ABO incompatible

liver
transplantation
Author Journal HA agglutinin Immunosuppression Monoclonal Additional
reduction antibodies treatment

Troisi Liver transpl Immunoadsorption(post- FK 506 Daclizumab  

12:1412-17,2006 operative) MMF  
Skogsberg Xenotranspl Plasmapheresis ( post Methyprednisolone
  Rituximab  
2006:12:154-9 operative ) Daclizumab
Kawagishi Ther aphersis DFPP / Plasma exchange Azathioprine    
5(6):449-454 2001 FK 506
Egawa Liver Transpl Plasma exchange MP 506
FK Rituximab Splenectomy+/-
13:579-588 2007 Steroid    
CPM/MMF
Satoh Tohoku J.Exp med Plasma exchange FK 506    
(HA infusion)
211,359-367 2007 MP
MMF
Usui Clin Transplant Plasma exchange FK 506 Rituximab Splenectomy
2007 21: 24-31 MMF HAI infusion of
Tanabe  
Transplantation. Plasmapheresis MP
MP   PGE1 and MP
Intraportal infusion of
2002 Jun CPM MP, PGE1
27;73(12):1959-61. FK 506 Splenectomy
Yoshizawa Trans Proc, 37, Plasmapheresis FK 506 Rituximab HA infusion of PGE1
1718-19, 2005 CPM and MP
Ringe Transpl Proc, 37, Plamsapheresis MP 506
FK Daclizumab  
2169-2171 (2005) MMF/ sirolimus basiliximab
Kawagishi Trans Proc, 37 Plasma exchange MP
FK506 rituximab  
1205-06 MP
MMF / azathioprine
Heffron Liver Transpl Plasmapheresis ( post FK 506 daclizumab  
12:972-978 2006 operative )
 MMF
Nakamura Trans Proc 36, Plasma exchange Steroid
CPM   Intrahepatic artery
2269-2273, 2004 FK 506 PGE1
MP Splenectomy
Yamada J of Paed surgery Plasma exchange FK 506 Rituximab Intraportal infusion of
Azathioprine
2006: 41: 1976-79 MP ( since 2004) PGE1 and MP
Ashizawa Trans Proc, 38, Plasmapheresis CPM
FK 506   Intraportal / HA
3629-3632 (2006) ( perioperative ) MP infusion of PGE1 and
MMF MP
Usuda Transpl. Vol 79 (1) Plasma exchange FK 506 Rituximab Intraportal infusion of
CPM Splenectomy
Jan 15 2005 12-16 MMF PGE1 and MP
Urbani Transpl Int. 2007 Plamapheresis MP 506
FK daclizumab splenectomy
IVIg
May;20(5):467-70. ( perioperative ) MMF
Kozaki Ther Apher Dial See figure 1 MP
     
Vol 10. No.5 441-
448
 Practical issues
 Patient / donor selection
 Antibody removal
 Immunosuppression and monoclonal
antibodies
 Auxiliary treatment
 Other issues: platelet transfusion,
splenectomy
 Logistics: ICU admission, HA titre
monitoring, IRB, cost
 Patient selection
 Stable enough to undergo preparation
treatment
 Apparently not suitable for fulminant hepatic
failure or liver failure complicated with
sepsis / variceal bleed or other life
threatening conditions
 Blood group A / B patients probably better
than blood group O patients to start with
 Donor selection
 A2 donor or B non secretor to start
with: less epitopes / secretor negative
 Apparently better results obtained from

A2 to B or B to A combinations
 Pretransplant removal
of anti A/B antibodies
 Plasma exchange
 Plasmapheresis (DFPP)
 Immunoabsorption column

 Regardless of the method, needs to reduce

the antibody titre to less than 1: 16
 Usually achieved by performing at least 3
consecutive sessions just before
transplantation
 DFPP
 Double filtration
plasmapheresis
 Requires an additional circuit
for plasma fractionation
 Reomoves antibodies only, no
replacement fluid is needed
 Less risk of infection
 Theoretically no FFP needed
 Technically more difficult and
more expensive
 Plasma exchange
 Removal of plasma with
replacement by FFP or
suitable colloid
 In liver failure patients,
only FFP is suitable
because patients are
already coagulopathic
 Technically easier to
perform
 Each plasma exchange
will need at least 1.5 - 2
times plasma volume
 Donor - Recipient FFP needed for

replacement
 A- O AB, A
 B-O AB, B
 A-B, B-A AB
 AB-A, AB-B AB
 Glycosorb
 Low molecular
carbohydrate column
with A or B blood group
antigen linked to
sepharose matrix
 Only applicable to blood
group A or B recipient
 safety: CE marked
according to Europeqan
Medical device directive.
Clinical use approved in
all EC- countries
 Rituximab ( Rituxan)
 Monoclonal human –murine chimeric anti
CD20 antibody originally developed to treat
B cell lymphoma
 Effective for humoral rejection caused by B
cells
 Action: binds to CD20 antigen on B cell
surface, activating complement-dependent
cytotoxicity
 Dosage
 Dose: 375mg/m2. Start infusion slowly and
increase as tolerated
 Induction therapy given on weekly basis
 3 to 4 wks before transplant
– Donauer Xenotransplantation. 2006 Mar;13(2):108-10.
– Usui Clin Transplant 2007 21: 24-31

 2 to 14 days before transplant

– Yoshizawa, Trans Proc, 37, 1718-19, 2005
 Single dose induction
– Usuda et al. Transpl. Vol 79 (1) Jan 15 2005 12-16
 Rituximab
administration
 BSA calculated by ([BH(cm)xBW(kg)] ^0.5)/60
 Pretreatment: hydrocortisone 100mg and
piriton10mg ivi 30 mins before infusion
 Anti-CD20 into NS 1:1 dilution
 Initial infusion: start at 50mg/hr. If no
hypersensitivity/ anaphylaxis, increase rate in
50mg/hr increment every 30mins.
 Subsequent infusion: start at 100mg/hr and
increase rate by 100mg/hr every 30 mins
 Maximum infuision rate: 400mg/hr
Daclizumab ( Zenepax)
 Chimeric human-murine monoclonal
antibody blocking the interlukin-2-
receptor(CD25) on lymphocyte surface
 Unlabelled use for graft versus host disease
0.5-1.5mg/kg to be administered within 4
hours of preparation
 Repeat dose 11-48 days following initial
dose
 Immunosuppression
 Azathioprine
 MMF

 Sirolimus

 Steroid

 FK 506

 Cyclophosphamide
 Splenectomy
 Survey of 101 cases of ABO
incompatible living related kidney
transplantation revealed that
splenectomy is probably not necessary
– Ishida et al: Transplantation. 2000 Aug 27;70(4):681-5.
 Risk of sepsis following splenectomy is high
in ABOI liver transplantation, especially in
paediatric cases
– Renard:Transplantation. 1992 Jan;53(1):116-21.
 Anti-infective
prophylaxis
 Board spectrum antibiotics for
immediate post operative period
 Board spectrum antifungal

 Septrin for 6 months

 Gancyclovir for 3 months in

donor+/recipient - conditions
 Platelet transfusion
 Transfusion of donor specific / Group
AB platelet
 because platelet products could

contain some plasma

 IVIg
 Immunomodulatory properties
 Used when plasmapheresis failed to control
HA titres and further immunosuppression
not appropriate due to risk of infection
 1.5gm/kg for 7 days then 1g/kg for 7 days
 Administered at the end of plasmaphersis
 Accommodation achieved despite high HA
titres (1: 4096)
Urbani et al. Transpl Int. 2007 May;20(5):467-70.
Monitoring of rejection
 ABH antigen in the liver expressed on
hepatic artery, portal vein, capillary,
sinusoidal ling cells and bile duct epithelium
 Not expressed on bile ductule and
hepatocyte
 Significantly higher incidence of hepatic
artery thrombosis and biliary stricture
compared with ABO compatible
transplantation
 Main causes of death in
ABO-I liver transplantation
 Accommodation
 State of tolerance
 Expression of antigens in an
incompatible transplanted organ could
be changed post transplantation and
the organ can function even if large
amount of incompatible antigen are
present.
– Platt & Bach, Transplantation 52: 937-947, 1991
The trend of therpauetic strategy for
ABO-I living donor liver trnapslantation in Kyoto