Metabolic Syndrome Components After Pediatric Liver Transplantation: Prevalence and the Impact of Obesity and Immunosuppression

Metabolic syndrome is associated with long-term morbidity and mortality after adult liver transplant (LT). Whether pediatric LT recipients have a higher prevalence of metabolic syndrome remains controversial. In a cross-sectional study, we evaluated pediatric LT recipients aged 8–30 years using National Health and Nutrition Examination Survey (NHANES) protocols. LT recipients were matched by gender, race/ethnicity, and age with controls from NHANES. Pediatric LT recipients (n=83), after adjusting for overweight/obesity and glucocorticoid use, had increased prevalence of pre-hypertension and hypertension, impaired glucose tolerance (IGT; 2-hour glucose after oral glucose tolerance test ≥ 140mg/dL), and low HDL than matched NHANES controls (n=235) despite a lower prevalence of overweight/obesity. Among LT recipients, the adjusted odds of IGT doubled for every 7.5 years on calcineurin-inhibitors (CNIs, OR 2.10, 95% CI 1.06–4.17 per 7.5 years on CNIs, p=0.03). Among all subjects with IGT, LT recipients had a lower prevalence of overweight/obesity and less insulin resistance (HOMA-IR) than controls with IGT. Among normal weight subjects, LT recipients were significantly more likely than controls to have pre-hypertension/hypertension, IGT, low HDL, and metabolic syndrome. Pediatric LT recipients have unique metabolic syndrome profiles and risk factors, and will require tailored screening and management protocols

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