Complete Immunosuppression Withdrawal After Liver Transplantation: An International Multicenter Study

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Angelico R., Sensi B., Tisone G., Feng S., Roll G. R., Herrero I., ...Daha Fazla

Clinical Gastroenterology and Hepatology, 2026 (SCI-Expanded, Scopus)

Özet

Background & Aims 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. Methods 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. Results 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). Conclusions 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.