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Hepatic Failure:Nutrition Issues in Liver
Disease
John K. DiBaise, MDJohn K. DiBaise, MD
Associate Professor of MedicineAssociate Professor of Medicine
Mayo Clinic ArizonaMayo Clinic Arizona
2007 AGA GI Fellows’ Nutrition Course
Liver Functions
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 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;92:734Zaina FE et al. Transpl Proc 2004;36:923
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 1996;23:1041
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 2000;70:1347Stephenson G et al. Transplantation 2001;72:666
Which of the following is the most important contributor to malnutrition in cirrhotics?A. Poor oral intakeB. MalabsorptionC. Altered metabolismD. 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/tumorPeng S et al. Am J Clin Nutr 2007;85:1257Selberg O et al. Hepatology 1997;25:652
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 1991;11:265Scolapio JS et al. JPEN 2000;24:150
Which of the following is a useful marker of nutritional status in decompensated cirrhosis?
A. BMIB. PrealbuminC. Harris-Benedict equationD. None of the above
Nutritional Assessment History
– GI symptoms– Weight loss– Calorie/diet intake (prospective)– Food preferences
Exam– Fluid retention– Muscle wasting
Nutritional AssessmentCaveats Weight/Body mass index (BMI)
– ? BMI adjusted for ascites
Biochemical tests– Albumin, prealbumin
Campillo B et al. Gastro Clin Biol 2006;30:1137
Serum protein half-lives
ProteinHalf-life
Albumin 18 d
Transferrin 8 d
Prealbumin 2–3 d
Retinol-binding protein
2 d
Ferritin 30 h
Nutritional AssessmentAlternatives
Anthropometric measurements– Triceps skin-fold thickness– Mid-arm muscle circumference
Assessment of muscle function– Hand-grip strength– Respiratory-muscle strength
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
Nutritional AssessmentAlternatives
Global nutrition assessment scheme– BMI, MAMC, dietary intake data– Reproducible, validated, predictive method in
cirrhotics
Morgan MY et al. Hepatology 2006;44:823
Nutritional AssessmentBody Composition Body cell mass
– Isotope dilution– Whole-body potassium– In vivo neutron activation
– Bioelectrical impedance– Dual-energy x-ray absorptiometry
(DXA)
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 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 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 1997;16:43
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 < 120
mEq/L
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 2004;41:38
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 2004;41:38
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
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
BCAA in Protein-Intolerant Cirrhotics 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
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 BCAAMarchesini G et al. Gastro 2003;124:1792
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 transplantCabre E et al. Gastro 1990;98:715Kearns PJ et al. Gastro 1992;102:200
Practical Issues in Practical Issues in Nutrition TherapyNutrition 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
Parenteral Nutrition in Cirrhosis Reserve for those who can’t
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
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 2001;96:2442
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 1997;3:532
Madden AM et al. Hepatology 1999;30:655
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
Pre-Transplant Nutrition Support - Enteral
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 pre-transplant survival in enteral feed group (p=0.075)
Le Cornu KA et al. Transplantation 2000;69:1364
Post-Transplant Nutrition Support – Enteral (< 12 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 1995;19:437
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 1990;14:386
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 1998;11:S289
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 supportSchutz 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 workingSchutz T et al. Clin Nutr 2004;23:975
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
Recommended