Can Liver Transplant Recipients Safely Lower Immunosuppression?

With more liver transplant recipients surviving for decades, the long-term toxicity of immunosuppression has become a central concern in posttransplant care, according to Timucin Taner, MD, PhD, a transplant surgeon at Mayo Clinic in Rochester, Minnesota. Taner addressed the challenge during a session at AASLD The Liver Meeting 2026 on balancing immunosuppression minimization or discontinuation against the risk of rejection.¹

In an interview with HCPLive, Taner noted 20-year survival after liver transplant now exceeds 50%, a trade-off accompanied by metabolic complications and heightened infection and cancer risk from global immunosuppression. A European single-center analysis of 313 recipients reported 20-year patient survival of 52.5%, with infection and de novo malignancy among the most common causes of death. Impaired renal function at 6 months was also associated with long-term survival in the analysis.² Taner emphasized the goal is reducing exposure while maintaining enough immunosuppression to protect the graft.

Should Clinicians Reduce or Withdraw Immunosuppression After Liver Transplant?

Taner drew a clear distinction between lowering immunosuppression and stopping it entirely. Complete withdrawal requires protocol biopsies to detect graft injury and safeguards to restart therapy quickly if rejection develops.

“Immunosuppression withdrawal should only be done in trial settings under guidance and under necessary precautions to restart immunosuppression,” Taner said.

Reduction, by contrast, is an approach most patients could likely benefit from, he said. Timing matters, and most programs begin tapering after the first posttransplant year, continuing toward the lowest level each patient tolerates.

Patient selection remains difficult. Most minimization studies to date have excluded patients transplanted for autoimmune liver diseases, given their presumed higher rejection risk. Taner suggested starting with recipients transplanted for alcohol-associated or metabolic dysfunction-associated liver disease, who may also gain the most given their metabolic burden.

Withdrawal trials illustrate both the promise and the limits of this approach. In a multicenter trial of stable pediatric liver transplant recipients, 37.5% were operationally tolerant after complete immunosuppression withdrawal, and allograft histology did not deteriorate in tolerant or nontolerant participants. Rejection typically occurred at 32% or less of the trial-entry immunosuppression dose and resolved with corticosteroids and/or tacrolimus.³

Why Are Biomarkers the Biggest Gap in Immunosuppression Minimization?

According to Taner, the absence of reliable tools to detect rejection remains the central barrier, leaving liver biopsy as the primary means of monitoring patients during reduction.

“The biomarker field is not there yet,” Taner said.

Recent trial data reinforce this point. The European LIFT trial randomized 116 adult liver transplant recipients to biomarker-guided or nonbiomarker-guided immunosuppression withdrawal using a liver tissue transcriptional test of tolerance, and 80 patients initiated withdrawal. The trial was terminated early after an interim analysis showed poor diagnostic performance, with a positive predictive value of 16%, negative predictive value of 81%, and accuracy of 44%.⁴

Investigators concluded withdrawal was feasible in selected recipients but succeeded in a much lower proportion of patients than originally estimated.⁴ Taner said efforts to reduce immunosuppression should continue with close follow-up and a backup plan to resume therapy, while larger trials work to validate biomarkers capable of guiding these decisions.

References:

1. Taner T. The challenge in balancing immunosuppression minimization or discontinuation with the risk of various types of rejection. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.

2. Schoening WN, Buescher N, Rademacher S, et al. Twenty-year longitudinal follow-up after orthotopic liver transplantation: a single-center experience of 313 consecutive cases. Am J Transplant. 2013;13(9):2384-2394. doi:10.1111/ajt.12384

3. Feng S, Bucuvalas JC, Mazariegos GV, et al. Efficacy and safety of immunosuppression withdrawal in pediatric liver transplant recipients: moving toward personalized management. Hepatology. 2021;73(5):1985-2004. doi:10.1002/hep.31520

4. Vionnet J, Miquel R, Abraldes JG, et al. The clinical utility and safety of biomarker-guided immunosuppression withdrawal in liver transplantation: the LIFT prospective RCT. Efficacy Mech Eval. 2025;12(3). doi:10.3310/FWXV5380