From the Guidelines
Operational tolerance in liver transplantation is a state where approximately 20% of long-term surviving adult recipients and 30% of pediatric recipients can maintain normal graft function without immunosuppressive medications, but attempts at immunosuppression withdrawal should only be made under close monitoring due to the risk of rejection 1. This phenomenon is characterized by the ability of the transplant recipient to tolerate the graft without the need for immunosuppressive drugs, which can have significant side effects such as nephrotoxicity, increased cancer risk, metabolic complications, and opportunistic infections. Key characteristics of operational tolerance include:
- The ability to discontinue all immunosuppressive drugs without experiencing rejection
- Normal liver function tests
- A stable clinical course for at least 3-5 years post-transplant
- No history of autoimmune disease The liver's unique immunological properties, including its dual blood supply, large size, regenerative capacity, and presence of resident immunoregulatory cells, contribute to this tolerance 1. However, complete withdrawal of immunosuppression should not be an aim of standard care, and attempts at withdrawal should be made with caution and close monitoring of rejection, including histological assessments 1. Regular monitoring of liver function is crucial to detect any signs of rejection, and withdrawal of immunosuppression should only be attempted under strict medical supervision in carefully selected patients. The benefits of achieving operational tolerance include eliminating the significant side effects of long-term immunosuppression, but there is no evidence indicating that successful immunosuppression withdrawal results in improved clinical outcomes 1.
From the Research
Definition and Prevalence of Operational Tolerance
- Operational tolerance after liver transplantation has been described in around 20% of the recipients, where patients are able to maintain a normal graft function in the absence of immunosuppressive drugs 2.
- The rate of operational tolerance varies considerably, ranging from 15% to less than 5% of the total liver transplant patient population, depending on the center and patient population 3.
- Operational tolerance is more common in liver transplantation than in other types of organ transplantation, with the liver being considered an immune-privileged organ 4.
Characteristics and Sustainability of Operational Tolerance
- Patients with operational tolerance can maintain a stable and normal graft function without immunosuppressive drugs, but this state is not always permanent 5.
- A 10-year prospective study found that 61% of patients with operational tolerance maintained it for a median of 10.4 years, while 39% lost tolerance after a median of 3.2 years 5.
- Factors such as the time from transplantation, rapidity of weaning, and maintenance and induction immunosuppression may contribute to the variation in operational tolerance rates 3.
Monitoring and Maintenance of Operational Tolerance
- Regular follow-up, laboratory monitoring, and surveillance biopsies are essential for patients who are clinically stable off immunosuppression to rule out subclinical rejection 5.
- There is a need for reliable immunological parameters to identify patients who can be withdrawn from immunosuppressants without the risk of rejection 4.
- Collaboration between clinicians, immunologists, and basic scientists is desirable to achieve a better understanding of operational tolerance and to develop strategies for its maintenance 4.