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" Nutritional support in patients with chronic disease Anne S Henkel and Alan L Buchman*

SUMMARY INTRODUCTION is an increasingly recognized Malnutrition is highly prevalent among patients with chronic of chronic liver disease that and is nearly universal among patients awaiting liver transplantation. has important prognostic implications. Malnutrition in patients with leads to increased morbidity and Malnourished patients with cirrhosis have a mortality rates. Furthermore, patients who are severely malnourished higher rate of complications and, overalI, an before transplant surgery have a higher rate of complications and a decreased overalI survival rate after liver transplantation. In light of the increased mortality rate.1,2 Malnutrition has high incidence of malnutrition among patients with chronic liver disease significant implications for livertransplantation; and the complications that result from malnutrition in these patients, it it has been shown that patients with poor is essential to assess the nutritional status of alI patients with liver disease, nutritional status before transplantation have and to initiate treatment as indicated. This review addresses the etiologies increased complications and higher mortality of malnutrition, methods used to assess nutritional status, and appropriate rates postoperatively. 3~ Screening alI patients with chronic liver disease for nutritional abnor- treatment strategies. malities can identify those at risk of developing KEYWORDScirrhosis, liver disease, deficiency, nutritional status, protei~alorie malnutrition preventable complications.7 The initiation of nutritional therapy has the potential to reduce REVIEW CRITERIA the risk of such complications, and to improve PubMed was searched in June 2005 using the terms "liver disease", "cirrhosis", the overalI mortality rate. "Iiver transplant", "nutritional status", "malnutrition", "-calorie malnutrition", "nutrient deficiency", "enteral nutrition'; "", PREVALENCE and "branched-chain amino acid" in various combinations. The search was Protein-calorie malnutrition (PCM)-a condi- restricted to full papers published in English-language journals. Papers in the authors' own collections were also included in the search. The reference list was tion of body wasting related to dietary deficiency updated in November 2005. of calories and protein-is found in 65-90% of patients with advanced liver disease and in almost 100%of candidates for livertransplanta- tion.8,9 Patients with chronic liver disease also frequently develop deficiencies, which can have a more insidious presentation than the overt seen in patients with PCM. There is a direct correlation between the progression of the liver disease and the severity of malnutrition.lO,11 Malnutrition develops in patients with cirrhosis irrespective of the etiology of their disease12and occurswith AS Henkel isa Fellowin theDivision ofHepat%gy, and AL Buchman roughly equal incidence in patients with alco- holic and nonalcoholic liver disease.13Patients isAssociate Professor of Medicine in the Division of , Department of Medicine, Northwestern University Feinberg Schoo/ with cholestatic liverdiseaseare subjectto calorie of Medicine, Chicago, IL, USA. depletion, whereas patients with noncholestatic diseasepredominantly experience protein deple- Correspondence 'Northwestem University Feinberg School of Medicine, 676 N St Clair St, Suite 1400, Chicago, tion.14 Additionally, cholestatic disease is more IL60611, USA frequently associated with a deficiency in - [email protected] soluble than noncholestatic disease.15 Malnutrition is not typicalIy a complication of Received 24 July2005 Accepted 6 January 2006 www.nature.com/clinicalpractice acute liverinjury, but manifests with progression doi:1 0.1 O38Incpgasthep0443 to .

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SEQUELAE mechanism that contributes to malabsorption in Malnutrition is associated with increased patients with advanced liver disease is bacterial morbidity and mortality rates in patients with overgrowth resultingfrom impaired small-bowel chronic liver disease. Patients with cirrhosis motility.22The presenceofportal hypertensionhas who are malnourished have a higher rate of also been implicated asa cause of malabsorption , infection, and variceal and gastrointestinal protein loss.23,24An addi- bleeding.3,16They are also twice as likelyto have tional factor isthe administration of medications refractory ascites.8Although numerous studies that lead to malabsorption, such as neomycin, have found a correlation between poor nutri- which is used in the treatment ofhepatic enceph- tional status and a decreased survival rate, there alopathy.25Fat malabsorption not only contrib- is debate as to whether the increased mortality utes to undernourishment, but also results in a rate iscaused by malnutrition or bythe advanced deficiencyin fat-soluble vitamins. liver disease itself. Alberino et ai. identified Another factor that might contribute to malnutrition as an independent predictor of malnutrition, around which there has been mortality in patients with cirrhosis.1 considerable debate, is increased energy expend- Nutritional status has prognostic implications iture. Although several studies have suggested inlivertransplant candidates.Malnutrition before that cirrhosis does not significantly alter resting transplantation is associatedwith a higher rate of energy expenditure (REE),26,27other studies post-transplant complications, including infec- suggest that patients with cirrhosis are actu- tion and variceal bleeding.;4,16,17Patients who ally hypermetabolic when measurements of are severely malnourished require more blood REE are corrected for lean body mass.28,29 products intraoperatively, remain on ventila- Hypermetabolism is found in as many asa third tory support longer postoperatively,and have an of patients with stable cirrhosis; however, it increasedlength ofhospital star,4,9 and a higher seems that there is significant variability in REE incidence of graft failure.18Ultimately, patients among patients with cirrhosis. In fact, it has with poor nutritional status before transplant been suggested that up to 30% of patients with surgery have a decreased survival rate after liver cirrhosis are actually hypometabolic.30,31 transplantation.5,6,9 The exact cause of hypermetabolism remains unclear, but certain predisposing factors have ETIOLOGIES been identified. Infection, a common compli- The primary etiology of malnutrition is poor cation in patients with advanced liver disease, oral intake, stemming from multiple factors. tends to induce a state of hypermetabolism. Manypatients with advanced liver disease have Ascites has also been shown to increase energy an altered sense of taste, which might be related expenditure; this effect tends to be reversed to A and/or deficiency.19Patients with the removal of ascitic fluid.32Muller et ai. with cirrhosis often experience eariy satiety demonstrated that hypermetabolism cannot that is related to mechanical compression from be readily identified by clinical or biochemical massiveascites.Eariysatiety can also result from markers of liver disease, suggesting that an increased serum concentration of leptin, hypermetabolism might be an extrahepatic whichhas been found in patients with advanced manifestation of liver disease.31 It has also liver disease.20The dietary restrictions that are been demonstrated that an increase in energy commonly recommended to these patients, such expenditure caused by hypermetabolism seems asrestriction of , protein, and fluids, can to be matched by a reduction in activity-related discourage adequate oral intake. In addition, energy expenditure.33 Successful treatment of weakness,fatigue,and low-gradeencephalopathy with transjugular intra- can contribute to decreased oral intake. hepatic portosystemic shunt placement results Malabsorption is another important factor in in a reduction of the hypermetabolic state.34 the development of malnutrition in this patient Patients with advanced liver disease also population.A number of mechanisms contribute have an altered pattern of fuel consumption, in to malabsorption. There might be a reduction which there is a more rapid transition from the in the bile-salt pool in patients with advanced use of to the use of fat stores as liver disease, leading to fat malabsorption,21 a substrate for metabolismo This increased use which is particulariy problematic in patients of lipids is a metabolic pattern that is seen in with cholestatic liver disease. Another potential starvation.6,35,36Chang et aI.showed that, after

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GLOSSARY an overnight fast, 58% of the energy used by more usefui when taken serially.39Hand-grip THIRD-SPACING patients with cirrhosis was derived from fat A shift of fluid from lhe strength is a highly sensitivetest and might actu- inlravascular space 10lhe oxidation, whereas control participants derived allyoverestimate the prevalence of malnutrition. inlerslilium 55% of their energy from carbohydrates.36 Nonetheless, hand-grip strength seems to be a ISOTOPE DILUTlON good predictor of complications in patients with A melhod of assessing body NUTRITIONALASSESSMENT advanced liver disease.A recent study compared composilion using a Iracer dose of slable isolope, Considering the complications created by SGA, the prognostic nutritional index, and which is adminislered orally malnutrition, a thorough nutritional assess- hand-grip strength as predictors of outcome in and analyzed in body fluids using mass speclroscopy ment should be performed for everypatient with patients with cirrhosis.40In this study,decreased WHOLE-BODY chronic liverdisease.This,however,might not be hand-grip strength accurately predicted a poor easilyaccomplished. clinical outcome that was related to a higher The measuremenl of whole- There are several factors that complicate the body radiolabeled isolope rate of complications, including ascites,hepatic of polassium can be used evaluation of nutritional status in patients with encephalopathy, spontaneous bacterial peri- 10calculale fal-free mass by cirrhosis. Many of the commonly used markers slandardlzed formulas tonitis, and , whereas of malnutrition are not usefui parameters for SGA and the prognostic nutritional index BIOELECTRICAL IMPEDANCE the prediction of malnutrition in this patient did noto The prevalence of malnutrition was An assay of lolal body population. Weight, for example, is not a reli- highest when measured by hand-grip strength, waler, whereby a weak able indicator of malnutrition, because the suggesting that hand-grip strength could be currenl is passed Ihrough lhe body: lhe vollage drop presence of ascites and will increase the most sensitive technique. Figueiredo et aI. between two eleclrodes the measured weight, whereas lean body mass showed that decreased handgrip strength before is measured and is proportional 10lhe body's might actually be reduced. AIso, many of the transplantation is associated with longer staysin fluid volume in Ihal region laboratory tests that are typical markers of the intensive-care unit and more postoperative nutritional status are less reliable in patients infections.17 with cirrhosis. For example, concentrations of Depletion ofbody cellmass (BCM) is a useful albumin and prealbumin could be low because estimation of nutritional status.41 Decreased of low levelsof synthesis, rather than because of BCM before transplantation has been shown to poor nutritional status. Other parameters must correlate with a threefold increase in post-trans- be used in the evaluation of these patients. A plant mortality rates.5,6 ISOTOPEDILUTION, commonly used method is anthropometry. measurement of WHOLE-BODYPOTASSIUM, Anthropometric measurements include triceps and in vivo neutron activation analysis are skin-fold thickness and midarm circumference, arguably the most accurate methods currently which assess fat storage and skeletal muscle available to assess body composition; however, mass, respectively. This method is, however, these techniques are costly and labor intensive, aiso not without its problems. Potentiallimi- making them less practical for routine nutri- tations of anthropometry include poor inter- tional screening. BIOELECTRICAL IMPEDANCE observer reproducibility and overestimation is a more readilyavailable tool for estimating of these values because of the THIRD-SPACING BCM. Although this is a reliable tool in many of fluidoII patient populations, the accuracy of these Subjective global assessment (SGA) is a measurements in patients with cirrhosis can technique that combines multiple elements of be affected by fluid retention.42 Pirlich et aI., nutritional assessment to classifythe severity of however, showed that estimation of BCM using malnutrition.37 These components are weight bioelectrical impedance correlated closelywith loss during the previous 6 months, changes BCM measured by total body potassium in in dietary intake, gastrointestinal symptoms, patients with and without ascites.43Figueiredo functional capacity, metabolic demands, signs et aI.studied whether the traditionally measured of muscle wasting, and the presence of presacral nutritional parameters correia te with BCM. or pedal edema. SGAhas been shown to have an Although depleted BCM correlated most closely interobserver reproducibility rate of 80%,38and with arm-muscle circumference and hand-grip is useful in predicting outcome following liver strength, most parameters, nonetheless, did not transplantation.3 correlate well with depleted BCM.44 The assessment of muscle function measuring An evaluation of the status of energy metab- hand-grip strength and respiratory-muscle olism might be a reasonable component of a strength has also been used in nutritional evalu- nutritional assessment, because there seems ation; however, these measurements tend to be to be a correlation between hypermetabolism

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80 www.nature.com/cllnlcalpractlce/gasthep and malnutrition.6.31 This evaluation can outcome. It is thought that the patients who be accomplished using indirect calorimetry, received a nutritional supplement might have a widely accepted tool that is used to esti- compensated for taking the supplement by mate REE. Indirect calorimetry measures the decreasing their intake of food. This study consumption of oxygen and production of concluded that regular dietary counseling is as carbon dioxide, and REE is calculated using effectivein increasing energy intake asproviding the Weir equation: [kcal/d= [3.941 xV02 a nutritional supplement.49 (l/day)] + 1.l06 xVC02(l/day) ].45 The meas- ured REEis compared with the predicted energy Enteral nutrition expenditure, as calculated using the Harris- As a general guidetine, oral intake should be Benedict equation.46 A patient is generally encouraged; if patients are unable to maintain considered to be hypermetabotic if the meas- adequateintakeorally,a nasogastrictube should be ured REEis more than 10-20% greater than the inserted for enteralfeeding.Cabre et aI.found that, predicted REE.30.31In transplant recipients, in severelymalnourished patients with cirrhosis, hypermetabolism is associated with a decreased enteral feeding improved serum albumin levels survival rate after transplantation.5 The use of and Child- Turcotte-Pugh scores, and decreased indirect calorimetry enables the calculation in-hospital mortality rates, compared with the of the nonprotein respiratory quotient, defined standard oral diet.50 Hasse et ai. demonstrated asthe ratio of energy produced by the benefit of early initiation of enteral feeding metabolism to energy generated by fat oxida- after transplantation.51 Patients who received tion, which confirms whether a patient has an enteral feeds had an improved nitrogen balance altered pattern of fuel consumption. and fewer viral infections after transplantation. Kearns et ai. showed that aggressive nutritional TREATMENT intervention with enteral feeding accelerated The goals of nutritional therapy are to improve improvement in ; patients PCMand correct nutrient deficiencies.This can who receivedenteral feeds demonstrated a more be accomplished via oral, enteral, or parenteral rapid decrease in bilirubin levels and improve- methods, or a combination of these modalities. ment in hepatic encephalopathy compared with Intervention in the earlystagesof malnutrition control participants.52 can improve outcome. Hirsch et aI. studied the effects of nutritional supplementation Parenteral nutrition in patients with alcoholic cirrhosis.47 They Parenteral nutrition is a less desirable option found that patients receiving a daily supple- than enteral nutrition and should be reserved ment of 1,000kcal and 34g of protein (given as for patients in whom enteral feeding cannot a casein-based enteral nutrition product) had be achieved.53Wicks et ai. showed that enteral better outcomes compared with those in the feeding is as effective as parenteral feeding for control group; the number of hospitalizations maintaining nutritional status after tiver trans- was significantly fewer in the treated group, plantation, and has the benefit of decreasing and additional parameters, including midarm complications and cost. 54 There is some circumference, serum albumin concentration, evidence to suggest that parenteral feeding and hand-grip strength, also improved earlier might be superior to enteral feeding in patients in the treated group than in the control group. with portosystemic shunting, because enteral Mendenhall et ai. studied the effects of oral feeding might worsen hyperammonemia in this nutritional support in patients with alcoholic specific patient population.55 . In patients with severe malnutrition, inadequate caloric intake was associated with Guidelinesfor meetingnutritionalgoals 51% mortality compared with 19% mortality In 1997, the European Society for Clinical in patients who received adequate oral nutri- Nutrition and Metabolism created guidelines tion (greater than 2,500 kcal/day).48 One for meeting nutri tionaI goals in patients with randomized, controlled trial demonstrated end-stage liver disease.53 They recommend that providing nutritional supplementation initiation of enteral feeding when oral intake to pretransplant candidates did not increase is inadequate. In patients with compensated overall dietary energy or protein intake, and cirrhosis, the guidelines recommend that patients did not significantly improve post-transplant consume 25-35 kcal/kg body weight per day of

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nonprotein energy and 1-1.2 glkg body weight of malnutrition in patients with advanced per day of protein or amino acids. In patients cirrhosis. Marchesini et ai. performed a multi- with complicated cirrhosis associated with center, randomized trial examining the role of malnutrition, nonprotein energy should be oral BCAA supplementation in patients with increased to 35-40 kcal/kg body weight per day advanced liver disease.63 The trial consisted and protein intake should increase to 1.5glkg of 174 patients with advanced cirrhosis who body weight per day.Accordingto the guidelines, received 1 year of nutritional supplementation protein intake should decrease to 0.5-1.5 glkg with BCAAs, lactoalbumin, or maltodextrins. body weight/day if stage I or 11encephalopathy BCAA administration wasadvantageouswith is present, and to 0.5 glkg body weight/day if regard to rates of mortality, progression of liver stage III or IV encephalopathy is present. More failure,and hospital admission. The most signif- recent evidence suggests that protein restriction icant limitation that the investigators found was should not be recommended, even in the setting poor compliance with the BCAA-enriched diet; of episodic hepatic encephalopathy.56 in the BCAA group, 15% of patients did not complete the treatment course. Poor compli- Distribution of calorie intake ance was attributed to poor palatability of The distribution of calorieintake throughout the the BCAA supplement.A recent multicenter, day has also been studied. It has been proposed randomized, nutrient-intake-controlled trial that eating a late evening snack could alleviate demonstrated that oral supplementation with the shift towards lipid oxidation by reducing the BCAAs for 2 years improved survival, serum length of time a patient fasts overnight. Indeed, albumin concentration, and quality of life in a late evening meal has been shown to improve patients with decompensated cirrhosis.64 the nitrogen balance57and raise the nonprotein Recent studies advocate the use of nocturnal respiratory quotient.58 A typical recommenda- BCAA administration.65 It is believed that tion for patients with advanced liverdisease is to BCAAs that are consumed during the day are consume four to fivesmall meals per day,as well primarily used asa source of energy for physical as a late evening snack. exercise, whereas when administered at night, BCAAsmight be preferentially used for protein Supplementationwith branched-chainamino acids synthesis. The usefulness of branched-chain amino acid (BCAA) supplementation in patients Correctingnutrient deficiencies with cirrhosis has long been debated. It was Nutritional therapy in patients with chronic proposed that depletion of BCAAs,as seen in liver disease shouJd not only focus on treatment many patients with advanced liverdisease,might of PCM, but should also aim to correct specific promote the development of hepatic encepha- nutrient deficiencies. Patients with advanced lopathy by enhancing the passage of aromatic liver disease commonly develop micronutrient amino acids across the blood-brain barrier, deficiencies.For example,patients with alcoholic resulting in the synthesis of false neurotrans- liver disease who continue to consume alcohol mitters. For this reason, it was hypothesized that are particularly at risk for deficiency of thia- BCAAsupplementationmightimprovehepatic mine, , and magnesium.66 Most patients encephalopathy. Early investigations, therefore, with advanced liver disease, but particularly focused on BCAAs as a potential treatment those with cholestatic liver disease, develop a for hepatic encephalopathy. Although some deficiency of fat-soluble vitamins.67 controlled trials showed no benefit of BCAAs Decreased serum vitamin A levelsresult from with respect to mental function,59 several trials fat malabsorption, as well as defective mobi- showed a significant improvement in hepatic lization of vitamin A from the liver.68 One encephalopathy with BCAA treatment.60,61 A of the common complications of vitamin A 2003 review of 11 randomized trials concluded deficiency is night blindness, which has been that BCAAs improve hepatic encephalopathy, shown to improve with vitamin A supplemen- particu]ar]y when administered enteraJJy to tation, generaJJy at a dose of 25,000 units/day patients with chronic encephalopathy.62 for 4-12 weeks.69Persistent problems with dark ~ Although there are conflicting data, there adaptation, despite adequate supplementation, is more evidence of the beneficial effects of might result from concomitant zinc deficiency.70 BCAAs to support their use in the treatment Vitamin A deficiency typically resolves within I

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2 weeks of liver transplantation.69 Vitamin A these patients. Treatment should focus on main- toxicity is a potential risk of vitamin A supple- taining adequate protein and caloric intake and mentation. Vitamin A toxicity typically causes correcting nutrient deficiencies.Strategiesinclude elevated transaminase levelsand can eventually the consumption of frequent small meals and a lead to cirrhosis, chronic hepatitis, or portal late evening snack to reduce protein breakdown. hypertension.70 Although it was tradition- When oral intake is insufficient, eariy implemen- ally thought that the development of vitamin tation of enteral feeding should be considered. A toxicity requires doses well in excess of the The use of BCAAs remains controversial, but recommended range, data now suggest that the most recent data promote their therapeutic cirrhosis can develop at therapeutic doses of potential. Malnutrition is a potentially revers- vitamin A (e.g. 25,000IU/day for 6 years).71 ible condition that, when identified and treated Liverdisease resulting from vitamin A toxicity appropriately, can lead to improved outcomes. can persist for up to 1 year after discontinuation of the supplement. KEY POINTS deficiency is another complica- Malnutrition is an increasingly recognized tion of chronic liver disease, resulting primarily complication ot chronic liver disease that has from malabsorption; decreased UV light expo- important prognostic implications sure and inadequate dietary intake might also Etiologies include poor oral intake, be contributing factors to . malabsorption, increased energy expenditure, and Impaired hepatic 25-hydroxylation of vitamin D an altered pattem ot tuel consumption is alsoseen in patients with alcoholiccirrhosis.72 The nutritional status ot ali patients with liver deficiency, and eventually oste6- disease should be assessed to identify those at risk malacia or , results from decreased ot developing preventable complications intestinal calcium absorption. Up to 43% of patients undergoing transplant evaluation have Initiating nutritional therapy can reduce the risk ot complications and improve the overall mortality rate osteoporosis.73 There are conflicting data on whether vitamin D supplementation improves References osteoporosis in patients with advanced liver 1 Alberino F et alo(2001) Nutrition and survival in patients disease.It has been suggested that osteoporosis with liver cirrhosis. Nutritíon 17: 445-450 2 Caregaro L et aI. (1996) Malnutrition in alcoholic and does not respond to vitamin D supplementation virus-related cirrhosis. Am J Clin Nut' 63: 602-609 in patients with primary biliary cirrhosis,62but 3 Pikul J et aI. (1994) Degree of preoperative malnutrition it can improve in patients with alcoholic liver is predictive of postoperative morbidity and mortality in liver transplant recipients. Transplantation 57: 469-472 diseasewhen 25-hydroxyvitamin D supplemen- 4 Harrison J et aI. (1997) A prospective study on the tation (25-50mglday) is taken.74 A proposed effect of recipient nutritional status on outcome in liver guideline is to supplement alipatients who have transplantation. Transpllnt 105: 369-374 5 Selberg O et aI. (1997) Identification of high- and low- chronic liver disease with calcium (1glday) and risk patients before liver transplantation: a prospective vitamin D3 (8001U/day).75,76 cohort study of nutritional and metabolic parameters in Zinc deficiency commonly occurs in patients 150 patients. Hepatology 25: 652-657 6 Mulier MJ et aI. (1992) Energy expenditure and with cirrhosis and has been implicated in the substrate oxidation in patients with cirrhosis: the pathogenesis ofhepatic encephalopathy.77Zinc impact of cause, clinical staging, and nutritional state. Hepatology 15: 782-794 supplementation at doses of 600mglday for 7 Kondrup J et aI.; Educational and Clinical Practice 3 months has been shown to improve mental Committee, European Society of Parenteral and functioning in patients with hepatic encephalo- Enteral Nutrition (ESPEN). (2003) ESPEN guidelines for nutrition screening 2002. Clin Nut, 22: 415-421 pathy,78although other studies show conflicting 8 Lautz HU et aI. (1992) Protein-calorie malnutrition in findings, and the role of zinc in treating hepatic liver cirrhosis. Clin Investig 70: 478--486 encephalopathy remains controversial. 9 DiCecco SR et aI. (1989) Assessment of nutritional status of patients with end-stage liver disease undergoing liver transplantation. Mayo Clin P,oc 64: CONCLUSION 95-102 Malnutrition is a well-known complication of 10 Merli M et aI. (1996) Does malnutrition affect survival in cirrhosis? Hepatology23: 1041-1046 advanced liver disease and is associated with 11 Prijatmoko D et alo(1993) Ea"y detection of protein detrimental consequences if left untreated. It depletion in alcoholic cirrhosis: role of body composition is, therefore, of critical importance to assessthe analysis.Gastroenterology105: 1911-1914 12 McCuliough AJ and Bugianesi E (1997) Protein nutritional status of alipatients with chronic liver calorie malnutrition and the etiology of cirrhosis. Am J disease and to optimize nutritional support in Gastroente,o/92: 734-738

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13 Thuluvath PJ and Triger DR (1994) Evaluation of 36 Chang WK et aI. (1997) Effects of extra-carbohydrate , I nutritional status by using anthropometry in adults supplementation in the late evening on energy with alcoholic and nonalcoholic liver disease. Am J expenditure and substrate oxidation in patients with Clín Nutr 602: 269-273 liver cirrhosis. JPEN J Parenter Enteral Nutr 21: 96-99 14 Zaina FE et aI. (2004) Prevalence of malnutrition in liver 37 Detsky AS et aI. (1987) What is subjective global transplant candidates. Transplant Proc 36: 923-925 assessment of nutritional status? JPEN J Parenter 15 Feranchek A et aI. (2005) Comparison of indices of Enteral Nutr 11: 8-13 vitamin A status in children with chronic liver disease. 38 Hasse J et aI. (1993) Subjective global assessment: Hepatology42: 782-792 alternative nutrition-assessment technique for liver- 16 Moller S et aI. (1994) Prognostic variables in patients transplant candidates. Nutritíon 9: 339-343 with cirrhosis and oesophageal varices without prior 39 Buchman AL. (2004) Practícal Nutrítíon Support bleeding. J Hepato/21: 94~946 Techníques. Thorofare: Slack Inc 17 Figueiredo FA et aI. (2000) Impact of nutritional 40 Alvares-da-Silva MR and Reverbel da Silveira T (2005) status on outcomes after liver transplantation. Comparison between handgrip strength, subjective Transplantatíon 70: 1347-1352 global assessment, and prognostic nutritional index in 18 Stephenson G et aI. (2001) Malnutrition in liver assessing malnutrition and predicting clinical outcome transplant patients: preoperative subjective global in cirrhotic outpatients. Nutritíon 21: 113-117 assessment is predictive of outcome after liver 41 Jensen MD (1992) Research techniques for body transplantation. Transplantatíon 72: 666-670 composition assessment. J Am Díet Assoc 924: 19 Garrett-Laster M et aI. (1984) Impairment of taste and 469-472 olfaction in patients with cirrhosis: the role of vitamin 42 Schloerb PR et ai. (1996) Bioelectrical impedance in A. Hum Nutr Clin Nutr 38: 203-214 the clinical evaluation of liver disease. Am J Clin Nutr 20 Testa R et aI. (2000) Serum leptin levels in patients with 64:S51~514 virar chronic hepatitis or liver cirrhosis. J Hepato/33: 43 Pirlich M et aI. (2000) Bioelectrical impedance is a 33-37 useful bedside technique to assess malnutrition in 21 VhlachevicZR etal. (1971) metabolism in patients with and without ascites. Hepatology 32: patients with cirrhosis. I. Kinetic aspects of cholic acid 1208-1215 metabolism. Gastroenterology 60: 491-498 44 Figueiredo FA et aI. (2000) Utility of standard nutritional 22 Gunnarsdottir SA et aI. (2003) Small intestinal motility parameters in detecting body cell mass depletion in disturbances and bacterial overgrowth in patients patients with end-stage liver disease. Uver Tranpl65: with liver cirrhosis and portal hypertension. Am J 575-581 Gastroenterol98: 1362-1370 45 Weir JB (1949) New methods for calculating metabolic 23 Romiti A et aI. (1990) Malabsorption and nutritional rate with special reference to protein metabolism. abnormalities in patients with liver cirrhosis. Ital J J Physío/109: 1-9 Gastroenterol 22: 118-123 46 HarrisJAand Benedict FG (1919)A Bíometric Study 24 Conn HO et aI. (1998) Is protein-Iosing a of Basal Metabolism ín Man. Washington: Carnegie significant complication of portal hypertension. Am J Institute of Washington Gastroenterol93: 127-128 47 Hirsch S et ai. (1993) Controlled trial on nutrition 25 Thompson GR et aI. (1971) Action of neomycin on supplementation in outpatients with symptomatic intraluminal phase of lipid absorption. J Clin Invest 50: alcoholic cirrhosis. JPEN J Parenter Enteral Nutr 17: 319-323 119-124 26 Merli M et aI. (1990) Basal energy production rate and 48 Mendenhall CL et aI. (1993) A study of oral nutritional substrate use in stable cirrhotic patients. Hepatology support with oxandrolone in malnourished patients 12: 106-112 with : results of a Department of 27 Green J et aI. (1991) Are patients with primary biliary Veterans Affairs cooperative study. Hepatology 17: cirrhosis hypermetabolic? A comparison between 564-576 patients before and after liver transplantation and 49 Le Cornu KA et aI. (2000) A prospective randomized controls. Hepatology 14: 464-472 study of preoperative nutritional supplementation 28 Shanbhogue R et aI. (1989) Resting energy expenditure in patients awaiting elective orthotopic liver in patients with end-stage liver disease and in normal transplantation. Transplantatíon 69: 1364-1369 population. JPEN J Parenter Enteral Nutr 11: 305-308 50 Cabre E et aI. (1990) Effect of total enteral nutrition 29 Schneeweiss B et aI. (1990) Energy metabolism on the short-term outcome of severely malnourished in patients with acute and chronic liver disease. cirrhotics. Gastroenterology 98: 715-720 Hepatology 11: 387-393 51 Hasse JM et aI. (1995) Early enteral nutrition support 30 Muller MJ et aI. (1999) Hypermetabolism in clinically in patients undergoing liver transplantation. JPEN J stable patients with liver cirrhosis. Am J Clin Nutr 69: Parenter Enteral Nutr 19: 437-443 1194-1201 52 Kearns PJ et ai. (1992) Accelerated improvement 31 Muller MJ et aI. (1994) Are patients with liver cirrhosis of alcoholic liver disease with enteral nutrition. hypermetabolic? Clin Nutr13: 131-144 Gasuoentero~gy102:20~205 32 Dolz C et aI. (1991) Ascites increases the resting 53 Plauth M et aI. (1997) ESPEN guidelines for nutrition in energy expenditure in liver cirrhosis. Gastroenterology liver disease and transplantation. Clin Nutr 16: 43-55 100:738-744 54 Wicks C et aI. (1994) Comparison of enteral feeding 33 De Lissio M et aI. (1991) Effects of treadmill exercise and total parenteral nutrition after liver transplantation. on fuel metabolism in hepatic cirrhosis. J Appl Physíol Lancet344:837-840 70:21~215 55 Plauth M et aI. (2000) Post-feeding hyperammonaemia 34 Plauth M et aI. (2004) Weight gain after transjugular with transjugular intrahepatic portosystemic shunt and intrahepatic portosystemic shunt is associated with liver cirrhosis: role of small intestinal ammonia release improvement in body composition in malnourished and route of nutrient administration. Gut 46: 849-855 patients with cirrhosis and hypermetabolism. 56 Cordoba J et aI. (2004) Normal protein diet for episodic J Hepato/40: 228-232 hepatic encephalopathy. J Hepato/41: 38-43 35 Owen OE (1983) Nature and quantity of fuels 57 Swart GR et aI. (1989) Effect of a late evening meal on consumed in patients with alcoholic cirrhosis. J Clin nitrogen balance in patients with cirrhosis of the liver. Invest 72: 1821-1832 BMJ 299: 1202-1203

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r Reprinted with pennission from Nature Clinical Practice Gastroenterology and Hepatology 2006; 3(4):202-9. HenkelAS, Buchman AL. Nutritional support in patients with chronic liver disease. Copyright ~ 2006 Nature Publishing Group, a division ofMacmillan Publishers Limited. Ali rights reserved.

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