)

p = ns


Outcome Data


025

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Primary Graft Survival by EraAdults and Children


2006 - 2015No at risk 503 212


1996 - 2005No at risk 412 365 319 118


1986 - 1995No at risk 222 197 165 148 124 40


2006 – 2015 (n = 651)

1996 – 2005 (n = 486)

1986 - 1995 (n = 307)

p < .05


025

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Primary Graft Survival by EraAdults


2006 – 2015No at risk 417 165


1996 – 2005No at risk 336 294 256 97


1986 – 1995No at risk 179 157 127 111 90 26


2006 – 2015 (n = 538)

1996 – 2005 (n = 397)

1986 – 1995 (n = 244)

p < .05


Outcome Data


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Primary Graft Survival by EraChildren


2006 – 2015No at risk 86 47


1996 – 2005No at risk 76 72 63 21


1986 – 1995No at risk 43 41 40 38 34 14


2006 – 2015 (n = 113)

1996 – 2005 (n = 89)

1986 – 1995 (n = 63)

p < . 01

Split vs Reduced vs Whole Grafts


025

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Split vs Whole Grafts (Adults)Primary Graft Survival 2002 – 2015

1yr 5yr 10yr

SplitNo at risk 91 54 23


WholeNo at risk 487 255 102


Split (n = 110)

Whole (n = 608)

p = ns


Outcome Data


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Split vs Reduced vs Whole Grafts (Children)Primary Graft Survival 2002 – 2015

1yr 5yr 10yr



ReducedNo at risk 25 22 6




Whole (n = 25)

Reduced (n = 31)

Split (n = 102)

p = ns


025

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Split vs Reduced vs Whole Grafts (Children)Patient Survival 2002 – 2015

1yr 5yr 10yr





ReducedNo at risk 31 22 8


Whole (n = 25)

Split (n = 102)

Reduced (n = 31)

p = ns


Outcome Data

Cause of Death

Cause of Death

Graft Failure 122 (26.4%)

Rejection: Chronic 27 Rejection: Acute 10 Recurrent disease Hepatitis C 40 Biliary Complications 10 Hepatitis B 11 Vascular 12 PNF 4 NASH 2 Other 6

Malignancy 89 (19.3%)

De Novo 57 Recurrent disease 31 Transferred from donor 1

Sepsis 87 (18.9%)

Cardiovascular 32 (6.9%)

Cerebral 32 (6.9%)

Respiratory 25 (5.4%)

Multi-organ Failure 12 (2.6%)

Operative 11 (2.4%)

Gastrointestinal 10 (2.2%)

Vascular 8 (1.7%)

GVHD 4 (0.9%)

Renal Failure 4 (0.9%)

Other 25 (5.5%)

TOTAL 461 (34.1% of all patients)


Outcome Data


Cause of Death(n = 461)

Operative2%

Sepsis19%

Cardiovascular7%

Cerebral7%

Malignancy - De Novo13%

Malignancy -Recurrent

7%

Respiratory5%

Rejection8%

GI2%

Miscellaneous11%

Recurrent Disease12%

Biliary Complications2% PNF

1%Vascular (pt)3%

Other1%

Graft failure27%

461 patients, or 34.1% of all patients transplanted, have died. Of these, 87 (18.8%) have died due to sepsis and 122 (26.5%) from graft failure. Of the 122 cases of death due to graft failure, 37 (30.3%) patients lost grafts due to rejection, 56 (45.9%) from recurrent disease and 4 (3.2%) from primary non function (PNF).


Cause of Death(n = 461)

Operative3%

Sepsis18%

Cardiovas8%

Cerebral6%

Malignancy20%

Respiratory5%

GI2%

Misc11%

Graft Failure27%

Adults (n = 413)

Sepsis23%

Cardiovas2%

Cerebral17%

Malignancy10%

Respiratory8%

GI2%

Misc15%

Graft Failure23%

Children (n = 48)

The majority of adult deaths were due to Graft Failure (111 or 26.9%), Malignancy (84 or 20.3%) and Sepsis (76 or 18.4%). The majority of child deaths were due to Graft Failure (11 or 22.9%), Sepsis (11 or 22.9%) and Cerebrovascular accident (8 or 16.7%).


Outcome Data


7 7 7 6 3 1

152

2

41

2

14

1

1

42

26

20

12

83

22

14

98

13

242

1

16

10

7

6 5

28

3

9

3

3

4 1

1

40

1114

44

3

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

<1 year 1 - 5 years 5 - 10 years 10 - 15 years

15 - 20 years

>20 years

Sepsis

Respiratory

Operative

Miscellaneous

Recurrent Malignancy

De Novo Malignancy

Graft Failure

Gastrointestinal

Cerebral

Cardiovascular

Cause of Death by Time - Adults(n = 413; 39.6% of adults)


18

7 2

11

1

1

21

5

2

2

1

1

6 1

2

1

1

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%


15 - 20 years

>20 years

Gastrointestinal

Sepsis

Respiratory

Miscellaneous


De Novo Malignancy

Graft Failure

Cerebral

Cardiovascular

Cause of Death by Time - Children(n = 48; 20.4% of children)


Outcome Data


10 14 7

15 4 5

4748

16

1624

14

8 9

13

14 16 169 6

628 35

136 3 24 4 1

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1986 - 1995 1996 - 2005 2006 - 2015

GI

Operative

Sepsis

Respiratory

Miscellaneous


De Novo Malignancy

Graft Failure

Cerebral

Cardiovascular

Cause of Death by Transplant Era - Adults(n = 413; 39.6% of adults)


1

5

21

4 6 1

41

4

2

113

7 31

1

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1986 - 1995 1996 - 2005 2006 - 2015

GI

Sepsis

Respiratory

Miscellaneous


De Novo Malignancy

Graft Failure

Cerebral

Cardiovascular

Cause of Death by Transplant Era - Children(n = 48; 20.4% of children)


Outcome Data


Cause of Death – HCV Recipients(n = 121)

Cardiovascular5%

Gastrointestinal1%

Other Graft Failure4%

Malignancy - De Novo12%

Malignancy -Persistent

13%

Operative4%

Sepsis15%

Respiratory1%

Recurrent HCV32%

Other 13%


Outcome Data

Cause of Graft Failure

Cause of Graft Failure Rejection 71 (12.3%) Acute 15 Chronic 49 ABO incompatibility 6 Subacute 1 Vascular complications 46 (7.9%) Hepatic artery thrombosis 36 Portal vein thrombosis 4 Dissection in donor 1 Graft infarction 1 Graft compression 1 Hepatic vein stenosis 1 Rupture 1 Vena Cava obstruction 1 Recurrent disease 97 (16.8%) Hep C 47 Malignancy 27 Hep B 13 PSC 5 NASH 3 Alcohol 1 Cryptogenic cirrhosis 1 Primary non function 21 (3.6%) Graft infarction 7 Severe steatosis 2 Antibody mediated rejection 1 Arterial thrombosis 1 Blood loss 1 HA occlusion 1 Preservation injury 1 Profound hypotension 1 Vena 1 Other 5 Patient deaths 295 (50.9%) Sepsis 80 Malignancy 61 Cerebral 32 Cardiovascular 26 Respiratory failure 25 Intraoperative 15 GI haemorrhage 8 GVHD 4 Pancreatitis 3 Other 41 Biliary complications 31 (5.3%) Biliary strictures 21 Other 10 Other 18 (3.1%) TOTAL 579 (42.8%) of all grafts


Outcome Data


Cause of Graft Failure(n = 579)

Rejection12%

PNF4%

Vascular8%

Recurrent Disease17%

Other3% GVHD

1%

Malignancy11%

Other6%

Cardiac4% Intraop

3%Respiratory4%

Cerebral6%

Sepsis14%

GI1%

Biliary5%

Pancreatitis1%

Patient Death51%

579 of 1562 grafts (37.1%) have failed. 295 grafts (50.9%) were lost due to patient deaths, 97 (16.8%) due to disease recurrence and 71 (12.3%) due to rejection. Sepsis was the most significant cause of patient death (83 patients), followed by malignancy (62 patients) and cerebral catastrophe (32 patients).


Cause of Graft Failure(n = 579)

Rejection10%

PNF3%

Patient Death54%

Vascular6%

Recurrent Disease

20%

Other 3%

Biliary4%

Adults (n = 486)

Rejection24%

PNF7%

Patient Death33%

Vascular18%

Other 6%

Biliary12%

Children (n = 93)

Patient death was the most significant cause of graft failure, followed by rejection.


Outcome Data


4 3 5 4 22

3 43 1

1

15

104

52

49

3120

8

26 40

20

7

427

97

1

4122

5 1 1

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%


15 - 20 years

>20 years

Vascular

Rejection

Recurrent Disease

Pt Death

PNF

Other

Biliary

Cause of Graft Failure by Time - Adults(n = 486; 38.7% of adult grafts)


2 1

53

21

1

2

6

24

2

2

1

1

1

7

7

5 1

1

1

12 4

1

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%


15 - 20 years

>20 years

VascularRejectionPt DeathPNFOtherBiliary

Cause of Graft Failure by Time - Children(n = 93; 30.4% of child grafts)


Outcome Data


9 10 12 3 71 6 8

94106

64

32

4124

33 115

7 16 6

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1986 - 1995 1996 - 2005 2006 - 2015

Vascular

Rejection

Recurrent Disease

Pt Death

PNF

Other

Biliary

Cause of Graft Failure by Transplant Era - Adults(n = 486; 38.7% of adult grafts)


36

21

2 3

4

218

8

5

10

9

3

6

9

2

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1986 - 1995 1996 - 2005 2006 - 2015

VascularRejectionPt DeathPNFOtherBiliary

Cause of Graft Failure by Transplant Era - Children(n = 93; 30.4% of child grafts)


Outcome Data


CANCER AND

TRANSPLANTATION


Cancer and Transplantation

Malignancy at Transplantation


1 2 1 1 2 13

7

119

11

7 79

15 14

11

18

12

18

15

25

19 20

23 22

1

1

11 2 1

1

1

11

1 2

1

1 2

2

1

3

1

1

1

1

1

1

2

2

1

1

0

5

10

15

20

25

3019

8719

8819

8919

9019

9119

9219

9319

9419

9519

9619

9719

9819

9920

0020

0120

0220

0320

0420

0520

0620

0720

0820

0920

1020

1120

1220

1320

1420

15

Cholangiocarcinoma (n = 16)Miscellaneous (n = 18)Hepatoblastoma (n = 2)HCC (n = 284)

Malignancy at Transplantation(n = 296 Pts/320 Ca; 20.4% of patients)


1 1 1 13

21 1

5

87 7

5 5

8

14

1110

14

9

16

13

20

13

1720

17

1 1

2

2

3

24

2 2

1

1

3

3

2

2

2

5

6

2

3

5

0

5

10

15

20

25Unknown Pre Tx: Found in Explant (n = 54)

Known Pre Tx: Confirmed at Explant (n = 226)

Chemo or Injection Pre Tx: No Tumour at Explant (n = 4)

HCC at Transplantation(n = 284)




Cancer in Liver Transplant Recipients1986 - 2015

At Transplant (1444 patients) Patients (n,%)

Liver cancer as primary diagnosis 136 9.4%

Liver cancer as secondary diagnosis 174 12.0%

No. of Patients with a cancer diagnosis at transplant 310 21.5%

Post Transplant

Recurrent liver cancer 36 2.5% of all pts, 11.6% of cancer at tx pts

De novo non-skin cancer 114 7.9% of all pts, 36.8% of cancer at tx pts

De novo skin cancer 207 14.3% of all pts, 66.8% of cancer at tx pts

No. of Patients with a post transplant cancer 357 24.7% of all pts

Patients with multiple cancers 197 13.6% of all pts

Pre transplant cancer developed de novo cancer 61 19.6% of cancer at tx pts

Transferred from donor 4

Developed non-skin cancer within 90 days 1


025

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0 5 10 15 20Years Post Transplant

HCC vs EraPrimary and Secondary Indication

1yr 5yr 10yr 15yr 20yr

2006 – 2015No at risk 149 50


1996 – 2005No at risk 79 66 57 18


1986 – 1995No at risk 8 5 5 3 2


2006 – 2015 (n = 183)

1996 – 2005 (n = 93)

1986 – 1995 (n = 8)

p = ns




025

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Benign Disease vs Malignancy


BenignNo at risk 928 686 463 261 134 43


MalignancyNo at risk 253 131 65 24 5 1


Benign (n = 1134)

Malignant (n = 310)

p < . 01


025

5075

100

% S

urvi

ving


Primary and Secondary HCC vs No HCC

No HCC (n = 1267)

With HCC (n = 295)

p = ns


No HCCNo at risk 1018 752 497 282 146 45


With HCCNo at risk 242 125 61 20 2




De Novo Non Skin Cancer Post Transplant


De Novo Cancer (Excluding Skin)n = 114 Pts, 123 Ca; 8.4% pts transplanted

No Male FemaleAge of

patients (years)

Time to diagnosis (months)

Died of This Cancer

Died Other

Alimentary 48 37 1113 - 78

(m = 59)0 - 266

(m = 74)23 48% 8

Lymphoma (inc PTLD) 27 16 111 - 70

(m = 49)4 -281

(m = 87 )8 30% 6

Genitourinary 15 12 321 - 74

(m = 59)2 - 228

(m = 83)2 13% 5

Respiratory 11 9 229 - 68

(m = 61)7 - 193

(m = 56)8 73% 0

Breast 9 0 930 - 60

(m = 44)50 - 252

(m = 135)6 67% 1

Endocrine 8 2 636 - 70

(m = 48)14 - 144(m = 56)

2 25% 0

CNS 2 1 166 - 75

(m = 70)14 - 93

(m = 53)2 100% 0

Bone 1 0 1 69 69 1 100% 0

Fibrous Histiocytoma 1 0 1 62 120 0 0

Kaposi’s 1 1 0 32 48 0 1

Total 123 78 451 - 78

(m = 56)0 - 281

(m = 69)52 42% 21

NB: m = median


De Novo Cancer (Excluding Skin)n = 114 Pts, 123 Ca; 8.4% pts transplanted

Breast7%

CNS2%

Endocrine6%

Genitourinary12%

Kaposi's Sarcoma

1%

Lymphoma22%

Respiratory9%

Lower GI27%

Pancreas5%

Upper GI7%

Fibrous Histiocytoma1%

Bone1%

Alimentary40%



Pre Transplant Liver Disease and De Novo Non Skin Cancer


Pre Transplant Liver Disease andDe Novo Cancer (Excluding Skin)

n = 123

7

5 5

4

3

1 1 1

0

1

2

3

4

5

6

7

PSC + Autoimmune27/; 22% of all De Novo

3

2 2 2 2

1 1

0

1

2

3

4

5

6

7

HBV14/; 11% of all De Novo


Pre Transplant Liver Disease andDe Novo Cancer (Excluding Skin)

n = 123

6

5

4 4

2 2

1 1

0

1

2

3

4

5

6

7

8

HCV25/123; 20% of all De Novo

8

5

4

2 2

1 1 1 1

0

1

2

3

4

5

6

7

8

Alcohol25/123; 20% of all De Novo




12 1210

5

1

5 5

1

3

4

3

4

2

3

2

1

2

3

0

5

10

15

20

25

PSC + AI HCV ALD HBV PBC

Bone (n = 1)Fibrous Histiocytoma (n = 1)Respiratory (n = 5)Kaposi's Sarcoma (n = 1)Genitourinary (n = 11)Endocrine (n = 7)Lymphoma (n = 14)Alimentary (n = 40)

Primary Liver Disease andDe Novo Cancer (Excluding Skin)


1

5

16

13 13

1

3

5

1 1

4

3

11

2 2

3

7

1

3

5

8

11

1

5

1

4

1

0

2

4

6

8

10

12

14

16

0 - 6 months 6 - 12 months 1 - 5 years 5 - 10 years >10 years

Alimentary (n = 48)Breast (n = 9)CNS (n = 2)Endocrine (n = 8)Genitourinary (n = 15)Kaposi's Sarcoma (n = 1)Lymphoma (n = 27)Respiratory (n = 11)Fibrous Histiocytoma (n = 1)Bone (n = 1)

Time to DiagnosisDe Novo Cancer (Excluding Skin)



Cumulative Risk of Diagnosis of Cancer


Cumulative Risk of Diagnosis of CancerFollowing Liver Transplantation 1986 – 2015

0

20

40

60

80

100

0 5 10 15 20 25Years Post Tx

Any CancerSkinDe Novo Non SkinAge Matched Gen. Pop

Documents

Australian National Liver Transplantation Unit...There are several key issues to report. 1. A number of new heights were reached in 2015. These were: 98 orthotopic liver transplant