Biliary complications in recipients of living donor liver transplantation: A single-centre study

Table 1 Descriptive categorical data for the whole study population

Variable		n (%)
Etiology of cirrhosis	HCV	148 (87.6)
	HBV	5 (3)
	Combined HCV & HBV	4 (2.4)
	Others	12 (7.1)
Hepatocellular carcinoma	-	109 (64.5)
	+	60 (35.5)
Donors’ gender	Male	141 (83.4)
	Female	28 (16.6)
Recipients’ gender	Male	150 (88.8)
	Female	19 (11.2)
HCV PCR viremia prior to transplantation	Negative	33 (19.52)
	Below 200 000 IU	59 (34.91)
	200000 to 2 million	69 (40.82)
	More than 2 million	8 (4.73)
Antiviral treatment for HCV prior to transplantation	-	138 (81.7)
	+	31 (18.3)
Arterial complications	-	155 (91.7)
	+	14 (8.3)
Number of anastomosis	1 Anastomosis	109 (64.5)
	2 Anastomosis	57 (33.7)
	3 Anastomosis	3 (1.8)
Number of ducts	1 Duct	78 (46.2)
	2 Ducts	78 (46.2)
	3 Ducts	12 (7.1)
	4 Ducts	1 (0.6)
Number of stents introduced at surgery	Nil	7 (4.1)
	1 Stent	71 (42)
	2 Stents	79 (46.7)
	3 Stents	11 (6.5)
	4 Stents	1 (0.6)
Immunosuppressant	Tacrolimus	118 (69.8)
	Cyclosporine	51 (30.2)
Biliary leakage	-	114 (67.5)
	+	55 (32.5)
Need of pigtail catheter for biloma	-	46 (83.6)
	+	9 (16.4)
Biliary infection	-	72 (42.6)
	+	97 (57.4)
Frequency of biliary infection	1-2 Episodes	84 (49.7)
	≥ 3 Episodes	13 (7.7)
Biliary stricture	-	109 (64.5)
	+	60 (35.5)
Frequency of biliary stricture	1-2 Episodes	43 (25.4)
	≥ 3 Episodes	17 (10.1)
Need for ERCP	-	109 (64.5)
	+	60 (35.5)
Frequency of ERCP	1-2 ERCP	42 (24.9)
	≥ 3 ERCP	18 (10.7)
Need for PTC	-	161 (95.3)
	+	8 (4.7)
Frequency of PTC	1 PTC	7 (4.1)
	2 PTC	1 (0.6)
Surgical intervention for stricture	-	168 (99.4)
	+	1 (0.6)
HCV PCR during occurrence of stricture	Negative	15 (25)
	Below 200 000 IU	15 (25)
	200000 to 2 million	19 (31.7)
	More than 2 million	11 (18.3)
HCV antiviral treatment in relation to stricture diagnosis	No treatment	27 (45)
	Before stricture	14 (23.3)
	During occurrence of stricture	13 (21.7)
	After stricture	6 (10)
Admission related to BC	-	95 (56.2)
	+	74 (43.8)
Mortality	-	141 (83.4)
	+	28 (16.6)
Cause of mortality (total number: 28)	Biliary sepsis	5 (17.9)
	Graft rejection	4 (14.3)
	Recurrent HCV	3 (10.7)
	Other causes	16 (57.1)
Chronic rejection	-	142 (84)
	+	27 (16)
Recurrent HCV infection	-	128 (75.7)
	+	41 (24.3)
Resolution of recurrent HCV	-	4 (9.8)
	+	37 (90.2)
Graft failure	-	149 (88.2)
	+	20 (11.8)
Causes of graft failure (total number: 20)	Biliary sepsis	5 (25)
	Graft rejection	6 (30)
	Recurrent HCV	3 (15)
	Other causes	6 (30)
Early biliary infection (total = 97)	-	6 (6.18)
	+	91 (93.81)
Early biliary stricture (total = 60)	-	45 (75)
	+	15 (25)

Data presented in number (n) and percentage (%). HCV: Hepatitis C virus; HBV: Hepatitis B virus; PCR: Polymerase chain reaction; ERCP: Endoscopic retrograde cholangiopancreatography; PTC: Percutaneous transhepatic cholangiography; BC: Biliary complication.

Table 2 Descriptive numerical data for the whole study population

Variable	Data
MELD score	16 ± 4
Child score	10 ± 2
Donors’ age (yr)	27 ± 6
Donors’ BMI (kg/m2)	24 ± 3
Recipient's age (yr)	50 ± 8
Recipient's BMI (kg/m2)	28 ± 4
Total bilirubin (mg/dL)	2.6 (1.9-3.8)
Direct bilirubin (mg/dL)	1.3 (0.7-2.1)
Alkaline phosphatase (IU/L)	104 ± 48
Gamma-glutamyl transferase (IU/L)	36 (19-61)
Platelets (109/L)	79 ± 35
Cold ischemia time (min)	49 ± 24
Warm ischemia time (min)	48 ± 20
Graft arterialization time (min)	141 ± 51
Time to biliary infection (d)	16 (11-30)
Time to biliary stricture (d)	150 (120-218)
Time to mortality (d)	285 (55-808)
Time to chronic graft rejection (d)	490 (230-920)
Time to recurrent HCV (d)	391 (180-714)
Time to graft failure (d)	556 (135-1267)

Data are presented as mean ± SD or median and range. MELD: Model for end-stage liver disease; BMI: Body mass index; HCV: Hepatitis C virus.

Table 3 Risk factors for biliary strictures: Categorical factors

Variable		Biliary strictures		OR	CI		P value1
		No stricture (n = 109)	Stricture (n = 60)		95% LCL	95% UCL
		n, Row %	n, Row %
Etiology of cirrhosis	HCV	95 (64.2)	53 (35.8)				0.1422
	Isolated HBV	5 (100)	0 (0)
	Combined HCV & HBV	1 (25)	3 (75)
	Causes other than viral hepatitis	8 (66.7)	4 (33.3)
Donors’ gender	Male	90 (63.8)	51 (36.2)	0.8	0.4	2.0	0.684
	Female	19 (67.9)	9 (32.1)
Recipients’ gender	Male	96 (64)	54 (36)	0.8	0.3	2.3	0.704
	Female	13 (68.4)	6 (31.6)
HCV PCR viremia prior to transplantation	Negative	20 (60.6)	13 (39.4)				0.7683
	Below 200000 IU	41 (69.5)	18 (30.5)
	200000 to 2 million	44 (63.8)	25 (36.2)
	More than 2 million	4 (50)	4 (50)
Antiviral treatment prior to transplantation	-	92 (66.7)	46 (33.3)	1.6	0.7	3.6	0.214
	+	17 (54.8)	14 (45.2)
Hepatocellular carcinoma	-	71 (65.1)	38 (34.9)	1.1	0.6	2.1	0.815
	+	38 (63.3)	22 (36.7)
Arterial complications	-	102 (65.8)	53 (34.2)	1.9	0.6	5.8	0.2552
	+	7 (50)	7 (50)
Number of anastomoses	One	70 (64.2)	39 (35.8)				0.9103
	Two	37 (64.9)	20 (35.1)
	Three	2 (66.7)	1 (33.3)
Number of ducts	1 Duct	50 (64.1)	28 (35.9)				0.8573
	2 Ducts	52 (66.7)	26 (33.3)
	3 Ducts	6 (50)	6 (50)
	4 Ducts	1 (100)	0 (0)
Number of stents	Nil	5 (71.4)	2 (28.6)				0.5783
	1 Stent	43 (60.6)	28 (39.4)
	2 Stents	53 (67.1)	26 (32.9)
	3 Stents	7 (63.6)	4 (36.4)
	4 Stents	1 (100)	0 (0)
Immunosuppressant	Tacrolimus	81 (68.6)	37 (31.4)	1.8	0.9	3.5	0.087
	Cyclosporine	28 (54.9)	23 (45.1)
Biliary leakage	-	80 (70.2)	34 (29.8)	2.1	1.1	4.1	0.026
	+	29 (52.7)	26 (47.3)
Biliary infection	-	62 (86.1)	10 (13.9)	6.6	3.0	14.4	< 0.001
	+	47 (48.5)	50 (51.5)
Frequency of biliary infection	Nil	62 (86.1)	10 (13.9)				< 0.0013
	1-2 Episodes	45 (53.6)	39 (46.4)
	≥ 3 Episodes	2 (15.4)	11 (84.6)
Early biliary infection	-	64 (82.1)	14 (17.9)	4.7	2.3	9.5	< 0.001
	+	45 (49.5)	46 (50.5)
Chronic graft rejection	-	99 (69.7)	43 (30.3)	3.9	1.7	9.2	0.001
	+	10 (37)	17 (63)
Recurrent HCV	-	87 (68)	41 (32)	1.8	0.9	3.8	0.096
	+	22 (53.7)	19 (46.3)

¹Pearson chi-squared test unless otherwise indicated.

²Fisher’s exact test.

³Chi-squared test for trend.

Data are presented as number (n) and percentage (%). OR: Odds ratio; LCL: Lower confidence limit; UCL: Lower confidence limit. HCV: Hepatitis C virus; HBV: Hepatitis B virus; PCR: Polymerase chain reaction.

Table 4 Risk factors for biliary stricture: Numerical factors

Variable	No biliary stricture (n = 109)	Biliary stricture (n = 60)	P value1
MELD score	15 (13-18)	15 (13-19)	0.588
CHILD score	10 (9-11)	9 (8-11)	0.198
Donors’ age (yr)	27 (23-30)	25 (24-30)	0.727
Donors’ BMI (kg/m2)	25 (23-26)	24 (22-26)	0.155
Recipient's age (yr)	51 (46-56)	52 (48-55)	0.961
Recipient's BMI (kg/m2)	27 (25-30)	27 (26-30)	0.219
Total bilirubin (mg/dL)	2.6 (1.9-3.7)	2.5 (1.9-4.1)	0.911
Direct bilirubin (mg/dL)	1.3 (0.8-2.1)	1.3 (0.7-1.9)	0.405
Alkaline phosphatase (IU/L)	99 (70-118)	84 (68-143)	0.982
GGT (IU/L)	36 (19-63)	34 (22-60)	0.992
Platelets (109/L)	70 (51-104)	68 (51-102)	0.830
Cold ischemia time (min)	45 (30-60)	45 (30-60)	0.929
Warm ischemia time (min)	45 (35-60)	45 (35-60)	0.860
Graft arterialization time (min)	120 (90-150)	155 (120-205)	< 0.001

¹Mann-Whitney U test.

Data are presented as median and interquartile range (IQR). MELD: Model for end-stage liver disease; BMI: Body mass index.

Table 5 Multivariable binary logistic regression model for prediction of biliary stricture

Variable	P value	Odds ratio	95%CI
Graft arterializations time > 130 min	0.001	3.705	1.669-8.224
Biliary leakage	0.649	1.208	0.536-2.726
> 1 Episode of biliary infection	< 0.0001	9.892	4.086-23.952
Chronic graft rejection	0.173	2.088	0.725-6.014

CI: Confidence interval.

Table 6 Relation between biliary complications and chronic graft rejection

Variable		No Chronic graft rejection (n = 142), n (%)	Chronic graft rejection (n = 27), n (%)	OR	CI		P value1
					95% LCL	95% UCL
Biliary leakage	-	100 (87.7)	14 (12.3)	2.2	1.0	5.1	0.059
	+	42 (76.4)	13 (23.6)
Insertion of pigtail catheter for biliary leakage	-	135 (84.4)	25 (15.6)	1.5	0.3	7.9	0.6372
	+	7 (77.8)	2 (22.2)
Biliary infection	-	68 (94.4)	4 (5.6)	5.3	1.7	16.1	0.001
	+	74 (76.3)	23 (23.7)
Frequency of biliary infection	Nil	68 (94.4)	4 (5.6)				< 0.0013
	1-2 Episodes	68 (81)	16 (19)
	≥ 3 Episodes	6 (46.2)	7 (53.8)
Early biliary infection	-	73 (93.6)	5 (6.4)	4.7	1.7	13.0	0.002
	+	69 (75.8)	22 (24.2)
Biliary stricture	-	99 (90.8)	10 (9.2)	3.9	1.7	9.2	0.001
	+	43 (71.7)	17 (28.3)
Frequency of biliary strictures	Nil	99 (90.8)	10 (9.2)				0.0013
	1-2 Episodes	32 (74.4)	11 (25.6)
	≥ 3 Episodes	11 (64.7)	6 (35.3)
Early biliary stricture	-	134 (87)	20 (13)	5.9	1.9	17.9	0.0032
	+	8 (53.3)	7 (46.7)
Need for ERCP	-	99 (90.8)	10 (9.2)	3.9	1.7	9.2	0.001
	+	43 (71.7)	17 (28.3)
Frequency of ERCP	Nil	99 (90.8)	10 (9.2)				0.0013
	1-2 ERCP	31 (73.8)	11 (26.2)
	≥ 3 ERCP	12 (66.7)	6 (33.3)
Number of stents introduced for stricture	Nil	102 (91.1)	10 (8.9)				0.0023
	1-2 stents	25 (73.5)	9 (26.5)
	≥ 3 stents	15 (65.2)	8 (34.8)
Need for PTC	-	136 (84.5)	25 (15.5)	1.8	0.3	9.5	0.6152
	+	6 (75)	2 (25)
Frequency of PTC	Nil	136 (84.5)	25 (15.5)				0.1903
	1 PTC	6 (85.7)	1 (14.3)
	2 PTC	0 (0)	1 (100)
Surgical intervention for stricture	-	141 (83.9)	27 (16.1)	0.8	0.8	0.9	1.0002
	+	1 (100)	0 (0)
HCV PCR at occurrence of stricture	Negative	10 (66.7)	5 (33.3)				0.6603
	Below 200000 IU	12 (80)	3 (20)
	200000 to 2 million	15 (78.9)	4 (21.1)
	More than 2 million	6 (54.5)	5 (45.5)
Antiviral treatment in relation to stricture	Not given	21 (77.8)	6 (22.2)				0.5362
	Before stricture	9 (64.3)	5 (35.7)
	After stricture	4 (66.7)	2 (33.3)
	During occurrence of stricture	9 (69.2)	4 (30.8)
Admission related to BC	-	85 (89.5)	10 (10.5)	2.5	1.1	5.9	0.028
	+	57 (77)	17 (23)
Frequency of admissions related to biliary complications	Nil	85 (89.5)	10 (10.5)				0.0023
	1-2	35 (87.5)	5 (12.5)
	≥ 3	22 (64.7)	12 (35.3)
Recurrent HCV	-	116 (90.6)	12 (9.4)	5.6	2.3	13.3	< 0.001
	+	26 (63.4)	15 (36.6)
Resolution of recurrent HCV	-	1 (25)	3 (75)	0.2	0.0	1.7	0.1302
	+	25 (67.6)	12 (32.4)

¹Pearson chi-squared test unless otherwise indicated.

²Fisher’s exact test.

³Chi-squared test for trend.

Data are presented as number (n) and percentage (%). OR: Odds ratio; LCL: Lower confidence limit; UCL: Lower confidence limit; ERCP: Endoscopic retrograde cholangiopancreatography; PTC: Percutaneous transhepatic cholangiography; PCR: Polymerase chain reaction; HCV: Hepatitis C virus; BC: Biliary complication.

Table 7 Multivariable binary logistic regression model for prediction of chronic graft rejection

Variable	P value	Odds ratio	95%CI
Biliary infection	0.001	4.301	1.97-8.224
Early biliary infection	0.061	1.105	0.89-1.20
Frequency of biliary infection	0.025	1.208	0.536-2.726
Biliary stricture	< 0.0001	3.882	4.056-9.952
Need for ERCP	0.02	2.91	1.85-7.97
Frequency of ERCP	0.074	1.098	0.99-1.114
Number of stents	0.62	1.22	0.57-2.42
Admission related to BCs	0.082	1.102	0.99-1.40
Frequency of admission	0.51	1.73	0.56-7.5
Recurrent HCV	0.032	3.11	1.97-8.07

CI: Confidence interval; ERCP: Endoscopic retrograde cholangiopancreatography; HCV: Hepatitis C virus; BC: Biliary complication.

Table 8 Relation between biliary complications and graft failure

Variable		No graft failure (n = 149), n (%)	Graft failure (n = 20), n (%)	OR	CI		P value1
					95% LCL	95% UCL
Biliary leakage	-	105 (92.1)	9 (7.9)	2.9	1.1	7.5	0.022
	+	44 (80)	11 (20)
Insertion of pigtail catheter	-	144 (90)	16 (10)	7.2	1.8	29.6	0.0122
	+	5 (55.6)	4 (44.4)
Biliary infection	-	68 (94.4)	4 (5.6)	3.4	1.1	10.5	0.029
	+	81 (83.5)	16 (16.5)
Frequency of biliary infection	Nil	68 (94.4)	4 (5.6)				0.0213
	1-2 Episodes	71 (84.5)	13 (15.5)
	≥ 3 Episodes	10 (76.9)	3 (23.1)
Early biliary infection	-	73 (93.6)	5 (6.4)	2.9	1.0	8.3	0.043
	+	76 (83.5)	15 (16.5)
Biliary stricture	-	98 (89.9)	11 (10.1)	1.6	0.6	4.0	0.345
	+	51 (85)	9 (15)
Frequency of biliary stricture	Nil	98 (89.9)	11 (10.1)				0.1683
	1-2 Episodes	38 (88.4)	5 (11.6)
	≥ 3 Episodes	13 (76.5)	4 (23.5)
Early biliary stricture	-	137 (89)	17 (11)	2.0	0.5	7.9	0.3922
	+	12 (80)	3 (20.0)
Need for ERCP	-	98 (89.9)	11 (10.1)	1.6	0.6	4.0	0.345
	+	51 (85)	9 (15.0)
Frequency of ERCP	Nil	98 (89.9)	11 (10.1)				0.1883
	1-2 ERCP	37 (88.1)	5 (11.9)
	≥ 3 ERCP	14 (77.8)	4 (22.2)
Number of stents introduced for stricture	Nil	101 (90.2)	11 (9.8)				0.1363
	1-2 Stents	30 (88.2)	4 (11.8)
	≥ 3 Stents	18 (78.3)	5 (21.7)
Need for PTC	-	142 (88.2)	19 (11.8)	1.1	0.1	9.2	1.0002
	+	7 (87.5)	1 (12.5)
Frequency of PTC	Nil	142 (88.2)	19 (11.8)				0.3743
	1 PTC	7 (100)	0 (0)
	2 PTC	0 (0)	1 (100)
Surgical intervention for stricture	-	148 (88.1)	20 (11.9)	0.9	0.8	0.9	1.0002
	+	1 (100)	0 (0)
HCV PCR at occurrence of stricture	Negative	13 (86.7)	2 (13.3)				0.2923
	Below 200000 IU	13 (86.7)	2 (13.3)
	200000 to 2 million	18 (94.7)	1 (5.3)
	More than 2 million	7 (63.6)	4 (36.4)
Antiviral treatment in relation to stricture	Not given	24 (88.9)	3 (11.1)				0.8362
	Before stricture	11 (78.6)	3 (21.4)
	After stricture	5 (83.3)	1 (16.7)
	During occurrence of stricture	11 (84.6)	2 (15.4)
Admission related to BC	-	85 (89.5)	10 (10.5)	1.3	0.5	3.4	0.551
	+	64 (86.5)	10 (13.5)
Frequency of admissions related to BC	Nil	85 (89.5)	10 (10.5)				0.119
	1-2 ERCP	38 (95)	2 (5)
	≥3 ERCP	26 (76.5)	8 (23.5)
Recurrent HCV infection	-	118 (92.2)	10 (7.8)	3.8	1.5	10.0	0.0102
	+	31 (75.6)	10 (24.4)
Resolution of recurrent HCV	-	0 (0)	4 (100)	6.2	3.0	12.8	0.0022
	+	31 (83.8)	6 (16.2)

¹Pearson chi-squared test unless otherwise indicated.

²Fisher’s exact test.

³Chi-squared test for trend.

Data are presented as number (n) and percentage (%). OR: Odds ratio; LCL: Lower confidence limit; UCL: Lower confidence limit; ERCP: Endoscopic retrograde cholangiopancreatography; PTC: Percutaneous transhepatic cholangiography; PCR: Polymerase chain reaction; HCV: Hepatitis C virus; BC: Biliary complication.

Table 9 Multivariable binary logistic regression model for prediction of graft failure

Variable	P value	Odds ratio	95%CI
Biliary leakage	0.021	1.82	1.34-5.57
Insertion of pigtail catheter	0.010	3.76	1.45-11.83
Biliary infection	0.032	3.11	1.03-9.06
Early biliary infection	0.05	1.34	0.65-2.86
Frequency of biliary infection	0.001	2.52	1.28-4.91
Nonresponse to HCV anti-viral therapy	0.001	3.6	1.8-9.34
Recurrent HCV	0.001	3.56	1.86-10.71

CI: Confidence interval; HCV: Hepatitis C virus.

Table 10 Relation between biliary complications and mortality

Variable		Survivors (n = 141), n (%)	Non-survivors (n = 28), n (%)	OR	CI		P value1
					95% LCL	95% UCL
Biliary leakage	-	97 (85.1)	17 (14.9)	1.4	0.6	3.3	0.405
	+	44 (80)	11 (20)
Biliary infection	-	60 (83.3)	12 (16.7)	1.0	0.4	2.2	1.0002
	+	81 (83.5)	16 (16.5)
Frequency of biliary infection	Nil	60 (83.3)	12 (16.7)				0.9403
	1-2 Episodes	70 (83.3)	14 (16.7)
	≥ 3 Episodes	11 (84.6)	2 (15.4)
Early biliary infection	-	64 (82.1)	14 (17.9)	0.8	0.4	1.9	0.6552
	+	77 (84.6)	14 (15.4)
Biliary stricture	-	89 (81.7)	20 (18.3)	0.7	0.3	1.7	0.4012
	+	52 (86.7)	8 (13.3)
Frequency of biliary strictures	Nil	89 (81.7)	20 (18.3)				0.3963
	1-2 Episodes	37 (86)	6 (14)
	≥ 3 Episodes	15 (88.2)	2 (11.8)
Early biliary stricture	-	128 (83.1)	26 (16.9)	0.8	0.2	3.6	1.0002
	+	13 (86.7)	2 (13.3)
Need for ERCP	-	89 (81.7)	20 (18.3)	0.7	0.3	1.7	0.4012
	+	52 (86.7)	8 (13.3)
Frequency of ERCP	Nil	89 (81.7)	20 (18.3)				0.3753
	1-2 ERCP	36 (85.7)	6 (14.3)
	≥ 3 ERCP	16 (88.9)	2 (11.1)
Number of stents introduced for stricture	Nil	92 (82.1)	20 (17.9)				0.5203
	1-2 Stents	29 (85.3)	5 (14.7)
	≥ 3 Stents	20 (87)	3 (13)
Need for PTC	-	134 (83.2)	27 (16.8)	0.7	0.1	6.0	1.0002
	+	7 (87.5)	1 (12.5)
Frequency of PTC	Nil	134 (83.2)	27 (16.8)				0.6743
	1 PTC	7 (100)	0 (0)
	2 PTC	0 (0)	1 (100)
Surgical intervention for stricture	-	140 (83.3)	28 (16.7)				1.0002
	+	1 (100)	0 (0)
HCV PCR at occurrence of stricture	Negative	12 (80)	3 (20)				0.8493
	Below 200 000 IU	14 (93.3)	1 (6.7)
	200000 to 2 million	18 (94.7)	1 (5.3)
	More than 2 million	8 (72.7)	3 (27.3)
Antiviral treatment in relation to stricture	Not given	23 (85.2)	4 (14.8)				1.0002
	Before stricture	12 (85.7)	2 (14.3)
	After stricture	5 (83.3)	1 (16.7)
	During occurrence of stricture	12 (92.3)	1 (7.7)
Admission related to BC	-	75 (78.9)	20 (21.1)	0.5	0.2	1.1	0.0762
	+	66 (89.2)	8 (10.8)
Recurrent HCV	-	108 (84.4)	20 (15.6)	1.3	0.5	3.2	0.5602
	+	33 (80.5)	8 (19.5)
Resolution of recurrent HCV (n = 41)	-	0 (0)	4 (9.7)	9.3	3.7	23.3	0.0012
	+	33 (80.4)	4 (9.7)

¹Pearson chi-squared test unless otherwise indicated.

²Fisher’s exact test.

³Chi-squared test for trend.

Data are presented as number (n) and percentage (%). OR: Odds ratio; LCL: Lower confidence limit; UCL: Lower confidence limit; ERCP: Endoscopic retrograde cholangiopancreatography; PTC: Percutaneous transhepatic cholangiography; PCR: Polymerase chain reaction; HCV: Hepatitis C virus; BC: Biliary complication.