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

Outline

Chronic liver disease

Liver transplantation

Acute liver failure

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

T/F: Fluid restriction should be initiated in all cirrhotics with evidence of fluid retention.

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

T/F: BCAA have been recommended for use in protein-intolerant cirrhotics.

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

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