Risk factors and clinical indicators for the development of biliary strictures post liver transplant: Significance of bilirubin

Table 1 Baseline donor and recipient characteristics n (%)

Characteristics	Overall (n = 296)	Biliary strictures (n = 45)	Nil biliary strictures (n = 251)	P value
Donor characteristics
Age (yr)	42 (28-54)	48 (40-57)	42 (27-54)	NS
Gender (male)	165 (55.7)	25 (55.6)	140 (55.8)	NS
BMI (kg/m2)				NS
< 18.5	5 (1.7)	0 (0.0)	5 (2.0)
18.5-24.9	137 (46.3)	18 (40.0)	119 (47.4)
25-29.9	117 (39.5)	20 (44.4)	97 (38.6)
> 30	37 (12.5)	7 (15.5)	30 (12.0)
Donor type				NS
Donation after brain death	285 (96.3)	44 (97.8)	241 (96.0)
Donation after circulatory death	11 (3.7)	1 (2.2)	10 (4.0)
Cause of death				NS
Stroke	154 (52.0)	29 (64.4)	125 (49.8)
Hypoxia	43 (14.5)	6 (13.3)	37 (14.7)
Accident	37 (12.5)	3 (6.7)	34 (13.5)
Other	62 (20.9)	7 (15.6)	55 (21.9)
Recipient characteristics
Age at transplant (yr)	52 (45-57)	53 (40-58)	52 (45-57)	NS
Gender (male)	207 (69.9)	31 (68.8)	176 (70.1)	NS
BMI (kg/m2) (n = 267)	267	44	223	NS
Underweight (≤ 18.5)	5 (1.9)	0 (0.0)	5 (2.0)
Normal weight (18.5-24.9)	94 (35.2)	17 (38.6)	77 (30.7)
Overweight (25-29.9)	93 (34.8)	15 (34.1)	78 (31.1)
Obese ≥ 30	75 (28.1)	12 (27.3)	63 (25.1)
Reason for transplant				NS
Viral hepatitis (B, C) ± hepatocellular carcinoma	124 (41.9)	19 (42.2)	105 (41.8)
Hepatocellular carcinoma without hepatitis	22 (7.4)	1 (2.2)	21 (8.4)
Alcohol	33 (11.1)	6 (13.3)	27 (10.8)
Biliary1	29 (9.8)	8 (17.8)	21 (8.4)
Non-alcoholic steatohepatitis	14 (4.7)	3 (6.7)	11 (4.4)
Acute/fulminant liver failure	12 (4.1)	2 (4.4)	10 (4.0)
Complications first transplant	21 (7.1)	3 (6.7)	18 (7.2)
Other	41 (13.8)	3 (6.7 )	38 (15.1)
Previous transplant	25 (8.5)	5 (11.1)	20 (8.0)	NS

¹Biliary - Primary sclerosing cholangitis, primary biliary cirrhosis. BMI: Body mass index; NS: Not significant.

Table 2 Transplant procedure characteristics n (%)

Characteristic	Total (n = 296)	Biliary strictures (n = 52)	Nil biliary strictures (n = 244)	P value
Cold ischemic time (min)	415 (308-520)	414 (319-530)	415 (307-520)	NS
Warm ischemic time (min)	27 (23-32)	28 (23-33)	27 (23-32)	NS
Time until hepatic artery anastomosis (min)	74 (61-88)	70 (60-86)	74 (61-89)	NS
Time between portal vein and hepatic artery anastomosis (min)	47 (35-60)	41 (36-57)	48 (35-60)	NS
Anastomosis used			246	NS
Duct to duct	213 (72.0)	29 (64.4)	184 (73.3)
Roux-en-Y	78 (26.4)	16 (35.6)	62 (24.7)
T-drain used (n = 231)	23 (7.8)	3 (6.7)	19 (8.0)	NS

NS: Not significant.

Table 3 Interventions required per type of biliary stricture n (%)

Complication	Total frequency (n = 45)1	Requiring intervention (ERCP/PTC) (n = 29)1	Reoperation of biliary anastomosis (n = 22)1	Retransplant (n = 12)1
Anastomotic stricture	25 (55.6)	17 (58.6)	15 (68.2)	2 (16.7)
< 6 mo	15 (33.3)	10 (34.4)	8 (36.4)	1 (8.3)
> 6 mo	10 (22.2)	7 (24.1)	7 (31.8)	1 (8.3)
Right split graft	3 (6.7)	1 (3.4)	2 (9.1)	1 (8.3)
Ischemic type biliary stricture2	10 (22.2)	7 (24.1)	6 (27.3)	6 (50.0)
< 6 mo	8 (17.8)	5 (17.2)	5 (22.7)	5 (41.7)
> 6 mo	2 (4.4)	2 (6.9)	1 (4.5)	1 (8.3)
DCD donor	1 (2.2)	1 (3.4)	1 (4.5)	1 (8.3)
Right split graft	3 (6.7)	2 (6.9)	1 (4.5)	1 (8.3)
PSC recurrence	8 (17.8)	3 (10.3)	2 (9.1)	1 (8.3)
Ischemic cholangiopathy due to HAT	3 (6.7)	3 (10.3)	0 (0.0)	3 (25.0)
Total patients1	46 (100.0)	0 (100.0)3	23 (100.0)	12 (100.0)

¹One patient had two complications;

²Excluding hepatic artery thrombosis, including primary sclerosing cholangitis and ischemic type biliary stricture with anastomotic stricture;

³Some patients were represented more than once as they underwent two interventions for biliary stricture formation. PSC: Primary sclerosing cholangitis; HAT: Hepatic artery thrombosis; DCD: Donation after circulatory death; ERCP: Endoscopic retrograde cholangiography; PTC: Percutaneous trans-hepatic cholangiography.

Table 4 Risk factors associated with biliary stricture formation

Characteristic	Univariate regression		Multivariate regression
	Odds ratio (95%CI)	P value	Odds ratio (95%CI)	P value
Biliary strictures (n = 45)1
Donor age > 55 yr	1.54 (0.80-3.00)	NS
Cause of death - stroke	1.88 (1.00-3.52)	0.049	1.49 (0.72-3.08)	NS
Donation after circulatory death	0.55 (0.07-4.39)	NS
Split vs whole graft	1.09 (0.43-2.79)	NS
Primary sclerosing cholangitis as primary indication for transplant	2.40 (0.82-7.07)	0.11	3.10 (1.13-8.51)	0.028
Hepatic artery thrombosis	22.93 (4.59-114.52)	< 0.001	25.23 (4.73-143.64)	< 0.001
≥ 2 prior transplants	1.44 (0.51-4.07)	NS
Day 7 total bilirubin > 55 μmol/L	2.19 (1.11-4.30)	0.024	2.54 (1.22-5.29)	0.013

¹Inclusive of anastomotic, ischemic type biliary strictures, primary sclerosing cholangitis and ischemic cholangiopathy due to hepatic artery thrombosis. NS: Not significant.