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Nutritional Support in children for Liver Transplantation for End stage Liver Disease
Malnutrition and growth failure is present in more than 50% of children with end stage liver diseases (ESLD) at the time of liver transplantation. Growth retardation in children with ESLD is also one of the indications for liver transplantation for some cholestatic liver diseases. Liver transplantation has been shown to improve the nutrition in terms of all anthropometric parameters with significant catch-up growth at 1-year posttransplantation. Improved nutritional status was associated with increased muscle bulk and subsequent improvement in motor scores. Malnutrition, in itself, is an important risk factor for complications and survival post-liver transplantation. Major complications such as uncontrolled ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome have been shown to occur in 65.5% of malnourished patients versus 11.8% of well-nourished ones. As nutritional status at transplantation is a significant factor in both morbidity and mortality post liver transplantation, proper evaluation of malnutrition and intensive nutritional support pre-transplant is vital.

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Etiology of malnutrition in ESLD: As liver plays a central role in protein, carbohydrate and lipid metabolism, end-stage liver disease interferes with the patients nutrition status by either interrupting a key metabolic process or allowing a metabolic imbalance to persist. Malnutrition in end-stage liver disease has varied etiology and is attributed to various processes such as fat malabsorption, hypoalbuminemia, metabolic alterations like hypercatabolism, increased energy expenditure, increased lipid utilization, insulin resistance, defective glucose storage, enhanced thermogenesis, and overall negative energy balance, recurrent infections, anorexia and alterations in the growth hormone (GH) axis and GH resistance.

Nutritional assessment in children with ESLD: Assessment of malnutrition by anthropometric indices by parameters dependent on weight, like weight-for-age and weight-for-height and body mass index, often overestimates nutritional adequacy because of presence of ascites and edema secondary to excessive tissue sequestration of water, poor intravascular colloid osmotic status, renal retention of salt and water, and hyperaldosteronism. Also, enlarged liver and spleen addup to the inflated weight of a cirrhotic child. Instead, serial estimates of body fat using triceps and subscapular skinfold thickness and of body protein using mid-arm muscle circumference compared with age- and height-matched normal values are a better estimation of nutritional status in ESLD. Nutritional management: Energy: The goal for caloric intake should be approximately125% of the recommended dietary allowance (RDA) based on ideal body weight (50th percentile of weight for

height). Children with severe growth retardation may need additional calories (150200%) to allow catch-up growth. The infant formula can be mixed with less water to provide 24 or 27 kcal/oz. Alternatively, glucose polymers (8 cal/teaspoon of Polycose powder) or medium-chain triglycerides (7.7 cal/mL) can be added to the standard 20 cal/oz dilution of the formula. Feeding can be given either orally or via nagogastric tube. Whenever possible, oral feeding is preferred. Compared with bolus gavage feeding techniques, continuous formula infusion leads to better energy balance and reduces the hazard of significant regurgitation. The advantage of nocturnal nasogastric feedings is that it can be safely administered at home. Percutaneous endoscopic gastrostomy tubes are generally not advocated in this setting because of deranged coagulation profile, thrombocytopenia related to hypersplenism and platelet dysfunction, and also associated portal hypertensive gastropathy and gastric varices which make the feasibility of the procedure unlikely. Fat: Infant formulas containing significant quantities of medium chain triglycerides (MCTs) containing 8 to 12 chain fatty acids, provide better energy balance during cholestasis. MCTs, unlike long-chain triglycerides (LCTs), do not require bile acid micelles for solubilisation, are relatively water soluble and directly absorbed into the portal circulation. Pregestimil and Alimentum are MCT oil predominant formulas frequently used in cholestasis and contain approximately 60% and 50% of fat calories as MCT oil, respectively. Corn oil or safflower oil, with 5.4 and 7.2 g linoleic acid/mL, respectively may be added to foods to supply essential fatty acids accordingly. Protein: Protein intake should be preserved between 23 g/kg/day in children with ESLD awaiting liver transplantation while delivering optimal energy intake. BCAA-enriched formula has been shown to improve nutritional status and body composition in children with ESLD. However, MCT-containing complete BCAA formulas are rather expensive and not readily available. In case of hepatic encephalopathy, the usual dogma is to prefer vegetable proteins and restrict protein intake to 0.51.0 g/kg/day. Vitamins: Fat soluble vitamins should be given 3-10 times of recommended dietary allowance (RDA). Water soluble vitamins are prescribed in a dose of 1-2 times of RDA. Mineral and trace elements: Calcium is supplemented in a dose of 25100 mg/kg/day up to 8001200 mg/day and phosphorus 2550 mg/kg/day up to 500 mg/day. In cases of magnesium deficiency (serum magnesium < 1.4 mEq/L) magnesium oxide is given orally is given in a dose of 12 mEq/kg/day. Iron is supplemented in cases of confirmed deficiency with ferrous sulphate or gluconate in dose of 5-6 mg/kg/day of elemental iron. Zinc and selenium are supplemented in doses of 1-2 mg/kg/day and 1-2 g/kg/day, respectively. Problems in children: Although salt restriction is very much feasible in adult patients who present with ascites or restriction of proteins is acceptable in those presenting with early grades of encephalopathy, concerns of palatability and poor intake come in way while managing a child with ESLD.

Post-transplant growth failure: After liver transplantation, most children show very good catch-up growth, but persistent growth failure may be seen in 15% to 20% of children. The origin of posttransplant growth failure is complex. It is related to the degree of preoperative malnutrition. Also, use of glucocorticoids and immunosuppressant medications has significant effect on growth. Significant hepatic dysfunction such as chronic rejection or the development of lymphoproliferative disease that requires alteration in immunosuppressive regimes or prolonged hospitalization may also inhibit linear growth. Certain transplant procedures necessitating extensive dissection around the vena cava like those where jump grafts between portal vein and inferior vena cava are constructed, there is risk of chylous ascites secondary to lymphatic rupture. In such a scenario, complete restriction of fat with use of total MCT based preparations like Portagen or Monogen are needed for 6-12 weeks. Important strategies to prevent posttransplant growth failure thus include early referral for liver transplantation before the development of malnutrition, a multidisciplinary approach to pre- and postoperative nutritional intervention, and the early withdrawal of steroid therapy after transplantation. References: 1. Kelly DA. Nutritional factors affecting growth before and after liver transplantation. Pediatr Transplant. 1997 Aug;1(1):80-4. 2. van Mourik ID, Beath SV, Brook GA, Cash AJ, Mayer AD, Buckels JA, Kelly DA. Long-term nutritional and neurodevelopmental outcome of liver transplantation in infants aged less than 12 months. J Pediatr Gastroenterol Nutr. 2000 Mar;30(3):269-75. 3. Mike A. Leonis, William F. Balistreri. Evaluation and management of endstage liver stage in children. Gastroenterology Volume 134, Issue 6, Pages 1741-1751 4. Roberts GA, Holt RI, Ghatei MA, Baker AJ, Bloom SR, Miell JP. Serum leptin and insulin in paediatric end-stage liver disease and following successful orthotopic liver transplantation. Clin Endocrinol (Oxf). 1998 Apr;48(4):401-6. 5. Kelly DA. Posttransplant growth failure in children. Liver Transpl Surg. 1997 Sep;3(5 Suppl 1):S32-9. 6. Uslu N, Saltik-Temizel IN, Demir H, Usta Y, Ozen H, Grakan F, Yce A, Koak N. Bone mineral density in children with cirrhosis. J Gastroenterol. 2006 Sep;41(9):873-7.

7. Schneider AC, Pinto RB, Silveira TR. Nutritional risk and malnutrition determination by anthropometry in cirrhotic children and adolescents. Arq Gastroenterol. 2007 Oct-Dec;44(4):345-9. 8. Holt RI, Baker AJ, Jones JS, Miell JP. The insulin-like growth factor and binding protein axis in children with end-stage liver disease before and after orthotopic liver transplantation. Pediatr Transplant. 1998 Feb;2(1):76-84.

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