LIVER TRANSPLANTATION AND IMMUNOSUPPRESSION

Important issues:

• A major barrier to increasing the number of liver transplantations performed is the ever increasing shortage of livers/available donors

  • > 16,000 patients are on the transplant waiting list

  • between 4-5,000 transplants performed each year

  • approx 2,000 pts died in 1999 while on the list

• Possible solutions presently undergoing investigation to improve the donor shortage include:

  • Increasing the number of donors through education of hospital staff re: appropriate donors and “the public” re: organ donation awareness

  • Expanded use of donors:

    • Hep B or Hep C positive donors for Hep B or Hep C infected recipients (or non-infected recipients)

    • Use of older donors (> 50 years old)

    • “Split livers” to provide 2 organs from one donor

    • Adult to Adult and Adult to Child living related donation

    • Non-heart beating donors (undergoing investigation)

• “Future” therapies may include Xenotransplantation (? Transgenic pig) and Hepatocyte transplantation

• Short term and long term immunosuppression related complications

  • Prednisone

    • Diabetes, osteoporosis, risk of infection

  • Cyclosporine

    • HTN, renal insufficiency, neurotoxicity, gingival hyperplasia, hypertrichosis, increased triglycerides

  • Tacrolimus

    • HTN, renal insufficiency, neurotoxicity, hyperglycemia

  • Mycophenolate mofetil

    • Abdominal pain, diarrhea, leucopenia

• In an attempt to minimize post transplant nephrotoxicity, alternative immunosuppressive agents are being investigated

  • Sirolimus (in combination with low dose Cyclosporine or Tacrolimus)

    • Decreased nephrotoxicity, but associated with hyper-lipidemia, bone marrow suppression

  • Il-2 receptor antibodies

    • Basiliximab

    • Daclizumab

  • Thymoglobulin

• Finally, the “Holy Grail” of liver or any other organ transplantation is the induction of tolerance (i.e. the immune system of the recipient recognizes donor tissue as “self”). Ongoing studies towards inducing tolerance include:

  • Understanding how Chimerism, induced by the migration of “passenger lymphocytes” or other cells of donor origin from the liver to the periphery, and migration of recipient derived macrophages into the donor liver effects tolerance

  • Tolerance induction using donor derived bone marrow