Chronic Liver Disease in Childhood Management of Nutrition Stuart S. Kaufman, M.D.

Chronic Liver Disease
in Childhood
Management of Nutrition
Stuart S. Kaufman, M.D.
Liver and Intestinal Transplant
Program
Georgetown University Transplant
Institute & Children’s National Medical
Center
Washington, D.C.
Chronic Liver Disease
Malnutrition
• Rapid onset in infancy
• Incidence ~ 60%
• Severity proportional to that of original liver
disease
• May accelerate hepatic decompensation
Chronic Childhood Liver
Diseases
• Inflammation
– Infection
– Metabolic error
• Decreased bile flow → low intestinal bile
salt concentration
• Fibrosis (cirrhosis) → portal hypertension
Chronic Childhood Liver
Diseases
Infancy
•
•
•
•
•
Extrahepatic biliary atresia
α1 - Antitrypsin deficiency
Alagille syndrome
Cystic fibrosis
Bile acid synthetic and transport disorders
Chronic Childhood Liver
Diseases
Childhood
•
•
•
•
•
α1 - Antitrypsin deficiency
Cystic fibrosis
Autoimmune hepatobiliary disease
HIV
Secondary hemochromatosis
Why Does Malnutrition Develop
in Chronic Liver Disease?
REDUCED INTAKE!!
• Anorexia
– Inflammatory cytokines
• Early satiety
– ? Gastric compression
• Hepatosplenomegaly
• Ascites
Why Does Malnutrition Develop
in Chronic Liver Disease?
Reduced Assimilation
• Bile acid deficiency → lipid
• Intestinal factors → all nutrients
– Rapid intestinal transit
– Intestinal bacterial overgrowth
• Pancreatic insufficiency (CF, Alagille
syndrome) → all nutrients
Why Does Malnutrition Develop
in Chronic Liver Disease?
Increased Energy Consumption
• 130 – 170 cal/kg/day for weight gain
– Inefficient cellular oxidation
– Vasodilatation - high cardiac output
– Abdominal distention - increased work
of breathing
Nutrition Assessment in
Chronic Liver Disease
Essentials
•
•
•
•
Relevant history
Relevant physical examination
Focused laboratory testing
Potential practical ancillary studies
Not Essential
• REE/AEE based on formulas
Nutrition-Focused History
•
•
•
•
•
•
Liver disease status
Diet: composition and quantity
GI tract function
Developmental milestones
Medications
Co-morbid disorders
– Cardiac
– Pulmonary
– Renal
Nutrition-Focused Examination
• Growth parameters and anthropometry for
serial assessment
• Vital signs
• Activity
• Liver and spleen size
• Edema
• Skin and hair quality
• Developmental milestones
Laboratory Testing
• Liver function: bilirubin, albumin,
coagulation
• Plasma iron & binding capacity
• Blood vitamin & trace element levels
• Plasma lipids and fatty acids
• Urine calcium, zinc
• Acute phase reactants
Serum Albumin
A Poor Nutrition Marker in Chronic
Liver Disease
• Increased fractional catabolic rate
• Increased vascular flux
• Reduces synthesis independent of
nitrogen balance
Ancillary Tests
Relatively Available
• Dual energy x-ray absorptiometry
– Bone mineral density
– Body composition
• Indirect calorimetry - critical care setting
Delivery of Nutrition Support in
Progressive Liver Disease
Principles
• Poor nutrition independently predicts poor
survival
• Improving nutrition does not improve
survival overall
• Improving nutrition does reduce perioperative morbidity and mortality after liver
transplantation
Delivery of Nutrition Support in
Progressive Liver Disease
Principles
• Low and excess nutrition undesirable
• Adequate nutrition should not undermine
fluid and electrolyte management
Aims
• Total calories for body fat in low-normal
range
• No routine protein restriction
Delivery of Nutrition Support in
Progressive Liver Disease
Enteral
• When low intake > malabsorption
• Route
– PO – mild liver disease
– Tube: bolus - less appetite suppression
pump - less emesis & diarrhea
• Type
– Dietary additives
– Complete formulas
Enteral Nutrition Support
Principles of formula composition
• MCT oil – based probably advantageous
• Peptide/amino acid – based usually not
advantageous, except
– Hypersensitivity
– Pancreatic insufficiency
• Increase caloric density to minimize fluid
overload
Enteral Nutrition Support
Practice – macronutrient goals
• Total calories: 130 – 160 cal/kg/day
• Protein: 3.5 – 4.0 g/kg/day
• Lipid: 35 – 45% of total calories, ⅓ – ½
MCT
• Density
– Infants: ~ 1 cal/mL
– Children: ~ 2 cal/mL
Parenteral Nutrition Support
Indications
• Intolerance of adequate enteral energy
– GI: vomiting and/or diarrhea
– Renal: fluid and sodium retention
Contraindications
• Absolute: none, but
• Hazard of central vein access with
immune compromise and coagulopathy
Parenteral Nutrition Support
Practice – macronutrient goals
• Total calories (nitrogen and non-nitrogen):
~100 – 130 cal/kg/day
• Amino acid: 1.5 – 2.5 g/kg/day
• Lipid emulsion: 20-25% of total calories
– Query less if intestinal failure
Parenteral Nutrition Support
Additional concerns in chronic liver
disease
• Query increased free radical injury:
additional selenium, cysteine, vitamin C
• Query conditional carnitine and taurine
deficiency
• Increased urinary zinc loss
• Reduced biliary copper & manganese loss
Management of Nutrition in Childhood Cholestasis
Stuart S Kaufman, MD
Liver and Intestinal Transplantation Program
Georgetown University Transplant Institute and Children's National Medical Center
Washington, DC
1. Overview - Types of cholestatic liver disease affecting children
A. In infants, disorders include intrahepatic and extrahepatic biliary obstruction disorders, e.g.
biliary atresia, familial intrahepatic cholestasis, etc. and systemic metabolic disorders with a
hepatobiliary component, e.g. cystic fibrosis.
B. In older children, disorders include late onset of symptomatic 1-antitrypsin deficiency,
secondary hemochromatosis, autoimmune liver diseases, and rarely, chronic hepatitis C and
HIV.
C. Additional considerations
Time over which malnutrition develops and over which preventive or corrective measures
must be taken often shorter in infants (weeks to months) than older children (months-years)
Therapeutic endpoint for nutritional support is often survival to liver transplant
2. Metabolic and digestive alterations in pediatric chronic liver disease
A. Final endpoint is malnutrition (body size parameters <5th percentile)
i. Common = 60% incidence
ii. Changes are qualitatively similar to those in adults with chronic liver diseases
iii. But, abnormalities in infants and children develop and become apparent more rapidly
than in adults due to higher metabolic rates associated with body growth
iv. Specific contributors to malnutrition in chronic liver diseases
1. Reduced nutrient intake
2. Impaired nutrient digestion and assimilation
3. Increased energy consumption
B. Reduced nutrient intake – most important
i. Primary anorexia, probably CNS-effect of pro-inflammatory cytokine response to chronic
liver disease
ii. Increased satiety and vomiting secondary to gastric compression (ascites,
hepatosplenomegaly)
C. Impaired digestion and assimilation
i. Bile acid deficiency with cholestatic liver disease reduces net lipid absorption from • 95%
to 75%. Also,
1. Fat-soluble vitamin deficiency
2. Essential fatty acid deficiency – symptoms = dry skin and hair loss
ii. Portal hypertension impairs motility and increases GI protein loss
iii. Pancreatic insufficiency (Alagille syndrome, cystic fibrosis)
iv. Small intestinal bacterial overgrowth; probably secondary to all of above
D. Energy consumption
i. Resting energy expenditures (REE) are generally increased per kg of total body weight by
about 140-160% or to approximately 75 cal/kg/day in infants
1. Because the body cell compartment constitutes an increased fraction of body size
2. Because energy expenditure per unit of body cell compartment is increased
ii. Active energy expenditures (AEE) are increased from usual 160% of REE to about 200% of
REE (140-160 cal/kg/day in infants)
1. Because of chronically increased cardio-pulmonary expenditures (vasodilatation,
hepatosplenomegaly, and ascites)
2. Because of intermittent acute inflammatory stresses
E. Significance of malnutrition: predicts reduced survival after liver transplantation independent of
other features of advanced liver disease
i. Implication: any chronic liver disease causes malnutrition, and malnutrition, in turn,
promotes further deterioration in liver function irrespective of original cause
ii. Implication: Because malnutrition reflects severity of the causative liver disease, correction
of malnutrition does not improve survival with a chronic liver disease unless transplantation
is the primary outcome measure
3. Nutrition assessment
A. Key Points of Historical Interest
i. Cause and prognosis of underlying liver disease
ii. Composition and trend (increasing or decreasing) in nutrient intake
iii. GI function: propensity for emesis, diarrhea, and GI bleeding
iv. Co-existing disorders
1. Those increasing caloric expenditures, e.g. heart and/or lung disease
2. Renal diseases that may reduce fluid and protein tolerance
3. Those disorders undermining calorie tolerance, e.g. glucose intolerance and
hyperlipidemias
B. Physical findings
i. Height, weight, head circumference; absolute values and percentiles for age; weight for
length percentile
ii. Vital signs and assessment of activity, suggesting increased or decreased REE and/or AEE
iii. Triceps skin fold and mid-arm muscle area and percentiles for age
iv. Enlargement of liver and/or spleen
v. Ascites
vi. Peripheral edema
C. Laboratory tests pertinent to nutrition assessment
i. Serum electrolytes including calcium, phosphorus, and magnesium
ii. Blood urea nitrogen and creatinine
iii. Urine calcium to creatinine ratio
iv. Fat soluble vitamin levels (A, 25-OH D, E)
v. Prothrombin time, albumin
vi. Serum zinc and urine zinc to creatinine ratio
vii. Fatty acid profile, including C20:3 9
viii. ESR, C-reactive protein, ferritin
ix. Iron and iron binding capacity
x. Serum lipids
D. Other useful studies
i. DEXA for areal bone density
ii. Indirect calorimetry to estimate REE when actual requirements appear to deviate from
predicted
4. Objectives of pediatric nutrition support
A. Deliver sufficient calories to obtain some fat stores and to insure that linear growth is not
limited by nutrient supply
i. While maintaining fluid and electrolyte balance (avoid fluid overload, hyponatremia, etc)
ii. Without triggering other metabolic disturbance, e.g. hyperglycemia
B. Prevent vitamin and trace element deficiencies that can accompany chronic liver disease (Table
1)
5. Delivering nutrition to the pediatric patient
A. Enteral nutrition support
i. Indication: Formula substitution for infants and supplemental products for children falling
behind in growth and development on standard diet
ii. Routes
1. Oral may be adequate for mild liver disease in conjunction with dietary additives
a. MCT oil (7.7 cal/mL)
b. Modular protein
c. Glucose polymers
A. Moducal - 10 cal/teaspoon
B. Polycose® - 8 cal/teaspoon
2. Supplemental tube feeding
a. Intermittent daytime gavage may preserve appetite but is limited by tendency to
cause emesis and diarrhea
b. Continuous pump infusion delivers best tolerance (minimal emesis/diarrhea) but
suppresses appetite
c. Nasogastric route easiest to employ and usually well-tolerated
d. Gastrostomy usually contraindicated by portal hypertension
e. Nasojejunal route usually impractical for protracted use
iii. Enteral formulas (Table 2)
1. Infant (examples)
a. Alimentum®
b. Pregestimil® (diluted 0.67 – 1.0 cal/mL)
2. Child (examples)
a. Pregestimil® (diluted 1.0 cal/mL)
b. Peptamen Junior®
c. Deliver 2.0® (diluted 1.0 – 2.0 cal/mL)
iv. Macronutrient goals with enteral nutrition
1. Total calories: 130-160/kg/day
2. Protein: 3.5-4.0 g/kg/day
3. Lipid: 35-45% of total calories, 1/3 to 1/2 as MCT oil
v. Practice points
1. Formulas containing MCT oil may have 25-50% better lipid absorption than those
containing LCT alone
2. No advantage to peptide or amino acid formulas in absence of coexisting enteropathy
or protein hypersensitivity
3. Amino acid formulas mainly for hydrolysate hypersensitivity (intolerance)
4. Infants usually tolerate formula density up to 1 cal/mL if mandated by need to restrict
fluid while older children usually tolerate up to 2 cal/mL
B. Parenteral nutrition support
i. Indications
1. Sustained intolerance to enteral calories needed to achieve nutrient goals, e.g.
a. Intractable emesis
b. Intractable diarrhea
c. Intractable fluid overload
2. Transient intolerance to enteral feeding because of acute critical illness resulting in
ileus and/or loss of airway protection
ii. Macronutrient goals
1. Total (nitrogen plus non-nitrogen calories): usually 100-130 cal/kg/day
2. Amino acid: 1.5-2.5 g/kg/day
3. Lipid emulsion: 20-25% of total calories (usually up to 3 g/kg/day)
iii. Practice points
1. Advantage of parenteral over enteral nutrition in decompensated liver disease (ascites,
reduced renal function) is ability to deliver a very high caloric load with easily varied
macronutrient mix (based on nitrogen, triglyceride, and glucose tolerance) with
relatively little fluid and sodium.
2. Disadvantages of parenteral nutrition in decompensated liver disease are dangers
associated with placement and retention of a central venous catheter, particulary
bleeding and infection, in patients with coagulopathy and compromised immunity
3. Although parenteral nutrition may be delivered at home, patients requiring it because
of advanced liver disease usually require hospitalization
4. Cysteine may be essential in chronic liver disease; add up to 1 g/L
5. Carnitine status may be compromised, particularly with high lipid intake. If free
plasma level reduced, add up to 10 mg/kg/day
6. Zinc requirement increased; add up to 0.3 mg/kg/day
7. In cholestatic patients, withhold copper and manganese and add up to selenium, 3-5
µg/kg/day and chromium, 0.2 – 0.3 µg/kg/day
8. Proprietary pediatric injectable vitamin solutions (M.V.I. Pediatric ) are adequate
9. Taurine is conditionally essential in chronic liver disease; use TrophAmine in lieu of
standard amino acid solutions
Table 1. Fat-soluble vitamin supplements for prophylaxis and treatment.
Vitamin
Brand
Typical Dose
Route
Deficiency
Comments
Vitamin A
Vitamin D
(Calcitriol)
Vitamin E
(TocopherylPEGS)
Vitamin K
(phytonadion
e)
ADEKs® Pediatric
Drops^
5,000-25,000
units daily
USP
PO
Aquasol®
Parenteral
A
5,000-50,000 daily
for 1-2 weeks
IM
Rocaltrol®
-Solution
(1
µg/mL)
-Capsules (0.25
and 0.5 µg/mL)
Nutre-E-Sol®; 400
IU/15 mL
ADEKs® Pediatric
Drops^
0.025 µg/kg-1.0 µg
daily
PO
Rickets
Osteomalacia
25 IU/kg/day
PO
Peripheral
neuropathy
Ataxia
2.5-5 mg daily
PO
Coagulopathi
c hemorrhage
5-10 mg every 2
weeks
SQ
Mephyton® 5 mg
tabs
ADEKs® Pediatric
Drops^
AquaMEPHYTON®
Xerophthalmia
(dry eye)
Hyperkeratosis
Night
blindness
Normal
plasma
level=300400
µg/L
Symptoms @
100 µg/L
Plasma levels
correlate
poorly
with
stores-aim to
maintain low
levels
Monitor
calcium,
phosphorus,
intact
PTH
levels
Desired
plasma level
(5-15 µg/mL)
affected
by
serum lipids
Monitor with
prothrombin
time (PT)
Use SQ if PO
ineffective
^ADEKs® Pediatric Drops include 3,170 USP units of vitamin A, 40 IU of tocopheryl-PEGS, and 0.1
mg of phytonadione per mL
Table 2. Proprietary enteral formulas with MCT for chronic liver diseases.
Brand
Std Density
(cal/mL)
1.0
1.0
Nitrogen (g/dL)
Alimentum®
Pregestimil®
Peptamen Junior®
Deliver 2.0®
TwoCal HN®
Elecare®
Neocate
Advance®
MCT:LCT
Amino acid (3.0)
Amino acid (2.5)
Lipid cals
(% of total)
43
32
0.67
0.67
1.0
Hydrolysate (1.8)
Hydrolysate (1.9)
Hydrolysate (3.0)
48
48
33
33:67
55:45
60:40
2.0
2.0
Casein (7.4)
Casein (8.4)
45
40
30:70
19:81
33:67
35:65