Hepatic Failure: Nutrition Issues in Liver Disease

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Hepatic FailureNutrition Issues in Liver Disease
2007 AGA GI Fellows Nutrition Course

• John K. DiBaise, MD
• Associate Professor of Medicine
• Mayo Clinic Arizona

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Outline

• Chronic liver disease
• Liver transplantation
• Acute liver failure

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Liver Functions

• Metabolism of carbohydrate, protein and fat
• Activation and storage of vitamins
• Detoxification and excretion of substances

Severe liver injury ? Metabolic derangements ? PEM
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Protein Energy Malnutrition in Liver Disease

• Rare in most acute liver disease and chronic
  liver disease w/o cirrhosis
  
• Up to 20 with compensated disease
• 65-90 with advanced disease
• Nearly 100 awaiting liver transplant
• Correlation between severity of liver disease and
  severity of malnutrition
  
• Cholestatic calorie and fat-soluble vitamin
  deficiencies
  
• Non-cholestatic protein deficiency

McCullough AJ et al. AJG 199792734
Zaina FE et al. Transpl Proc 200436923
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Consequences of Malnutrition in Chronic Liver
Disease

• Increased rate of portal hypertensive
  complications
  
• Decreased survival rate
• Unclear whether PEM independent predictor of
  survival or reflects severity of liver disease

Merli M et al. Hepatology 1996231041
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Prognostic Implications of PEM in Liver
Transplant Candidates

• Increased rate of transplant complications
• Increased intraop PRBC requirements
• Increased time on ventilator postop
• Higher incidence of graft failure
• Decreased survival postop
• Increased costs

Figueiredo FA et al. Transplantation
2000701347 Stephenson G et al. Transplantation
200172666
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Which of the following is the most important
contributor to malnutrition in cirrhotics?

• Poor oral intake
• Malabsorption
• Altered metabolism
• None of the above

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Contributing Factors to Malnutrition in CLD

• Poor oral intake
• Anorexia
• Nausea, early satiety
• Altered taste
• Dietary and fluid restrictions
• Low-grade encephalopathy
• Lifestyle

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Contributing Factors to Malnutrition in CLD

• Malabsorption
• Bile salt deficiency
• Small bowel bacterial overgrowth
• Portal hypertensive enteropathy
• Medications
• Diuretics, cholestyramine, lactulose, neomycin
• Pancreatic insufficiency

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Contributing Factors to Malnutrition in CLD

• Metabolic abnormalities - hypermetabolism
• State of catabolism similar to starvation/sepsis
• Up to one-third with stable cirrhosis
• Another third hypo-metabolic
• Lower respiratory quotient
• Not readily identified by markers of liver
  disease
  
• ? extrahepatic manifestation
• Adversely effects survival after liver
  transplant
  
• No association with gender, etiology, severity,
  protein deficit or presence of ascites/tumor
  

Peng S et al. Am J Clin Nutr 2007851257
Selberg O et al. Hepatology 199725652
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Predisposing Factors of Hypermetabolism

• Infection
• Ascites
• Altered pattern of fuel metabolism
• Glucose intolerance/hyperinsulinemia/insulin
  resistance
  
• Decreased glycogen storage
• Increased protein catabolism
• Decreased meal-induced protein synthesis
• Accelerated gluconeogenesis from AA
• Increased lipid catabolism

McCullough AJ et al. Sem Liver Dis 199111265
Scolapio JS et al. JPEN 200024150
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Which of the following is a useful marker of
nutritional status in decompensated cirrhosis?

• BMI
• Prealbumin
• Harris-Benedict equation
• None of the above

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Nutritional Assessment

• History
• GI symptoms
• Weight loss
• Calorie/diet intake (prospective)
• Food preferences
• Exam
• Fluid retention
• Muscle wasting

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Nutritional AssessmentCaveats

• Weight/Body mass index (BMI)
• ? BMI adjusted for ascites
• Biochemical tests
• Albumin, prealbumin

Serum protein half-lives
Campillo B et al. Gastro Clin Biol 2006301137
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Nutritional AssessmentAlternatives

• Anthropometric measurements
• Triceps skin-fold thickness
• Mid-arm muscle circumference
• Assessment of muscle function
• Hand-grip strength
• Respiratory-muscle strength

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Nutritional AssessmentAlternatives

• Subjective global assessment (SGA)
• Weight loss last 6 months, changes in diet
  intake, GI symptoms, functional capacity, fluid
  retention
  
• High specificity but poor sensitivity in
  cirrhotics
  
• Useful in predicting outcome after transplant

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Nutritional AssessmentAlternatives

• Global nutrition assessment scheme
• BMI, MAMC, dietary intake data
• Reproducible, validated, predictive method in
  cirrhotics

Morgan MY et al. Hepatology 200644823
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Nutritional AssessmentBody Composition

• Body cell mass
• Isotope dilution
• Whole-body potassium
• In vivo neutron activation
• Bioelectrical impedance
• Dual-energy x-ray absorptiometry (DXA)

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Nutritional AssessmentEnergy Expenditure

• Indirect calorimetry
• Evaluate status of energy metabolism
• Allows calculation of RQ
• Hypermetabolic if measured REE 10-20 predicted
  REE
  
• Predictive equations
• Harris-Benedict, Mifflin-St. Jeor, etc.
• Limited by dependence upon weight

Muller MJ et al. Am J Clin Nutr 1999691194
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Treatment Goals

• Improve PEM
• Correct nutritional deficiencies

Oral, enteral, parenteral or combination
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General Nutrition Guidelines (ESPEN Consensus)

• Compensated cirrhosis
• 25-35 kcal/kg/day 1-1.2 g/kg/day protein
• Complicated cirrhosis
• 35-40 kcal/kg/day 1.5 g/kg/day protein
• Mild-moderate encephalopathy
• 25-35 kcal/kg/day 0.5-1.5 g/kg/day protein
• Restrict protein as briefly as possible
• Severe encephalopathy
• 25-35 kcal/kg/day 0.5 g/kg/day protein
• Restrict protein as briefly as possible

Plauth M et al. Clin Nutr 19971643
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T/F Fluid restriction should be initiated in
all cirrhotics with evidence of fluid retention.
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General Nutrition Guidelines

• Consume 6-7 small meals/day including a bedtime
  snack rich in CHO
  
• Initiate enteral intake when oral intake
  inadequate
  
• Nasoenteral vs. gastrostomy
• Identify and correct nutrient deficiencies
• Alcohol/HCV thiamine, folate
• Cholestatic fat-soluble vitamins
• Sodium restrict only when fluid retention
• Fluid restrict only when sodium

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No Need for Routine Protein Restriction in
Encephalopathy

• RCT of 20 malnourished cirrhotics hospitalized
  with PSE (mean, stage 2)
  
• Gradual increase in protein vs. 1.2 g/kg/d via
  feeding tube
  
• All received lactulose precipitating factors
  treated

Cordoba J et al. J Hepatol 20044138
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No Need for Routine Protein Restriction in
Encephalopathy

• Outcomes
• No difference in PSE, survival, ammonia level
• Better nitrogen balance in 1.2 g/kg/d group

Cordoba J et al. J Hepatol 20044138
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T/F BCAA have been recommended for use in
protein-intolerant cirrhotics.
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What About Branched Chain Amino Acids (BCAA)?

• Isoleucine, leucine and valine
• Play role in protein breakdown
• Depleted in cirrhosis (and sepsis/trauma)
• Increase uptake by muscle to generate substrates
  for gluconeogenesis
  
• BCAA/AAA imbalance
• ? mediated by hyperinsulinemia

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BCAA and Hypothetical Role in Encephalopathy

• BCAA depletion enhances passage of AAA
  (tryptophan) across BBB ? false
  neurotransmitters
  
• Role of supplementation to treat PSE remains
  controversial
  
• ? role in refractory PSE

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BCAA in Protein-Intolerant Cirrhotics

• Tolerate
• Randomized to 70 g/day either as casein or BCAA
  supplement
  
• Treatment failure worsening PSE
• 7/12 failures in casein group vs. 1/14 in BCAA
  group

Basis for ESPEN recommendation to use BCAA in
this situation
Horst D et al. Hepatology 19844279
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BCAA Supplementation in Advanced Cirrhosis

• RCT of 174 advanced cirrhotics (B and C)
• 1 year BCAA, maltodextrins or lactoalbumin
• Patients not malnourished or encephalopathic
• BCAA tended to improve survival, disease
  progression and hospital admits (PP not ITT
  analysis)
  
• Results limited d/t large number of drop-outs b/c
  poor palatability of BCAA
  

Marchesini G et al. Gastro 20031241792
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Enteral Nutrition in Cirrhosis

• Should be encouraged early if PO intake
  inadequate
  
• Nasoenteral preferred
• At least 3 weeks
• Benefit seen mainly in severely malnourished
• Improved in-hospital survival, Child score,
  albumin, bilirubin, encephalopathy
  
• Improved nitrogen balance and reduced infections
  post transplant

Cabre E et al. Gastro 199098715
Kearns PJ et al. Gastro 1992102200
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Practical Issues in Nutrition Therapy

• Oral supplementation
• Often unsuccessful due to GI symptoms
• Short-term tube feeding
• Generally helpful but of uncertain long-term
  benefit
  
• Long-term tube feeding
• Difficult due to reliance on nasoenteral tubes

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Parenteral Nutrition in Cirrhosis

• Reserve for those who cant tolerate EN
• Increased cost and complications
• Standard AA adequate for most
• Optimal macronutrient composition remains
  unclear
  
• ? role in perioperative liver transplant setting
  for severely malnourished

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Effect of TIPS on Nutritional Status

• Open-label study of 14 consecutive cirrhotics
  with refractory ascites
  
• Improved body composition and several nutritional
  parameters at 3 and 12 months
  
• Dry body weight
• Total body nitrogen
• Muscle strength
• REE
• Food intake

Allard JP et al. AJG 2001962442
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Liver Transplantation

• Most candidates are malnourished
• PEM associated with poor outcome
• Body cell mass assessment is better predictor of
  outcome than Child-Pugh score
  
• Predictive equations of BEE compare poorly to
  indirect calorimetry

Deschennes M et al. Liver Transpl Surg
19973532 Madden AM et al. Hepatology 19993065
5
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Pre-Transplant Nutrition Support

• Goal prevent further depletion and slow
  deterioration
  
• Establish calorie and protein goals
• Avoid protein, sodium and fluid restrictions when
  possible
  
• Provide multivitamin and other micronutrient
  supplementation as needed

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Pre-Transplant Nutrition Support - Enteral

• RCT of 82 ESLD pts with MAMC
• Enteral feeds oral diet vs. oral diet alone
  until transplantation
  
• No effect on post-transplant complications or
  survival
  
• Trend toward improved pre-transplant survival in
  enteral feed group (p0.075)

Le Cornu KA et al. Transplantation 2000691364
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Post-Transplant Nutrition Support Enteral (hrs)

• 50 transplant recipients received either
  nasoenteral feeding (placed during surgery) or
  IVF until oral intake resumed
  
• Greater calorie/protein intake and faster
  recovery of grip strength but no difference in
  REE
  
• Reduced viral infections (17.7 vs. 0) and trend
  toward reduced overall infections (47.1 vs.
  21.4)

Hasse JM et al. JPEN 199519437
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Post-Transplant Nutrition Support - Parenteral

• RCT of 28 patients after transplant
• TPN (35 kcal/kg/d) w/BCAA (1.5 g/d) vs. TPN
  w/standard AA vs. no TPN for 1 week
  
• Decreased ICU length of stay
• Improved nitrogen balance
• No difference b/w BCAA and standard AA
• Offset the expense of TPN

Reilly J et al. JPEN 199014386
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Post-Transplant Nutrition Support

• Recommendations generally based on uncontrolled
  studies
  
• Recommend nasoenteral feeding in severely
  malnourished postoperatively with transition to
  PO as tolerated
  
• TPN only when unable to use the gut

Weimann A et al. Transpl Int 199811S289
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Acute Liver Failure

• No data from controlled trials regarding benefit
  of nutrition support
  
• Metabolic physiology similar to acute stress
  syndrome (hypercatabolic)
  
• Severe protein catabolism with increased AA
  overall but decreased BCAA
  
• ? benefit more from supplying BCAA than
  conventional AA
  
• Lack of liver impairs the ability to tolerate
  nutrition support

Schutz T et al. Clin Nutr 200423975
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Acute Liver Failure

• General recommendations
• Limit fluid intake prevent hypoglycemia
• High calorie/protein requirements start slowly
• Limit protein (0.6 g/kg/day) in coma/severe PSE
  (? role of BCAA)
  
• Make adjustments based on patients condition
• Try enteral feeding first if gut working

Schutz T et al. Clin Nutr 200423975
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Take Home Points

• Malnutrition is an important complication of
  cirrhosis with prognostic implications
  
• Multifactorial causation
• Nutritional assessment should be performed in all
  with chronic liver disease

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Take Home Points

• Nutrition therapy can reduce the risk of
  complications and improve survival
  
• Standard products are safe in most situations
• Adequate protein can safely be administered to
  patients with encephalopathy
  
• ?? BCAA in severely malnourished or refractory
  encephalopathy