Posttransplant metabolic syndrome in children and adolescents after liver transplantation: A systematic review

Abstract

In long-term follow-up, 18-67% of pediatric liver transplant recipients are overweight or obese— with rates varying by age and pre-transplant weight status. Similar prevalence of post-transplant obesity is seen in adults. Adults also develop post-transplant metabolic syndrome, with consequent cardiovascular disease, at rates that exceed age and gender-matched populations. Post-transplant metabolic syndrome has never been studied in pediatric liver transplant recipients—a growing population as transplant outcomes continue to improve. This paper systematically reviews the literature on each component of metabolic syndrome—obesity, hypertension, dyslipidemia, and glucose intolerance—in pediatric liver transplant recipients. Rates of obesity are similar to that of the general U.S. population of children. But hypertension, dyslipidemia, and diabetes are more common than expected for age, gender, and obesity severity in transplant recipients. Immunosuppressive medications are major contributors. Limitations of prior studies—including heterogeneous methods of diagnosis, follow-up times, and immunosuppressive regimen—hinder the analysis of risk factors. Importantly, no studies report on graft or patient outcomes associated with metabolic syndrome components after pediatric liver transplant. However, if trends in children are similar to those seen in adults, these conditions may lead to significant long-term morbidity. Further research on the prevalence, causes, and consequences of post-transplant metabolic syndrome in pediatric liver transplant is needed and ultimately will help improve long-term outcomes.

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

“…Prevalence of PTMS in the WISP-R cohort and among matched controls appeared to be higher than in the general U.S. pediatric population—as has been hypothesized by previous studies (Table 3) (4). …”

“…However, UNOS data suggests that 20–50% of these children are overweight or obese in long-term follow-up (3). Hypertension, dyslipidemia and diabetes appear to be more common than expected for age, gender and obesity severity (4). …”

Keys to long-term care of the liver transplant recipient

“…Paediatric patients often have a longer life time exposure to immunosuppressive treatments and resulting adverse effects than many adult recipients. 12,13 Malignancies such as lymphoproliferative disease after transplantation are more prevalent in children than in adults. 14 Paediatric recipients have a longer lifetime expectancy of the allograft, but frequently struggle with medication compliance as they emerge from adolescence.…”

Prediabetes in Pediatric Recipients of Liver Transplant: Mechanism and Risk Factors

“…It describes the β-cell secretion capacity; lower CIRs suggests insulin hyposecretion for the glucose level, and higher CIR suggests insulin hypersecretion. (21) We thus used CIR to investigate (1) whether insulin hypo- or hypersecretion drove IGT and (2) whether predictors contributed to IGT by reducing insulin secretion or causing insulin resistance. Calcineurin inhibitor exposure was our main predictor of interest; we considered both current exposure (medication, trough at study visit) and chronic exposure (years since transplant, in those on tacrolimus at study visit).…”

“…(1) In pediatric liver transplant recipients, diabetes prevalence estimates have ranged from 1.2–14.1% depending on the diabetes definition and patient cohort, but existing studies focus on symptomatic diabetes early post-transplant. (2,3) Neither the long-term impact of diabetes, nor the prevalence of pre-diabetes, which includes impaired glucose tolerance (IGT; blood glucose ≥140mg/dL, 2 hours after glucose load) and impaired fasting glucose (IFG; fasting glucose ≥100mg/dL), have been systematically studied in these children. (4,5) In non-transplanted children, glucose intolerance in childhood increases the risk of diabetes, cardiovascular disease, and premature death in adulthood.…”