Analyzing predictors of graft survival in patients undergoing liver transplantation with donors aged 70 years and over

Table 1 Donor characteristics n (%)

	Donors < 70 years old (n = 212)	Donors ≥ 70 years old (n = 212)	P value
Age (yr)	47 (26)	76 (7)	0.00
Gender (male/female)	139/73 (65.6/34.3)	87/125 (41.0/59.0)	0.00
BMI ≥ 30 (kg/m2)	33 (15.6)	57 (27.3)	0.00
Cause of death
Trauma	72 (34.0)	32 (15.1)
Cerebrovascular	108 (50.9)	172 (81.1)	0.06
Other	32 (15.1)	8 (3.8)
History of hypertension	55 (25.9)	122 (57.5)	0.00
History of diabetes	14 (6.6)	43 (20.3)	0.00
ICU stay (h)	48 (24-96)	211 (24-48)	0.00
Cardiac arrest	53 (25.0)	14 (6.6)	0.00
Hemodynamic instability	68 (32.1)	60 (28.3)	0.39
Vasopressor use	173 (81.6)	159 (75.0)	0.09
Glucose (mg/dL)	145 (63)	156 (69)	0.00
Creatinine (mg/dL)	0.9 (0.5)	0.8 (0.3)	0.24
Sodium (mEq/L)	148 (12)	145 (11)	0.00
GOT (IU/L)	39 (55)	28 (19)	0.00
GPT (IU/L)	27 (53)	20 (17)	0.00
Biopsy findings
Normal	125 (57.8)	107 (49.8)
Microsteatosis	26 (12.6)	41 (19.5)
Mild macrosteatosis (< 30%)	54 (26.1)	56 (26.7)	0.12
Moderate macrosteatosis (30%-60%)	7 (3.5)	7 (3.5)
Severe macrosteatosis (≥ 60%)	0 (0.0)	1 (0.5)

BMI: Body mass index; ICU: Intensive care unit; GOT: Glutamic-oxaloacetic transaminase; GPT: Glutamic-pyruvic transaminase.

Table 2 Recipient characteristics n (%)

	Donors < 70 years old (n = 212)	Donors ≥ 70 years old (n = 212)	P value
Age (yr)	54 (14)	59 (13)	0.00
Gender (male/female)	161/51 (75.9/24.1)	167/45 (78.8/21.2)	0.48
Cirrhosis
Alcoholic	61 (28.8)	95 (44.8)
HBV	13 (6.1)	24 (11.3)	0.00
HCV	105 (49.5)	72 (34.0)
Other	33 (15.6)	21 (9.9)
HCC	82 (38.7)	84 (39.3)	0.89
Child-Pugh
A	47 (22.1)	46 (21.7)
B	75 (35.4)	89 (42)	0.22
C	90 (42.5)	77 (36.3)
MELD	15 (8)	13 (5)	0.20
MELD-Na	16 (11)	14 (9)	0.12
D-MELD	629 (475)	1051 (842)	0.00
Glucose (mg/dL)	107 (44)	105 (48)	0.70
Creatinine (mg/dL)	0.9 (0.4)	0.9 (0.3)	0.07
Total bilirubin (mg/dL)	2.7 (3.4)	1.9 (2.4)	0.10
GOT (IU/L)	54 (67)	58 (58)	0.77
GPT (IU/L)	40 (49)	37 (43)	0.60
Albumin (mg/dL)	3.3 (0.9)	3.4 (1.0)	0.77
Prothrombin activity (%)	62 ± 20 (11.8-120)	65 ± 18 (5-119)	0.07
Platelets (n)	77900 (54925)	82500 (60250)	0.16
UNOS
ICU	0	3 (1.4)	0.77
Hospital	17 (8)	12 (5.7)
Home	195 (92)	197 (92.9)

HBV: Hepatitis B virus; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; MELD: Model for end-stage liver disease; D-MELD: The product of donor age and preoperative MELD; GOT: Glutamic-oxaloacetic transaminase; GPT: Glutamic-pyruvic transaminase; UNOS: United network for organ sharing; ICU: Intensive care unit.

Table 3 Perioperative characteristics and post-liver transplantation complications n (%)

	Donors < 70 years old (n = 212)	Donors ≥ 70 years old (n = 212)	P value
CIT (min)	386 ± 168 (100-1038)	445 ± 158 (60-975)	0.00
WIT (min)	64 ± 17 (40-200)	61 ± 13 (30-130)	0.04
Transfusional requeriments
RBC (U)	6 (3-10)	5 (3-10)	0.98
FFP (U)	12 ± 9 (0-60)	13 ± 9 (0-58)	0.40
Platelets (U)	3 ± 3 (0-37)	3 ± 3 (0-16)	0.53
Basal immunosuppressant drugs
Cyclosporine plus steroids	33 (15.6)	30 (14.3)	0.71
Tacrolimus plus steroids	179 (84.4)	180 (85.7)
ICU stay (d)	4 (2-5)	4 (2-6)	0.58
Hospital stay (d)	18 ± 17 (0-105)	16 ± 12 (0-83)	0.34
Primary non-function	6 (2.8)	7 (3.3)	0.24
Acute rejection	61 (28.8)	53 (25.1)	0.39
Infectious complications	56 (26.4)	41 (19.3)	0.08
Medical complications	90 (42.5)	93 (43.9)	0.76
Surgical complications	38 (17.9)	34 (16)	0.60
Vascular complications	11 (5.2)	14 (6.6)	0.80
Biliary complications	24 (11.3)	11 (5.2)	0.41
Reoperation	27 (12.7)	20 (9.4)	0.28
De novo tumors	24 (11.3)	22 (10.4)	0.57
HCV recurrence	73 (61.9)	42 (57.5)	0.55
Days	141 (58-535)	148 (51-316)	0.90
Hepatitis F3 or F4	18 (24.7)	21 (50)	0.00
Fibrosing cholestatic hepatitis	7 (9.6)	7 (16.7)	0.26
Re-transplantation	11 (5.2)	12 (5.7)	0.83

CIT: Cold ischemia time; WIT: Warm ischemia time; RBC: Red blood cells; FFP: Fresh frozen plasma; ICU: Intensive care unit.

Table 4 Multivariate Cox-regression analysis for the risk of graft loss

	Univariate analysis		Multivariate analysis
	HR (95%CI)	P value	HR (95%CI)	P value
Donor age	1.23 (0.90-1.68)	0.19	1.15 (0.73-1.81)	0.52
Female donor	1.08 (0.78-1.49)	0.63
Donor BMI
25-29	1.56 (1.05-2.31)	0.08
≥ 30	1.53 (0.95-2.47)	0.07
Cause of death
Cerebrovascular	1.091 (0.75-1.58)	0.65
Others	0.68 (0.34-1.36)	0.28
Donor history of hypertension	1.53 (1.10-2.12)	0.00	1.43 (0.97-2.12)	0.07
Donor history of diabetes	0.99 (0.62-1.58)	0.97
Donor ICU stay	1.00 (0.99-1.00)	0.37
Donor cardiac arrest	0.94 (0.59-1.52)	0.82
Donor last serum sodium level	0.97 (0.96-0.99)	0.01	0.96 (0.94-0.99)	0.00
Donor last serum GOT	1.00 (1.00-1.00)	0.13
Donor last serum GPT	1.00 (1.00-1.00)	0.02	1.00 (1.00-1.00)	0.00
Biopsy findings
Normal	1.00 (0.64-1.59)	0.96
Microsteatosis	1.22 (0.82-1.82)	0.31
Mild macrosteatosis (< 30%)	1.89 (0.93-3.82)	0.07
Moderate macrosteatosis (30%-60%)	0.93 (0.57-1.53)	0.78
Recipient age	1.03 (1.01-1.05)	0.00	1.04 (1.02-1.06)	0.00
HCV+ recipient	1.82 (1.32-2.50)	0.00	2.35 (1.55-3.56)	0.00
HCC presence	1.24 (0.90-1.71)	0.18
MELD	1.03 (1.00-1.06)	0.05
D-MELD	1.00 (1.00-1.00)	0.00	1.00 (1.00-1.00)	0.00
Prothrombin activity	0.99 (0.98-1.00)	0.28
CIT	0.99 (0.99-1.00)	0.13
WIT	1.01 (0.99-1.02)	0.38

HR: Hazard ratio; CI: Confidence interval; BMI: Body mass index; ICU: Intensive care unit; GOT: Glutamic-oxaloacetic transaminase; GPT: Glutamic-pyruvic transaminase; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; MELD: Model for end-stage liver disease; D-MELD: The product of donor age and preoperative MELD; CIT: Cold ischemia time; WIT: Warm ischemia time.

Table 5 Studies comparing liver transplantation with donors ≥ 70 years old vs liver transplantation with younger donors that provide multivariate analysis identifying predictors of graft survival

Author	Country	n	Donor age	Donor diabetes	Donor GPT	Donor Na	Recipient age	Recipient BMI	UNOS	HCV positive	MELD	D-MELD	BAR	CIT	Period	Renal replacement
Segev, 2007	United States	1043					X	X	X	X				X
Cescon, 2008	Italy	152	X						X	X	X
Jimenez Romero, 2013	Spain	50						X
Cepeda Franco, 2016	Spain	423								X
Bertuzzo, 2017	Italy	278								X			X		X	X
Montenovo, 2017	United States	1749	X				X		X
Ghinolfi, 2017	Italy	515	X	X						X				X
Present study, 2018	Spain	212			X	X	X			X		X

GPT: Glutamic-pyruvic transaminase; Na: Serum sodium; BMI: Body mass index; UNOS: United network for organ sharing status; HCV: Hepatitis C virus; MELD: Model for end-stage liver disease; D-MELD: The product of donor age and preoperative MELD; BAR: Balance of risk score; CIT: Cold ischemia time.