Post-transplant biliary complications using liver grafts from deceased donors older than 70 years: Retrospective case-control study

Table 1 Donor characteristics

	BC (n = 21)	Non-BC (n = 229)	P value
Age (yr)	77.5 ± 5.8	77.2 ± 5.2	0.757
Sex (female), n (%)	7 (33.3)	138 (60.3)	0.017
BMI (kg/m2)	26.1 ± 5.1	27.4 ± 4.7	0.366
Obesity (BMI ≥ 30), n (%)	5 (23.8)	57 (25.2)	0.409
ICU stay (h)	34 ± 24	24 ± 24	0.964
Cause of death, n (%)
Cerebrovascular	14 (66.7)	183 (79.9)	0.773
Head trauma	5 (23.8)	36 (15.7)
Other	2 (9.5)	10 (4.4)
Hypertension, n (%)	13 (61.9)	131 (57.2)	0.677
Diabetes, n (%)	5 (23.8)	47 (20.5)	0.452
Cardiac arrest, n (%)	4 (19.0)	13 (5.7)	0.043
Hemodynamic instability, n (%)	9 (42.9)	67 (29.3)	0.195
Norepinephrine use, n (%)	15 (71.4)	163 (71.2)	0.981
Laboratory values
Serum glucose (mg/dL)	158 ± 42	174 ± 70	0.378
Serum creatinine (mg/dL)	0.9 ± 0.5	0.8 ± 0.4	0.148
Serum sodium (mEq/L)	145 ± 7	146 ± 8	0.402
AST (IU/L)	23 ± 17	28 ± 19	0.191
ALT (IU/L)	22 ± 19	26 ± 22	0.444
GGT (IU/L)	24 ± 49	21 ± 35	0.447
Platelets/m3	134 ± 84	172 ± 86	0.016
Prothrombin rate (%)	77 ± 16	72 ± 23	0.426
Partial thromboplastin time (s)	30 ± 6	30.5 ± 7.3	0.495
Steatosis (biopsy findings) , n (%)
Microsteatosis	6 (28.6)	39 (17.0)	0.509
Mild macrosteatosis	4 (19.0)	61 (26.6)
Moderate macrosteatosis	0	8 (3.5)
Cold ischemia time (min)	442 ± 225	429 ± 235	0.783
Warm ischemia time (min)	55 ± 15	55 ± 15	0.486
Preservation solution, n (%)
Celsior	18 (85.7)	189 (82.5)	0.496
Belzer	3 (14.3)	40 (17.5)

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BMI: Body mass index; GGT: Gamma-glutamyl transpeptidase.

Table 2 Pre-liver transplantation recipient characteristics

Variables	BC (n = 21)	Non-BC (n = 229)	P value
Age (yr)	59 ± 10	59 ± 12	0.767
Sex (female)	3 (14.3)	53 (23.1)	0.264
LT indications, n (%)
Alcohol	11 (52.4)	97 (42.4)	0.705
HCV	7 (33.3)	80 (34.9)	0.883
HBV	0	27 (11.8)	0.081
Biliary related	1 (4.8)	5 (2.2)	0.413
Other	2 (9.5)	20 (8.7)	0.244
HCC, n (%)	7 (43.8)	70 (30.6)	0.793
Pre-LT TACE, n (%)	3 (42.9)	31 (44.3)	0.631
MELD	11 ± 7	13 ± 7	0.334
MELD-Na	11 ± 8	13 ± 8	0.189
D-MELD	810 ± 526	996 ± 510	0.360
UNOS status, n (%)
Home	19 (90.5)	212 (93.4)	0.343
Hospital	1 (4.8)	13 (5.7)
ICU	1 (4.8)	2 (5.2)
Medical history, n (%)
Hypertension	6 (28.6)	46 (20.1)	0.254
Diabetes	6 (28.6)	44 (19.2)	0.223
Pre-LT major abdominal operations	5 (23.8)	23 (10)	0.069
Laboratory values, n (%)
Serum glucose (mg/dL)	130 ± 56	128 ± 63	0.801
Serum creatinine (mg/dL)	1.1 ± 0.8	1 ± 0.6	0.823
Serum albumin (g/dL)	3.6 ± 0.6	3.4 ± 0.6	0.203
AST (IU/L)	53 ± 42	54 ± 56	0.836
ALT (IU/L)	33 (33)	33 ± 36	0.955
GGT (IU/L)	57 ± 129	61 ± 70	0.645
Total bilirubin (mg/dL)	1.1 ± 0.9	1.7 ±2	0.036
Leukocytes/mm3	4483 ± 2819	5356 ± 3110	0.063
Hemoglobin (g/100 mL)	12.6 ± 4.4)	12.3 ± 3.1	0.986
Platelets × 103/mm3	100.7 ± 75.6	94.2 ± 50.2	0.496
Prothrombin rate (%)	70.6 ± 22.2	65 ± 18.3	0.030
aPTT (s)	34.9 ± 5.3	36.4 ± 8.1	0.272

BC: Biliary complications; ALT: Alanine aminotransferase; aPTT: Activated partial thromboplastin time; AST: Aspartate aminotransferase; D-MELD: Donor model for end-stage liver disease; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; ICU: Intensive care unit; LT: Liver transplantation; MELD: Model for end-stage liver disease; TACE: Transarterial chemoembolization; UNOS: United Network for Organ Sharing.

Table 3 Perioperative variables and morbidity/mortality

Variables	BC (n = 21)	Non-BC (n = 229)	P value
Biliary reconstruction, n (%)
Chol-Chol-without T-tube	16 (76.2)	212 (86.9)	0.013
Chol-Chol-with T-tube	3 (14.3)	11 (4.8)
RYHJ	2 (9.5)	6 (2.6)
Transfusion (units)
Packed red blood cells	7 ± 10	5 ± 8	0.147
Fresh frozen plasma	9 ± 12	10 ± 10	0.647
Platelets	1 ± 1	1 ± 3	0.100
Initial immunosuppression, n (%)
Tacrolimus + steroids	20 (95.2)	199 (86.9)	0.231
Cyclosporine + steroids	1 (4.8)	30 (9.8)
Early allograft dysfunction	4 (19.0)	32 (14.0)	0.357
Acute renal failure	5 (23.8)	54 (13.1)	0.581
Non-surgical related infections	6 (28.6)	30 (13.1)	0.062
Acute rejection	6 (28.6)	54 (23.6)	0.608
HCV recurrence	1 (4.8)	43 (18.8)	0.085
HCC recurrence	0	9 (3.9)	0.446
Non-biliary related reoperation	1 (4.8)	12 (5.2)	0.701
Re-transplantation	0	6 (2.8)	0.643
ICU stay (d)	4 ± 5	4 ± 4	0.559
Hospital stay (d)	15 ± 13	12 ± 10	0.326
Patient follow-up (mo)	46 ± 56	72 ± 95	0.099
Overall mortality rate, n (%)	6 (28.6)	89 (38.9)	0.352
Causes of death, n (%)
Cardiovascular disease	1 (4.8)	20 (8.7)	0.041
Infections	4 (19.0)	12 (5.2)
Malignancies	1 (4.8)	23 (10)
HCV recurrence	0	13 (5.7)
Other	0	21 (9.3)

BC: Biliary complications; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; ICU: Intensive care unit; RYHJ: Roux-en-Y hepaticojejunostomy.

Table 4 Univariate and multivariate analysis of predictors of biliary complications

	Univariate analysis		Multivariate analysis
	OR (95%CI)	P value	OR (95%CI)	P value
Donor variables
Age (per year)	1.01 (0.93-1.10)	0.755	-	-
Sex (female)	0.33 (0.13-0.85)	0.021	0.27 (0.08-0.90)	0.033
Obesity (BMI ≥ 30) (Y/N)	1.26 (0.44-3.64)	0.661	-	-
Cause of death
Cardiovascular vs trauma	0.55 (0.18-1.62)	0.143	-	-
Other causes vs trauma	1.44 (0.24-8.56)	0.420
Cardiac arrest (Y/N)	3.91 (1.14-13.30)	0.029	7.66 (1.52-38.61)	0.013
Donor hypertension (Y/N)	1.21 (0.48-3.04)	0.677	-	-
Donor diabetes (Y/N)	1.21 (0.42-3.47)	0.722	-	-
Platelets/mm3 (per unit)	1.00 (1.00-1.00)	0.031	1.00 (1.00-1.00)	0.141
Cold ischemia time (per min)	0.99 (0.99-1.00)	0.685	-	-
Recipient variables
Age (per year)	1.01 (0.96-1.06)	0.620	-	-
Sex (female)	0.55 (0.15-1.95)	0.357	-	-
Recipient hypertension (Y/N)	1.59 (0.58-4.32)	0.362	-	-
Recipient diabetes (Y/N)	1.68 (0.61-4.58)	0.309	-	-
HCC (Y/N)	1.13 (0.43-2.93)	0.792	-	-
MELD (per unit)	0.96 (0.88-1.05)	0.481	-	-
Total bilirubin (per unit)	0.63 (0.40-1.02)	0.160	-	-
Leukocytes/mm3 (per unit)	1.00 (1.00-1.00)	0.221	-	-
Prothrombin rate (%) (per unit)	1.01 (0.99-1.04)	0.195	-	-
PRBC transfusion (per unit)	1.02 (0.97-1.06)	0.332	-	-
Pre-LT major abdominal operations (Y/N)	2.80 (0.93-8.35)	0.064	3.08 (0.83-11.33)	0.090
Biliary reconstruction
Chol-Chol-with T-tube	3.61 (0.91-14.27)	0.486	-	-
RYHJ	4.41 (0.82-23-67)	0.342

BMI: Body mass index; HCC: Hepatocellular carcinoma; LT: Liver transplantation; MELD: Model for end-stage liver disease; PRBC: Packed red blood cells; RYHJ: Roux-en-Y hepaticojejunostomy.

Table 5 Diagnosis, management, and outcomes of patients with biliary complications post-liver transplantation with grafts older than 70 years

Cases	Donor age (yr)	Recipient age (yr)	LT indication	Biliary anastomosis technique	BC type	Diagnosis	Time from LT to BC	PTB dilation (times)	Reoperation: surgical procedure	Current status (causes of death)
Donors aged 70-79 yr (13/175, 7.4%)
1	M (70)	M (49)	Alcohol	Chol-chol-T tube	ABL	US	7 d	-	-	Deceased (57 m): CV disease
2	M (73)	M (50)	Alcohol	Chol-chol-T tube	ABS	US, CT scan	12 m	1	-	Deceased (88 m): tumor
3	M (76)	M (50)	Alcohol	Chol-chol	ABL	US, CT scan	10 d	-	Roux-en-Y HJ	Deceased (1 m): BC-infection
4	M (72)	M (61)	HCV	Roux-en-Y HJ	ABS	US	1 m	1	-	Deceased (3 m): aspergillus
5	F (70)	M (63)	HCV	Chol-chol	ABL	Drainage	6 d	-	-	Deceased (1 m): BC-infection
6	M (70)	M (64)	Alcohol + HCC	Chol-chol	ABS	CT scan	1 m	-	Roux-en-Y HJ	Alive (119 m)
7	M (73)	M (67)	HCV	Chol-chol	ABS	US, MRIC	1 m	4	Roux-en-Y HJ	Alive (86 m)
8	M (75)	M (59)	HCV + HCC	Chol-chol	ABS	US, MRIC	12 m	4	-	Alive (65 m)
9	F (73)	F (37)	Policystic disease	Chol-chol-T tube	ABL	Drainage	8 d	-	Primary suture	Alive (55 m)
10	F (79)	M (69)	Cryptogenic	Chol-chol	ABS	US, MRIC	32 m	-	Roux-en-Y HJ	Alive (46 m)
11	F (73)	M (57)	HCV + HCC	Chol-chol	ABL	Drainage	10 d	-	-	Alive (44 m)
12	M (79)	M (63)	HCV + HCC	Chol-chol	ABL	Drainage, CT scan	6 d	-	Primary suture	Alive (21 m)
13	M (75)	M (55)	HCV + HCC	Chol-chol	ABS	MRIC	13 m	-	Roux-en-Y HJ	Alive (19 m)
Donors ≥ 80 yr (8/75, 10.7%)
14	M (84)	M (52)	Alcohol	Chol-chol	ABS	CT scan	11 m	-	Roux-en-Y HJ	Alive (249 m)
15	M (85)	M (71)	Alcohol + HCC	Chol-chol	ABS	CT scan	13 m	-	-	Alive (126 m)
16	M (89)	M (58)	Autoimmune	Chol-chol	NABS	MRIC	21 m	-	-	Alive (52 m)
17	M (80)	M (54)	Alcohol	Chol-chol	ABS	MRIC	5 m	2	Roux-en-Y HJ	Alive (48 m)
18	F (81)	F (54)	NASH	Chol-chol	ABS	MRIC	38 m	6	-	Alive (45 m)
19	F (83)	M (61)	Alcohol + HCC	Chol-chol	ABS	MRIC	16 m	2	Roux-en-Y HJ	Alive (39 m)
20	F (85)	M (59)	NASH	Chol-chol	ABS	CT scan, MRIC	3 m	3	Roux-en-Y HJ	Alive (39 m)
21	M (84)	M (67)	SBC	Roux-en-Y HJ	ABL	Drainage, CT scan	8 d	-	Several procedures	Deceased (2 M): BC-infection

ABL: Anastomotic biliary leakage; ABS: Anastomotic biliary stricture; BC: Biliary complication; Chol-chol: Choledocho-choledochostomy; CT: Computed tomography; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; MRIC: Magnetic resonance imaging cholangiography; NABS: Non-anastomotic biliary stricture; NASH: Nonalcoholic steatohepatitis; LT: Liver transplantation.