Donor-recipient age mismatch and outcomes in liver transplantation: A scientific registry of transplant recipients database analysis

Table 1 Donor and recipient demographics stratified by donor:recipient pairs, n (%)

Characteristics	YAD:YAR (n = 41202)	YAD:OAR (n = 31737)	MAD:YAR (n = 22124)	MAD:OAR (n = 26164)	OAD:YAR (n = 1587)	OAD:OAR (n = 3371)	P value
Donor characteristic
Age (year), mean ± SD	25.67 ± 11.58	29.64 ± 8.87	54.57 ± 6.50	55.59 ± 6.73	74.34 ± 3.68	74.73 ± 3.93	< 0.001
Female	14934 (36.25)	11243 (35.43)	10286 (46.49)	11976 (45.77)	832 (52.43)	1842 (54.64)	< 0.001
Race							< 0.001
NHW	26140 (63.45)	20935 (65.96)	14941 (67.53)	17171 (65.63)	1186 (74.73)	2460 (72.98)
NHB	7062 (17.14)	5114 (16.11)	3964 (17.92)	5009 (19.14)	207 (13.04)	459 (13.62)
Hispanic	6646 (16.13)	4565 (14.38)	2435 (11.01)	2984 (11.40)	131 (8.25)	322 (9.55)
Asian	895 (2.17)	756 (2.38)	673 (3.04)	867 (3.31)	54 (3.40)	120 (3.56)
Other	458 (1.11)	367 (1.16)	111 (0.50)	133 (0.51)	9 (0.57)	10 (0.30)
Cold ischemia time, hours, mean ± SD	6.39 ± 3.21	6.20 ± 2.97	6.48 ± 3.05	6.30 ± 2.87	6.62 ± 2.80	6.32 ± 2.80	< 0.001
Recipient characteristic
Age (year), mean ± SD	35.46 ± 18.68	61.61 ± 4.67	45.40 ± 9.37	61.81 ± 4.78	47.18 ± 7.54	62.95 ± 4.97	< 0.001
Female	16252 (39.44)	10947 (34.49)	7489 (33.85)	8631 (32.99)	607 (38.25)	1277 (37.88)	< 0.001
Race							< 0.001
NHW	27052 (65.66)	3361 (73.61)	15797 (71.40)	19446 (74.32)	1113 (70.13)	2481 (73.60)
NHB	4578 (11.11)	2221 (7.00)	1975 (8.93)	1738 (6.64)	119 (7.50)	167 (4.95)
Hispanic	6821 (16.56)	4325 (13.63)	3131 (14.15)	3573 (13.66)	256 (16.13)	487 (14.45)
Asian	1980 (4.81)	1512 (4.76)	900 (4.07)	1146 (4.38)	82 (05.17)	197 (5.84)
Others	771 (1.87)	318 (1.00)	321 (1.45)	261 (1.00)	17 (1.07)	39 (1.16)
Comorbidities							< 0.001
BMI	26.23 (7.27)	28.69 (5.64)	28.68 (6.36)	28.88 (5.63)	28.24 (6.31)	28.28 (5.53)
Coronary artery disease	76 (1.56)	121 (5.72)	46 (1.71)	95 (5.69)	7 (2.43)	17 (5.61)
Cerebrovascular disease	92 (0.46)	141 (1.06)	58 (0.51)	114 (1.03)	6 (0.63)	18 (1.12)
Diabetes	5166 (12.71)	10031 (31.88)	3869 (17.76)	8587 (33.14)	348 (22.34)	1223 (36.64)
Hypertension	2587 (12.89)	4049 (30.58)	1992 (17.60)	3498 (31.74)	162 (16.89)	534 (33.40)
COPD	267 (1.33)	358 (2.71)	198 (1.75)	293 (2.66)	00017 (1.77)	46 (2.89)
Functional status at transplant							< 0.001
Independent	14138 (39.69)	11730 (38.71)	7924 (38.51)	10111 (40.41)	686 (47.64)	1588 (49.66)
Mildly dependent	10605 (29.77)	11509 (37.98)	6981 (33.93)	10096 (40.35)	482 (33.47)	1275 (39.87)
Totally dependent	10877 (30.54)	7060 (23.30)	5672 (27.56)	4814 (19.24)	272 (18.89)	335 (10.48)
Primary diagnosis							< 0.001
Alcoholic liver disease	8689 (21.15)	5236 (16.53)	5905 (26.77)	4462 (17.09)	421 (26.54)	630 (18.74)
Autoimmune hepatitis	1436 (3.50)	653 (2.06)	725 (3.29)	475 (01.82)	52 (3.28)	68 (2.02)
Biliary	8130 (19.79)	2131 (6.73)	2252 (10.21)	1614 (06.18)	169 (10.66)	278 (8.27)
HBV	841 (2.05)	639 (2.02)	561 (2.54)	495 (1.90)	47 (2.96)	70 (2.08)
HCC	2483 (6.04)	6869 (21.68)	1981 (8.98)	6248 (23.92)	173 (10.91)	826 (24.57)
HCV	7502 (18.26)	7400 (23.36)	5316 (24.10)	5503 (21.07)	289 (18.22)	441 (13.12)
Idiopathic	8567 (20.85)	3397 (10.72)	3224 (14.61)	2688 (10.29)	261 (16.46)	410 (12.20)
MASH	2149 (5.23)	5083 (16.05)	1712 (7.76)	4384 (16.79)	127 (8.01)	591 (17.58)
Others	1286 (3.13)	270 (0.85)	384 (1.74)	247 (0.95)	47 (2.96)	48 (1.43)
MELD/PELD, mean ± SD	21.74 ± 12.08	20.27 ± 9.98	22.86 ± 9.78	19.19 ± 9.25	20.26 ± 8.72	16.67 ± 7.21	< 0.001

YAD: Younger age donors, ≤ 45-years; MAD: Middle-aged donors, 46-69-years; OAD: Older age donors, ≥ 70-years; YAR: Younger age recipients, ≤ 55-years; OAR: Older age recipients, > 55-years; NHW: Non-Hispanic White; NHB: Non-Hispanic Black; CVA: Cerebrovascular accident; BMI: Body mass index; DCD: Donation after cardiac death; LDLT: Living donor liver transplantation; COPD: Chronic obstructive pulmonary disease; MASH: Metabolic dysfunction-associated steatohepatitis; ALD: Alcohol-related liver disease; HCV: Hepatitis C virus; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; MELD: Model for end-stage liver disease, PELD: Pediatric end-stage liver disease model.

Table 2 Multivariable logistic regression analysis for odds of improving functional status at 5 years of post-transplant follow-up

Donor-recipient age pairs	OR	95%CI LL	95%CI UL	P value
YAD:YAR	Reference	-	-	-
YAD:OAR	0.893	0.829	0.963	0.0033
MAD:YAR	0.830	0.767	0.898	< 0.0001
MAD:OAR	0.798	0.734	0.867	< .0001
OAD:YAR	0.527	0.416	0.667	< 0.0001
OAD:OAR	0.674	0.509	0.893	0.006
Recipient diagnosis	-	-	-	-
ALD	Reference	-	-	-
Autoimmune hepatitis	1.045	0.889	1.228	0.595
Biliary	0.774	0.696	0.86	< 0.0001
HBV	1.258	1.056	1.498	0.0102
HCC	0.556	0.486	0.635	< 0.0001
HCV	0.727	0.668	0.791	< 0.0001
Idiopathic	1.443	1.321	1.576	< 0.0001
MASLD/MASH	0.986	0.883	1.102	0.8099
Other	1.032	0.743	1.432	0.852
LDLT (vs DDLT)	0.772	0.644	0.926	0.0051

Adjusted for donor:recipient age pairs, recipient diabetes, indication for transplant, living donor liver transplantation vs deceased donor liver transplantation, model for end-stage liver disease/pediatric end-stage liver disease model. LL: Lower limit; UL: Upper limit; CI: Confidence interval; OR: Odds ratio; YAD: Younger age donors, ≤ 45-years; MAD: Middle-aged donors, 46-69-years; OAD: Older age donors, ≥ 70-years; YAR: Younger age recipients, ≤ 55-years; OAR: Older age recipients, > 55-years; MASH: Metabolic dysfunction-associated steatohepatitis; ALD: Alcohol-related liver disease; DDLT: Deceased donor liver transplantation; HCV: Hepatitis C virus; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; MELD: Model for end-stage liver disease; PELD: Pediatric end-stage liver disease model; LDLT: Living donor liver transplantation.

Table 3 Multivariate Fine-Gray competing risk regression analysis identifying independent risk factors for different causes of death within 5-year outcomes

Characteristics	All-cause mortality			Graft-related				Infection-related			Cardioneurovascular-related		Malignancy-related			Renal-related
	sHR	95%CI		sHR	95%CI	sHR		95%CI	sHR		95%CI	sHR	95%CI	sHR		95%CI
Donor:recipient age pairs
YAD:YAR	Reference	-	-	Reference	-	-	Reference	-	-	Reference	-	-	Reference	-	-	Reference	-	-
YAD:OAR	1.22	1.17	1.27	0.68	0.60	0.77	1.44	1.27	1.63	1.46	1.32	1.62	1.36	1.22	1.51	1.56	1.07	2.29
MAD:YAR	1.21	1.16	1.26	1.42	1.27	1.59	1.53	1.34	1.74	1.04	0.92	1.17	0.93	0.82	1.05	1.30	0.85	1.99
MAD:OAR	1.34	1.29	1.40	0.87	0.76	0.98	1.91	1.69	2.17	1.45	1.30	1.61	1.31	1.17	1.45	1.90	1.29	2.79
OAD:YAR	1.38	1.24	1.53	1.72	1.32	2.25	2.28	1.71	3.05	0.85	0.59	1.23	0.86	0.63	1.18	1.01	0.32	3.27
OAD:OAR	1.33	1.23	1.44	0.99	0.76	1.28	3.06	2.50	3.74	1.18	0.94	1.49	1.09	0.89	1.33	2.49	1.37	4.53
Recipient diabetes	1.06	1.02	1.09	0.92	0.83	1.02	1.13	1.03	1.24	1.30	1.20	1.41	0.89	0.82	0.96	1.78	1.36	2.32
Recipient diagnosis
ALD	Reference	-	-	Reference	-	-	Reference	-	-	Reference	-	-	Reference	-	-	Reference	-	-
Autoimmune hepatitis	1.13	1.03	1.24	1.12	0.82	1.52	1.32	1.04	1.69	1.29	1.03	1.60	0.72	0.50	1.04	1.19	0.53	2.64
Biliary	0.93	0.87	0.99	1.03	0.84	1.27	1.05	0.88	1.25	0.87	0.74	1.03	1.09	0.90	1.33	0.54	0.26	1.11
HBV	0.96	0.86	1.08	0.93	0.64	1.37	0.73	0.51	1.03	0.86	0.65	1.15	1.96	1.49	2.57	0.64	0.20	2.07
HCC	1.48	1.41	1.56	0.72	0.72	0.72	0.99	0.85	1.16	1.02	0.89	1.17	3.05	2.65	3.50	1.01	0.65	1.57
HCV	1.30	1.25	1.36	2.14	1.87	2.44	1.24	1.10	1.41	1.09	0.97	1.21	1.38	1.21	1.58	1.22	0.84	1.77
Idiopathic	1.06	1.01	1.12	1.03	0.87	1.22	1.01	0.87	1.17	1.26	1.11	1.42	0.88	0.74	1.05	1.13	0.73	1.74
MASH	1.19	1.13	1.26	0.93	0.75	1.14	0.99	0.85	1.16	1.17	1.02	1.33	0.94	0.78	1.14	1.18	0.74	1.85
Other	2.14	1.94	2.36	0.96	0.63	1.45	1.04	0.71	1.52	1.02	0.72	1.44	7.04	5.85	8.47	0.66	0.16	2.77
Recipient functional status
Independent	Reference	-	-	Reference	-	-	Reference	-	-	Reference	-	-	Reference	-	-	Reference	-	-
Mildly dependent	1.25	1.21	1.30	1.09	0.99	1.21	1.34	1.21	1.49	1.30	1.19	1.43	1.08	1.00	1.17	1.10	0.82	1.47
Totally dependent	1.72	1.65	1.80	1.15	1.00	1.32	2.02	1.78	2.30	1.83	1.63	2.04	1.12	0.99	1.26	1.36	0.91	2.05
LDLT (vs DDLT)	1.07	1.00	1.15	0.67	0.51	0.89	1.22	0.98	1.51	0.87	0.71	1.06	0.94	0.79	1.13	0.97	0.48	1.97

Adjusted for donor:recipient age pairs, functional status at transplant, recipient diabetes, transplant indication, living donor liver transplantation vs deceased donor liver transplantation, model for end-stage liver disease/pediatric end-stage liver disease model. CI: Confidence interval; sHR: Subdistribution hazard ratio; YAD: Younger age donors, ≤ 45-years; MAD: Middle-aged donors, 46-69-years; OAD: Older age donors, ≥ 70-years; YAR: Younger age recipients, ≤ 55-years; OAR: Older age recipients, > 55-years; MASH: Metabolic dysfunction-associated steatohepatitis; ALD: Alcohol-related liver disease; HCV: Hepatitis C virus; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; LDLT: Living donor liver transplantation; DDLT: Deceased donor liver transplantation.