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Related Experiment Video

Updated: Jun 3, 2026

Operant Procedures for Assessing Behavioral Flexibility in Rats

Operant Procedures for Assessing Behavioral Flexibility in Rats

Published on: February 15, 2015

Operational tolerance: past lessons and future prospects.

Josh Levitsky¹

¹Division of Hepatology and Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. j-levitsky@northwestern.edu

Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society

|March 9, 2011

Summary

This summary is machine-generated.

Liver transplant patients often discontinue immunosuppressive (IS) therapy due to side effects. Achieving operational tolerance without IS is rare, necessitating lifelong therapy and highlighting the need for better strategies.

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Area of Science:

Immunology
Transplantation Medicine
Pharmacology

Background:

Maintenance immunosuppressive (IS) therapy after liver transplant (LT) carries significant risks, including cardiovascular disease, infections, and malignancy.
Calcineurin inhibitors (CNI), a cornerstone of IS, are linked to high rates of chronic kidney disease and mortality in LT recipients.
Current IS withdrawal protocols are not standard-of-care due to high failure rates and risk of rejection.

Observation:

Some LT recipients can successfully discontinue IS therapy, achieving operational tolerance with normal allograft function.
However, the majority of patients fail IS withdrawal attempts, requiring re-initiation of therapy to prevent acute rejection or hepatitis.
Detrimental effects of long-term IS therapy underscore the need for alternative approaches.

Findings:

Strategies for IS withdrawal are being explored, including dose minimization, alternative agents, and complete withdrawal.
Biomarker assays are needed to identify patients with potential for tolerance.
Controlled approaches to IS withdrawal are crucial for improving success rates.

Implications:

Developing reliable biomarkers and tolerogenic conditioning strategies could enable systematic IS withdrawal in LT recipients.
Successful IS withdrawal could reduce long-term morbidity and mortality associated with immunosuppression.
This research paves the way for personalized, less toxic post-transplant management strategies.