From Journal of Gastroenterology and Hepatology
Feeding the Child with Liver Disease
A Review and Practical Clinical Guide
Kathryn Mary Smart; George Alex; Winita HardikarAuthors and Disclosures
AbstractA Review and Practical Clinical Guide
Kathryn Mary Smart; George Alex; Winita HardikarAuthors and Disclosures
Nourishing children with liver disease is a challenging task; however, appropriate assessment and well-timed nutritional interventions are paramount for a good long-term outcome in these patients. An appropriate balance of macronutrients, micronutrients, and vitamins is important, as is the route of administration. This review aims to highlight the practical points in nutrition assessment and also provides a guide to the various nutritional interventions available for children with chronic liver disease.
Introduction
Pediatric liver disease is rare and has many varied etiologies. Nutrition management is dependent on whether the presenting liver disease is acute, chronic, or caused by an inborn error of metabolism. Optimal nutrition is important in preventing further damage to the liver by increasing energy available for synthesis, storage, and detoxification functions.[1] Nutrition also promotes growth, improves immunological status, and maximizes the success of liver transplantation.[2–5] Poor nutrition pretransplant in a child with chronic liver disease (CLD) can also contribute to long-term post-transplant complications, such as linear growth failure, delayed intellectual development, and metabolic bone disease.[2,4,6] These patients provide a significant challenge, especially when the liver disease is cholestatic and its onset is in the first months of life.[3,7,8] Portal hypertension, organomegaly, and ascites can all contribute to enteral feed intolerance, particularly in the young infant. In addition to these problems, the use of often unpalatable, modified formulas and dietary supplements provides a further challenge in the provision of optimal nutrition in these children.
CLD will be the main focus of this paper. The nutrition management of liver disease caused by inborn errors of metabolism is beyond the scope of this review.Chronic Liver Disease
The most common cause of CLD is extrahepatic biliary atresia, which in Australia, occurs in approximately one in 8000 live births.[9] Biliary atresia accounts for approximately 60% of children under the age of 2 years who require liver transplantation.[10] Other common chronic liver conditions requiring nutrition intervention are alpha-1-antitrypsin deficiency and Alagille's syndrome.[2]
Assessment
Assessment
A thorough nutrition assessment of a child with liver disease is essential.[11] This includes the collection of anthropometric and biochemical data, as well as a clinical, social, and dietary assessment.
Anthropometry
Infants over 8 kg at the time of transplant have a significantly greater chance of survival.[10] Unfortunately, weight alone is a poor indicator of nutrition status in patients where ascites and organomegaly are present. Regular abdominal girth measures can assist by indicating the likelihood of weight gain being attributable to ascitic fluid or nutrition-related growth. In many cases, actual or dry weight can only be approximated post-diuresis, with estimated organomegaly also considered.
Linear growth is a good indicator of long-term nutrition, but provides little guidance for acute management.Anthropometry
Infants over 8 kg at the time of transplant have a significantly greater chance of survival.[10] Unfortunately, weight alone is a poor indicator of nutrition status in patients where ascites and organomegaly are present. Regular abdominal girth measures can assist by indicating the likelihood of weight gain being attributable to ascitic fluid or nutrition-related growth. In many cases, actual or dry weight can only be approximated post-diuresis, with estimated organomegaly also considered.
Serial measurements of mid upper arm circumference (MUAC) and tricep skin folds (TSF) using standard technique can be used to calculate arm muscle area, which reflects muscle mass and is sensitive to nutrition status (Table 1).[11–13]
Percentile figures published by the World Health Organization Multicentre Growth Reference Study Group 2004, provide a reference for plotting MUAC, TSF, and also mid thigh circumference measures.[11,14] There is a strong correlation between liver disease severity evaluated by liver function tests and poor nutrition status estimated by anthropometric indicators.[15] It is important to note that circumferences and skin folds can be falsely increased by peripheral edema, thus anthropometric measures need to be used in conjunction with biochemical markers and clinical features in order to plan appropriate nutrition management.[2,11]
Dietary Assessment
A thorough diet history is essential and is best done by a dietician. This includes an assessment of the impact of the stage of liver disease on nutrition status and the ability of the child to feed, as well as social and cultural issues that affect the family's ability to administer and comply with a complex dietary regime.
Nutrition Requirements
Total Energy
Estimated energy requirements (EER) in infants < 12 months with CLD can be up to 150% of the nutrient reference value (NRV) for energy for age,[2,11] or initially 505–630 kJ/kg (120–150 kcal/kg). These infants are hypermetabolic, with an increase in resting energy expenditure of approximately 30% in end-stage liver disease.[16] Even older children might require 120–170% NRV for energy for age to maintain growth and development. These high energy requirements are likely to be due to disordered metabolism, leading to inefficient use of energy, increased respiratory effort due to ascites, or other disease-complications, such as variceal hemorrhage.[17]
Estimated energy requirements (EER) in infants < 12 months with CLD can be up to 150% of the nutrient reference value (NRV) for energy for age,[2,11] or initially 505–630 kJ/kg (120–150 kcal/kg). These infants are hypermetabolic, with an increase in resting energy expenditure of approximately 30% in end-stage liver disease.[16] Even older children might require 120–170% NRV for energy for age to maintain growth and development. These high energy requirements are likely to be due to disordered metabolism, leading to inefficient use of energy, increased respiratory effort due to ascites, or other disease-complications, such as variceal hemorrhage.[17]
Carbohydrate
Infants and children with chronic liver disease are at increased risk of fasting hypoglycemia. Reduced gluconeogenesis and capacity for glycogen storage are a result of reduced hepatocellular mass and compromised function.[18] Blood glucose levels should be monitored closely when a patient is fasted, and intravenous dextrose given to cover fasting for procedures (Table 2).
Infants and children with chronic liver disease are at increased risk of fasting hypoglycemia. Reduced gluconeogenesis and capacity for glycogen storage are a result of reduced hepatocellular mass and compromised function.[18] Blood glucose levels should be monitored closely when a patient is fasted, and intravenous dextrose given to cover fasting for procedures (Table 2).
Fat
With interrupted or absent bile flow, infants with cholestasis will malabsorb fat. Some evidence suggests that increasing total fat intake in these patients might increase absorption, despite causing steatorrhea.[2,19] However, medium-chain triglyceride (MCT) supplementation is commonly required to maintain growth. Total bilirubin > 100 μmol/L or conjugated bilirubin > 70 μmol/L might also indicate that MCT supplementation is needed. MCT are a readily-available energy source, as they do not require emulsification with bile and can be absorbed directly into the portal venous system. Recent literature suggests that between 30% and 70% of fat should be provided as MCT.[2,3] Less than this will lead to continued malabsorption and growth failure; however, providing > 80% of total fat as MCT increases the risk of essential fatty acid (EFA) deficiency.[19,20]
With interrupted or absent bile flow, infants with cholestasis will malabsorb fat. Some evidence suggests that increasing total fat intake in these patients might increase absorption, despite causing steatorrhea.[2,19] However, medium-chain triglyceride (MCT) supplementation is commonly required to maintain growth. Total bilirubin > 100 μmol/L or conjugated bilirubin > 70 μmol/L might also indicate that MCT supplementation is needed. MCT are a readily-available energy source, as they do not require emulsification with bile and can be absorbed directly into the portal venous system. Recent literature suggests that between 30% and 70% of fat should be provided as MCT.[2,3] Less than this will lead to continued malabsorption and growth failure; however, providing > 80% of total fat as MCT increases the risk of essential fatty acid (EFA) deficiency.[19,20]
EFA are the polyunsaturated fatty acids (PUFA) linoleic acid (C18:2) and α-linolenic acid (C18:3). These fatty acids cannot be produced endogenously and are precursors to long-chain PUFA (LCPUFA), which are important for growth and brain and eye development.[21] EFA deficiency is a risk in CLD due to both fat malabsorption and low EFA intake with high MCT diets.[20–22] The risk of EFA deficiency has also been shown to increase with progressive elevation of serum bilirubin.[21]
In chronic liver disease, there is also disturbed metabolism of LCPUFA. LCPUFA-supplemented formulas have been shown to improve LCPUFA status in infants with severe cholestasis.[23] It has been suggested that > 10% total energy should be provided as PUFA in children with cholestasis.[24] European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines suggest that infant formula should contain 4.5–10.8% energy as linoleic acid, and the ratio of linoleic : α-linolenic should be 1:5–15.[25]
Many centers have limited means to measure EFA levels, and more data are needed to show improved functional outcomes of EFA supplementation. However, it seems reasonable to assume that children with cholestasis will have greater EFA requirements, and they should be supplemented.[26] Based on best-estimate calculations and experience from other international centers, it is recommended that 0.7 mL walnut oil be given for every 420 kJ (100 kcal) of a 50% MCT-containing formula (e.g. Peptijunior Gold). This recommendation is for exclusively formula-fed infants. Older children can improve their EFA intake by adding other dietary sources to their diets, for example, canola, sunflower, and soybean oils. Fish oil and egg yolk are also good sources of LCPUFA.
Fat-soluble vitamins (FSV) are also malabsorbed in cholestasis, and regular supplementation and monitoring of blood levels is required (Table 3).
Protein
CLD alters amino acid metabolism, lowering blood levels of branched-chain amino acids (BCAA) and elevating levels of aromatic amino acids. While this is an observed phenomenon, the clinical outcome of nutrition supplementation has been inconclusive. Some studies have shown that adding BCAA to feeds can improve nitrogen retention, reduce protein catabolism, and increase protein synthesis.[27,28] Larger studies in adults have shown some reduction in the complication of cirrhosis,[29] but there have been no large-scale trials in pediatrics. The use of BCAA is also limited by cost and palatability. A Cochrane review of the use BCAA in children with liver disease is underway.
CLD alters amino acid metabolism, lowering blood levels of branched-chain amino acids (BCAA) and elevating levels of aromatic amino acids. While this is an observed phenomenon, the clinical outcome of nutrition supplementation has been inconclusive. Some studies have shown that adding BCAA to feeds can improve nitrogen retention, reduce protein catabolism, and increase protein synthesis.[27,28] Larger studies in adults have shown some reduction in the complication of cirrhosis,[29] but there have been no large-scale trials in pediatrics. The use of BCAA is also limited by cost and palatability. A Cochrane review of the use BCAA in children with liver disease is underway.
Table 3 summarizes macronutrient and micronutrient requirements for CLD.
Taking the above requirements into account, an ideal feed for infants with liver disease would be a palatable (whole protein) formula with 50% MCT, EFA levels within the ESPGHAN range, added LCPUFA, low osmolality, low sodium, and lactose free.At our institution we use Peptijunior Gold as the MCT-containing infant formula of choice, when combined with walnut oil supplementation. This best meets the nutrition requirements of infants, as outlined above. MCT Peptide 1+ is used for older children. Heparon Junior might also be used if available.
Feeding Plan for Infants with CLD
Oral Feeding
All infants should be encouraged to feed orally, unless they are unable to meet their energy needs, to maintain growth. Organomegaly and the complications of portal hypertension, including ascites, might result in gastroesophageal reflux and poor volume tolerance.
If growth is faltering and bile flow is compromised, then an MCT-containing formula (e.g. Peptijunior Gold) is required.[1] A breastfed infant should be offered an MCT-containing formula as complementary feeds, with a set volume offered at each feed, for example, 60 mL/kg formula is offered, then graded up to 120 mL/kg, depending on growth and tolerance. A bottle-fed infant should grade over from standard infant formula to an MCT-containing formula. If the formula is refused, then consider temporarily flavoring with vanilla essence (1–2 drops) or golden syrup (one-quarter teaspoon per bottle), with a reduction in flavoring once the infant is taking bottles well.
If the addition of an MCT-containing formula has not improved growth, then consider fortifying the formula from 280 kJ (13%) to 350 kJ (17%) or 420 kJ (20%)/100 mL to improve energy and nutrient intake to meet growth requirements. An MCT emulsion (e.g. Liquigen) can also be added to the feed, grading up to 4% of formula volume; for example, 420 kJ MCT-containing feed + 4% MCT emulsion = 490 kJ/100 mL. It is then important to supplement with 0.7 mL walnut oil per 420 kJ (100 kcal) of formula intake. This is best given as a split over the day, either orally via syringe or via a nasogastric (NG) tube flushed through thoroughly with water.The addition of Polyjoule is not recommended for infants, as it further decreases the protein : energy ratio of the feed.[5] It will also increase feed osmolality, further contributing to diarrhea.
The introduction of solids is essential to support the development of oral feeding skills. Exposure to solids at 6 months is encouraged, even if the child is not hungry and might only taste small amounts. Promote a positive oral experience and socialization around food, and encourage as rapid progression in texture as possible. If significant amounts are taken, consider adding extra energy to solids as PUFA, MCT emulsion, or MCT oil.If weight is static for up to 3 weeks or the child begins to cross percentiles in a downward direction, or oral intake in an infant is < 120 mL/kg of a fortified formula (490 kJ/100 mL), then NG feeding is indicated.
Enteral Feeding
NG feeding has been shown to be very effective in feeding cholestatic infants. It often reduces parental anxiety, allows for better feed tolerance, and parents have reported an improved sense of well-being in infants.[2,4,5] NG feeding will interrupt the normal introduction of solids and override appetite in an effort to meet energy requirements, but this is a necessary compromise to achieve adequate growth.
NG feeding has been shown to be very effective in feeding cholestatic infants. It often reduces parental anxiety, allows for better feed tolerance, and parents have reported an improved sense of well-being in infants.[2,4,5] NG feeding will interrupt the normal introduction of solids and override appetite in an effort to meet energy requirements, but this is a necessary compromise to achieve adequate growth.
If NG feeds are indicated, 50% EER should be provided overnight as continuous feeds over 10–12 h and the infant allowed to drink during the day. This supports normal daytime eating patterns and reduces the risk of oral aversion.[1] As CLD progresses, it might be necessary to feed the infant continuously for 20–24 h for best tolerance and nutrient absorption.[2] FSV levels should be continually monitored and supplemented as required. If vomiting is an issue, continuous nasojejunal feeding might be required.
These fortifying and NG feeding principles can also be applied to older children with CLD.Gastrostomy feeding is rarely used in CLD due to placement difficulty with organomegaly, risk of peritoneal infection with ascites, and stomal variceal bleeding with portal hypertension.[2,8]
Parenteral Nutrition
Only when enteral nutrition is not possible or ineffective should parenteral nutrition (PN) be considered.[2,3,30] PN might be appropriate when there is osmotic intolerance to feeds leading to unmanageable diarrhea and growth faltering, despite maximal energy provision, especially if the infant is less than 8 kg. Where possible, continue trophic enteral feeds alongside PN, and rechallenge with greater feed volumes as tolerated. Trophic feeds (up to 10 mL/kg) assist in protecting the liver and promote gut integrity.[2] Close clinical and biochemical monitoring with PN is essential, especially fluid, sodium, copper, manganese, and triglycerides due to altered fat clearance.[2] Limitations of PN include hospitalization, risk of line infections, and further-compromised liver function.
Only when enteral nutrition is not possible or ineffective should parenteral nutrition (PN) be considered.[2,3,30] PN might be appropriate when there is osmotic intolerance to feeds leading to unmanageable diarrhea and growth faltering, despite maximal energy provision, especially if the infant is less than 8 kg. Where possible, continue trophic enteral feeds alongside PN, and rechallenge with greater feed volumes as tolerated. Trophic feeds (up to 10 mL/kg) assist in protecting the liver and promote gut integrity.[2] Close clinical and biochemical monitoring with PN is essential, especially fluid, sodium, copper, manganese, and triglycerides due to altered fat clearance.[2] Limitations of PN include hospitalization, risk of line infections, and further-compromised liver function.
It should be noted that children with growth failure as a result of CLD progression can reach a point where even the most intensive dietetic support might not improve nutritional status. This indicates deterioration of liver function, and is further support to expedite liver transplant.[4]
Liver Transplant and Post-transplant Nutrition
Feeding post-transplant should start as soon as possible, ideally within the first 72 h if the child is stable. If the child was eating orally up until transplant, then clear fluids followed by full fluids and a normal full ward diet is encouraged. Sensible food safety should be encouraged at all times.
If the child was fed a high-energy, MCT-containing feed pretransplant, then this should be continued. Once bile flow is re-established, the child can be changed to a standard age-appropriate feed until oral diet is reintroduced. Many children are undernourished at the time of transplant[31] and require continued support with NG feeds while oral intake is encouraged. Catch-up growth is usually seen within 18 months, but many factors, such as organ rejection, sepsis, severe undernutrition pretransplant, and behavioral feeding problems can delay the weaning of NG feeds.[32] An audit of feeding patterns post-liver transplant for children under 2 years revealed that NG feeding at the time of transplant is very common, and likely to be needed for up to 2 months post-transplant. It was also observed that a normal diet for age is usually achieved within 6 months.[33]
The child should be encouraged to eat a healthy, age-appropriate diet; however, small, frequent snacks and favorite foods might be used initially to improve intake. Grapefruit and its juice are the only dietary restrictions, due to interaction with tacrolimus.[34] The child should also be encouraged to try foods they disliked pretransplant, as taste changes are common. Feeding-behavior problems are common, especially if the child has had prolonged NG feeding prior to transplant.[33] Referrals to the speech pathologist and maternal child health nurse should be made where appropriate.
Loose bowel actions post-transplant are common, but usually resolve within a few days. Prolonged diarrhea should be investigated, with possible causes including infection and magnesium supplementation. New food allergies can develop post-transplant, and dietary manipulation might be required.[2,35]
The use of steroids post-transplant for rejection or autoimmune complications will improve appetite, and in some cases, weight gain needs to be monitored closely. Conversely, the weaning of steroids can result in a decreased appetite and inadequate nutrition, and the need for high energy supplements should be reviewed at this time. Unfortunately, steroid exposure also contributes to linear growth failure.[4]
Summary
Appropriate and aggressive nutrition management is vital in providing optimal care in children with liver disease. Management needs to be individualized and depends on presenting symptoms, interpretation of nutrition assessment, as well as concurrent medical management. Infants presenting early with chronic cholestatic disease are particularly susceptible to undernutrition and stand to benefit the most from early and ongoing appropriate nutrition intervention. These medically-complex children are best managed by a dedicated multidisciplinary team
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