Complete Immunosuppression Withdrawal After Liver Transplantation: An International Multicenter Study

Immunosuppression withdrawal after liver transplantation is feasible in selected individuals but the risk of chronic graft damage is unknown. We aimed to describe the clinical characteristics and long-term outcomes of patients with successful immunosuppression withdrawal after liver transplantation.

This was a retrospective cohort study involving 31 liver transplantation centers in 15 countries. Adult and pediatric patients with complete immunosuppression withdrawal for ≥12 months following liver transplantation were eligible. We evaluated long-term outcomes, including evidence of histologic graft injury, rejection, and mortality.

In all, 287 patients (223 adults and 64 children) were included, representing 0.46% of the reference liver transplantation population. The median time from liver transplantation to immunosuppression withdrawal was 9.4 years, followed by 7.8 years of postwithdrawal follow-up. The most common reasons for immunosuppression withdrawal were participation in a clinical trial (53%), patient decision (25.1%), and immunosuppression-related side effects (16.7%). Immunosuppression withdrawal was associated with metabolic improvement including reductions in diabetes (34.1%-19.7%) and hypertension (58.7%-31.4%). Paired liver biopsies before and after immunosuppression withdrawal were available in 108 patients (37.6%), and among them, 43.5% achieved operational tolerance. Worsening fibrosis (≥1 Ishak's stage) and new-onset inflammation occurred in 30.5% and 22.2% of patients, respectively. Five-year overall survival after immunosuppression withdrawal was 93%, and no patient experienced immunologically mediated graft loss. Neither worsening fibrosis nor inflammation had an impact on mortality (hazard ratio, 1.77; 95% confidence interval, 0.63-4.96 and hazard ratio, 1.46; 95% confidence interval, 0.39-5.49, respectively).

Immunosuppression withdrawal after liver transplantation may improve metabolic comorbidities. Mild histologic graft changes may occur, but do not appear to affect long-term outcomes. Future studies should focus on safely expanding immunosuppression withdrawal to a broader subset of liver transplantation patients.