Long-term renal benefit of a biopsy-guided personalized calcineurin inhibitor-sparing regimen late after liver transplantation

Long-term success after liver transplantation (LT) is often hindered by side effects from lifelong immunosuppression (IS). Standard liver enzyme tests are poor indicators of graft inflammation or fibrosis. To address this, a program of surveillance liver biopsy (svLbx)-guided personalized IS has been implemented to inform decisions on IS minimization. This study, spanning from 2018 to 2024, extends previous short-term observations to assess the long-term impact of biopsy-guided Calcineurin Inhibitor (CNI) reduction in LT recipients, including follow-up biopsies. Patients’ IS was adjusted based on svLbx findings, donor-specific antibodies, liver function, and comorbidities. Analyzing 242 LT recipients, the study compared outcomes in those whose CNI dosage was reduced (n=89) versus those whose dosage was maintained or increased (n=83). CNI reduction proved safe, with no increase in rejection, graft loss or death. Crucially, it significantly preserved kidney function (ΔeGFR: +0.5 vs. −6.5 mL/min) over a median follow-up of 47 months, even when controlling for baseline kidney function, CNI score, graft injury and time post-LT. Sequential biopsies revealed no worsening of fibrosis or inflammation, and non-invasive measures corroborated these findings. In conclusion, svLbx-guided CNI reduction safely maintains kidney function and prevents graft injury late after LT, making it a viable strategy for long-term IS minimization.