Download Nutrition Issues in Liver Disease

2007 AGA GI Fellows’ Nutrition Course
Hepatic Failure:
Nutrition Issues in Liver Disease
John K. DiBaise, MD
Associate Professor of Medicine
Mayo Clinic Arizona
Outline
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Chronic liver disease

Liver transplantation

Acute liver failure
Liver Functions

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Metabolism of carbohydrate, protein
and fat
Activation and storage of vitamins
Detoxification and excretion of
substances
Severe liver injury  Metabolic derangements  PEM
Protein Energy Malnutrition
in Liver Disease
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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 1997;92:734
Zaina FE et al. Transpl Proc 2004;36:923
Consequences of Malnutrition
in Chronic Liver Disease
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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 1996;23:1041
Prognostic Implications of PEM
in Liver Transplant Candidates
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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 2000;70:1347
Stephenson G et al. Transplantation 2001;72:666
Which of the following is the
most important contributor
to malnutrition in cirrhotics?
A.
B.
C.
D.
Poor oral intake
Malabsorption
Altered metabolism
None of the above
Contributing Factors to
Malnutrition in CLD

Poor oral intake
– Anorexia
– Nausea, early satiety
– Altered taste
– Dietary and fluid restrictions
– Low-grade encephalopathy
– Lifestyle
Contributing Factors to
Malnutrition in CLD

Malabsorption
– Bile salt deficiency
– Small bowel bacterial overgrowth
– Portal hypertensive enteropathy
– Medications

Diuretics, cholestyramine, lactulose, neomycin
– Pancreatic insufficiency
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 2007;85:1257
Selberg O et al. Hepatology 1997;25:652
Predisposing Factors of
Hypermetabolism
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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 1991;11:265
Scolapio JS et al. JPEN 2000;24:150
Which of the following is a
useful marker of nutritional
status in decompensated
cirrhosis?
A.
B.
C.
D.
BMI
Prealbumin
Harris-Benedict equation
None of the above
Nutritional Assessment

History
– GI symptoms
– Weight loss
– Calorie/diet intake (prospective)
– Food preferences

Exam
– Fluid retention
– Muscle wasting
Nutritional Assessment
Caveats

Weight/Body mass index (BMI)
– ? BMI adjusted for ascites
Serum protein half-lives

Biochemical tests
– Albumin, prealbumin
Protein
Halflife
Albumin
18 d
Transferrin
8d
Prealbumin
2–3 d
Retinolbinding
protein
2d
Ferritin
30 h
Campillo B et al. Gastro Clin Biol 2006;30:1137
Nutritional Assessment
Alternatives
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Anthropometric measurements
– Triceps skin-fold thickness
– Mid-arm muscle circumference

Assessment of muscle function
– Hand-grip strength
– Respiratory-muscle strength
Nutritional Assessment
Alternatives

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
Nutritional Assessment
Alternatives

Global nutrition assessment scheme
– BMI, MAMC, dietary intake data
– Reproducible, validated, predictive method in cirrhotics
Morgan MY et al. Hepatology 2006;44:823
Nutritional Assessment
Body Composition

Body cell mass
– Isotope dilution
– Whole-body potassium
– In vivo neutron activation
– Bioelectrical impedance
– Dual-energy x-ray absorptiometry (DXA)
Nutritional Assessment
Energy Expenditure

Indirect calorimetry
– Evaluate status of energy metabolism
– Allows calculation of RQ
– Hypermetabolic if measured REE > 10-20%
predicted REE
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Predictive equations
– Harris-Benedict, Mifflin-St. Jeor, etc.
– Limited by dependence upon weight
Muller MJ et al. Am J Clin Nutr 1999;69:1194
Treatment Goals


Improve PEM
Correct nutritional deficiencies
Oral, enteral, parenteral or combination
General Nutrition Guidelines
(ESPEN Consensus)

Compensated cirrhosis
– 25-35 kcal/kg/day; 1-1.2 g/kg/day protein
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Complicated cirrhosis
– 35-40 kcal/kg/day; 1.5 g/kg/day protein
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Mild-moderate encephalopathy
– 25-35 kcal/kg/day; 0.5-1.5 g/kg/day protein
– Restrict protein as briefly as possible
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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 1997;16:43
T/F: Fluid restriction should
be initiated in all cirrhotics
with evidence of fluid
retention.
General Nutrition
Guidelines
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
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
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Sodium restrict – only when fluid retention
Fluid restrict – only when sodium < 120 mEq/L
No Need for Routine Protein
Restriction in Encephalopathy
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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 2004;41:38
No Need for Routine Protein
Restriction in Encephalopathy
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Outcomes
– No difference in PSE, survival, ammonia level
– Better nitrogen balance in 1.2 g/kg/d group
Cordoba J et al. J Hepatol 2004;41:38
T/F: BCAA have been
recommended for use in
protein-intolerant cirrhotics.
What About Branched Chain
Amino Acids (BCAA)?
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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
BCAA and Hypothetical
Role in Encephalopathy
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BCAA depletion enhances passage of AAA
(tryptophan) across BBB  false
neurotransmitters
Role of supplementation to treat PSE
remains controversial
? role in refractory PSE
BCAA in ProteinIntolerant Cirrhotics
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Tolerate < 40 g protein/day
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 1984;4:279
BCAA Supplementation in
Advanced Cirrhosis
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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 2003;124:1792
Enteral Nutrition in
Cirrhosis
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Should be encouraged early if PO intake
inadequate
– Nasoenteral preferred
– At least 3 weeks
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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 1990;98:715
Kearns PJ et al. Gastro 1992;102:200
Practical Issues in
Nutrition Therapy
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Oral supplementation
– Often unsuccessful due to GI symptoms
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Short-term tube feeding
– Generally helpful but of uncertain longterm benefit

Long-term tube feeding
– Difficult due to reliance on nasoenteral
tubes
Parenteral Nutrition in
Cirrhosis
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Reserve for those who can’t tolerate EN
– Increased cost and complications
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Standard AA adequate for most
Optimal macronutrient composition
remains unclear
? role in perioperative liver transplant
setting for severely malnourished
Effect of TIPS on
Nutritional Status
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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 2001;96:2442
Liver Transplantation
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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 1997;3:532
Madden AM et al. Hepatology 1999;30:655
Pre-Transplant Nutrition
Support
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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
Pre-Transplant Nutrition
Support - Enteral
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RCT of 82 ESLD pts with
MAMC < 25 percentile
Enteral feeds + oral diet vs.
oral diet alone until
transplantation
No effect on post-transplant
complications or survival
Trend toward improved pretransplant survival in enteral
feed group (p=0.075)
Le Cornu KA et al. Transplantation 2000;69:1364
Post-Transplant Nutrition
Support – Enteral (< 12 hrs)
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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 1995;19:437
Post-Transplant Nutrition
Support - Parenteral
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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 1990;14:386
Post-Transplant Nutrition
Support
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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 1998;11:S289
Acute Liver Failure
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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 2004;23:975
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 patient’s
condition

– Try enteral feeding first if gut working
Schutz T et al. Clin Nutr 2004;23:975
Take Home Points
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Malnutrition is an important complication
of cirrhosis with prognostic implications
Multifactorial causation
Nutritional assessment should be
performed in all with chronic liver
disease
Take Home Points

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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