Successful ABO Incompatible Adult Living Donor Liver Transplantation with New Simplified Protocol without Local Infusion Therapy and Splenectomy

Gi Won Song; Sung Gyu Lee; Deok Bog Moon; Chul Soo Ahn; Shin Hwang; Ki Hun Kim; Tae Yong Ha; Dong Hwan Jung; Gil Chun Park; Jung Man Namgung; Sam Yeol Yoon; Sung Won Jung

doi:10.4285/jkstn.2011.25.2.95

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Song, Lee, Moon, Ahn, Hwang, Kim, Ha, Jung, Park, Namgung, Yoon, and Jung: Successful ABO Incompatible Adult Living Donor Liver Transplantation with New Simplified Protocol without Local Infusion Therapy and Splenectomy

Original Article

J Korean Soc Transplant 2011;25(2):95-105.

Published online: 10 June 2011

DOI: https://doi.org/10.4285/jkstn.2011.25.2.95

Successful ABO Incompatible Adult Living Donor Liver Transplantation with New Simplified Protocol without Local Infusion Therapy and Splenectomy

Gi Won Song, M.D., Sung Gyu Lee, M.D., Deok Bog Moon, M.D., Chul Soo Ahn, M.D., Shin Hwang, M.D., Ki Hun Kim, M.D., Tae Yong Ha, M.D., Dong Hwan Jung, M.D., Gil Chun Park, M.D., Jung Man Namgung, M.D., Sam Yeol Yoon, M.D., Sung Won Jung, M.D.

Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

책임저자：이승규, 서울시 송파구 올림픽로 43길 88 서울아산병원 외과, 138-736 Tel: 02-3010-3485, Fax: 02-474-9027 E-mail: sglee2@amc.seoul.kr

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Since the time various strategies have been introduced to overcome the ABO-blood barrier including local infusion therapy (LIT), plasmapheresis and rituximab, the graft and patient survival outcome of ABO-incompatible (ABOi) adult living donor liver transplantation (ALDLT) has remarkably improved. But, the need for LIT under rituximab prophylaxis should be reevaluated because of high incidence of the LIT-related complications. The aim of this study was to verify the safety and efficacy of the protocol without local infusion therapy in ABOi ALDLT.

Methods

From November 2008 to December 2010, 43 cases of ABO-incompatible adult living donor liver transplantation were performed. In all cases, the spleen was preserved. From the 1st to 20th case, LIT was employed (group I, n=20). From the 21th case onwards, LIT was eliminated from the protocol (group II, n=23). The 3-month and 1-year patient and graft survival rates were compared between the two groups. The clinical parameters including recipient, donor and graft-related factors were also compared. The graft function was assessed in each group based on the serial changes in serum AST/ALT, total bilirubin and prothrombin time.

Results

There was 1 case of in-hospital mortality (2.3%) among the 43 cases. Overall 3-month and 1-year patient and graft survival rate was 97.7% and 92.1% during a mean period of 11.4 ± 0.4 (0.9∼28.9) months. There was no significant difference in the 3-month and 1-year patient and graft survival rates (95.0 vs. 100% and 90.0 vs. 92.9%, P=0.60) between groups. LIT-related complications occurred in 4 patients (20.0%). One case of antibody-mediated rejection occurred in group II. Both groups showed no difference in graft function at postoperative 3rd month.

Conclusions

ABOi ALDLT without splenectomy and LIT resulted in promising outcomes. Therefore, LIT can be safely eliminated from the protocol.

Keywords: ABO incompatibility, Anti-CD20 monoclonal antibody, Living donor liver transplantation, Local infusion therapy

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Fig. 1.

The change of immunosuppression protocol for ABOi LDLT. (A) From Nov 2008 to Aug 2009, hepatic arterial infusion, cyclophosphamide (2 mg/kg/day), high level of tacrolimus trough level (15∼20 ng/dl) and 375 mg/BSA mm² rituximab have been employed for first 10 patients (case #1∼ case #10). (B) From Sep 2009 to Apr 2010, portal vein infusion, lower level of tacrolimus trough level (10∼15 ng/dl) and reduced dosage of rituximab (300 mg/BSA mm²) have been used for 10 patients (case #11∼case #20). Cyclophosphamide was eliminated from protocol due to frequent side effect. (C) Since Apr 2010, tacrolimus trough level has been reduced further more (8∼12 ng/dl). And local infusion has been abandoned for remaining 23 patients (case #21∼case #43).

Fig. 2.

Three-month and 1-year patient and graft survival rates in each group.

Fig. 3.

Hepatic artery injuries by the insertion of catheter for local infusion therapy. (A) Hepatic artery injury (white arrow) was detected by doppler ultrasonography and hepatic arteriography on postoperative 1^st day. (B) Hepatic artery injury (white arrow) was detected during the procedure of hepatic arterial catheter insertion under fluoroscopy. Hepatic artery injury in both cases was successfully corrected by surgical revision with right gastroepiploic artery.

Table 1.

ABO blood type relation between recipient and donor

Recipient and donor relation R ← D	Number of case
Recipient blood type O (n=25)
O ← A	15 (34.9%)
O ← B	9 (20.9%)
O ← AB	1 (2.3%)
Recipient blood type A (n=10)
A ← B	6 (14.0%)
A ← AB	4 (9.3%)
Recipient blood type B (n=8)
B ← A	2 (4.7%)
B ← AB	6 (14.0%)
Total	43 (100.0%)

Table 2.

Forty three complications occurred in 23 patients after ABOi living donor liver transplantation

Type of Complication	Number of case
Infectious complication	9 (20.9%)
Fungal pneumonia	3
Bacterial pneumonia	2
Pulmonary tuberculosis	1
Cryptococcal meningitis	1
Surgical site infection	1
Sepsis*	1
Rejection	9 (20.9%)
Acute cellular rejection	8
Antibody-mediated rejection	1
Biliary Stricture	8 (18.6%)
Anastomosis stricture	6
Multiple intrahepatic stricture	2
Postoperative bleeding	7 (16.3%)
LIT-related complication	5 (11.6%)
Bleeding	2
Hepatic artery injury	2
Infection	1
Hepatic vein stenosis	3 (7.0%)
RHV stenosis	1
MHV tributary stenosis	2
Portal vein stenosis	1 (2.3%)
Hepatic artery stenosis	1 (2.3%)
Total	43 (100%)

*excluding 2 episodes of biliary sepsis due to biliary stricture in mortalities.

Abbreviations: LIT, local infusion therapy; RHV, right hepatic vein; MHV, middle hepatic vein.

Table 3.

Comparison of demographic and clinical data of recipient and donor between group I and II

Variable	Group I (n＝20)	Group II (n＝23)	P value
Recipient age	49.8±6.5(38∼62)	46.9±9.5 (25∼68)	0.95
Recipient sex (M/F)	16 (80.0%)/4	15 (65.2%)/8	0.28
Original disease	HBV 17(85.0%)	HBV 20 (87.0%)	0.73
	HCV 1 (5.0%)	HCV 0
	Alcoholic LC 1 (5.0%)	Alcoholic LC 1 (4.3%)
	Wilson’ s disease 1 (5.0%)	Wilson’ s disease 1 (4.3%)
	Cryptogenic LC 0	Cryptogenic LC 1 (4.3%)
Combined HCC (Y/N)	5 (25.0%)/15	12 (52.2%)/11	0.07
Recipient ABO type	A 4 (20.0%)	A 6 (26.1%)	0.20
	B 6 (30.0%)	B 2 (8.7%)
	O 10 (50.0%)	O 15 (65.2%)
Recipient-donor	A ← B 2 (10.0%)	A ← B 4 (17.4%)	0.32
ABO match	← AB 2 (10.0%)	← AB 2 (8.7%)
	B ← A 2 (10.0%)	B ← A 0
	← AB 4 (20.0%)	← AB 2 (8.7%)
	O ← A 7 (35.0%)	O ← A 8 (34.8%)
	← B 2 (10.0%)	← B 7 (30.4%)
	← AB 1 (5.0%)	← AB 0
MELD score	15.4±5.3 (8∼25)	13.5±6.0 (6∼29)	0.28
CTP score	8.3±6.5 (6∼11)	7.3 ± 1.8 (6∼10)	0.08
Graft type	MRL 14 (70.0%)	MRL 20 (87.0%)	0.25
	ERL 0	ERL 1 (4.3%)
	Dual 5 (25.0%)	Dual 2 (8.7%)
	LL+S1 1 (5.0%)	LL+S1 0
GRWR (%)	1.1±0.3 (0.8∼1.8)	1.2±0.3 (0.7∼2.1)	0.39
Graft fatty change (%)	5.9±8.9 (0∼10)	2.9±4.5 (0∼20)	0.14
Donor age (years)	29.1±9.7 (15^‡∼53)	30.3±10.2 (16∼55)	0.67
Donor sex (M/F)	19 (76.0%)/6	16 (64.0%)/9	0.36
Donor BMI	23.5±5.4 (20.3∼32.4)	23.4±2.2 (19.1∼28.3)	0.95
Operation time (minute)	917.9±182.3 (685∼1101)	806.2±100.3 (605∼1014)	0.02
Transfusion of P-RBC* (unit)	13.0±17.7 (3∼107)	6.3±7.5 (2∼50)	0.02
Total ischemic time (minute)	143.5±54.9 (92∼189)	125.0±25.8 (83∼201)	0.18
Length of hospital stay^†(day)	46.3±21.3 (26∼99)	31.9±12.5 (17∼76)	0.01
Follow-up period (month)	17.7±7.5 (0.9∼28.9)	6.7±2.5 (3.0∼11.7)	0.00

Abbreviations: CTP, Child-Turcotte-Pugh; MRL, modified right lobe; ERL, extended right lobe; GRWR, graft-to-recipient weight ratio; BMI, body mass index

^† during operation

^‡ after operation

^‡ deceased donor

Table 4.

Incidence (number of patient) of postoperative complication in each group

	Group I (n＝20)	Group II (n＝23)	P value
Complication rate	13 (65.0%)	10 (43.5%)	0.16
Infectious	5 (25.0%)	1 (4.3%)	0.04
complication
Biliary complication	4 (20.0%)	4 (17.4%)	0.83
Acute cellular	4 (20.0%)	4 (17.4%)	0.92
rejection
Antibody-mediated	0 (0%)	1 (4.3%)	0.56
rejection

^‗ spontaneous bacterial peritonitis in patient with underlying CRF on postoperative 3-month.

Table 5.

Comparison of graft function by serum AST/ALT, total bilirubin and prothrombin time between group I and II

Variable	Group I (n＝19*)	Group II (n＝23)	P value
Serum AST (IU/L)
Preoperative	36.0±14.9 (17∼75)	35.6±12.3 (17∼64)	0.95
Postoperative 7 ^th day	51.3±31.8 (21∼164)	50.4±27.1 (16∼138)	0.93
Postoperative 1 ^st month	111.2±348.8 (15∼1550^†)	34.9±24.4 (13∼119)	0.35
Postoperative 3 ^rd month	25.6±10.4 (11∼47)^†	24.5±10.4 (14∼57)	0.75
Peak	556.5±912.3 (103∼4086^†)	306.2±180.5 (66∼708)	0.24
Required time for normalization (day)	11.7±14.2 (3∼67)	12.3±13.6 (1∼54)	0.88
Serum ALT (IU/L)
Preoperative	22.9±10.5 (9∼48)	23.0±8.6 (12∼40)	0.99
Postoperative 7 ^th day	93.0±51.3 (23∼210)	97.8±44.6 (30∼167)	0.75
Postoperative 1 ^st month	99.5±159.8 (10∼713^†)	81.5±72.3 (5∼309)	0.65
Postoperative 3 ^rd month	26.4±23.7 (6∼105)	34.5±28.3 (8∼125)	0.32
Peak	378.1±111.9 (101∼1363^†)	378.0±172.4 (64∼676)	0.31
Required time for normalization (day)	29.1±26.8 (4∼115)	38.6±34.8 (3∼120)	0.32
Serum total bilirubin (mg/dl)
Preoperative	2.6±1.8 (0.8∼7.1)	2.6±2.3 (0.6∼11.7)	0.98
Postoperative 7 ^th day	3.8±2.4 (1.8∼10.3)	3.9±3.1 (1.0∼21.3)	0.93
Postoperative 1 ^st month	1.6±1.4 (0.5∼5.9^†)	1.7±2.2 (0.4∼11.1^‡)	0.85
Postoperative 3 ^rd month	1.2±1.4 (0.7∼7.0^‡)	1.2±1.5 (0.6∼8.0^‡)	0.94
Peak	8.8±5.6 (4.0∼28.3)	9.0±4.6 (4.0∼20.8)	0.87
Required time for normalization (day)	23.6±22.1 (1∼95)	31.1±37.4 (6∼160)	0.42
Prothrombin time (%)
Preoperative	60.7±14.2 (35.0∼106.1)	65.2±18.2 (33.2∼108.0)	0.37
Postoperative 7 ^th day	70.2±9.7 (53.9∼87.8)	78.8±11.8 (52.5∼112.5)	0.12
Postoperative 1 ^st month ^rd	87.3±18.8 (57.6^†∼135.7)	96.8±16.4 (74.2∼128.0)	0.09
Postoperative 3 ^rd month	89.6±15.9 (79.3∼123.8)	98.6±12.3 (77.6∼119.7)	0.05
Required time for normalization (day)	9.4±11.8 (3.0∼53.0)	4.9±2.0 (2.0∼9.0)	0.11

^‗ excluding in-hospital mortality

^† in patient who developed hepatic arterial stenosis and graft infarction,

^‡ in patient with biliary stricture.

Table 6.

Comparison of hemagglutinin titer and anti-CD19 anti-body population between group I and II

Variable	Group I (n＝19*)	Group II (n＝23)	P value
Hemagglutinin IgM
Initial	117.9±224.1	146.1±175.5	0.65
	(1∼1024)	(16∼1024)
Postoperative peak	47.4±11.3	147.5±426.8	0.29
	(1∼512)	(0∼2048)
Hemagglutinin IgG
Initial	39.1±77.1	35.6±56.4	0.87
	(0∼256)	(0∼256)
Postoperative peak	3.4±7.2	18.7±52.8	0.18
	(0∼32)	(0∼256)
Anti-CD19 antibody (%)
Initial	11.7±7.6	14.5±6.5	0.21
	(3.3∼30.9)	(4.8∼32.2)
1 week after rituximab	0.8±1.2	0.6±0.8	0.65
	(0.6∼5.7)	(0∼2.5)
Postoperative peak	6.6±5.9	2.2±1.6	0.07
	(0.6∼24.0)	(0.5∼6.9)

^‗ excluding in-hospital mortality.

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