Risk factor for ischemic-type biliary lesion after ABO-incompatible living donor liver transplantation

Table 1 Characteristics of all 27 ABO-incompatible adult living donor liver transplantation patients

Case No.	Age/sex	Etiology	MELD	Donor age/relationship	Blood type (R/D)	Initial B-cell	Initial isoagglutinin titer IgM/IgG	Actual GRWR	Graft ischemic time1 (min)	HAIT
1	48/M	HBV + HCC	10	24/Son	B/A	16%	1:16/1:2	0.86	355	Y
2	52/F	HBV	25	24/Daughter	B/AB	13%	1:16/1:8	0.6	210	Y
3	53/M	Alcohol	33	21/Son	O/A	14%	1:64/1:256	1.14	220	Y
4	50/F	HBV + HCC	13	53/Husband	O/A	21%	1:256/1:32	0.81	203	Y
5	53/M	HCV	13	18/Daughter	B/A	22%	1:32/1:8	0.97	130	Y
6	42/M	HBV + HCC	13	39/Wife	B/A	9%	1:64/1:256	0.67	175	Y
7	65/M	HBV + HCC	10	38/Daughter	O/A	19%	1:64/1:256	1.04	128	N
8	51/M	HBV + HCC	9	23/Son	A/AB	14%	1:32/1:32	1.36	85	N
9	43/M	HBV	34	29/Wife	O/B	18%	1:32/1:32	1.02	157	N
10	49/M	HBV + HCC	7	21/Son	A/AB	21%	1:32/1:32	0.87	180	N
11	49/M	HBV + HCC	13	21/Son	O/A	18%	1:256/1:1024	0.74	201	N
12	53/M	Alcohol	13	21/Son	A/B	14%	1:64/1:512	1.07	225	N
13	59/M	HBV + HCC	12	28/Son	O/A	16%	1:64/1:512	0.93	120	N
14	47/M	HBV	14	37/Wife	O/A	29%	1:128/1:512	1.17	167	N
15	31/F	Wilson’s disease	10	29/Sister	O/A	19%	1:32/1:32	0.95	80	N
16	52/M	HBV + HCC	9	25/Daughter	O/B	9%	1:128/1:512	0.71	143	N
17	57/M	HBV + HCC	9	44/Nephew	B/A	16%	1:16/1:32	0.91	136	N
18	48/M	HBV	17	24/Daughter	O/B	32%	1:32/1:64	0.62	180	N
19	50/M	HBV + HCC	9	21/Daughter	B/A	15%	1:16/1:16	0.64	190	N
20	56/M	HBV + HCC	6	22/Son	B/AB	21%	1:16/1:16	1.14	154	N
21	45/F	HBV	13	43/Husband	O/A	6%	1:32/1:32	1.48	100	N
22	49/M	HBV + HCC	9	21/Son	O/A	11%	1:64/1:128	1.12	131	N
23	53/F	HBV + HCC	11	19/Daughter	B/AB	6%	1:8/1:2	1.21	115	N
24	43/F	HBV	22	50/Husband	B/A	10%	1:32/1:32	1.55	155	N
25	47/M	HBV + HCC	9	19/Daughter	O/A	4%	1:32/1:1024	0.89	200	N
26	52/M	HBV + HCC	10	24/Son	A/B	31%	1:32/1:32	1.01	162	N
27	35/M	HBV + HCC	6	35/Wife	O/A	20%	1:64/1:256	0.85	175	N

¹Cold ischemic time + warm ischemic time. ABO-I ALDLT: ABO-incompatible adult living donor liver transplantation; HBV: Hepatitis B virus; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; MELD: Model for end-stage liver disease; GRWR: Graft to recipient weight ratio; HAIT: Hepatic artery infusion therapy.

Table 2 Clinical data of four recipients with ischemic-type biliary lesion after ABO-incompatible adult living donor liver transplantation

Case No.	No. of pre-LT PE	Post-LT isoagglutinin peak titer (IgM/IgG)	No. of post-LT PE	Post-LT infection	Post-LT Liver Bx day	Pathology of liver Bx	LOS after LT (d)	ITBL free time (d)	Tx for ITBL	Tx period for ITBL (mo)	Outcome of ITBL tx	Patient's survival	Patient's survival time (mo)
2	1	1:4/1:8	0	No	27	ACR	35	90	PTBD	12	Graft failure	Dead	14
12	5	1:256/1:512	4	No	22	NSI	28	45	PTBD	5	Graft dysfunction, PVT	Alive	33
14	4	1:16/1:128	4	No	27	AMR	51	60	PTBD	11	Normal graft function	Alive	31
19	0	1:32/1:32	0	No	25	NSI	43	112	PTBD	20	Graft dysfunction	Alive	23

ITBL: Ischemic-type biliary lesion; ABO-I ALDLT: ABO-incompatible adult living donor liver transplantation; LT: Liver transplantation; PE: Plasma exchange; Bx: Biopsy; LOS: Length of hospital stay; Tx: Treatment; ACR: Acute cellular rejection; NSI: Non-specific inflammation; AMR: Antibody-mediated rejection; PTBD: Percutaneous transhepatic biliary drainage; PVT: Portal vein thrombosis.

Table 3 Comparison of ABO-incompatible adult living donor liver transplantation recipients between ischemic-type biliary lesion group and non-ischemic-type biliary lesion group

	ITBL group (n = 4)	non-ITBL group (n = 23)	P value
Preoperative characteristics
Recipient age (yr)	51 (47-53)	49 (31- 65)	0.721
Recipient sex (M/F)	3/1	18/5	1.000
Donor age (yr)	22 (21-37)	24 (18-53)	0.545
Donor BMI	21.6 ± 2.5	22.8 ± 3.2	0.495
Blood type-A barrier	3 (75%)	17 (73.9%)	1.000
MELD	13 (9-25)	10 (6-34)	0.567
CTP score	7 (5-11)	5 (5-12)	0.322
Initial isoagglutinin titer
IgG (≥ 1:64)	2 (50%)	10 (43.5%)	1.000
IgM (≥ 1:64)	2 (50%)	9 (39.1%)	1.000
No. of PE (preoperative)	2.5 (0-5)	2 (0-15)	0.802
Initial B-cell (%)	17.7 ± 3.7	16.2 ± 1.5	0.945
Operative outcomes
Operation time (min)	678.3 ± 28.8	645.6 ± 90.8	0.336
Actual graft weight (g)	585.5 ± 135.6	682.3 ± 105.9	0.117
Actual GRWR (%)	0.87 ± 0.29	0.99 ± 0.24	0.373
Cold ischemic time (min)	149.3 ± 28.7	114.4 ± 53.3	0.219
Warm ischemic time (min)	48.7 ± 11.8	45.8 ± 12.3	0.659
Intra-operative transfusion (unit)
RBC	1.7 ± 1.5	2.9 ± 3.9	0.572
FFP	1.7 ± 2.1	2.3 ± 2.7	0.678
P-conc.	2.0 ± 4.0	7.1 ± 6.7	0.159
HAIT	1 (25%)	5 (21.7%)	1.000
Postoperative outcomes
Peak level of AST (IU/L)	330.2 ± 240.7	223.5 ± 151.3	0.258
Peak level of ALT (IU/L)	435.0 ± 444.5	323.0 ± 230.5	0.462
Peak level of total bilirubin (mg/dL)	5.5 ± 2.2	3.9 ± 1.4	0.071
Peak isoagglutinin titer
IgG (≥ 1:64)	2 (50%)	4 (17.4%)	0.204
IgM (≥ 1:64)	1 (25%)	3 (13.1%)	0.279
No. of PE (postoperative)	2 (0-4)	0 (0-6)	0.090
Post-operative transfusion (unit)
RBC	2.3 ± 2.6	2.8 ± 4.2	0.811
FFP	0.5 ± 1.0	4.8 ± 7.5	0.264
P-conc.	9.0 ± 2.0	11.5 ± 13.7	0.721
Post-LT ICU stay (d)	4 (1-5)	4 (3-6)	0.900
Post-LT hospital stay (d)	39 (28-51)	28 (20-75)	0.277
BPACR	1 (25%)	5 (21.7%)	1.000
BPAMR	1 (25%)	0	0.148
Complications
Post-LT hemorrhage	0	4 (17.4%)	1.000
CMV infection	0	7 (30.4%)	0.545
Bacterial infection	0	1 (4.3%)	1.000
B-cell follicle score in spleen	3.7 ± 0.5	2.6 ± 1.1	0.067
Plasma cell count in spleen	73.0 ± 19.0	76.8 ± 47.9	0.878

ABO-I ALDLT: ABO-incompatible adult living donor liver transplantation; ITBL: Ischemic-type biliary lesion; BMI: Body mass index; MELD: Model for end-stage liver disease; CTP: Child-Turcotte-Pugh; PE: Plasma exchange; GRWR: Graft-to-recipient weight ratio; RBC: Red blood cell; FFP: Fresh frozen plasma; P-conc.: Platelet concentrate; HAIT: Hepatic artery infusion therapy; AST: Aspartate transaminase; ALT: Alanine transaminase; LT: Liver transplantation; ICU: Intensive care unit; BPACR: Biopsy-proven acute cellular rejection; BPAMR: Biopsy-proven antibody-mediated rejection; CMV: Cytomegalovirus.

Table 4 Comparison of lymphocyte subsets in the recipients between ischemic-type biliary lesion and non- ischemic-type biliary lesion groups

	ITBL group (n = 4)	Non-ITBL group (n = 23)	P value
At patient's admission (Lф -1)
WBC counts (/μL)	3750.0 ± 1658.3	4213.0 ± 2015.5	0.767
Lymphocyte counts (/μL)	1075.0 ± 471.7	965.2 ± 527.1	0.531
B-cell counts (/μL)	197.5 ± 121.5	140.6 ± 106.9	0.336
T-cell counts (/μL)	647.0 ± 300.9	675.3 ± 387.6	0.818
T4/T8 ratio	2.5 ± 0.6	2.2 ± 1.3	0.272
NK cell counts (/μL)	182.3 ± 98.7	100.0 ± 64.5	0.069
After the administration of rituximab (Lф -2)
WBC counts (/μL)	4500.0 ± 3213.5	4234.8 ± 2177.1	0.921
Lymphocyte counts (/μL)	887.5 ± 480.2	739.1 ± 428.3	0.576
T-cell counts (/μL)	646.7 ± 500.8	574.5 ± 267.9	0.974
T4/T8 ratio	2.1 ± 0.5	1.9 ± 0.7	0.974
NK cell counts (/μL)	158.7 ± 71.5	77.6 ± 59.2	0.034
After the transplantation (Lф -3)
WBC counts (/μL)	8800.0 ± 2412.5	8500.0 ± 6925.1	0.448
Lymphocyte counts (/μL)	687.5 ± 243.9	700.0 ± 342.5	0.974
T-cell counts (/μL)	429.0 ± 213.1	575.9 ± 320.4	0.448
T4/T8 ratio	1.3 ± 0.4	2.5 ± 2.8	0.111
NK cell counts (/μL)	170.0 ± 98.2	76.0 ± 63.7	0.027

ABO-I ALDLT: ABO-incompatible adult living donor liver transplantation; ITBL: Ischemic-type biliary lesion; WBC: White blood cell; NK cell: Natural killer cell.

Table 5 The univariate analysis for development of ischemic-type biliary lesion

	n	RR	95%CI	P value
NK cell count at Lф-2
≥ 150 /μL	6	20	1.5-260.8	0.022
< 150 /μL	21	1
NK cell count at Lф-3
≥ 120 /μL	7	14.3	1.2-174.8	0.038
< 120 /μL	20	1

ITBL: Ischemic-type biliary lesion; NK cell: Natural killer cell; RR: Relative risk.