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SUPPLEMENTAL DIGITAL CONTENT

Table S1. Demographic and baseline characteristics of 48,261 study patients according to original disease. The median and interquartile range of recipient age, donor age, cold ischemia time, and MELD score are shown (global P value of all characteristics <0.001).

Characteristic Hepatitis C

n = 13,504

Alcoholic n = 8,906

HCC n = 7,715

Acute n = 3,270

Other n = 14,866 Geographical region

Europe Other

11,963 (89%) 1,541 (11%)

8,331 (94%) 575 ( 6%)

7,369 (96%) 346 ( 4%)

3,080 (94%) 190 ( 6%)

13,038 (88%) 1,828 (12%) Transplant year

2000 – 2008 2009 – 2017

7,876 (58%) 5,628 (42%)

3,910 (44%) 4,996 (56%)

3,194 (41%) 4,521 (59%)

1,739 (53%) 1,531 (47%)

7,645 (51%) 7,221 (49%)

Female recipient 3,164 (24%) 1,802 (20%) 1,262 (16%) 1,889 (59%) 6,741 (44%)

Recipient age (years) 54 [48 – 60] 55 [49 – 60] 58 [52 – 63] 32 [48 – 55] 51 [42 – 59]

Donor age (years) 53 [41 – 65] 54 [42 – 66] 57 [45 – 69] 50 [38 – 60] 51 [38 – 62]

Cold ischemia time (hours) 8 [6 – 10] 8 [7 – 10] 8 [6 – 10] 8 [7 – 10] 8 [6 – 10]

Cause of Donor Death Cerebrovascular Trauma

Anoxia Other

8,042 (64%) 2,793 (22%) 962 ( 8%) 814 ( 6%)

5,344 (63%) 1,633 (19%) 827 (10%) 630 ( 7%)

4,814 (66%) 1,478 (20%) 543 ( 7%) 477 ( 7%)

2,016 (66%) 623 (20%) 201 ( 7%) 216 ( 7%)

8,756 (63%) 2,992 (22%) 1,185 ( 9%) 980 ( 7%)

DCD 111 ( 1%) 183 ( 2%) 171 ( 2%) 18 ( 1%) 164 ( 1%)

MELD Score 20 [14 – 28] 21 [15 – 30] 22 [13 – 28] 35 [29 – 40] 24 [16 – 31]

Calcineurin inhibitors (initial) Cyclosporine Tacrolimus None

2,364 (29%) 5,048 (62%) 668 ( 8%)

961 (21%) 3,216 (71%) 375 ( 8%)

897 (20%) 3,588 (73%) 451 ( 9%)

327 (22%) 1,022 (67%) 168 (11%)

1,802 (24%) 5,210 (68%) 624 ( 8%)

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Figure S1. Kaplan-Meier curves demonstrating the impact of donor age on (a) 10-year patient survival and (b) patient survival from year 1 to 10 on a logarithmic scale to illustrate the constant hazard rates after the first post-transplant year.

(a) Kaplan-Meier Estimates

0 100 90 80 70 60 50 40 30 20

Patient survival (%)

0 2 4 6 8 10

Time post-transplant (years)

18−34 35−49 50−64 65−79

80

Patients Year 10 N %

18−34 8,173 67.8

35−49 12,138 64.1 50−64 15,796 60.2 65−79 10,686 55.4

80 1,468 51.7 P < 0.001

(b) Half-Life Regression

30 100

80

60

40

0 2 4 6 8 10

Time post-transplant (years)

18−34 35−49 50−64 65−79

80

10-Year Half-Life Estimate (Years)

18−34 68 % 25.2

35−49 64 % 21.6

50−64 60 % 18.5

65−79 55 % 15.7

80 53 % 14.0

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Figure S2. Results of multivariable Cox regression analysis of the impact of donor age on 5-year patient survival. Cox regression coefficients (red diamond) with 95% confidence interval (blue line) of 5-year donor age categories are shown. The age category 50–54 years with the highest numbers of donors served as reference.

−0.4

−0.3

−0.2

−0.1 0.0 0.1 0.2 0.3 0.4

18

24 25

29 30

34 35

39 40

44 45

49 50

54 55

59 60

64 65

69 70

74 75

79

80

Cox regression coefficient

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Figure S3. Kaplan-Meier curves demonstrating the impact on 5-year patient survival of (a) the three main original disease categories alcoholic cirrhosis, hepatocellular carcinoma (HCC), and hepatitis C, and acute liver failure and (b) other less frequent original diseases, such as primary biliary cholangitis (PBC), congenital liver disease, hepatitis B, metabolic liver disease, autoimmune hepatitis, primary sclerosing cholangitis (PSC), and miscellaneous other liver diseases (Misc).

(a) Main Diseases

0 100

90

80

70

60

50

Patient survival (%)

0 1 2 3 4 5

Time post-transplant (years)

Other Alcoholic HCCHepatitis C Acute

Patients Year 5 N % Hepatitis C 13,504 68.8

Alcoholic 8,906 75.0

HCC 7,715 70.7

Acute 3,270 68.4

Other 14,866 79.6

(b) Other Diseases

0 100

90

80

70

60

50

0 1 2 3 4 5

Time post-transplant (years)

Congenital PBCHepatitis B PSCMetabolic Autoimmune Misc

Patients Year 5 N %

Autoimmune 3,391 77.1

Hepatitis B 2,606 81.8

PSC 2,461 80.2

PBC 2,027 83.5

Metabolic 1,322 78.7

Congenital 790 85.1

Misc 2,269 74.7

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Figure S4. Hazard ratios (HR, blue dots) with 95% confidence intervals of multivariable Cox regression analysis for 5-year patient survival per each year of donor age for the different original disease categories (HCC, hepatocellular carcinoma; PBC, primary biliary cholangitis; PSC, primary sclerosing cholangitis; Misc, miscellaneous other liver diseases).

Hazard Ratio of Donor Age

N Total: 48,261 Transplants HR P

Misc PSC PBC Metabolic HCC Hepatitis C Hepatitis B Congenital Autoimmune Alcoholic Acute

2,269 2,461 2,027 1,322 7,715 13,504 2,606 790 3,391 8,906 3,270

1.003 1.010 1.005 1.010 1.001 1.014 1.013 1.008 1.003 1.005 1.007

0.35 0.004 0.21 0.031 0.47

<0.001

<0.001 0.29 0.24 0.003 0.002

1.00 1.01 1.02 1.03

0.98 0.99 1.00

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