Can transplant rejection occur more than 20 years after transplantation?

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Last updated: July 7, 2025View editorial policy

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From the Guidelines

Transplant rejection can occur more than 20 years after transplantation, and it is crucial for patients to continue taking immunosuppressive medications and undergo regular monitoring to prevent and detect late rejection. This is known as late or chronic rejection and can happen at any time after transplant, even decades later [ 1 ]. Patients who have received organ transplants must continue taking immunosuppressive medications for life to prevent rejection, including drugs like tacrolimus, cyclosporine, mycophenolate mofetil, sirolimus, or prednisone.

The dosage typically decreases over time but complete discontinuation is rarely recommended. Regular monitoring through blood tests, biopsies, and clinical evaluations remains essential even decades post-transplant [ 1 ]. Late rejection occurs because the recipient's immune system can still recognize the donor organ as foreign tissue despite years of stable function. Risk factors for late rejection include:

  • Medication non-adherence
  • Reduction in immunosuppression
  • Intercurrent infections
  • Development of donor-specific antibodies

Patients should report any changes in organ function promptly, such as decreased urine output for kidney transplants, shortness of breath for lung or heart transplants, or jaundice for liver transplants, as early intervention improves outcomes in late rejection episodes [ 1 ].

From the Research

Transplant Rejection After 20 Years

  • Transplant rejection can occur at any time after transplantation, including more than 20 years later 2.
  • The incidence of chronic rejection is low in living donor liver transplant (LDLT) patients, with a reported incidence of 1.9% in one study 2.
  • Factors that may contribute to late rejection include noncompliance with immunosuppression, cytomegalovirus (CMV) viremia, acute cellular rejection, and history of anastomotic biliary strictures 2.
  • Treatment with mammalian target of rapamycin (mTOR) inhibitors can reverse graft dysfunction in approximately half of patients with chronic rejection 2.
  • Subclinical rejection, defined as histologic acute rejection in the absence of graft dysfunction, is also possible, although its incidence is reported to be low in tacrolimus-treated renal allograft recipients, at around 2.6% 3.
  • Acute rejection episodes, including late acute rejection, can increase the risk of allograft failure, highlighting the importance of compliance with immunosuppressive therapy and monitoring for signs of rejection 4, 5.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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