Desensitization Protocol for ABO-Incompatible Liver Transplant
For ABO-incompatible liver transplant recipients who received pre-operative rituximab and plasma exchange, the optimal post-operative desensitization protocol should include continued plasma exchange with intravenous immunoglobulin (IVIG), maintenance immunosuppression with tacrolimus/mycophenolate mofetil/corticosteroids, and close monitoring of anti-blood type isoagglutinin titers.
Post-Operative Management Protocol
Immediate Post-Operative Period (Days 1-7)
- Continue plasma exchange sessions (typically daily for 5-7 days) to maintain low anti-blood type isoagglutinin titers 1
- Administer IVIG (0.5-1 g/kg) after each plasma exchange to neutralize remaining antibodies and provide immunomodulation 1, 2
- Monitor anti-blood type isoagglutinin titers daily initially, then twice weekly until stable 3
- Target anti-blood type isoagglutinin titers below 1:8 to minimize risk of antibody-mediated rejection 3
Early Post-Transplant Period (Weeks 1-4)
- Maintain triple immunosuppression with tacrolimus, mycophenolate mofetil, and corticosteroids 4, 5
- Consider additional rituximab dose (375 mg/m²) if CD19+ B-cell counts begin to rise or antibody titers increase 6, 5
- Continue monitoring anti-blood type isoagglutinin titers twice weekly, then weekly as they stabilize 3
- Perform liver function tests daily, with vigilance for signs of antibody-mediated rejection 1
Maintenance Phase (Beyond 1 Month)
- Continue triple immunosuppression with target tacrolimus trough levels appropriate for post-liver transplant patients 1
- Monitor anti-blood type isoagglutinin titers weekly initially, then monthly as they stabilize 3
- Perform surveillance liver biopsies at 1,3, and 6 months post-transplant to detect subclinical rejection 5
Management of Suspected Antibody-Mediated Rejection
First-Line Treatment
- Intensify immunosuppression with high-dose corticosteroids (methylprednisolone 500-1000 mg/day for 3 days) 1
- Resume plasma exchange (daily sessions) with IVIG (0.5-1 g/kg after each session) 1, 2
- Increase tacrolimus target trough levels 1
Second-Line Treatment
- If no response to first-line treatment within 2-3 days, consider additional rituximab (375 mg/m²) 1, 6
- Consider eculizumab to inhibit complement activation in severe cases 1
Monitoring Protocol
- Anti-blood type isoagglutinin titers: Daily initially, then twice weekly until stable, then weekly/monthly 3
- CD19+ B-cell counts: Weekly for first month, then monthly until 6 months 3
- Liver function tests: Daily initially, then as clinically indicated 1
- Surveillance liver biopsies: At 1,3, and 6 months post-transplant 5
- Monitor for infections, particularly CMV and HCV reactivation, which may be more common in ABO-incompatible recipients 3
Special Considerations
- Patients with hepatitis C may require more careful monitoring as they are prone to accelerated viremia and CMV antigenemia under this protocol 3
- The duration of plasma exchange and IVIG therapy should be guided by anti-blood type isoagglutinin titers rather than a fixed schedule 3
- Splenectomy is no longer routinely recommended when rituximab is used 4, 7
- Local graft infusion therapy and cyclophosphamide have been discontinued in modern protocols due to adverse events 5
Pitfalls to Avoid
- Failure to monitor anti-blood type isoagglutinin titers regularly may lead to missed early signs of antibody-mediated rejection 3
- Excessive immunosuppression increases risk of infections, particularly CMV and fungal infections 3
- Inadequate immunosuppression may lead to antibody-mediated rejection manifesting as diffuse intrahepatic biliary strictures 5
- Delayed recognition and treatment of antibody-mediated rejection can lead to graft loss and mortality 5
This protocol has demonstrated excellent outcomes with graft survival rates comparable to ABO-compatible liver transplantation when properly implemented 4, 5.