jkstn The Journal of the Korean Society for Transplantation J Korean Soc Transplant 1598-1711 The Korean Society for Transplantation 10.4285/jkstn.2011.25.2.95 jkstn-25-95 Original Article Successful ABO Incompatible Adult Living Donor Liver Transplantation with New Simplified Protocol without Local Infusion Therapy and Splenectomy SongGi WonM.D. LeeSung GyuM.D. MoonDeok BogM.D. AhnChul SooM.D. HwangShinM.D. KimKi HunM.D. HaTae YongM.D. JungDong HwanM.D. ParkGil ChunM.D. NamgungJung ManM.D. YoonSam YeolM.D. JungSung WonM.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 06 2011 10 06 2011 25 2 95 105 Copyright © 2011 The Korean Society for Transplantation 2011 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.

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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).

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

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 1st 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.

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%)

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.

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

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.

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.

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.