Figure 42.1 Height after paediatric LT. (a) Height z-score at yearly intervals from transplant by gender (mean ± standard error). (b) Change in height z-score from transplant to yearly follow-up intervals after transplant by gender (mean ± standard error). (From Alonso EM, et al., American Journal of Transplantation 2009, 9: 1389–1397. With permission.)
Improving linear growth potential before and after transplant is of utmost importance. Pretransplant nutrition should be maximised by providing necessary calories and vitamin replacements. Patients with cirrhosis may require 1.5–2 times the amount of calories required by healthy children. Unfortunately, despite careful attention to pretransplant nutrition, zHs at the time of transplant have not increased significantly over the last 20 years [4]. Posttransplant, improvement in linear growth has been achieved with early steroid withdrawal and by supplemental use of recombinant human growth hormone (rhGH) therapy [8]. The association between prolonged steroid use and linear growth impairment is well known [9]. Steroids negatively impact bone formation, impair GH release and can result in chronic graft dysfunction, which often leads to poor linear growth. Current immunosuppression protocols aim to eliminate steroids between 6 and 18 months if there are no signs of rejection or autoimmune hepatitis. Aggressive steroid-withdrawal protocols or steroid-free regimens have been shown to improve posttransplant linear growth [10,11].
Linear growth improvement has also been observed after administration of rhGH. In a European study, patients who were treated with rhGH had significant improvements in their zH without experiencing significant side effects [12,13]. rhGH treatment response has been shown to continue in the second and third treatment years without advancing bone age beyond chronologic age, suggesting no negative impact on adult height potential [12]. Improved mood, feelings of well-being and self-esteem have all been reported in children with short stature who were successfully treated with GH therapy [14]. Future research will be required to ensure that rhGH does not result in late allograft rejection. At this time, rhGH should only be considered for patients who are unlikely to reach an adult height greater than the fifth percentile.
Further studies will be necessary to evaluate how improvements in final adult height may improve the health-related quality of life (HRQOL) of LT recipients. Such understanding would be important in determining how heavily growth failure should be weighed in determining organ allocation.
Obesity and posttransplant metabolic syndrome (PTMS) are emerging problems that require careful attention by paediatricians caring for LT recipients. PTMS (obesity, hypertension, elevated triglycerides, low high-density lipoprotein [HDL] and glucose intolerance) has been identified as a major contributor to cardiovascular morbidity in adults after liver transplantation and has been associated with the de novo development of nonalcoholic fatty liver disease (NAFLD) [15,16]. About 30% of adult LT recipients are obese, and many suffer from comorbid diseases, including diabetes, hyperlipidaemia and hypertension [17]. Calcineurin inhibitors, which have been instrumental in preventing allograft rejection, may cause hypertension, dyslipidaemia and glucose intolerance, likely contributing to this morbidity.
United Network for Organ Sharing (UNOS) data suggests that up to 50% of paediatric LT recipients are overweight or obese in long-term follow-up [18]. Obesity-related comorbidities such as hypertension, dyslipidaemia and diabetes are more prevalent in paediatric LT recipients than in the general paediatric population [19]. In a cohort of 66 LT recipients with a median follow-up of 12 years, Kosola et al. reported an obesity prevalence of 20% and a PTMS prevalence of 14%. In this study, PTMS was more prevalent in older teens and those with elevated body mass index (BMI). However, even among children of normal weight, 40% had some component of PTMS (Figure 42.2). Liver steatosis was associated with the presence of metabolic syndrome. There was no association between obesity and PTMS with immunosuppressive medications [20]. In a prospective study of 12 paediatric LT recipients who had successfully undergone immunosuppression withdrawal, 17% had full PTMS and 58% had at least two components of PTMS, suggesting that immunosuppression alone is not entirely responsible for PTMS [21].
Figure 42.2 Metabolic syndrome. (a) Metabolic syndrome in paediatric LT recipients divided by weight. (b) Metabolic syndrome in paediatric LT recipients divided by age. (From Kosola S, et al., Liver Transplantation 2014, 20: 1185–1192. With permission.)
This data demonstrates the importance of screening for obesity, PTMS, hypertension, elevated triglycerides, low HDL and glucose intolerance in all paediatric LT recipients, even those patients on low or no immunosuppressive medication. Patients with components of metabolic syndrome are at risk for hepatic steatosis, NAFLD, cardiovascular disease and impaired long-term survival of the patient and the graft.
Chronic disease during childhood is known to have a negative impact on cognitive development [22]. Paediatric LT recipients are at even greater risk for cognitive delays, as they experience nutritional deficiencies and chronic hepatic encephalopathy before transplant, and are exposed to calcineurin inhibitors with neurotoxic potential after transplant [23]. Multiple studies have demonstrated that children who have survived LT are more likely to have significantly lower intelligence than healthy children [24–26]. In long-term follow-up after LT, patients have mean intelligence quotient (IQ) scores in the low normal range (IQ = 80–90), with up to 27% having IQ scores that indicate significant mental disability (IQ < 70) [24,26–28]. Transplant recipients often have impaired hearing, verbal and language skills [26
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