Evolution of indications and results of liver transplantation in Europe. A report from the European Liver Transplant Registry (ELTR).

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Evolution of indications and results of liver transplantation
in Europe. A report from the European Liver Transplant Registry
(ELTR)
René Adam1,⇑, Vincent Karam1, Valérie Delvart1, John O’Grady2, Darius Mirza3,
Jurgen Klempnauer4, Denis Castaing1, Peter Neuhaus5, Neville Jamieson6, Mauro Salizzoni7,
Stephen Pollard8, Jan Lerut9, Andreas Paul10, Juan Carlos Garcia-Valdecasas11,
Fernando San Juan Rodríguez12, Andrew Burroughs13, All the contributing centers (www.eltr.org)
and the European Liver and Intestine Transplant Association (ELITA)?
1Paul Brousse Hospital, Villejuif, France;2King’s College Hospital, London, UK;3The Queen Elizabeth Hospital, Birmingham, UK;
4Medizinische Hochschule Hannover, Hannover, Germany;5Charité – Campus – Virchow klinikum, Berlin, Germany;6Addenbrooke’s Hospital,
Cambridge, UK;7Centro de Trapianti di Fegato, Torino, Italy;8St. Jame’s & Seacroft University Hospital, Leeds, UK;9Cliniques Universitaires Saint
Luc, Brussels, Belgium;10C. U. K. GHs Essen, Essen, Germany;11Hospital Clinic I Provincial de Barcelona, Barcelona, Spain;12Hospital
Universitario LA FE, Valencia, Spain;13Royal Free Hospital, London, UK
Introduction
Background of the European Liver Transplant Registry
Since 1968 the European Liver Transplant Registry (ELTR) collects
prospectively the data of liver transplantation (LT) in 145 centers
all over Europe. It represents more than 95% of the overall
European data compared to the published official figures [1]. This
collection is made prospectively through a standardized question-
naire. The first part of the questionnaire includes items regarding
date and indication for LT, donor and recipient data, surgical tech-
niqueofLT,andtheimmediatepostoperativeimmunosuppression
therapy. The second part concerns graft and patient outcome, and
immunosuppressive regimen follow-up. Participation in the ELTR
is voluntary and a standard computerized database is provided to
contributing centers with detailed instructions for the collection
of accurate and uniform information [2].
Along with reports concerning LT for specific hepatic diseases
[3–12],ELTRhas allowedthe developmentof riskmodelsforliver-
transplantation mortality according to the characteristics of the
donor and recipient, and of the transplant procedure [13,14].
Qualityofthedataisassessedroutinely.Aregularauditingpro-
cessisconductedeachyeartoensurethereliabilityofthescientific
analysis of the data, a control of the good adequacy between ELTR
questionnaire and patient charts is performed by randomly con-
ducted auditvisits.Resultsof these auditvisitshaveindicatedthat
ELTR data were reliable and the scientific results of ELTR can be
considered credible and representative of LT in Europe [15–18].
In addition, a control quality program has been developed inter-
nally. The data are subjected to checks for completeness, consis-
tency, and range. Comprehensive logical intra- and inter-updates
are performed. Moreover, the ELTR has established agreements
with the European Organ Sharing Organizations (OSO): United
Kingdom Transplant Service Support Authority (UKTransplant),
Spanish Organizaciòn Nacional de Transplantes (ONT), Scandina-
vian Scanditransplant (SKT), Dutch Transplant Foundation (NTS),
Eurotransplant (ET), French Agence de la Biomédecine (ABM) to
exchangedata collectedfrom European Centers and to crosscheck
common data between OSO and ELTR.
Patients and methods
We have first considered all data since 1968 to show the evolu-
tion of results of LT in Europe since its initial development. The
rest of the analysis has been undertaken during two different
periods: (a) from January 1988 to December 2009 (89,865 LT –
80,347 patients), where the date from January 1988 was chosen
Journal of Hepatology 2012 vol. 57j675–688
Keywords: Liver transplantation; Registry; Outcome.
Received 18 August 2011; received in revised form 4 April 2012; accepted 5 April 2012
⇑Corresponding author. Address: Centre Hépatobiliaire, Hôpital Paul Brousse,
12-14, Av Paul-Vaillant-Couturier, B.P. 200, F-94804 Villejuif Cedex, France. Tel.:
+33 1 45 59 32 88; fax: +33 1 45 59 38 57.
E-mail address: rene.adam@ap.pbr-hop-paris.fr (R. Adam).
?The order of the sixteen co-authors was determined according to the
decreasing number of liver transplants recorded in the ELTR. The list with all the
centers is available at the following link: www.eltr.org/spip.php?page=centers-
tous.
Abbreviations: ELTR, European Liver Transplant Registry; ELITA, European Liver
and Intestine Transplant Association; ESOT, European Society of Organ Trans-
plantation; LT, liver transplantation; HCV, hepatitis C virus; HBV, hepatitis B
virus; ALD, alcoholic liver disease; Retx, Retransplantation.
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as corresponding to the diffusion of cyclosporine-based immuno-
suppression and to the standardization of the surgical procedure,
(b) the last 10-year period data from January 2000 to December
2009 (54,088 LT – 48,218 patients) to give a more recent evalua-
tion of LT results in Europe.
Data were analyzed as a whole without distinction of pediat-
ric transplants that represent 10% of LTs in Europe.
Data are analyzed with Statistical Analysis System (SAS). The
dynamics of data control are continued during the statistical ana-
lyzes. Calculation of survival rates are determined by the actuar-
ial method.
Results
From May 1968 to December 2009, the ELTR collected data con-
cerning 93,634 liver transplantations (LTs) in 83,816 patients
from 145 centers of 26 countries (Fig. 1). These data give a com-
prehensive overview of the status and evolution of LT in Europe.
Both the number of transplant centers and the annual number of
LTs performed in Europe have gradually increased since the cre-
ation of ELTR (Fig. 2). However, after an exponential increase
from the eighties, a plateau has become to be reached in recent
years with about 5800 LTs performed all over Europe.
Main indications for LT in Europe
Main indications for LT in Europe with the corresponding graft
and patient survival rates at 1, 5 and 10 years are listed in Table 1.
Cirrhosis is the most frequent indication (52%), mainly related to
either viral infection (21% with 13% of hepatitis C virus infection
(HCV) and 7% of hepatitis B virus infection (HBV)), or alcohol
abuse (19%). Combined viral and alcoholic (ALD) cirrhosis repre-
sents 3% of cases, with 2% of HCV–ALD. Cirrhosis is followed by
three major indications: primary liver tumors (14% with 12.1%
of hepatocellular carcinoma), cholestatic disease (11%), and acute
hepatic failure (8%, 2% of which are virus-related). Cholestatic
disease includes primary biliary cirrhosis (6%) and extra-hepatic
biliary atresia (4%). Primary sclerosing cholangitis represents 4%
of cases. Biliary atresia is the most frequent indication (57%) in
the pediatric population, followed by metabolic disease (19%).
Metabolic disease represents 6% of indications with familial
amyloïdotic polyneuropathy as the major indication (2%),
followed by three indications of equal frequency (1%): Wilson
734
2193
140
4316
1089
801
16,366
14,116
13,684
425
653
11,697
11
1972
734
1462
1645
206
15,714
2163
1475
1946
16
30
12
34
2193
34
4316
30
1089
734
12
801
16,366
14,116
13,684
425
653
ITALY 11,697
11
734
1462
1645
206
140
SPAIN15,714
2163
SWITZERLAND1475
1972
1946
16
38
0
341
15
1
8
0
0
409
715
138
3
0
212
0
1
135
26
47
0
189
54
59
14
1217
1
OverallLRLT
TOTAL 93,634 3622
AUSTRIA
BELARUS
BELGIUM
BULGARIA
CZECH REPUBLIC
DENMARK
ESTONIA
FINLAND
FRANCE
GERMANY
GREAT BRITAIN
HUNGARY
IRELAND
MONACO
NORWAY
POLAND
PORTUGAL
ROMANIA
SLOVENIA
SWEDEN
THE NETHERLANDS
TURKEY
EX-YUGOSLAVIA
Fig. 1. Number of LTs performed in each country, overall and living related liver transplantation (LRLT) (May 1968–December 2009).
Frontiers in Liver Transplantation
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Journal of Hepatology 2012 vol. 57j675–688

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disease, alpha-1-antitrypsin deficiency and hemochromatosis.
Secondary tumors (mainly carcinoid), Budd Chiari and benign
liver tumors (mainly polycystic disease) represent only 1% of indi-
cations in Europe.
The percentage of main indications for LT has significantly
changed with time. While cancers represented 50% of indications
before 1980, they dramatically decreased during the nineties
(10%) before resuming a linear increase since 2000, to currently
represent more than 20%. Conversely, acute hepatic failure that
led anecdotally to LT before 1986 has since become a recognized
indication for LT. (Fig. 3).
In the 10 recent years, two groups of indication have shown
an increase: primary liver tumors (16%), mainly related to HCC,
and cirrhosis (53%), mainly alcoholic (20%). Drug-related fulmin-
ant hepatitis is henceforth the leading disease in the group of
acute hepatic failures. In the same way, primary sclerosing cho-
langitis is the main indication in the group of cholestatic diseases.
Patient and graft survival of this 10-recent-year population are
summarized in Table 1.
Mortality of LT
One, 3 and 6-month patient’s survivals were 90%, 85% and 82%
before 2000. Survival rates dramatically increased to reach 94%,
91% and 88%, respectively. The critical period for post-LT outcome
is the first 6 months: 46% of deaths and 65% of re-LT occurs
within 6 months after LT (Fig. 4). In 49% of cases, re-LT is indi-
cated in the month after primary LT, and one quarter of deaths
occurs within the first month after LT.
Data represented in Tables 2 and 3 correspond to main cause
of death or graft failure. Main causes of death in the 18,186
patients (about 23%) who died after primary LT or re-LT were,
by decreasing order: (1) general causes as multiple organ failure
and cerebrovascular, cardiovascular, pulmonary, and renal com-
plications (29%); (2) recurrence of primary disease (20%), mostly
cancer (11%); (3) sepsis (18%) mostly bacterial (9%); (4) technical
complications (5%), mostly hemorrhage and vascular (3%); and
(5) rejection (4%) mostly chronic (3%) (Table 2). Intra-operative
deaths and primary non-function represented 3% of all deaths.
When we consider only the patients who survive beyond
6 months (Fig. 5), there are less technical complications, infection
and general complications (cerebrovascular, cardiovascular, pul-
monary, and renal), but more tumoral and non-tumoral recur-
rences, de novo tumor and rejection.
The data of the last 10 years show a decrease in overall mor-
tality (16%) with the same distribution of the causes of death
observed in the population from 1988.
Overall patient survival
When all indications are considered during the entire study per-
iod, patient survival rates are 82% at 1 year, 71% at 5 years, 61% at
7 10 7 5 36 4 10 2222 15 25 25 497073158285
533
823
1265
1698
2126
2531
2782
3030
3366
3645
3798
4077
4336
4668
4929
5081
5336
5255
5630
5761
5811
5956
5765
4584
6870727476788082 848688 90 92 9496982000 2002 2004 2006 2008
Italy
Finland
Switzerland

Sweden
Spain
Norway
Ireland



Denmark
Poland
Hungary
Slovenia
Estonia
Portugal
Bulgaria
Ex-Yugoslavia
Great Britain Germany
Austria France
Belgium
The Netherlands
Romania
Turkey
Czech Rep.
European Liver Transplant Registry
Belarus
*
Years
Fig. 2. Evolution of 93,634 LTs performed in Europe since May 1968. Arrows indicate the year the first LT was performed in indicated countries.⁄This decrease is owed to
the fact that some centers did not yet send their updating further to the recent changes of the questionnaire.
JOURNAL OF HEPATOLOGY
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677

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Table 1. Primary indications for LT in Europe and the corresponding survival.
From 1988 to 2009Last 10 years [1999-2009]
PercentagePercentageSurvival rate (%)
yr
10
Survival rate (%)
yr
No.
patients
of the
disease
(%)
of the
total
(%)
15 1520 No.
patients
of the
disease
(%)
of the
total
(%)
1 5
Indication for LTGraft
(%)
PatientGraft
(%)
PatientGraft
(%)
PatientGraft
(%)
PatientGraft
(%)
PatientGraft
(%)
PatientGraft
(%)
Patient
Acute hepatic failure
Virus
Drug
Toxic
Postoperative/traumatic
Unknown/others
Cholestatic disease
Primary biliary cirrhosis
Primary sclerosing cholangitis
Secondary biliary cirrhosis
Others
Congenital biliary disease
Extrahepatic biliary atresia
Alagille syndrom
Congenital biliary fibrosis
6507
1251
1187
242
178
3649
9114
4515
3582
550
467
4152
3346
228
193
196
37
152
41,593
18,348
4187
10,753
1382
683
165
1178
15,019
2244
1790
454
3443
1892
68
579
8
2
1
0.3
0.2
5
11
6
4
1
1
5
4
0.3
0.2
0.2
0.05
0.2
52
23
5
13
2
1
0.2
1.5
19
3
2
1
4
2
0
1
64
67
66
67
40
63
79
81
80
70
77
79
79
79
81
78
86
82
79
78
79
76
87
76
89
81
81
82
81
85
76
80
74
68
70
73
71
71
50
69
87
86
87
75
83
86
87
84
87
87
86
86
83
82
83
80
92
81
91
84
86
87
85
89
81
85
77
73
56
57
57
63
35
56
70
75
69
60
69
74
74
73
76
69
75
76
67
64
69
60
82
64
80
64
69
67
65
74
66
69
68
58
64
65
63
68
45
64
78
80
78
65
77
83
83
81
81
81
86
81
72
69
74
65
87
71
82
69
73
72
69
79
72
76
72
63
51
50
49
58
33
52
62
66
57
50
61
70
71
69
68
63
52
70
56
54
63
48
77
54
63
53
55
51
50
59
57
59
62
49
58
58
55
64
44
59
70
71
70
57
71
80
81
77
75
78
73
80
61
59
68
53
84
60
66
59
59
56
54
62
63
67
66
54
44
41
42
54
26
46
45
53
45
47
51
65
68
54
63
40
20
61
46
46
56
38
71
49
50
45
44
38
37
41
48
48
-
41
53
52
48
61
44
55
59
59
59
54
60
77
79
73
70
60
49
72
51
51
61
43
79
54
53
50
48
41
40
45
54
57
-
46
38
35
39
40
-
39
30
43
30
47
30
59
62
54
-
-
-
-
37
38
46
29
66
43
37
36
33
33
30
41
34
46
-
26
47
46
45
61
-
49
44
48
44
54
60
73
75
73
60
-
-
-
42
43
49
33
76
54
40
40
36
35
31
45
42
55
-
20
3449
645
728
164
120
1792
4675
1929
2170
307
269
2167
1662
147
98
138
17
105
25,424
11,030
2400
6590
835
407
106
692
9555
1531
1228
303
1892
1069
31
316
7
1
2
0.3
0.2
4
10
4
5
1
1
4
3
0.3
0.2
0.3
0.04
0.2
53
23
5
14
2
1
0.2
1.4
20
3
3
1
4
2
0.06
0.7
70
75
70
69
47
69
83
85
83
71
74
84
85
83
88
77
74
85
81
80
84
77
89
77
90
83
83
84
84
88
79
84
75
83
76
80
75
73
57
76
89
90
90
76
81
90
91
88
92
86
74
88
85
88
87
81
93
82
91
87
86
88
86
92
83
88
77
87
62
65
61
64
43
63
74
78
72
61
62
79
80
79
84
67
46
80
69
65
75
59
83
67
82
63
71
70
69
76
69
72
70
63
69
72
66
69
55
70
81
83
82
65
73
87
88
85
91
83
74
84
73
74
79
64
88
74
83
69
75
74
73
80
74
80
77
65
19
18
4
3
56
19
21
5
3
52
50
39
6
5
41
46
7
6
81
5
5
5
1
4
77
7
5
6
1
5
Caroli disease
Choledocal cyst
Others
Cirrhosis
Virus related cirrhosis
Virus B
Virus C
Virus BD
Virus BC
Virus BCD
Other viruses
Alcoholic cirrhosis
Combined viral and alcoholic
Viral C and alcoholic
Viral B and alcoholic
Cryptogenic (unknown)
Autoimmune cirrhosis
Drug-related
Others
44
10
26
3
2
0
3
36
5
4
1
8
5
0.2
1
43
9
26
3
2
0.4
3
38
6
5
1
7
4
0.1
1
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From 1988 to 2009Last 10 years [1999-2009]
PercentagePercentage Survival rate (%)
yr
10
Survival rate (%)
yr
No.
patients
of the
disease
(%)
of the
total
(%)l
1 5 15 20No.
patients
of the
disease
(%)
of the
total
(%)
1 5
Indication for LTGraft
(%)
PatientGraft
(%)
PatientGraft
(%)
PatientGraft
(%)
PatientGraft
(%)
PatientGraft
(%)
PatientGraft
(%)
Patient
Primary liver tumors
Hepatocellular carcinoma and
cirrhosis
Hepatocellular carcinoma and
non-cirrhotic liver
Hepatic cholangiocellular
carcinoma
Biliary tract carcinoma
(Klatskin)
Hepatoblastoma
Epithelioid
hemangioendothelioma
Hepatocellular carcinoma-
fibrolamellar
10,991
9122
14
11
72
80
76
83
49
58
52
62
40
46
40
49
34
37
37
40
24
25
27
29
7640
6874
16
14
81
82
83
86
61
62
64
66 8390
6386167 7140 432931 24 2620 2321530.47884 5761
33230.46266283119211417--14220.37379 3337
25220.3 6466 30 3222 24 1416 1213 791 0.2 656832 37
180
159
2
1
0.2
0.2
81
81
84
88
69
71
74
77
61
67
69
72
58
58
66
67
-
58
-
67
127
96
2
1
0.3
0.2
82
81
86
90
70
76
76
84
50 0.50.16570323627 332733--180.20.04657130 38
Angiosarcoma
Other liver malignancies
Secondary liver tumors
Carcinoid
Other neuroendocrine
Colorectal
GI non-colorectal
Non-gastrointestinal
Others
Metabolic diseases
Familial amyloïdotic
polyneuropathy
Wilson disease
Alpha-1-antitrypsin deficiency
21
237
516
196
160
47
15
18
80
4855
1280
0.2
2
0.03
0.3
1
0.2
0.2
0.1
0.02
0.02
0.1
6
2
27
67
74
81
69
70
72
64
61
80
81
33
71
79
86
74
79
72
64
65
86
87
7
41
43
55
44
31
36
24
28
72
69
13
43
50
58
49
33
36
24
32
78
76
-
36
29
33
27
14
29
-
18
63
56
-
38
32
34
30
14
29
-
22
70
62
-
29
24
24
26
-
29
-
15
57
43
-
31
25
24
26
-
29
-
19
65
50
-
-
15
16
-
-
-
-
-
48
-
-
-
15
16
-
-
-
-
-
59
-
5
84
361
109
108
25
5
6
108
2866
873
0.1
1
0.01
0.2
1
0.2
0.2
0.1
0.01
0.01
0.2
6
2
56
81
77
85
70
78
80
75
-
82
82
56
87
83
90
76
86
85
80
-
87
88
-
49
50
63
46
33
-
-
-
72
68
-
53
55
66
59
37
-
-
-
79
76
38
31
9
3
3
16
30
30
7
1
2
30
2630
812
542
468
225
212
230
98
95
86
59
21
17
11
10
5
4
5
2
2
2
1
0.4
1
1
1
0.3
0.3
0.3
0.1
0.1
0.1
0.1
0.0
81
84
73
79
83
79
84
83
85
88
83
88
89
76
84
93
85
91
90
87
97
83
76
77
63
65
80
71
73
79
83
79
74
84
83
66
71
92
78
85
86
84
92
74
68
68
49
53
77
65
72
79
62
79
50
79
75
53
59
87
71
83
86
63
92
74
62
63
38
53
72
60
69
68
-
79
50
75
69
39
56
83
67
83
73
-
92
74
56
37
-
-
72
60
69
59
-
-
-
70
63
-
-
83
67
83
62
-
-
-
514
293
269
155
101
148
35
66
84
31
15
18
10
9
5
4
5
1
2
3
1
1
1
1
1
0.3
0.2
0.3
0.1
0.1
0.2
0.1
0.03
84
88
75
80
85
77
87
84
85
86
83
90
91
78
86
94
85
90
91
86
100
83
78
83
62
62
79
70
67
76
83
76
64
85
87
66
67
92
78
84
82
84
95
64
Hemochromatosis
Cystic fibrosis
Byler disease
Primary hyperoxaluria
Tyrosinemia
Glycogen storage disease
Non-alcoholic steatohepatitis
Crigler-Najjar
Homozygous
hypercholesterolemia
JOURNAL OF HEPATOLOGY
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Table 1 (continued)
From 1988 to 2009Last 10 years [1999-2009]
PercentagePercentageSurvival rate (%)
yr
10
Survival rate (%)
yr
No.
patients
of the
disease
(%)
of the
total
(%)l
1 5 1520No.
patients
of the
disease
(%)
of the
total
(%)
1 5
Indication for LTGraft
(%)
PatientGraft
(%)
PatientGraft
(%)
PatientGraft
(%)
PatientGraft
(%)
PatientGraft
(%)
PatientGraft
(%)
Patient
Protoporphyria
Others
Budd-Chiari
Benign liver tumors or
polycystic disease
Polycystic disease
Hemangioma
Adenomatosis
Nodular regenerative
hyperplasia
Hepatic adenoma
Focal nodular hyperplasia
Others
Parasitic disease
Alveolar echinococcosis
Cystic hydatidosis
Schistosomiasis (Belharzia)
Others
Other liver diseases
Total
19
708
712
1015
0.4
15
0.0
1
1
1
78
79
72
83
84
84
78
86
72
69
64
77
72
75
71
82
66
62
55
71
66
69
64
75
57
60
49
64
57
67
59
68
57
58
40
61
57
62
49
65
7
275
400
733
0.2
10
0.01
1
1
2
68
-
76
85
68
-
81
89
48
-
66
79
48
-
73
85
732
99
38
33
72
10
4
3
1
0.1
0.05
0.04
86
80
83
81
89
85
83
81
80
78
74
63
85
84
74
63
73
73
74
63
77
80
74
63
66
66
74
52
69
72
74
52
66
-
-
-
69
-
-
-
548
60
27
19
75
8
4
3
1
0.1
0.06
0.04
88
79
85
88
91
84
85
88
81
75
85
68
87
82
85
68
27
16
70
68
47
7
4
10
824
80,347
3
2
7
0.03
0.02
0.1
0.1
0.1
0.01
0.005
0.01
1
100
60
74
71
75
77
57
75
80
71
75
71
93
79
77
79
57
75
80
74
82
50
66
63
67
67
43
-
80
61
63
61
93
73
68
69
43
-
80
66
71
33
45
57
56
55
43
-
-
52
53
61
51
57
57
57
43
-
-
57
61
33
-
57
52
49
43
-
-
47
44
61
-
62
53
52
43
-
-
53
51
-
-
-
26
30
-
-
-
44
36
-
-
-
27
31
-
-
-
51
43
19
12
48
31
23
4
2
2
472
48,218
3
2
7
0.04
0.02
0.1
0.1
0.05
0.01
0.004
0.004
1
100
71
74
68
81
89
-
-
-
74
79
77
91
73
81
89
-
-
-
79
85
55
74
63
55
62
-
-
-
66
66
61
91
70
55
62
-
-
-
71
73
69
10
6
15
74
13
6
6
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10 years, 51% at 15 years and 43% at 20 years. When we consider
only the patients who survive beyond 6 months, patient survival
rates are dramatically higher (96% at 1 year, 83% at 5 years, 71% at
10 years, 61% at 15 years and 52% at 20 years). After an improve-
ment between 1988 and 2000, the survival of these patients
appears to be relatively steady since 2000 (Fig. 6).
Survival has improved regularly year after year, reaching 85%
at 1 year after 2004 compared with 76% in 1990–1994 and only
33% before 1985 (Fig. 7). The improvement concerns all the indi-
cations but particularly LT for cancers (Fig. 8).
When we consider the last 10-year period, survival of patients
transplanted in the recent 10 years has improved to reach 85% at
1 year and 73% at 5 years.
Survival of pediatric versus adult liver transplant recipients
Ten percent of LTs have been performed in pediatric patients
(<15 years), with 3.4% of children younger than 2 years. Five-year
survival in children is significantly better than in adults (79% vs.
70%, p <0.0001). In the pediatric population, 5-year survival rate
is identical for children under 2 years and for those aged 3 to
15 years (79%).
In the 10 last years, the rate of pediatric LT has decreased to
8% and the corresponding 5 year-survival is still better than in
adults (82% vs. 72%, p <0.0001).
Survival according to the indication for LT
The 5-year patient survival rate is significantly better for cirrhosis
(72%) than for primary liver tumors (52%, p <0.001) and acute
hepatic failure (64%, p <0.001). In viral cirrhosis, HBV and HCV
co-infection have a better 5-year survival (82%) than mono-
infection with HCV (65%) or HBV (74%). The greater survival rates
obtained in metabolic diseases (78%), cholestatic disease (78%)
and congenital biliary disease (83%), occur partly because of the
high percentage of children in these groups. Details of survival
rates at 1, 5 and 10, 15 and 20 years according to the primary
indication are listed in Table 1.
Although 5-year survival in the last 10-year population was
improved in all indications, the most important gain in survival
was observed in LTs for primary liver tumors, which is presently
64%, liver metastases (55%) and acute hepatic failure (69%).
European Liver Transplant Registry
Cirrhosis: 47,443
Cancers: 12,013
Acute hepatic failure: 6671
Others: 16,078
0
20
40
60
80
100
Percentage (%)
Years
68-80 82 848688 909294 9698 200020022004 2006 2008
Fig. 3. Evolution of primary indications for LT in Europe (05.1968–12.2009).
Cumulative
proportions (%)
Percentage per period (%)
European Liver Transplant Registry
1 d
10
5
6
14
21
9
17
9
19
21
18
16
8
12
5
10
1 wk1 mo1 yr 3 yr5 yr >5 yr6 mo
1 d
10
5
1 wk
31
11
1 mo
49
25
1 yr
73
55
3 yr
85
72
5 yr
90
81
>5 yr
100
100
6 mo
65
46
40
35
30
25
20
15
10
5
0
Ret-LT
Death
Death
Re-LT
Fig. 4. Mortality and re-LT. Percentage per period and cumulative proportions
(01.1988–12.2009).
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Table 3. Recipient graft survival according to the type of LT in Europe.
Type of LT/graftFrom 1988 to 2009
Survival rate (%)
Last 10 years [1999-2009]
Survival rate (%)No.
grafts
No.
grafts
1 yr
78
73
76
72
80
79
81
69
81
5 yr
65
65
66
65
69
64
76
62
59
10 yr
55
56
52
59
61
51
71
58
41
15 yr
46
50
43
51
60
51
69
54
-
20 yr
36
50
-
-
-
-
-
51
-
1 yr
81
76
77
75
80
79
81
74
83
5 yr
68
67
67
66
68
65
76
68
62
Cadaveric full size
Split liver
Right
Left
Living donor
Right
Left
Reduced liver
Domino (sequential)
68,728
3919
1728
1738
3481
2113
1191
1988
665
40,268
2983
1327
1323
3099
2051
880
711
590
Table 2. Post-LT mortality after first LT in Europe. Complications correspond to first declared cause of death according to date of occurrence.
Cause of deathDate of the mortality occurenceTotalPercentage of
1 d1 wk1 mo6 mo1 yr3 yr5 yr >5 yrthe complication
(%)
100
100
100
25
44
26
5
100
51
12
6
31
100
71
27
2
249
56
44
100
100
29
18
19
11
6
17
100
100
100
of the total
(%)
3
3
5
1
2
1
0.3
18
9
2
1
6
4
3
1
0.1
20
11
9
10
29
8
5
6
3
2
5
2
7
100
Intra-operative death
Primary non-function
Technical
Haemorrhage
Vascular complications
Biliary complications
Hepatic infarction
Sepsis
Bacterial infection
Fungal infection
Viral infection
Sepsis not designated
Rejection
Chronic rejection
Acute rejection
Not designated
Recurrence of initial disease
Tumoral
Non-tumoral
Tumor de novo
General causes
Cardiovascular
Cerebrovascular
Pulmonary
Gastrointestinal
Renal
Mutiple organ failure
Other liver causes
Other or unknown causes
Total
508
115
91
67
21
0
3
22
13
1
0
8
6
0
6
0
0
0
0
1
333
181
55
26
26
3
42
7
69
1152
0
229
114
42
59
3
10
142
81
9
4
48
17
0
16
1
1
0
1
0
495
155
144
54
37
11
94
32
82
1112
0
172
257
69
157
17
14
801
390
125
23
263
85
0
82
3
10
1
9
5
1055
232
185
216
122
47
253
68
165
2618
0
0
246
46
96
95
9
1346
633
181
121
411
113
67
43
3
362
214
148
76
1208
230
198
305
140
58
277
54
225
3630
0
0
82
10
35
36
1
281
139
24
21
97
125
109
13
3
616
382
234
149
321
77
64
72
33
20
55
25
89
1688
0
0
111
8
35
60
8
295
154
24
19
98
164
153
10
1
1383
850
533
450
530
152
113
105
68
27
65
40
186
3159
0
0
30
5
9
13
3
133
74
11
4
44
55
50
5
0
599
338
261
381
324
115
43
53
47
35
31
27
110
1659
0
0
55
3
20
31
1
267
181
10
11
65
82
80
1
1
712
267
445
731
987
369
164
172
90
119
73
62
272
3168
508
516
986
250
432
255
49
3287
1665
385
203
1034
647
459
176
12
3683
2052
1631
1793
5253
1511
966
1003
563
320
890
315
1198
18,186
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Survival according to donor and recipient characteristics
Donor characteristics
The majority of donors were male (59%). Seventy-six percent
were younger than 55 years, whereas 11% were older than
65 years. An increasing percentage of livers are coming from
donors older than 60 years (1% in 1989, 15% in 1999 and 29% in
2009), in relation to the increasing gap between a growing wait-
ing list and a relatively stable donor pool (Fig. 9). Graft survival
when organs were procured from donors younger than 55 years
was significantly higher than that with organs from donors older
than 65 years (65% vs. 57% at 5 years, p <0.0001). With 71% at
1-year and 50% 5-year graft survival, there is no argument to dis-
card octogenarian grafts among aged subjects without associated
risk factors (Fig. 10).
When we consider the last 10-year period, 5-year graft sur-
vival was 69% with donors younger than 55 years and 59% with
donor older than 65 years. However, aged grafts are more fre-
quently transplanted to aged recipients (33% of grafts older than
60 years were used in recipients older than 70 years, and only
21% were used in recipients younger than 70 years, p <0.0001),
explaining at least in part, the difference in survival.
Intra-operative death
Primary non-function or dysfunction
Technical complication
Infection
General complication
Other liver complications
Graft rejection
Tumor de novo
Tumoral recurrence
Non-tumoral recurrence
Other complications
Percentage (%)
0
2.9
0
3
3
5
12
23
20
23
3
3
4
3.6
17
10
19
11
15
9
7
6
Percentages (%)
Patients who survive 6-mo
All patients
0510152025
Fig. 5. Cause of death after LT of patients who survive beyond 6 months.
0
0
1
20
40
60
85
78
85
81
6465
61
56
46
17
66
52
33
20
80
2345678910
100
Patient survival (%)
Year after liver transplantation
<85: 490
95-99: 18,281
85-89: 4065
2000-04: 23,559
90-94: 12,007
>2004: 25,110
Fig. 7. Patient survival according to year of LT.
0
0
1
20
40
60
80
2345678910
100
Patient survival (%)
88-90: 1849
2000-05: 18,988
90-95: 9480
2005-10: 16,744
95-2000: 15,091
Years after liver transplantation
Fig. 6. Evolution of patient survival in patients who survive beyond 6 months.
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Recipient age
In addition to the already mentioned better 5-year survival of
pediatric vs. adult LT recipients, an influence of recipient age is
observed for adults. Survival rates are 74% for adults aged 16–
45 years, 70% for those aged 46–60 years, and 64% for those older
than 60 years. However, average age of transplanted recipients
has increased steadily during the last decade, and patients older
than 60 years, who represented less than 5% in the 1980s, repre-
sented approximately 25% of transplant recipients in 2009
(Fig. 11).
When we consider the last 10-year period, 5-year survival has
increased in all the subgroups of adult recipients to reach 77% for
adults of 16–45 years, 73% for 46–60 years and 66% over 60 years.
Blood group type matching
Ninety-two percent of LTs were isogroup, and 7.6% were compat-
ible. Only 0.6% were incompatible and restricted to urgent proce-
dures. In emergencies, isogroup and compatible LTs have similar
survival. In elective conditions, isogroup LTs have a better 5-year
survival than compatible LTs (66% vs. 60%, p <0.0001). Incompat-
ible LTs have a decreased 5-year graft survival rate as compared
to isogroup and compatible LTs (27% vs. 53%, p <0.0001). How-
ever, use of these incompatible grafts in emergency indications
allows around 50% survival rate in patients otherwise destined
to a fatal outcome.
Although 5 year-survival in the last 10-year population was
improved in all the groups of type matching, the most important
gain in survival was observed in incompatible matching (+41%).
However, only 0.3% of LTs were incompatible.
Survival according to surgical technique
More than 99% LTs were done orthotopically, and 87% of grafts
were full size. Alternative procedures to full size LTs have been
used increasingly in recent years (9% before 2000 vs. 16% after
2000). In the 2000s, alternative procedures were represented by
reduced livers (2%), split livers (6%) living donors (6%), and dom-
ino transplants (1%). 1, 5, 10, 15 and 20-year graft survivals of
each type of graft are summarized in Table 3. Survival at 5 years
was similar between split liver and cadaveric full size grafts
(65%), but lower than that of living donors (69%) and higher than
that of reduced and domino grafts (62% and 59%, respectively).
Auxiliary grafts represented 0.8% of overall LTs with a lower graft
survival as compared to non-auxiliary grafts in urgent indications
(5-year survival rates: 45% vs. 52%), and in elective indications
(60% vs. 66%, p <0.0001). Graft survival was better when cold
ischemia time was less than 12 h and University of Wisconsin
solution was used for preservation (p <0.001).
When we consider the last 10-year period, 5-year graft sur-
vival has increased in all types of graft to reach 68% for reduced
grafts, 67% for split and 62% for domino.
Living related LT in Europe
The ELTR has cumulated data concerning 3622 living related LTs
(LRLTs) performed in 78 centers from 20 countries from October
1991 to December 2009 (Fig. 1). The results of this technique will
be published elsewhere. In summary, adults represented 65% of
LRLTs. Since 2001 adult LRLTs largely exceeded pediatric LTs.
The donor surgical mortality rate was 0.18%. Overall 5-year graft
survival of LRLT was 69%, better for children than for adults (78%
vs. 63%, p <0.001). Whereas graft survival of LRLT was better than
cadaveric LT for children (78% vs. 72%, p <0.001), it was similar for
adults (64% vs. 63%). Overall, graft loss included more technical
complications (26% vs. 14%), more infection (23% vs. 18%), more
rejection (8% vs. 4%), more tumor recurrence (12% vs. 9%), but less
38
25
25
55
47
44
62
56
51
61
59
74
72
71
77
75
87
79
69
68
29
82
72
67
59
52
59
23
20
78
Cirrhosis
ACHF
Cancer
<85: 182
95-99: 10,943
85-89: 1850
2000-04: 13,939
90-94: 6727
>2004: 13,744
<85: 23
95-99: 1505
85-89: 470
2000-04: 1757
90-94: 1216
>2004: 1692
0
0
1
20
40
60
80
23456789 10
100
Patient survival (%)
0
20
40
60
80
100
Patient survival (%)
Year after liver transplantation
012345678910
Year after liver transplantation
28
11
6
52
24
17
68
42
32
56
49
85
78
88
78
0
20
40
60
80
100
012
Year after liver transplantation
345678910
Patient survival (%)
<85: 204
95-99: 1946
85-89: 700
2000-04: 3232
90-94: 1247
>2004: 4666
Fig. 8. Patient survival according to indication for and year of LT.
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general complications (20% vs. 27%) and less non-tumor disease
recurrence (4% vs.12%) after LRLT than after cadaveric LT (all
p <0.05).
Re-LT
Main causes of re-LT
Re-LT was indicated in 5596 cases (7%) mainly for technical com-
plications (37%) (mostly vascular (27%) and biliary (10%)), for pri-
mary non-function (25%) and for rejection (19%), mainly chronic
(14%). Recurrence of primary disease (mostly non-tumoral) was
concerned in only 11% of cases (Table 4).
Survival
Five-year graft survival rates for the second and third LTs were
42% and 37%, respectively, significantly lower than those for pri-
mary LT (65% – p <0.0001) (Fig. 12).
The data of the last 10 years show a decrease in the use of re-
LT (5%) with an increase of technical complications (41%) and a
decrease of rejection (10%). Moreover, 5-year graft survival was
increased in all the ranks of re-LT and the gap between primary
LT (68%) and 2nd LT (52%) has been reduced.
Discussion
With more than 90,000-recorded LTs, the ELTR is a unique source
to evaluate the evolution and results of LT in Europe. It is repre-
sentative of LT in Europe (95% of LTs performed). Owing to a rou-
tine control of data including audit visits to randomly selected
centers, its scientific value has been recently emphasized [15–
18].
Almost 6000 LTs per year are currently performed in Europe, a
number similar to that of the United States (US). However, dona-
tion rates in Europe vary much more than in United Network for
Organ Sharing (UNOS) regions. Spain has by far the highest dona-
tion rate in Europe (34.2 per million inhabitants in 2008) fol-
lowed by most of the other European countries with a rate of
organ donation between 20 and 25 per million inhabitants, sim-
ilar to that of Region 8 in the US (Colorado, Kansas, Nebraska and
Wyoming) which has the highest donation rate (24 per million
inhabitants in 2008) [19]. To cope with a donor shortage that
presently represents the most important limiting factor of LT,
alternatives to cadaveric LT such as split, domino, or living related
LTs are increasingly used accounting for 15% of all procedures.
Although more technically demanding, these techniques give
results similar to that for cadaveric LT and allow a larger number
of patients to undergo LT. Nevertheless, they need high expertise
from the centers [13,14]. This expertise is also likely to minimize
the risk for donors in case of LRLT, although no relationship has
been clearly demonstrated between the centre’s expertise and
the diminution of the risk of donor mortality and morbidity.
In terms of indications, two main issues emerge from the
European experience: (1) as expected, cirrhosis continues to rep-
resent the main indication of LT with more than half of the
European Liver Transplant Registry
0 to 15: 5405
15 to 50: 50,255
50 to 60: 14,424
≥60: 14,066
0
20
40
60
80
100
Percentage (%)
Years
68-8082848688 909294 9698 20002002200420062008
Fig. 9. Evolution of donor age in Europe (05.1968–12.2009).
0
0
1
20
40
60
80
2
pLogRank = 0.0001
3456789 10
100
Recipient graft survival (%)
Years after liver transplantation
78
71
70
58
65
50
59
45
55
45
Donor age <80 yr: 76,175
Donor age ≥80 yr: 566
Fig. 10. Recipient graft survival according to donor age.
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European Liver Transplant Registry
0 to 2: 3211
2 to 15: 4455
15 to 45: 22,724
45 to 60: 38,306
≥60: 14,582
0
20
40
60
80
100
Percentage (%)
Years
68-8082 84 8688 90929496982000 2002 20042006 2008
Fig. 11. Evolution of recipient age in Europe (05.1968–12.2009).
Table 4. Cause of re-LT after the first LT in Europe. The complications correspond to the first cause of failure declared according to time of occurrence.
Cause of retransplantationDate of retransplantation occurrenceTotalPercentage of
1 d1 wk1 mo6 mo 1 yr 3 yr5 yr>5 yrthe complication
(%)
100
100
72
26
2
1
100
64
12
9
15
100
75
22
3
100
97
3
100
100
100
100
the total
(%)
25
37
27
10
1
0.3
3
2
0.3
0.2
0.4
19
14
4
1
11
11
0.3
0.4
11
25
100
Primary non-function
Technical
Vascular complications
Biliary complications
Hepatic infarction
Haemorrhage
Sepsis
Bacterial infection
Viral infection
Fungal infection
Not designated
Rejection
Chronic rejection
Acute rejection
Not designated
Recurrence of initial disease
Non-tumoral
Tumoral
Tumor de novo
Other liver causes
Other or unknown causes
Total
152
39
37
1
0
1
5
5
0
0
0
4
0
3
1
1
1
0
2
41
15
218
952
381
362
5
9
5
31
26
0
3
2
42
0
38
4
9
9
0
3
53
41
1459
309
584
525
34
20
5
26
16
2
3
5
139
0
129
10
7
7
0
3
89
58
1126
0
474
320
141
11
2
23
15
2
3
3
215
167
37
11
57
56
1
6
137
56
831
0
169
76
93
0
0
17
7
4
3
3
200
186
10
4
73
70
3
2
49
25
486
0
245
95
146
3
1
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patients, and a large predominance within this group of patients
with alcoholic (20%) and virus C related cirrhosis, (2) the major
change is occurring for cancer, mainly HCC, which represents cur-
rently 20% of all indications, after a significant decrease from 50%
in the eighties to only 10% in the nineties. The better selection of
patients within the Milan criteria [20] with consequently equiv-
alent results of survival between HCC and benign hepatic disease
obviously explains this evolution.
One of the most important findings in the evolution of LT is the
significant improvement of results with time, leading presently to
a 1-year survival rate of 85%, all indications confounded. This
results probably from a greater surgical expertise, a better
selection of patients and an improved post-LT management of
complications and immunosuppressive therapy. The improve-
ment is particularly significant for cancers, mainly hepatocellular
carcinoma as previously mentioned, with a gain of 36% in 1-year
survival rates from 1990 to 2004. This gain was confirmed with
the data of the last 10 years with an improved 5-year survival of
66%.
Donor and recipient age influence the quality of the results, as
shown by a previous analysis of ELTR data focused on mortality
after LT [13,14]. However, they are not prominent factors of mor-
tality. Despite the fact that donor age >55 has been demonstrated
as an independent risk factor of post-transplant outcome [13],
the evolution shows that older donors are increasingly used to
augment the donor pool. Similarly, recipient age has been consid-
ered as independently associated with higher post-transplant
mortality, the but older recipients increasingly undergo LT owing
to improved results and better selection of patients.
What has not changed with time is the critical period of the
first 6 months and, more generally, the first year to determine
the final outcome of the transplanted recipients. More than a half
of the deaths and three quarters of re-LTs occurred within the
first year after LT. That means that when patients have success-
fully reached the first year after LT, they have an optimal chance
to survive at long-term.
When required (in approximately 7% of patients), re-LT is
associated with much less optimal results than the first LT. How-
ever, there is no team that would consider this result a reason to
exclude a new LT suggesting that a sort of moral contract exists
with the patient, in addition to strict consideration of the optimal
use of organs. Interestingly, the gap of survival is observed
between first and second LT while third and fourth LTs are not
associated with results much worse than those of second LTs.
One of the prominent features of recent years has been the
development of LRLT, performed by almost half of the centers.
As with split LT, LRLT aims to provide more patients with trans-
plants, but with special attention to decrease as much as possible
risks for the donor, now estimated to be of 0.18% for mortality
and 23% for postoperative morbidity. However, LRLT has tended
to decrease in recent years in Europe mirroring the trend in the
US, where it has actually decreased [21]. Potential living liver
donors are best served by accurate information about donor mor-
tality. Access to such data is difficult and these individuals benefit
from living liver donor registries and peer-reviewed publication
of donor mortality. That may provide an impetus for centers with
unreported deaths to submit these outcomes to the liver trans-
plantation community [22,23].
In conclusion, LT is definitely a validated therapy of end-stage
liver disease, acute liver failure and HCC. It is becoming relatively
safe as compared to the initial years. Indications are oriented to
more optimal use of the limited donor pool. Survival is increasing
gradually in relation to greater expertise in the surgical proce-
dure and management of immunosuppressive therapy. Alterna-
tives to conventional use of cadaveric full size liver grafts are
expanding to palliate the organ shortage. This latter development
including the increasing use of non-heart beating donors, the
long-term evaluation of the MELD allocation policy now used in
the majority of countries will probably represent a key issue in
the near future. To increase the donor pool, to avoid patient death
on the waiting list, and to offer equal access to good indications of
LT have become the main challenges of a treatment that pres-
ently allows 70–80% of patients to survive at 5 years.
Conflict of interest
The authors declared that they do not have anything to disclose
regarding funding or conflict of interest with respect to this
manuscript.
Acknowledgments
The authors are indebted to all the 145 contributing centers listed
at the following link www.eltr.org/spip.php?page=centers-tous.
The registry is supported by a grant from Astellas, Novartis and a
logistic support of the Paul Brousse Hospital (Assistance Publique
– Hôpitaux de Paris). ELTR is a service of the European Liver and
Intestine Transplant Association (ELITA).
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2345678910
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Recipient graft survival (%)
Years after liver transplantation
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65
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