Warm ischemia time and elevated serum uric acid are associated with metabolic syndrome after liver transplantation with donation after cardiac death

Table 1 Demographics and baseline clinical characteristics for recipients n (%)

Variable	PTMS (n = 20)	Non-PTMS (n = 127)	P value
Demographics
Age, yr	46.3 ± 9.0	45.5 ± 11.0	0.746
Male	17 (85.0)	104 (81.9)	0.735
BMI, kg/m2	23.5 ± 4.3	21.8 ± 2.8	0.021
MELD score	18.4 ± 8.3	17.7 ± 8.5	0.768
Child-Pugh score	10.5 ± 2.2	10.0 ± 2.0	0.374
Smoking	5 (25.0)	39 (30.7)	0.604
Alcohol	6 (30.0)	19 (15.0)	0.096
HBV	13 (65.0)	85 (66.9)	0.865
HCV	1 (5.0)	14 (11.0)	0.408
Pre-LT comorbidity
Obesity	4 (20.0)	4 (3.1)	0.002
Diabetes mellitus	4 (20.0)	13 (10.2)	0.210
Hypertension	1 (5.0)	4 (3.1)	0.671
Dyslipidemia	2 (10.0)	13 (10.2)	0.974
Metabolic syndrome	3 (10.0)	4 (3.1)	0.020
Laboratory test
Pre-LT serum uric acid, μmol/L	265 ± 116	280 ± 97	0.545
Pre-LT serum creatinine, μmol/L	55.2 ± 16.9	60.0 ± 19.0	0.288
Pre-LT eGFR, mL/min per 1.73 m2	158.7 ± 54.6	139.2 ± 43.9	0.076
Operative characteristic
Anhepatic phase, min	50.8 ± 9.5	53.5 ± 11.3	0.193
Operation time, h	6.7 ± 1.5	6.2 ± 1.1	0.084
Length of ICU stay, d	6.9 ± 3.0	6.8 ± 3.6	0.923
Post-LT clinical characteristic
Steroid-free protocol for HCC	3 (15.0)	43 (33.9)	0.091
Tacrolimus use ≥ 24 mo	12 (60.0)	68 (53.5)	0.590
Cyclosporine use ≥ 24 mo	8 (40.0)	59 (46.5)	0.590
MMF use ≥ 24 mo	13 (65.0)	84 (66.1)	0.920
Acute graft rejection	3 (15.0)	12 (9.4)	0.446
Biliary complication	3 (15.0)	28 (22.0)	0.472
Acute kidney injury	7 (35.0)	13 (10.2)	0.002
Hyperuricemia	11 (55.0)	19 (15.0)	0.002

PTMS: Posttransplant metabolic syndrome; BMI: Body mass index; MELD: Model for end-stage liver disease; HBV: Hepatitis B virus; HCV: Hepatitis C virus; LT: Liver transplantation; eGFR: Estimated glomerular filtration rate; ICU: Intensive care unit; HCC: Hepatocellular carcinoma; MMF: Mycophenolate mofetil.

Table 2 Demographics and clinical characteristics for donors

Variable	PTMS (n = 20)	Non-PTMS (n = 127)	P value
Demographics
Age, yr	42.0 ± 13.7	41.0 ± 14.3	0.762
Male, n (%)	17 (85.0)	104 (81.9)	0.735
BMI, kg/m2	24.0 ± 4.7	22.2 ± 3.2	0.029
Operative characteristic
WIT, min	10.8 ± 2.7	9.2 ± 2.5	0.034
CIT, h	5.1 ± 1.9	5.2 ± 1.6	0.864

PTMS: Posttransplant metabolic syndrome; BMI: Body mass index; WIT: Warm ischemia time; CIT: Cold ischemia time.

Table 3 Univariate analysis for the factors associated with posttransplant metabolic syndrome

Variable	OR (95%CI)	P value
Age	1.26 (0.48-3.31)	0.642
Male	1.25 (0.34-4.64)	0.735
Smoking	1.33 (0.45-3.92)	0.605
Alcohol	2.44 (0.83-7.13)	0.104
HBV	0.92 (0.34-2.47)	0.865
HCV	0.43 (2.25-13.6)	0.408
BMI	7.69 (1.75-33.8)	0.007
Pre-LT diabetes mellitus	2.19 (0.64-7.55)	0.214
Pre-LT hypertension	1.62 (0.17-15.3)	0.674
Pre-LT dyslipidemia	2.17 (0.27-17.5)	0.469
Donor age	2.42 (0.67-8.74)	0.178
Donor BMI	1.91 (0.37-9.90)	0.443
WIT	1.21 (1.04-1.41)	0.014
CIT	0.95 (0.69-1.31)	0.741
Steroid-free protocol for HCC	0.35 (0.10-1.24)	0.065
Tacrolimus use ≥ 24 mo	1.77 (0.39-4.01)	0.591
Cyclosporine use ≥ 24 mo	1.30 (0.50-3.40)	0.591
MMF use ≥ 24 mo	1.05 (0.39-2.83)	0.920
Acute graft rejection	1.69 (0.43-6.61)	0.450
Biliary complication	0.48 (0.17-2.28)	0.467
Acute kidney injury	4.72 (1.60-14.0)	0.005
Hyperuricemia	6.95 (2.54-19.0)	< 0.001

OR: Odds ratio; CI: Confidence interval; HBV: Hepatitis B virus; HCV: Hepatitis C virus; BMI, Body mass index; WIT: Warm ischemia time; CIT; Cold ischemia time; LT: Liver transplantation; HCC: Hepatocellular carcinoma; MMF: Mycophenolate mofetil.

Table 4 Multivariate analysis for the factors associated with posttransplant metabolic syndrome

Variable	OR (95%CI)	P value
Steroid-free protocol for HCC	0.22 (0.41-1.16)	0.219
BMI	10.9 (1.38-86.3)	0.024
Warm ischemia time	1.23 (1.01-1.50)	0.045
Acute kidney injury	3.58 (0.94-13.6)	0.062
Hyperuricemia	11.8 (2.85-48.8)	0.001

OR: Odds ratio; CI: Confidence interval; HCC: Hepatocellular carcinoma; BMI: Body mass index.

Table 5 Serum uric acid level change of patients who did and did not develop posttransplant metabolic syndrome

Time point	PTMS		Non-PTMS
	Mean ± STD, μmol/L	Overall P value	Mean ± STD, μmol/L	Overall P value
Pre-LT(Baseline)	255 ± 96	< 0.001	273 ± 84	< 0.001
P1st mo	400 ± 118		350 ± 103
P3rd mo	432 ± 80		355 ± 81
P6th mo	446 ± 72		360 ± 78
P12th mo	460 ± 96		360 ± 83
P24th mo	512 ± 76		348 ± 90

PTMS: ^aP_{1 mo-Baseline} < 0.001, ^bP_{12 mo-1 mo} = 0.017, ^cP_{24 mo-1 mo} < 0.001; Non-PTMS: ^dP_{1 mo-Baseline} < 0.001, ^eP_{12 mo-1 mo} = 0.394, fP_{24 mo-1 mo} = 0.847. PTMS: Posttransplant metabolic syndrome.

Table 6 Correlation coefficient between serum uric acid level and estimated glomerular filtration rate in patients who did and did not develop posttransplant metabolic syndrome

	PTMS		Non-PTMS
	r	P value	r	P value
Pre-LT	-0.74	< 0.001	-0.28	0.002
P1 mo-Baseline	-0.44	0.052	-0.43	< 0.001
P3 mo-Baseline	0.076	0.750	-0.22	0.014

PTMS: Posttransplant metabolic syndrome; LT: Liver transplantation.