Posttransplant Metabolic Syndrome in the Withdrawal of Immunosuppression in Pediatric Liver Transplant Recipients (WISP‐R) Pilot Trial

Posttransplant metabolic syndrome (PTMS)—obesity, hypertension, elevated triglycerides, low HDL and glucose intolerance—is a major contributor to morbidity after adult liver transplant. This analysis of the Withdrawal of Immunosuppression in Pediatric Liver Transplant Recipients (WISP‐R) pilot trial is the first prospective study of PTMS after pediatric liver transplant. Twenty children were enrolled in WISP‐R, at median age 8.5 years (IQR 6.4–10.8), and weaned from calcineurin‐inhibitor monotherapy. The 12 children who tolerated complete immunosuppression withdrawal were compared to matched historical controls. At baseline, 45% of WISP‐R subjects and 58% of controls had at least one component of PTMS. Calcineurin‐inhibitor withdrawal in the WISP‐R subjects did not impact the prevalence of PTMS components compared to controls. At 5 years, despite weaning off of immunosuppression, 92% of the 12 tolerant WISP‐R subjects had at least one PTMS component and 58% had at least two; 33% were overweight or obese, 50% had dyslipidemia, 33% glucose intolerance and 42% systolic hypertension. Overweight/obesity increased the risk of hypertension in all children. Compared to controls, WISP‐R tolerant subjects had similar GFR at baseline but did have higher GFR at 2, 3 and 4 years. Further study of PTMS and immunosuppression withdrawal after pediatric liver transplant is warranted. In this pilot trial of calcineurin‐inhibitor withdrawal in pediatric liver transplant recipients, complete discontinuation of immunosuppression improves glomerular filtration rate but not metabolic syndrome or its components, which are more prevalent than expected for age and obesity in both participants and historical controls.