Influence of donor age on liver transplantation outcomes: A multivariate analysis and comparative study

Table 1 Donor and graft characteristics

Variable	Value (n = 656)
Male sex	389 (59.3)
Blood type
0	238 (36.3)
A	267 (40.7)
B	111 (16.9)
AB	40 (6.1)
Pancreas offered (yes)	145 (22.1)
Cardiac arrest (yes)	93 (14.2)
Age (yr)	60 (48-70)
BMI (kg/m²)	26.3 (24.4-28.4)
ET-DRI	1.72 (1.47-1.95)
Steatosis (%)	2 (0-10)
Na (mEq/L)	148 ± 9 (120-187)
ALT (U/L)	54.3 ± 79.6 (5-898)
GGT (U/L)	66.8 ± 99.8 (4-1129)
Bilirubin (mg/dL)	14 ± 12.6 (1-146)
CRP (mg/L)	162.6 ± 102.4 (1-621)
CIT (h)	7.11 ± 2.3 (1.22-13.87)

Data are presented as mean ± SD with ranges (min-max) or median with IQR (interquartile ranges) when the distribution is skewed for continuous variables. Categorical variables are presented as counts (%). BMI: Body mass index; Na: Sodium; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transferase; CRP: C-reactive protein; ET-DRI: Eurotransplant Donor Risk Index; CIT: Cold ischemia time.

Table 2 Recipient characteristics

Variable	Value (n = 656)
Male sex	469 (71.5)
Blood type
0	212 (32.3)
A	267 (40.7)
B	124 (18.9)
AB	53 (8.1)
Indication for LT
Alcoholic liver cirrhosis	197 (30.03)
Cancer (HCC, CCC)	184 (28.05)
Cholestatic liver disease	53 (8.08)
Hepatitis C virus	41 (6.25)
Retransplantation	83 (12.65)
Miscellaneous	98 (14.94)
	Median (IQR)
Age (yr)	59 (52-64)
BMI (kg/m²)	26 (23.9-29.4)
Days on the waiting list	25 (7-92)
Lab MELD	16 (11-21)
BAR	7 (4-10)

Data are presented as mean ± SD with ranges (min-max) or median with IQR (interquartile ranges) when the distribution is skewed for continuous variables. Categorical variables are presented as counts (%). BMI: Body mass index; LT: Liver transplantation; HCC: Hepatocellular carcinoma; CCC: Cholangiocarcinoma; BAR: Balance of risk; MELD: Model for End-Stage Liver Disease.

Table 3 Cox proportional hazards model – all variables and metrics

Variable	Coefficient (95%CI)	Hazard ratio (95%CI)	P value
Donor pre-procurement cardiac arrest (yes)	0.400 (0.027, 0.774)	1.493 (1.028, 2.168)	0.035
Recipient age	0.031 (0.014, 0.049)	1.032 (1.014, 1.050)	< 0.001
Donor CRP	0.001 (0.000, 0.003)	1.001 (0.999, 1.003)	0.055
BAR score	0.031 (-0.001, 0.064)	1.032 (0.999, 1.066)	0.060
Indication for LT-cancer (HCC, CCC)	0.137 (-0.275, 0.548)	1.146 (0.760, 1.730)	0.515
Indication for LT-hepatitis C virus	1.029 (0.510, 1.548)	2.798 (1.665, 4.702)	< 0.001
Indication for LT-re-transplantation	0.593 (0.098, 1.087)	1.809 (1.103, 2.965)	0.019
Indication for LT-miscellaneous	0.307 (-0.190, 0.803)	1.359 (0.827, 2.233)	0.226
Indication for LT-cholestatic disease	-0.371 (-1.168, 0.426)	0.690 (0.311, 1.532)	0.362

The model had no significant transformations and interactions, and the final model is the (linear) main effects model. Donor age was eliminated as insignificant in all previous steps of development. CRP: C-reactive protein; BAR: Balance of Risk; LT: Liver transplantation; HCC: Hepatocellular carcinoma; CCC: Cholangiocarcinoma.

Table 4 Cox proportional hazards model – excluded metrics (Model for End-Stage Liver Disease, Balance of Risk, and Eurotransplant Donor Risk Index score)

Variable	Coefficient (95%CI)	Hazard ratio (95%CI)	P value
Donor pre-procurement cardiac arrest (yes)	0.401 (0.029, 0.774)	1.494 (1.029, 2.168)	0.035
Recipient age	0.034 (0.016, 0.051)	1.034 (1.016, 1.053)	< 0.001
Donor CRP	0.001 (0.000, 0.003)	1.001 (0.999, 1.003)	0.060
Indication for LT-cancer (HCC, CCC)	0.062 (-0.342, 0.465)	1.064 (0.711, 1.592)	0.764
indication for LT-hepatitis C virus	1.033 (0.515, 1.552)	2.811 (1.673, 4.722)	< 0.001
Indication for LT-re-transplantation	0.806 (0.367, 1.245)	2.240 (1.444, 3.474)	< 0.001
Indication for LT-miscellaneous	0.353 (-0.140, 0.845)	1.423 (0.870, 2.328)	0.160
Indication for LT-cholestatic disease	-0.346 (-1.144, 0.451)	0.707 (0.319, 1.570)	0.395

The final model did not include any transformations and interactions, as they were insignificant, and the final model is the (linear) main effects model. CRP: C-reactive protein; LT: Liver transplantation; HCC: Hepatocellular carcinoma; CCC: Cholangiocarcinoma.

Table 5 Cox proportional hazards model – all variables; excluded retransplanted patients

Variable	Coefficient (95%CI)	Hazard ratio (95%CI)	P value
Donor pre-procurement cardiac arrest (yes)	0.393 (-0.0281, 0.813)	1.481 (0.972, 2.255)	0.067
Recipient age	0.001 (-0.039, 0.040)	1.001 (0.961, 1.041)	0.98
Donor CRP	0.002 (0.001, 0.004)	1.002 (1.001, 1.004)	0.006
Lab MELD	0.027 (-0.034, 0.088)	1.028 (0.967, 1.092)	0.380
BAR score	0.024 (-0.056, 0.104)	1.024 (0.946, 1.109)	0.557
Indication for LT-cancer (HCC, CCC)	-2.867 (-6.365, 0.631)	0.057 (0.002, 1.878)	0.108
Indication for LT-hepatitis C virus	-4.492 (-9.517, 0.532)	0.011 (0.000, 1.703)	0.080
Indication for LT-miscellaneous	-0.917 (-4.091, 2.257)	0.400 (0.017, 9.555)	0.571
indication for LT-cholestatic disease	0.325 (-3.841, 4.490)	1.384 (0.021, 9.146)	0.879
Lab MELD × cancer (HCC, CCC)	0.026 (-0.030, 0.083)	1.027 (0.970, 1.086)	0.363
Lab MELD × hepatitis C virus	-0.023 (-0.089, 0.044)	0.978 (0.915, 1.044)	0.500
Lab MELD × indication miscellaneous	-0.034 (-0.091, 0.024)	0.967 (0.913, 1.024)	0.253
Lab MELD × cholestatic disease	-0.177 (-0.331, -0.024)	0.838 (0.718, 0.977)	0.023
Recipient age × cancer (HCC, CCC)	0.047 (-0.009, 0.102)	1.048 (0.991, 1.107)	0.098
Recipient age × hepatitis C virus	0.103 (0.021, 0.186)	1.109 (1.022, 1.204)	0.013
Recipient age × indication miscellaneous	0.032 (-0.020, 0.083)	1.033 (0.980, 1.088)	0.228
Recipient age × cholestatic disease	0.038 (-0.036, 0.112)	1.039 (0.965, 1.118)	0.309

The final model did not include any transformations as they were insignificant, and the final model is the (linear) main effects model. Significant interactions between variables are presented. MELD Model for End-Stage liver disease; BAR: Balance of Risk; CRP: C-reactive protein; LT: Liver transplantation; HCC: Hepatocellular carcinoma; CCC: Cholangiocarcinoma.

Table 6 Cox proportional hazards model-excluded metrics (Model for End-Stage Liver Disease, Balance of Risk, and Eurotransplant Donor Risk Index score) and retransplanted patients

Variable	Coefficient (95%CI)	Hazard ratio (95%CI)	P value
Donor pre-procurement cardiac arrest (yes)	0.406 (-0.006, 0.817)	1.500 (0.994, 2.264)	0.053
Recipient age	0.035 (0.016, 0.055)	1.035 (1.016, 1.004)	< 0.001
Donor CRP	0.002 (0.000, 0.004)	1.002 (1.000, 1.004)	0.015
Indication for LT-cancer (HCC, CCC)	0.064 (-0.341, 0.469)	1.066 (0.711, 1.599)	0.757
Indication for LT-hepatitis C virus	1.058 (0.538, 1.578)	2.881 (1.712, 4.846)	< 0.001
Indication for LT-miscellaneous	0.365 (-0.128, 0.859)	1.442 (0.880, 2.361)	0.146
Indication for LT-cholestatic disease	-0.328 (-1.126, 0.470)	0.720 (0.324, 1.600)	0.420

The final model did not include any transformations and interactions, as they were insignificant, and the final model is the (linear) main effects model. CRP: C-reactive protein; LT: Liver transplantation; HCC: Hepatocellular carcinoma; CCC: Cholangiocarcinoma.

Table 7 Donor characteristics and comparison of the older and younger group

	Older (n = 87)	Younger (n = 124)	P value	Test
Gender			< 0.01	χ2 test
Male	44 (50.57)	88 (70.97)
Female	43 (49.43)	36 (29.03)
Steatosis			0.4	χ2 test
Negligible	70 (81.40)	96 (78.69)
Mild	12 (13.95)	13 (10.66)
Moderate	4 (4.65)	12 (9.84)
Severe	0 (0)	1 (0.82)
Cardiac arrest			0.01	χ2 test
No	81 (93.1)	99 (79.8)
Yes	6 (6.9)	25 (20.2)
Age	77 (76-80)	32 (23-40)	< 0.01	Mann-Whitney
BMI (kg/m²)	27.55 (25.23-29.4)	24.69 (22.75-26.31)	< 0.01	Mann-Whitney
ET-DRI	2.02 (1.85-2.05)	1.28 (1.15-1.46)	< 0.01	Mann-Whitney
Sodium(mEq/L)	147 ± 7.6 (133-165)	146 ± 8.9 (120-169)	0.51	t-test
ALT (U/L)	33.8 ± 51.3 (5-385)	93.9 ± 130.3 (8-898)	< 0.01	t-test
GGT (U/L)	48.5 ± 76.1 (4-581)	90.1 ± 163.1 (6-1129)	0.03	t-test
Bilirubin(mg/dL)	15.4 ± 10.9 (3-71)	13.6 ± 16.4 (1-146)	0.38	t-test
CRP (mg/L)	175.8 ± 104.7 (1-440)	157.6 ± 94.1 (1-360)	0.2	t-test
CIT (h)	6.44 ± 2.1 (2.17-11.45)	7.73 ± 2.7 (1.93-13.87)	< 0.01	t-test

Data are presented as mean ± SD with ranges (min-max) or median with IQR (interquartile ranges) when the distribution is skewed for continuous variables. Categorical variables are presented as counts (percentages). BMI: Body mass index; Na: Sodium; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transferase; CRP: C-reactive protein; ET-DRI: Eurotransplant donor risk index; CIT: Cold ischemia time.

Table 8 Recipient characteristics and comparison of the older and younger group

	Older (n = 87)	Younger (n = 124)	P value	Test
Gender			0.03	χ2 test
Male	70 (80.46)	82 (66.13)
Female	17 (19.54)	42 (33.87)
Indication for LT			0.4	χ2 test
Alcoholic cirrhosis	38 (43.68)	32 (25.81)
Cancer (HCC, CCC)	33 (37.94)	29 (23.39)
Viral hepatitis	6 (6.9)	18 (14.52)
Miscellaneous	10 (11.5)	45 (36.32)
Urgency
Elective	87 (100)	118 (95.16)	0.04	Fischer's exact test
High	0 (0)	6 (4.84)
Stay in ICU			0.57	χ2 test
No	65 (74.71)	98 (79.03)
Yes	22 (25.29)	26 (20.97)
Age	60 (55-66)	58 (50-63)	< 0.01	Mann-Whitney
BMI (kg/m²)	27.92 (24.61-29.91)	25.25 (23.45-27.3)	< 0.01	Mann-Whitney
MELD	15 (11-18)	16 (11-21)	0.13	Mann-Whitney
BAR	5 (4-9)	6 (2-9)	0.45	Mann-Whitney

Data are presented as mean ± SD with ranges (min-max) or median with IQR (interquartile ranges) when the distribution is skewed for continuous variables. Categorical variables are presented as counts (percentages). BMI: Body mass index; LT: Liver transplantation; HCC: Hepatocellular carcinoma; CCC: Cholangiocarcinoma; ICU: Intensive care unit; MELD: Model for End-Stage Liver Disease; BAR: Balance of risk.