ABOincompatible liver transplant

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ABO-incompatible liver transplant

• Dr Desmond Wai

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ABH system
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ABH system

• ABH antigens expressed widely in the body
• RBC, vascular tissues, solid organs
• Blood group A subdivided into A1 and A2
• A1 individuals express a larger no. of A epitopes
  in tissues compared to A2
• But 80 of A are A1
• In liver, ABH antigens are expressed in
• endothelium large bile duct
• Early experience
• single-organ DIC complements activation,
  thrombosis, cell destruction
• Higher rate of acute rejection, hepatic artery
  thrombosis, biliary stricture
• Lower graft survival

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Early experience
Sanchez-Urdazpal, Mayo, Ann Surg 1993
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Lessons from ABO-Incompatible renal transplant

• Early experience
• Higher rate of hyperacute and acute rejection
• Intravascular thrombosis
• 13 1-yr survival
• Solutions
• A2 graft
• Splenectomy
• Selective immunoadsorption/plasmapheresis
• 1 yr graft survival 70

Cook. Transpl Proc 1987
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• 441 ABO-I renal tp patients
• Pre-tp PE/ immunoadsorption
• triple immunosuppression
• CNI, pred, aza
• splenectomy
• anticoagulation

Takahashi. AJT 2004
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Solutions for ABO-I liver transplant

• Pretransplant removal of anti-A/B antibodies
• Plasmapheresis and/or immunoadsorption
• Splenectomy
• Importance not well proven in liver transplant
• ? risk of sepsis CMV disease
• Rituximab medical splenectomy
• Post transplant treatment
• Addition of OKT3, ALG, PEG-1
• Plasmapheresis
• Portal vein PGE1 infusion
• Hepatic artery infusion

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Rituximab

• A chimeric murine/human anti-CD20 monoclonal
  antibody
• Approved for treatment of refractory or relapsed
  B cell lymphoma
• CD20 a hydrophobic transmembrane protein located
  in pre-B and mature B lymphocytes (APC)
• Loss of APC leads to reduced stimulation on T
  cells

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Plasmapheresis alone

• 6 ABO-I liver transplant
• 4 DD post-tp PE
• 2 LD pre and post-tp PE
• 4 A1O 2 ABA
• PE done x 7-15 days post-tp till HA
• Immunosuppression CNI based
• No splenectomy

Lang. Tp Proceedings 2002
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Plasmapheresis alone

• No increase in acute rejection rate
• No vascular or biliary complications

Lang, Berlin. Tp Proceedings 2002
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PE and Splenectomy

• 14 ABO-I liver transplant
• 8 ALF, 3 2A, 3 2B
• 3 re-tp
• 8 A1O, 2 BO. 1 ABA, 1 ABO
• Pretp double vol TPE in 13
• Intraop
• Cytoxan or MMF Pred OKT3
• Splenectomy in 12
• Posttp
• PE till HA
• Cytoxan or MMF Pred OKT3 (7-10d) CNI
• bactrim, fluconazole (x 3m) ganclclovir (x 3m)

Hanto, Boston. Liver Tp 2003
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PE and Splenectomy
Hanto. Liver Tp 2003
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PE and Splenectomy

• No vascular complication
• 2 had biliary complications
• 1 had anastomotic stricture
• 1 had biliary sludge
• Mean 5.5 (range 0-12) TPE
• 6 had acute rejection, all respond to steroids

Hanto. Liver Tp 2003
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PE, splenectomy, portal vein infusion

• 2 cases of LDLT A1O and A1BA1
• Pre and Post tp PE to drop HA to 116
• Splenectomy
• Pred/Tac/Cytoxan
• Intraportal infusion
• methylpred x 21d
• PGE1 x 14d
• Gabexate mesilate (protease inhibitor) x 14d

Wakabayashi Transpl 2002
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PE, splenectomy, portal vein infusion

• Case 1
• POD12 intraabdominal hematoma
• 3rd wk biliary obstructin and cholangitis,s/p
  PTC
• Case 2
• 2nd wk Bile leak
• 9th wk CMV colitis
• No hemorrhagic necrosis/thrombosis/acute rejection

Wakabayashi Transpl 2002
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PE, splenectomy, systemic PGE1

• LDLT
• 22 AO, 17 BO, 9 BA, 9 ABA, 6 AB, 5 ABB
• Pre-Tp PE till HA 18
• Post-Tp PE if HA reached 164
• Tac/Pred
• Cytoxan D-7 to D30, then Aza
• Splenectomy for aged 6yrs
• IV PGE1 for 7-14d

Egawa, Kyoto. Transpl 2004
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PE, splenectomy, systemic PGE1
Egawa. Transpl 2004
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PE, Rituximab, HA infusion

• (PV thrombosis 37.5 in portal vein infusion)
• 8 ABO-I LDLT
• Pre-Tp Rituximab 2-14 days earlier
• Pre-Tp PE to drop HA to 18
• Tac/Pred/Cytoxan
• HA infusion PGE1 methylpred x 2-3 wk

Yoshizawa, Kyoto. Tp Proceed 2005
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PE, Rituximab, HA infusion

• 3/8 acute rejection
• No intrahepatic biliary complication or hepatic
  necrosis
• 38 CMV disease
• 2 died of aspiration pneumonia and intestinal
  perforation

Yoshizawa. Tp Proceed 2005
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Immunoadsorption/PE, IL2RA

• Immunoadsorption/PE D-3 till HA
• Tac and MMF from D-1
• Daclizumab, 1mg/kg, D-1, 1, 15, 30, 45
• Methylpred from reperfusion
• Fluconazole ganc x 3 weeks

Troisi. Liver Tp 2006
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Immunoadsorption/PE, IL2RA

• 2 graft loss
• 1 early bile leak with secondary HAT at 1m
• 1 thrombosis of conduit (for previous PVT)
• both retp cases
• 100 patient survival at 18.5m
• 1 had acute rejection
• Mean 5 immunoadsorption post-tp sessions needed

Troisi, Italy. Liver Tp 2006
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Summary
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Proposal

• Pre-tp plasma exchange with immunoadsorbent
  filter to drop HA to 116
• Rituximab 2-3d before tp
• Immunosuppressions start 2d before
• Fungal and CMV prophylaxis
• Post-tp plasma exchange if HA rises to 64 or more
• ALF patients only?

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Extra cost to proposal