Nutrition in Liver Disease

Nutrition in Liver Disease Mathias Plauth Klinik für Innere Medizin Städtisches Klinikum Dessau Nestlé 10 th Clinical Nutrition Course June 5-10, 2011, Lausanne, Switzerland

Malnutrition in Cirrhosis? Body Mass Index BMI 50 p<0.01 45 40 35 30 25 20 15 Controls n=39 Cirrhosis n=39 OLT n=42

Malnutrition in Liver Cirrhosis Ascites - Muscle Wasting

Liver Cirrhosis Body Composition 1.2 Nitrogen index 1.2 Total body water 1.0 0.8 * * * 1.0 0.8 * 0.6 0.6 0.4 0.4 0.2 0 Controls A B C 0.2 0 Controls A B C Prijatmoko et al, Gastroenterology 1993, 105:1839-1845

Malnutrition in Liver Cirrhosis Prognosis Equally Poor as Malignancy Survival Time [months] Caregaro et al, Am J Clin Nutr 1996, 63:602-609

Liver Cirrhosis Body Composition - Protein Depletion measured predicted Peng et al, Am J Clin Nutr 2007, 85:1257-66

Liver Cirrhosis Body Composition - Protein Depletion Men Women Body weight [kg] 79.7±1.1 71.1±1.6 Protein depletion [%] 63 28 Overhydration [%] 69 57 Hypermetabolism [%] 15 16 measured predicted measured predicted Total body protein [kg] Total body protein [kg] Peng et al, Am J Clin Nutr 2007, 85:1257-66

Liver Cirrhosis Protein Depletion - Muscle Function Not depleted Depleted M F M F Body composition Body weight [kg] 85,0 71,2 76,6 71,0 Total body protein [kg] 11,2 7,8 9,0 6,4 Total body water [L] 48,8 34,5 45,2 34,6 Fat free mass [kg] 64,2 45,4 58,0 43,7 Total body fat [kg] 20,8 25,8 18,6 27,3 Muscle strength Hand grip* [kg] 42,2 26,3 33,5 22,6 Respir. muscle* [cm H 2 O] 104,8 64,3 84,7 57,3 Depleted: PI < 0.82; * adjusted for age and height; all values are mean Peng et al, Am J Clin Nutr 2007, 85:1257-66

Liver Cirrhosis VO 2 max - Prognosis 153 LTx candidates, 41 transplanted VO 2 max < 60 % in two thirds of LTx candidates Dharancy et al, Transplantation 2008, 86:1077-

Liver Transplantation VO 2 max - Prognosis 153 LTx candidates, 41 transplanted MELD > 17 and VO 2 max < 60 % independent predictors of poor 360-day survival Dharancy et al, Transplantation 2008, 86:1077-

Body Composition in Liver Cirrhosis Correlation Between BCM BIA and BCM TBP Body cell mass (BIA) [kg] 50 No ascites 50 Ascites 40 40 30 30 20 r=0.97 p<0.001 20 r=0.75 p<0.001 10 10 10 20 30 40 50 10 20 30 40 50 Body cell mass (TBP) [kg] Pirlich et al, Hepatology 2000, 32:1208-1215

Body Composition in Liver Cirrhosis Loss of Body Cell Mass (BCM) BCM BIA [kg] p<0.05 50 p<0.01 p<0.01 40 30 20 10 Controls Cirrhosis OLT

Nutrition in Liver Cirrhosis Clinical Practice Survey in Great Britain, 1064 patients 64 hepatology / gastroenterology units Prescribed diet Physicians Dietitiens No protein restriction 27% 42% Restriction 30-50 g/d 40% 48% < 30 g/d 33% 10% In 44% units protein restriction prescribed solely as HE prophylaxis without any previous HE episode Soulsby & Morgan, BMJ 1999, 318:1391

Malnutrition in Liver Cirrhosis Increased Protein Requirements Balance [g protein/kg/d] 1.5 Undernutrition Cirrhosis 0 Controls Trauma, burns -1.5 0 0.5 0.8 Intake [g protein/kg/d] Kondrup & Nielsen, Z Gastroenterol 1996, 34(Suppl5):26-31

Malnutrition in Liver Cirrhosis Effect of Tube Feeding Controls Tube feeding week 0 week 4 week 0 week 4 Mortality 47% 12%* Albumin 24.3±0.9 25.9±1.5 25.2±1.1 29.4±1.3** Child-Pugh score 11.1±0.4 11.0±0.5 11.9±0.5 10.3±0.7** * p<0.05, ** p<0.01 Cabré et al, Gastroenterology 1990, 98:715-720

Body Composition in Liver Cirrhosis Reversible Loss of Body Cell Mass Body cell mass BCM BIA [kg] 50 *** 40 30 20 10 0 Controls Before TIPS 6 months after TIPS 12 months after TIPS Plauth et al, J Hepatol 2004, 40:228-233

Glutamine Metabolism Role of the Intestinal Mucosa Other tissues N loss Arg N retention Glc BCAA AA Ala Gln Glc Ala Urea NH 3 Gln Ala CO 2 NH 3 Gln Cit Nucleotides

Ammonia [µmol/l] Intestinal Ammonia Production Mesenteric Venous-Arterial Differences 250 200 150 enteral infusion 100 50 0-1 AA infusion 0.27 g kg -1 h parenteral infusion 0 15 30 60 90 120 180 240 [min] Plauth et al, Gut 2000, 46:849-855

Small Intestinal Ammonia Production Ammonia Load to the Liver AUC [µmol. L -1. min] 200 180 160 140 120 100 80 60 40 20 0 p<0.001 before during enteral infusion p<0.01 before during parenteral infusion Plauth et al, Gut 2000, 46:849-855

Malnutrition in Liver Cirrhosis Effect of Tube Feeding Bilirubin Encephalopathy 0 1 2 3 4 0 1 2 3 4 Wochen 0 1 2 3 4 0 1 2 3 4 Controls 0.78 g protein kg-1 d-1 Tube feeding 1.81 g protein kg-1 d-1 Kearns et al, Gastroenterology 1992, 102:200-205

Nutrition in Liver Cirrhosis ESPEN Guidelines Ensure adequate energy intake 1.3 x REE or 25 NP-kcal kg -1 d -1 Provide enough protein!! 1.2-1.5 g kg -1 d -1 Use fat 1.0 g kg -1 d -1 Special products BCAA-enriched solutions Oral BCAA supplements HE III -IV Protein intolerance Malnourished children Plauth et al, Clinical Nutrition 1997, 16:43-55

BCAA in Liver Cirrhosis Attenuation of Loss of Hepatic Function double-blind randomized study, three arms 14.4 g BCAA daily 14.4 g Maltodextrin (M-DXT) 12.6 g Lactalbumine (L-ALB) each for 52 weeks BCAA (vs M-DXT und L-ALB) less hospital admissions shorter hospital stay Marchesini et al, Gastroenterology 2003, 124:1792-1801

BCAA in Liver Cirrhosis Effects on Event-Free Survival Event-free survival [%] Prospective multi-centre study, 24 months, 12 g BCAA vs normal oral diet Primary end point: event-free survival (Death from any cause, HCC, variceal bleed, deterioriation of hepatic function) 100 Logrank Test p=0.015 Hazard Ratio 0.674 80 60 40 20 VKAS (n=314) Diät (n=308) 0 0 200 400 600 800 1000 Days after start of treatment Muto et al, Clin Gastroenterol Hepatol 2005, 3:705-13

BCAA in Liver Cirrhosis ESPEN Guidelines 2006 How should enteral nutrition be delivered? -which formula? Polymeric enteral formulas (sip feed or tube formula) are generally recommended. Diets with a high energy density are preferable in ascites patients for reasons of fluid balance (C). In case of hepatic encephalopathy arising during recommended protein intake the nitrogen intake goal can be achieved by using BCAA-enriched formulas (A). Oral BCAA supplementation may improve clinical outcome in advanced cirrhosis (B). www.espen.org Plauth M et al, Clin Nutr 2006, 25:285-294

Hepatic Encephalopathy Protein Restriction is not Advantageous! Encephalopathy grade 4 Protein restriction No protein restriction 3 2 1 0 day 0 day 7 day 14 Córdoba et al, J Hepatol 2004, 41:38-43

Liver Transplantation Preoperative Enteral Immunonutrition 15 patients Impact oral drink (median 54 days) pre-ltx and 5 days post-ltx 600 kcal, 7.7 g arginine, 1.8 g EPA + DHA, 0.8 g nucleotides Impact ESPEN 2010: No Advantage of Impact historic compared controls to Standard Feed as Control Total body protein improved; less infectious complications Plank et al, Clin Nutr 2005, 24:288-296

Nocturnal Supplemental Nutrition Effect on Total Body Nitrogen in Liver Cirrhosis Oral Supplement 09:00 19:00 h Oral Supplement 21:00 07:00 h Plank et al, Hepatology 2008, 48:557-566

HE after GI Bleeding Isoleucine Imbalance Hypothesis Olde Damink, Dejong, Deutz, van Berlo & Soeters, Medical Hypotheses 1999, 52:515-519 Upper gastrointestinal bleeding: an ammoniagenic and catabolic event due to the total absence of isoleucine in the haemoglobin molecule Upper GI bleeding Absorption of protein of low biologic value Isoleucine Intestinal protein synthesis Portal NH 3, amino acids Ammoniagenesis Ureagenesis Leucine, valine BCAA antagonism Isoleucine in tissues Protein synthesis in tissues HE Protein catabolism

Protein Metabolism after GI Bleeding Isoleucine Infusion NaCl 0.9% Isoleucine Liver Muscle Olde Damink et al, Hepatology 2007, 45:560-568

Nutrition in Alcoholic Hepatitis (No) Role for Anabolic Steroids Mortality [%] p<0.003 60 50 p<0.003 40 30 Malnutrition moderate severe 20 10 0 + - + - Oxandrolon + - + - + + - - Nutrition + + - - Mendenhall et al, Hepatology 1993, 17:564-576

Nutrition in Alcoholic Hepatitis Enteral Nutrition vs. Steroids Steroids (STE) vs. total enteral nutrition (TEN), each for 28 days Death weeks 1-4 weeks 5-52 Steroids 9/36 (25 %) 10/27 (9/10 due to infection) TEN 11/35 (31 %) 2/24 Probability of survival (intention to treat) Cabré et al, Hepatology 2000, 32:36-42

Feeding Malnourished Cirrhotics Vitamine, Trace Element, Mineral Deficiencies Phosphate Vitamine B 1 Other vitamines Zinc Refeeding syndrome i.v. glycerophosphate 15 mmol PO 4 - - i.v. in 2 h (maximum 45 mmol/24h) Lactic acidosis, Wernicke s encephalopathy prophylaxis 250 mg/d i.m./i.v. for 3-5 days Deficiency frequent in (alcoholic) cirrhosis oral supplement Impairment of ureagenesis, protein synthesis, glucose disposal 80 mg Zinc (200 mg ZnSO 4 ) t.i.d. Rosen GH et al, Crit Care Med 1995, 23:1204-1210 Sechi & Serra, Lancet Neurol 2007, 6:442-455 Marchesini et al, Hepatology 1996, 23:1084-92 and Metabolism 1998, 47:792-8

Feeding the Critically Ill Cirrhotic Summary Expect severe malnutrition requiring immediate treatment Protein malnutrition and hypermetabolism are associated with a poor prognosis Ensure adequate energy intake (non protein 25 kcal kg -1 d -1 ) Use indirect calorimetry if available Provide enough protein (1.2-1.5 g kg -1 d -1 ) Use BCAA after GI-bleeding and in HE III /IV Use fat as fuel (recommended fatty acid ratio n6:n3 = 2:1) Use enteral tube or sip feeding Use parenteral nutrition if enteral alone is not sufficient Avoid refeeding syndrome or vit./trace el. deficiencies How to feed critically ill cirrhotics? Like other critically ill patients with severe malnutrition!

Bariatric Surgery Long Time Outcome Sjöström L et al. NEJM 2007, 357:741-52

Bariatric Surgery Nonalcoholic Steatohepatitis (NASH) Gastric banding in 60 (12 m, 48 w) patients with obesity III Weight loss 31.5 ± 18 kg Paired liver biopsies before and after weight loss Dixon JB et al, Obes Surg 2006, 16:1278-86 before after p 29.5 10 Monate Histo: NASH 30 (50 %) 6 (10 %) < 0.001 lobular steatosis < 0.001 inflammation < 0.001 fibrosis < 0.001 ALT < 0.001 AST < 0.001 GT < 0.001 Decrease in GT is best predictor of improvement in inflammation, fibrosis and NASH

Clinical Nutrition Helpful Informationen Screening ESPEN Guidelines NRS-2002 Guidelines Enteral Nutrition Parenteral Nutrition Nutrition in Liver Disease Nutrition in Pancreatitis Nutrition in Renal Disease PEG Bioelectric Impedance Analysis etc. www.espen.org www.espen.org