Hepatic Failure: Nutrition Issues in Liver Disease

1. 2007 AGA GI Fellows’ Nutrition Course Hepatic Failure:Nutrition Issues in Liver Disease John K. DiBaise, MD Associate Professor of Medicine Mayo Clinic Arizona

2. Outline • Chronic liver disease • Liver transplantation • Acute liver failure

3. Liver Functions • Metabolism of carbohydrate, protein and fat • Activation and storage of vitamins • Detoxification and excretion of substances Severe liver injury  Metabolic derangements  PEM

4. 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;92:734 Zaina FE et al. Transpl Proc 2004;36:923

5. 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

6. 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;70:1347 Stephenson G et al. Transplantation 2001;72:666

7. Which of the following is the most important contributor to malnutrition in cirrhotics? • Poor oral intake • Malabsorption • Altered metabolism • None of the above

8. Contributing Factors to Malnutrition in CLD • Poor oral intake • Anorexia • Nausea, early satiety • Altered taste • Dietary and fluid restrictions • Low-grade encephalopathy • Lifestyle

9. Contributing Factors to Malnutrition in CLD • Malabsorption • Bile salt deficiency • Small bowel bacterial overgrowth • Portal hypertensive enteropathy • Medications • Diuretics, cholestyramine, lactulose, neomycin • Pancreatic insufficiency

10. 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

11. 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;11:265 Scolapio JS et al. JPEN 2000;24:150

12. Which of the following is a useful marker of nutritional status in decompensated cirrhosis? • BMI • Prealbumin • Harris-Benedict equation • None of the above

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

14. 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 2006;30:1137

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

16. 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

17. 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

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

19. 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

20. Treatment Goals • Improve PEM • Correct nutritional deficiencies Oral, enteral, parenteral or combination

21. 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

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

23. 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

24. 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

25. 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

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

27. 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

28. 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

29. 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

30. 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 2003;124:1792

31. 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 1990;98:715 Kearns PJ et al. Gastro 1992;102:200

32. 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

33. 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

34. 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

35. 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

36. 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

37. 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

38. 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

39. 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

40. 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

41. 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 2004;23:975

42. 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

43. 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

44. 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