Immunosuppressive Drug Levels in Liver Transplant Recipients: Impact in Decision Making

Abstract

To prevent rejection, liver transplant providers largely base their management decisions on their clinical impression and pharmacokinetics. Clinical impression relies on assessing graft function, liver enzymes, and biopsy. High immunosuppressive drug levels, although minimizing rejection, are related to significant side effects such as nephrotoxicity and metabolic syndrome, contributing to long-term morbidity and mortality. Similarly, levels that are lower than necessary can decrease the rate of side effects with a potential toll on rejection and graft survival. Herein, the authors present an update on immunosuppressive drug level monitoring and manipulation strategies according to different scenarios and time from transplant. They also provide a brief overview of next level immunosuppression monitoring strategies that aim to properly balance rejection rates with drug side effect profiles.

Donor-derived cell-free DNA levels predict graft injury in liver transplant recipients

“…As a result, there is a strong interest in IS minimization protocols to both prevent and treat IS complications, including nephrotoxicity due to CNI therapy among others 13,34–41 . Yet without specific tests indicating the onset of immune activation, clinicians currently perform arbitrary ‘trial and error’ IS reductions which can trigger rejection and alternatively the need for higher prolonged IS dosing and worse overall outcomes 5,42–47 . To mitigate this risk, non‐invasive biomarkers that can signal immune activation and imminent graft dysfunction in the context of IS tapering would be a welcome addition to LTR management.…”

Exosome‐based targeted RNA delivery for immune tolerance induction in skin transplantation

“…Organ transplantation is the most effective approach for the treatment of various end‐stage organ diseases, but DCs of recipients may recognize the antigens of the graft and deliver these antigens to T cells or B cells by direct recognition or indirect recognition, causing rejection (Marin, Cuturi, & Moreau, ; Thomson & Ezzelarab, ). Currently, immunosuppressive drugs are the primary strategy for the clinical prevention and treatment of transplant rejection, but their long‐term use often cause various side effects (Kourkoumpetis & Levitsky, ; Li et al, ). In consideration of the critical role of DCs in transplantation immunity, DCs were chosen as the target cells to induce immune tolerance.…”

A practical guide to real‐world implementation of pre‐emptive therapy for Cytomegalovirus disease prevention in high‐risk seronegative liver transplant recipients with seropositive donors

“…We limit CMV surveillance to the first 3 months post transplant when regular labs are part of the standard of care to encompass the duration during which new-onset primary donor-transmitted CMV infection in CMV D + R − LTRs occurs. 3,9,23 The 3-month surveillance period reflects the protocol used in the CAPSIL study and is supported by major society guidelines. 1,2 This approach minimizes the burden of extra blood draws and concentrates resources to the period of highest impact.…”