Clinical Nutrition (1997) 16:43-55© Pearson Professional Ltd 1997

CONSENSUS STATEMENTESPEN guidelines for nutrition in liver disease andtransplantation
M. PLAUTH, M. MERLI, J. KONDRUP, A. WEIMANN, P. FERENCI and M. J. MULLER
ESPEN CONSENSUS GROUP (Reprint requests and correspondence to MP, IV. Medizinische Klinik, Klinikum Charit#der Humboldt Universit#t, SchumannstraBe 20/21, D-10098 Berlin, Germany, Tel: +49 30 2802 2040/4072/3200,
Fax: +49 30 2802 8978)

Introduction

clinical stage of chronic liver disease: When diagnosedby anthropometric criteria, PEM may be present in 20%
of patients with well compensated liver cirrhosis and in
more than 60% of patients with severe liver insufficiency(5). The prevalence is even higher when body compositionis assessed by more sensitive methods (4, 6). The presenceof muscle wasting indicates an advanced stage and apparently is associated with poorer survival (7) particularly
following shunt surgery (8). The prevalence and degreeof PEM do not appear to relate to the etiology of liverdisease per se (4, 5). The higher prevalence of malnutritionin patients with alcoholic liver disease is generally restricted
to skid row alcoholics and patients from low socioeconomic classes.

Nutrition has long been recognized as a prognostic andtherapeutic determinant in patients with chronic liver disease (1) and was therefore included as one of the variablesin the original prognostic score devised by Child andTurcotte (2). Despite the increase in knowledge fromresearch in the fields of metabolism, clinical nutrition andintervention, there is no generally accepted or standardized
approach for the diagnosis and classification of malnutritionin these patients. Similarly, there is no general agreementon the criteria for when or how to implement nutritional
intervention. Even among clinical trials, criteria for patientclassification and study endpoints are heterogeneous andhave been used inconsistently. Therefore, ESPEN commisioned the work of a group of hepatologists and nutritionists
to prepare a consensus document on nutrition in liverdisease and liver transplantation. The aim of this consensus
was to disseminate current knowledge, propose common
terminology, agree consensus definitions and diagnostic andtherapeutic standards to be adopted in clinical practice andresearch, and to stimulate cooperative European studies.
The present paper is the result of meetings on the occasionsof the annual ESPEN and EASL meetings in Rome 1995
and Geneva 1996, a consensus group meeting in Berlinin 1996 and repeated discussions of circulars at various
stages of the work.

Conclusion. PEM is common in chronic liver disease
and positively correlated with functional severity of theliver injury.

Substrate metabolism in chronic liver disease
Decreased glucose but increased lipid oxidation are observed in postabsorptive cirrhotic patients. This modified
substrate utilization does not depend on the nutritional
status (9-11).
Glucose. The majority of patients with cirrhosis have impaired glucose tolerance with hyperinsulinemia and insulin
resistance. In 15-37% of patients overt diabetes may occur
and this represents a risk factor for long-term survival(12, 13). In the postabsorptive state, due to a depletionof hepatic glycogen stores the glucose oxidation rate is
reduced and the hepatic glucose production rate iis low
despite the increase in gluconeogenesis (14).
Under conditions of a euglycemic hyperinsulinemic ,clamp,
glucose oxidation is normalized, while non-oxidative
glucose disposal is impaired due to reduced glucose transport and uptake into skeletal muscle (15, 16). After a meal,
insulin resistance is overcome to a degree because of highinsulin and glucose levels and cirrhotics utilize the ingested
carbohydrate as immediate fuel (17). At present, it is unknown whether glucose deposition as glycogen is impaired
just in skeletal muscle or in both muscle and liver (18, 19).

Effect of liver disease on metabolism and nutritional
statusProtein-energy malnutrition
Acute liver disease induces the same metabolic effects as
any disease associated with an acute phase response. The
effect on nutritional status depends on the duration of thedisease and on the presence of any underlying chronic liverdisease which may have already compromised the patients'
nutritional status.
Malnutrition in chronic liver disease is better defined asprotein-energy malnutrition (PEM) because kwashiorkorlike malnutrition and marasmus frequently coexist (3, 4).
The prevalence and severity of PEM are related to the43

44

ESPEN GUIDELINES FOR NUTRITION IN LIVER DISEASE AND TRANSPLANTATION

Lipid. In the fasting state, plasma free fatty acids as well
as glycerol and ketone bodies are increased. Lipids areoxidized as preferential substrate, and lipolysis is increased
with active mobilisation of lipid deposits (10, 20). Insulin
apparently does not suppress lipolysis to the same degree as
in healthy controls, when plasma free fatty acid and glycerol
concentrations are measured during low insulin infusion
rates (21). There are controversial findings regarding maintenance (22) or loss (17) of suppression of postprandial
lipid oxidation. Plasma clearance and lipid oxidation rates
are not reduced (23, 24) and therefore, the net capacity
to store exogenous lipid does not seem to be impaired incirrhotics.
Essential and polyunsaturated fatty acids are decreasedin cirrhosis and this decrement correlates with nutritional
status (25) and the severity of liver disease (26).

Energy expenditure should be measured by indirectcalorimetry, especiNly in patients with decompensatedcirrhosis. In these patients, no validated factors for estimating resting energy expenditure are available. Indirectcalorimetry should be used in all metabolic studies. When
this method is not available energy expenditure may be
calculated from Harris and Benedict's equation (37) as an
auxiliary method with a mean deviation of 11% frommeasured values (9). It remains controversial, however,whether actual, ideal or 'dry' body weight should be used
for calculation, since ascites apparently is not an inert
compartment regarding energy expenditure (38, 39). Both,actual weight in severe hydropic decompensation or errors
in estimates of 'dry' weight may lead to erroneous values
deviating to the extremes and therefore, ideal body weight
may be accepted as a safe approach.

Protein. The effect of insulin on protein metabolism andamino acid disposal does not seem to be impaired inpatients with insulin resistance (27). Protein turnover incirrhotic patients has been found to be normal or increased.
Some authors have suggested that protein breakdown isincreased, while others suggest that protein synthesis is
reduced (28). Nevertheless, stable cirrhotic patients apparently are capable of efficient nitrogen retention andsignificant formation of lean body mass during oral hyperalimentation (29). Protein catabolism influences the aminoacid imbalance of cirrhosis and indirectly causes nitrogen
overload to the liver leading to hyperammonemia. Albumin
but not fibrinogen synthesis rates correlate with quantitative
liver function tests and clinical stages of cirrhosis (30, 31).

Body composition. In clinical practice, body compositionof cirrhotic patients is assessed by indirect techniques, suchas anthropometry, urinary creatinine excretion or bioelectric
impedance analysis which are inaccurate, due to the combination of reduced body cell mass and a variable degreeof extracellular fluid retention (6, 40). Therefore, it would
be desirable to directly assess fat mass and fat free masscomponents total body water, extracellular water and bodycell or muscle mass.
Anthropometry is a reasonably accurate bedside tool todetect the protein depleted status of cirrhotic patients whenused by a single trained examiner (5, 40-42) and four site
skinfold anthropometry has been considered the best indirect
method of assessing body fat stores in these patients (43).
The value of urinary creatinine excretion as a basis
to estimate muscle or body cell mass has been questioned
since creatine is synthetized by the liver (44). In more recent
studies, however, this method has been considered adequate(29) depending more on renal than on hepatic function(45). Total body potassium can be measured precisely andaccurately when a whole body counter is available (46, 47).
This non-invasive method is regarded as a reliable tool
to estimate body cell mass in general, but has not beenvalidated in cirrhotic patients yet.
The u s e of bioelectrical impedance analysis (BIA) iscontroversial in patients with ascites (4, 48, 49), but caution
should also be exerted in patients without clinical signs of
fluid overload (50, 51). In two studies a good correlation
was found between fat free mass or body cell mass by
BIA and muscle mass or body cell mass assessed by total
body potassium counting (9, 13). However, BIA was foundunable to accurately reflect changes in body composition
due to cirrhosis when direct methods were used (40).
Clearly, for metabolic studies a multi-compartmental
approach using direct methods, such as in vivo neutron
activation analysis, dual energy X-ray absorptiometry
or deuterium oxide dilution for determination of total body
nitrogen, total body fat or total body water is a prerequisite
for accurate quantification of changes in body composition.
These methods, however, are expensive and not generally
available. Therefore, the combination of anthropometry

Conclusions. Substrate metabolism in chronic liver disease
is characterized by insulin resistance which affects glucose
transport and non-oxidative glucose disposal by skeletal
muscle, but does not affect amino acid disposal. Protein
turnover occurs at normal or increased rates with an increase in protein degradation in some patients. Metabolic
clearance and oxidaton of lipids are normal in cirrhosis.
Assessment of nutritional status
For complete assessment of nutritional status information
on energy balance, body composition and tissue function isessential.
Energy balance. From analysis of spontaneous dietaryintake in control groups of nutritional intervention studies
it has become clear that a low intake is associated with apoor outcome (32-35). Despite limitations of the various
methods dietary intake should be assessed. In clinicalpractice a systematic dietary recall obtained by a skilled
dietitian will provide adequate information in most cases.
For metabolic studies in hospitalized patients, a food diaryshould be completed, weighing the food consumed, andappropriate tables for food composition should be used for
calculaton of proportions of different nutrients. Regarding
total energy intake, food analysis by bomb calorimetry may
be utilized as a 'gold standard' (29, 36).

CLINICAL NUTRITION

and assessment of body cell mass by an appropriate method
may serve as a useful approach (40).
Tissue function. Circulating concentrations of many visceral plasma proteins (albumin, prealbumin, retin01-binding
protein) are highly affected by the presence of liver disease,
excessive alcohol consumption and inflammatory states(53, 54). Immune status, which is often considered afunctional test of malnutrition, may be affected by hypersplenism, abnormal immunologic reactivity and alcoholabuse (54). At present, total lymphocyte count and CD8cell count seem to be of prognostic value in malnourishedpatients with alcoholic liver disease (55). In nutrition intervention trials, results from lymphocyte PHA stimulationindex (56) or skin anergy test (3, 35, 55, 57, 58) were
not useful for the detection of nutritional changes.
In patients with alcoholic liver disease, muscle function
as monitored by handgrip strength was an independent
predictor of outcome (55) and, therefore, tests of skeletal
muscle function that respond to nutrition (59), may be
useful also in patients with chronic liver disease.
Subjective global assessment. Subjective global assessment(SGA) when compared with anthropometry shows anagreement of 77% (5). SGA may prove a useful tool for
screening for malnutrition but this approach fails to provide
a sensitive quantitative measure of nutritional changes.
Composite scores. Various modifications of the protein
calorie malnutrition score (60) have been used by the
Veteran's Administration study group investigators (3, 35,
55, 57). In this scoring system, however, variables likemidarm muscle area, skinfold thickness, creatinine excretion, lymphocyte count, recall antigen testing and muscle
function have been combined with variables such as ideal
body weight or circulating levels of visceral proteins thatare of questionable value in chronic liver disease. The
prognostic nutritional index (61) was of no value in identifying cirrhotic patients at risk of complications following
liver transplantation (62).
Conclusions. At present, there is no general consensus onwhich technique should be used to assess nutritional status
in patients with chronic liver disease. Composite scores
are used in clinical trials in order to maximise information.
At present, a reliable evaluation of the spontaneous nutrient
intake appears to allow selection of patients at high risk.
Accurate anthropometric measurements with expressionof the results as percentiles of age- and sex-matched healthy
volunteers probably represent an acceptable evaluationof nutritional status for enrollment of patients into clinicalstudies. More systematic studies of body composition andtissue function are needed.
Consequences of protein-energy malnutrition for theliver

Effect on liver morphology and function
PEM may affect liver morphology in animals although
this has not been demonstrated to any convincing degree in45

humans (63). Rats, deprived of essential nutrients, develop
liver fibrosis and, occasionally, fibrosis is observed in thelivers of children with kwashiorkor. In both cases, fibrosis
is readily reversed by administration of an adequate diet.
Obese humans subjected to total starvation, or a severely
energy deficient diet, develop transient degenerativechanges with focal necrosis (63, 64).
PEM may affect liver function. In cirrhotic patients, anassociation between nutritional status and quantitatiw~ liverfunction, i.e. galactose elimination capacity and caffeine
clearance, has been found by some (36), but not by all
investigators (9). Thus, in nutritional intervention trials in
cirrhotic patients, quantitative liver function tests improved
more, or more rapidly in treatment groups. This included
antipyrine (34), aminopyrine (65) and ICG clearance.. (66),
as well as galactose elimination capacity (67, 68).
Quantitative liver function tests seem to be useful forfollowing the effects of nutritional intervention on liverfunction. They are not useful, however, for identificationof patients who will benefit from nutritional intervention,
since none of the tests can distinguish between impaired
liver function due to a reduction in functional hepatic
mass as opposed to impaired liver function secondary to
inadequate nutrition.
Conclusions. PEM impairs liver function but rarely causes
morphological alterations. Quantitative liver function tests
can be used as global indicators of functional impairment
but are not capable of separating between malnutritioninduced and disease-induced liver malfunction.

Association with clinical course

PEM is associated with an unfavourable clinical outcome.
In cirrhotic patients in general, there is an association
between nutritional status and mortality (4). Furthermore,
within Child groups A and B, there is an association
between nutritional status and mortality (7). Malnutrition
when defined by low dietary intake is associated withhigh mortality (35). Malnutrition has been shown to be an
independent predictor of both the first bleeding episodeand survival in cirrhotic patients with oesophageal varices(69). Malnutrition also is associated with the presenceof refractory ascites or the persistence of ascites (4),. Preoperative nutritional status is related to postoperative
morbidity and mortality in patients with cirrhosis (70).
In controlled trials, the rate of complications (ascites,
gastrointestinal bleeding, encephalopathy, infection andmortality) tended to respond favourably to nutritional
intervention that successfully increased nutrient intake intreated patients over controls (32-34, 66, 68, 71, 72).
Conclusions. Malnutrition negatively affects clinical outcome in terms of survival and complications. The relative
contribution to clinical outcome of either PEM associatedliver dysfunction or PEM associated malfunction of extrahepatic tissues cannot readily be differentiated. Ap~L from

46

ESPEN GUIDELINES FOR NUTRITION IN LIVER DISEASE AND TRANSPLANTATION

improvement of nutritional status and/or liver function, abeneficial effect of nutritional intervention should bedemonstrated on clinical outcome.

(80, 81). Long-term BCAA supplementation seems to be
associated with better nitrogen accretion and liver function,
while anthropometric measures are not clearly improved(82, 83).

Ways to influence the nutritional status in liver disease

Vegetable protein diets. Such diets do not consistently
improve nitrogen economy. The apparent increase in nitrogen retention as judged by urinary excretion apparently may
result from a nitrogen shift to increased incorporationand elimination in fecal bacteria (84).

Tools and strategies to influence nutritional status
Nutritional status can be influenced by manipulations in
the delivery of macro- and micronutrients with regard tocomposition and quantity in order to ensure an adequate
supply with nutritious substrates. Secondly the regulationof substrate metabolism may be modified by use of special
substrates and/or mediators or hormones. In another strategy,
poor nutrient intake due the loss of appetite could becorrected by modifiers of the central nervous regulationof appetite. Effective treatment of anorexia certainly would
have a major impact on nutritional state and prognosisof these patients (35). At present, however, it is not known
which mechanisms are involved in the loss of appetite incirrhotic patients.
Nutritional intervention by means of increased nutrient
supply, modified eating patterns or administration of nitrogenous substrates such as branched chain amino acids(BCAA) can improve a number of static variables of nutritional status such as nitrogen balance, serum protein
concentrations, anthropometric measures, or mortality (29,33-36, 57, 73). Other investigators have studied the effectof nutritional interventions on dynamic variables such as
substrate utilisation, energy expenditure and extra-hepatic
tissue function (17, 55, 74-79), and their observations are
discussed elsewhere in this paper.

Conclusion. Nutritional status may be influenced by altering
substrate availability, use of special substrates, manipulation of metabolic regulation or treatment of anorexia.

Nutritional intervention
All patients who are eating not enough to cover theirestimated/measured caloric needs should be offered systematical nutritional/dietary surveillance, advice and therapy
aimed at provision of adequate nutrient intake. All interventions by dietary counselling or nutritional supplementation
require cooperative and willing patients.

Eating pattern. A modified eating pattern with four toseven small meals including at least one late evening meal
improves nitrogen economy and substrate utilisation instable cirrhotic patients (73, 78).
Dietary supplements. Oral supplementation may provide
the patient with the desired amount of a particular substrate, while permitting the continuation of an oral diet.
Short-term supplementation with BCAA enables proteinintolerant patients with cirrhosis to attain positive nitrogenbalance without increasing the risk of encephalopathy

Artificial feeding. Many malnourished cirrhotic patientsare anorexic and cannot meet their nutrient requirements
by oral intake 'ad lib'. This has been demonstrated inintervention trials when artificial feeding by use of liquid
formulae proved to be more effective in providing adequate
amounts of nutrients than normal oral nutrition 'ad lib'.
Moreover, in patients with predominantly alcoholic liverdisease the magnitude of daily caloric intake in general is
positively correlated with survival (35).
Intervention by enteral nutrition using liquid formulae
to supplement spontaneous oral nutrition is associated withimproved survival and liver function (33-35, 57). Improvement of nutritional state, however, is not attained unequivocally when judged by improvement in serum proteins(albumin, transferrin, retinol binding protein), immunoreactivity (lymphocyte count, recall antigen test) and anthropometric variables (32-35, 57). In these trials, a protein
intake of up to 1.3-1.5 g.kg-l.d -1 was tolerated by many
patients without adverse effects on mental state (33-36, 57,
77, 79, 85).
Tube feeding. The decision, when to initiate tube feeding
is debated. While tube feeding yields superior results over'ad lib' oral feeding due to inadequate voluntary intake(33, 34), others are hesitant because of the risk of variceal
bleeding. From the evidence of published trials, however,there is no suggestion that enteral tube feeding increases
the incidence of variceal bleeding (33, 34). Slow or intermittent gastrointestinal (GI) bleeding is not an absolutecontraindication to enteral feeding. In any case, patients
must not be fasted and thus the introduction of tube feeding
should not be delayed.
There is no general agreement as to whether enteralfeeding should be intermittent (common clinical practice) or
continuous (33, 34). Liquid enteral formulae for cirrhotic
patients should preferably be of high energetic density(1.5 kcal/ml) with a low sodium content (40 mmol/d) sothat they can be used in patients with fluid retention (33).
Questions like optimal composition of non-nitrogenous
caloric substrates or the nutritional efficacy of increased
BCAA content in patients without encephalopathy have notbeen adressed in controlled trials.
Parenteral nutrition. Parenteral nutrition should be reserved
for those not capable or willing to participate in oral nutrition or enteral tube feeding. Regarding energy and nitrogenprovision the same guidelines should be followed as given
for enteral nutrition.

CLINICAL NUTRITION

Liver-adapted amino acid solutions. Solutions with an increased content of BCAAs (40-45%) and reduced amountsof aromatic amino acids and methionine have been introduced for the treatment of patients with liver disease (86).
While they may have some value in the treatment of hepatic
encephalopathy (vide infra) they have no documented effecton nutritional state. In some countries 'coma-solutions' aremarketed containing only BCAAs and other compounds
believed to be effective in hepatic encephalopathy. These
are unbalanced solutions and not recommended as anitrogen source for parenteral nutrition.
Special substrates. Ammonia lowering compounds suchas arginine, ornithine-aspartate or ornithine-o~-ketoglutarate
have no effect on the nutritional status of patients with liverdisease. Likewise, the nutritional value of special substrates
like glutamine, nucleotides or co-3-fatty-acids and of 'supernutrients' such as phosphatidylcholine or S-adenosyl-Lmethionine remains to be established.
Micronutrients. Apart from correcting established nutritional deficiency states no effect on nutritional state is
obtained by administration of the micronutrients zinc,selenium, vitamin A/carotenoids, or vitamin E/tocopherols.
Both, vitamin A and zinc supplementation, however, may
indirectly alter nutritional state by improving gustatory
function (87, 88) and thereby probably also volitional foodintake. Also, hepatic urea production capacity has beenshown to increase following oral zinc supplementation
when accompanied by normalization of previously low
plasma zinc levels (89). Since trace element deficiency may
be difficult to diagnose, oral supplementation may beinstituted liberally. In chronic cholestasis supplementation
with fat soluble vitamins either by parenteral route (Vitamin
ADEK) or orally using d-a-tocopheryl polyethylene glycole
100 succinate (TPGS) as a vehicle for vitamines E and D(90, 91) can prevent or correct deficiency states.
Anabolic hormones. Only moderately malnourished patients
may benefit from anabolic steroids such as oxandrolone(40-80 mg/day) provided their caloric intake is adequate,
whereas in severely malnourished patients this regimen is
not effective (35).
Growth hormone (GH) has been successfully given for
promotion of protein accretion, prevention of loss of intracellular water, and improvement in clinical outcome ofpatients with gut, renal, or pulmonary failure (92-95). In
patients with cirrhosis, plasma levels of GH and IGFBP-1
are elevated, whereas IGF-1 and IGFBP-3 levels are decreased (96-98) suggesting possible GH resistance (99).
Data from preliminary trials in patients given GH document
an increase in IGF-1 and IGFBP-3 in patients with cirrhosis
but no change in liver function, body weight or body massindex (100).
Intravenous IGF-1 (a potent mediator of biologic GH
effects) promotes protein anabolism as efficiently as subcutaneous GH in human volunteers made catabolic bycaloric restriction (101). No data are available yet on the47

effects of IGF-1 on nutritional state in cirrhotic patients,
although it is not clear as to whether this compound will
be available in the near future because of its side-effects.
Conclusions. Nitrogen economy can be improved !in the
majority of patients by frequent small meals and by special
dietary supplements in those who are intolerant of protein.
Nutrient intake can be increased by supplemental enteralnutrition and nutrient intake can be ensured by tube orparenteral feeding. Anabolic steroids may improve nutritional state, but only in moderatly malnourished cirrhotics
who also receive adequate oral or enteral nutritional supplementation. The role of anabolic hormones GH and IGF-1
remains to be established.

Effect of nutritional therapy on outcome

Oral diet
In general, patients with liver disease tolerate a normal diet.
The majority of patients do not need any dietary restrictions
and they may even be harmed by them. A decrease indietary fat may be useful to reduce symptoms of steatorrhea
in patients with cholestatic liver disease, but it is associatedwith the risk of inadequate energy intake and is notsupported by appropriate clinical trials.
If patients are able to eat more than 70 g protein.d-1
without deterioriation of mental status, no modificationof their diet is necessary or effective. The definition of intolerance to dietary protein, however, depends on the methods
used to document changes in mental status. In patientswith borderline protein intolerance (60-70 g protein.d-1) avegetable diet (102, 103), or a diet rich in fibre (84) may
help to prevent hepatic encephalopathy.
Salt restriction is of potential value in patients withascites not responding to diuretic treatment.
Supplements to oral nutrition
Supplementation of a normal oral diet is necessary only
when daily requirements of energy, protein, electrolytes,
trace elements or vitamins are not met by actual intake.
Energy. At present, it can safely be assumed that patientswith compensated cirrhosis do not require modificationof their intake of non-nitrogenous substrates. In patientswith severe hepatic insufficiency, frequent carbohydrate
feedings may help to avoid hypoglycemia and counteract
the metabolic situation of advanced liver failure (104).
Protein. Besides pharmacological methods to improvemental status (disaccharides, antibiotics) supplementationof a low protein diet with BCAA may be useful. Patientswith stable cirrhosis improved in psychometric testing
when their normal diet was supplemented with BCAA
(0.25 g.kg-l.d -1) rather than with isonitrogenous amountsof casein (82, 83). It is unclear what minor improvementsof psychometric tests mean for the quality of life of

48

ESPEN GUIDELINES FOR NUTRITION IN LIVER DISEASE AND TRANSPLANTATION

patients. Patients with abnormal psychometric tests may doquite well when their performance in daily life is tested(105).
In patients intolerant of a daily protein intake of
1.0 g.kg-l.d -1 dietary protein may need to be reduced to
an intake of 0.5 g-kg-l.d-I, but this should be avoided at
all cost. In this situation, positive nitrogen balance andimprovement in nitrogen intake can be achieved by oral
supplementation of BCAA at 0.25 g.kg -l.d -1 without undue
risk of encephalopathy (80-82). It should be recognized,
however, that protein intolerance may present as a transientphenomenon and that patients may later be tolerant of ahigher protein intake when the increment in daily dietary
protein has been slow (106). Generally, periods of protein
restriction should be kept as short as possible.

Micronutrients, electrolytes. While an association between
encephalopathy and zinc defidiency could be demonstrated(107, 108), three randomized controlled trials of oral
supplementation (600 mg zinc daily) produced conflicting
results in patients with subclinical encephalopathy (109111). Improved zinc status, however, may be associatedwith improvement of liver function as discussed above.
Supplementation with calcium and vitamin D has been
recommended for treatment of patients with osteopenia
in chronic liver disease, although these measures failed
to improve bone mineral density in patients with primarybiliary cirrhosis; estrogen replacement was more effective(112, 113).
Conclusion. Supplements to oral nutrition are of value inthe small subgroup of protein-intolerant patients (BCAA)
and in patients with documented deficiencies of micronutrients (zinc, vitamin A).
Enteral nutrition
There are several controlled trials of enteral nutrition
involving a substantial number of patients (32-34, 57,
114-116) with predominantly or exclusively alcohol related
liver disease. Most patients had either stable liver diseaseor acute alcoholic hepatitis, but no patients were proteinintolerant and protein restriction was not necessary.
Since many patients had reduced volitional oral intake,the observed beneficial effects seem to be arisen because
energy and nitrogen intake increased in the treatmentgroups. No information is available on the effects of enteralnutrition in patients with non-alcoholic liver disease.
In general, the observed results reflect effects of nutritional supplementation in treatment groups. A significant
effect on mortality was observed only in association withlonger nutritional support (> 3 weeks) and low spontaneous
nutrient intake (33). In addition, in a trial comparing
oxandrolone with placebo a drug effect was only observed
when adequate nutrition was provided (35). Beneficial
results have been obtained with standard as well as withBCAA-enriched formulae and therefore standard formulae
may be used except in cases of protein intolerance.

Conclusions. Supplementary enteral nutrition is of documented value in cirrhotic patients resulting in an improvement in nutritional status and possibly mortality. Liverfunction as well as hepatic encephalopathy may improve.
Parenteral nutrition in patients with alcoholic hepatitis
Parenteral nutrition using conventional amino acid solutions
has been given as a nutritional supplement in addition tooral nutrition ad lib in seven controlled trials. Parenteralenergy and nitrogen supply were in the range of 2003000 kcal.d -1 and 35-130 g protein-d-1, while oral intakes
ranged from 13 to 39kcal.kg-1.d -1 (58, 66-68, 71, 72,
115-118).
Using this approach, mortality remained unaffected most
likely due to the inclusion of patients with only moderately
severe disease. No detrimental effects of the increased
nitrogen intake were observed as far as neuropsychiatricstatus was concerned, although this was not optimally monitored. Improvement in visceral protein status was demonstrated by a majority of studies. Also, an improvement
in liver function (galactose elimination capacity, serum
bilirubin) was found.

Conclusions. Parenteral nutrition provides a useful therapeutic option for the treatment of malnutrition in alcoholic
hepatitis patients not suitable for or not tolerating enteralnutrition. It seems to have a beneficial effect on liver function, but in these patients studied it is difficult to separate
the effects of nutritional therapy from those of cessationof alcohol abuse and liver disease. There are no publishedrandomized trials comparing enteral vs parenteral nutritionin patients with alcoholic hepatitis or cirrhosis.
Perioperative parenteral nutrition in chronic liver disease
Patients with stable cirrhosis probably do not need any
specific treatment preoperatively, but no well-designed
prospective studies are available which have addressed
this topic. Malnourished cirrhotic patients undergoing
non-shunt laparotomy are at higher risk of postoperativecomplications including death than those who are notmalnourished (119). In cirrhotic patients undergoing hepatic
resection, esophageal transection with splenectomy or
distal splenorenal shunting procedures no difference in thefrequency of encephalopathy was observed during 14 days
postoperative parenteral nutrition with a conventional ora BCAA-enriched solution (120).
In patients having surgery for hepatocellular cancer
pre- and postoperative parenteral nutrition has a beneficial
effect on mortality and nutritional status as assessed byvisceral protein concentrations (56). More detailed information on liver function and mental state were not available
and it should be noted, that only 10% of the patients weremalnourished. The treatment group received parenteralnutrition with increased BCAA-content whereas controls
received isotonic glucose and electrolyte solutions.

Conclusions. Cirrhotic patients benefit from immediateCLINICAL NUTRITION

49

postoperative nutrition and, in the absence of encephalopathy, there is no need to use BCAA-enriched rather
than conventional amino acid solutions. Most likely, early
enteral nutrition may be at least as effective as parenteralnutrition, but this has not been formally investigated.

of fat soluble vitamins. At present, only the role of vitamin
D has been investigated to any greater extent as referred
to in the section on supplements. In the presence ofvitamin deficiency the respective vitamins should be given
parenterally.

Parenteral nutrition in cirrhosis

Nutrition in liver transplantation

Compensated cirrhosis. If patients with compensatedcirrhosis require parenteral nutrition then this can besupplied by standard solutions.

Impact of preoperative nutritional status on outcome ofliver transplantation

Cirrhosis with encephalopathy. Most of the controlled
studies performed 10-15 years ago adressed the question of
the value of BCAA in the treatment of hepatic encephalopathy (121-127). Their results are conflicting (for review
see 128). Studies cannot be compared directly because ofdifferences in design, patient selection, treatment schedules
and study endpoints. The effect on hepatic encephalopathy
is not readily discernable if complications of cirrhosis
such as GI bleeding, sepsis, or renal failure are present
which determine the final outcome. A meta-analysis (129)found a trend in favour of beneficial effects of BCAAenriched solutions on hepatic encephalopathy, but theauthors concluded that more and better designed studies
are needed to definitively prove or disprove the role ofthis treatment. From these short-term interventional studies
no meaningful data regarding the effect of BCAA-enrichedsolutions on nutritional status or liver function are available.
Less information is available on the optimal formulationand composition of the energy-yielding substrates carbohydrate and fat. In certain patients, the increase in fat intake
to cover 50% of non-protein calories may aid in reaching anadequate energy intake.
Conclusions. Adequate nutrition per se counteracts hepatic
encephalopathy; parenteral nutrition is only indicated, whenoral or enteral nutrition (including tube feeding) is notpossible. BCAA may improve mental state in patients with
hepatic encephalopathy provided that liver function does
not further deteriorate and major clinical complications
are absent. The improvement of encephalopathy by BCAA
is not necessarily a result of better nutrition alone. The
use of BCAA-enriched solutions has no effect on survival.
Parenteral nutrition in fulminant hepatic failure
There are no controlled studies in these patients. It is unknown whether such patients can appropriately metabolizeamino acids or fat at all. Glucose administration is mandatory to prevent or treat hypoglycemia. In clinical practise,plasma levels of lactate, glucose and triglycerides may be
used as a guide to monitor substrate utilisation.

Chronic cholestasis
From the point of nutrition, the basic defect in these conditions is impaired fat digestion and impaired absorption

Malnutrition is uncommon in individuals transplanted forfulminant hepatic failure, whereas it is often observed inthose suffering from advanced chronic liver disease (62,130, 131). Subjective global assessment of variables suchas muscle wasting, loss of subcutaneus fat, dietary intake,and functional capacity and physical activities have been
recommended for assessing nutritional state in transplantcandidates (132, 133). Composite scores to identify highrisk patients have been used with some success in one (130)but not in another study (62). In one large study bioelectrical impedance analysis was used to estimate bodycell mass and fat free mass and in a subgroup of patientsbody cell mass was also determined by total body potassiumcounting showing a close correlation to fat free mass values
obtained by BIA (9).
From these studies it can be concluded that poor nutritional state before transplantation is associated with prolonged stay in intensive care unit, on respirator therapy andin hospital and with increased mortality (9, 130, 133, 134).
Also, hypermetabolism prior to transplantation seems tobe associated with the persistence of hypermetabolism andan unsatisfactory course postoperatively (135). Judging
from answers to a questionnaire European transplant centers
do not regard malnutrition per se as a general contraindication to liver transplantation, since in cirrhosis it is partof the spectrum of clinical manifestations of the disease.
In malnourished children, growth, in terms of height andbody weight, prior to transplantation was observed only inthose on oral BCAA supplementation but not in controls(136). In view of these findings, it would be desirable
to have more information on the efficacy and impact ofnutritional support prior to transplantion.

Conclusions. Malnutrition is not a contraindication to transplantation but may negatively affect outcome. Systematic
evaluation of the effects of nutritional intervention prior
to elective transplantation is needed with regard to substratemetabolism, body composition and clinical outcome.
Postoperative nutrition in liver transplantation
Reilly and colleagues (137) compared the effects of twoparenteral nutritional regimens using either a standard or
a BCAA-enriched amino acid solution with isotonic electrolyte or glucose infusions in postoperative transplantpatients. Both groups of patients, who also received parenteral nutrition, had a better outcome in terms of shortened

50

ESPEN GUIDELINES FOR NUTRITION IN LIVER DISEASE AND TRANSPLANTATION

ventilator and intensive care treatment than those without
nutritional support and there was no difference between
those receiving a standard and those receiving a BCAAenriched solution.
Hasse and colleagues (138) compared early enteralfeeding, commenced at 12h after transplantation, withconventional intravenous electrolyte solutions until oral
feeding was started. Significantly fewer viral infections andbetter nitrogen retention were found in patients who wereenterally fed. Most frequently, nasogastric feeding tubes
are used, but jejunostomy tubes, placed at the time oftransplantation have been used without undue risk ofserious complications (139).
Direct comparison of parenteral and early enteral nutrition revealed comparable efficacy of both strategies withregard to provision of nutrients and nutritional state on
postoperative day 10 (140). At present, it may be concluded
that early postoperative enteral nutrition is well tolerated(138, 140, 141) and may reduce complication rates andcost (140).
Considering long-term results, protein turnover seems todecrease but not normalized 12 months after transplantation(142). At that time body composition analysis reveals adecrease in total body water, an increase in total body fat
but no change in body cell mass (135, 142). Despite supposedly normal dietary intake, excessive weight gain andhypercholesterolemia were observed within the first 18
months after transplantation (143, 144). This has been
attributed to obesity prior to transplantation as well as tochanges in energy expenditure and disturbance in cholesterol metabolism by immunosuppressive agents such as
cyclosporine (143, 144). Therefore, after transplantation
long-term metabolic and dietary evaluation and counseling
may prove useful.

Conclusions. Early postoperative nutrition is clearly beneficial following liver transplantation in terms of morbidity.
Nutrition should be given preferably by the enteral routeas early as possible. Few data are available on substratemetabolism and body composition from long-term followup after transplantation.
Substrate requirements
Energy. In general, non-protein energy requirement in
the graft recipient does not differ from other patients withabdominal surgery (145) and can be estimated from Harrisand Benedict's equations (37) using ideal body weight plus
30% (141, 146). At present, there are insufficient data
to delineate special patterns of substrate requirement andutilisation unique to patients with a liver graft. Someauthors have used indirect calorimetry in the pre- andpost-transplant period to estimate substrate requirementswith particular regard to impairment of glucose utilizationand compensation by fat emulsions (9, 141). In clinicalpractice, adequate substrate utilisation may be monitored
by determination of glucose, lactate, and triglyceride
levels in serum. In the early postoperative period glucose

metabolism may be disturbed and insulin resistance may
be observed. In preoperatively nondiabetic patients hyperglycemia should be treated by reducing glucose administration since in the presence of insulin resistance highdoses of insulin fail to improve glucose oxidation (147).

Protein. Grafted patients may exhibit considerable nitrogen
losses with a persistantly negative nitrogen balance for28 days postoperatively (146); therefore, protein or aminoacid requirements may be increased. In reported trials, however, a protein or amino acid intake of 1.0-1.5 g-kg-l.d-1 has
been used (133, 137), which does not differ from recommendations for surgical patients in general. Monitoringof postoperative urinary urea excretion may help todetermine actual nitrogen requirement. There seems to be
no advantage in using BCAA-enriched amino acid solutions
over conventional amino acid solutions (137).
Micronutrients and electrolytes. At present, no recommendations can be given on the basis of published trials.
Caution should be exerted when attempting to rapidly
correct chronic hyponatremia because of the risk for pontine
myelinolysis (148). Magnesium levels should be monitored
to look for cyclosporine or tacrolimus induced hypomagnesemia (149).
Conclusions. With the exception of potentially elevatednitrogen requirements transplanted patients do not differ
from surgical patients in general with regard to macronutrient requirements. Micronutrient and electrolyte status
should be monitored in order to identify and correct
deficiency states.
Requirements and recommendations
Energy and substrate requirements
Energy. Measured energy expenditure has been foundincreased over controls (38, 150, 151) or predicted values(9, 152) in patients with cirrhosis who therefore havebeen classified as hypermetabolic. But this is not a uniform
finding since hypometabolism as well as normometabolism
have been observed in patients with cirrhosis (9-11, 17, 39,
150, 152). The diagnosis and the degree of hypermetabolism, however, are highly dependent not only the reference
population (controls or predicted values), but also on
the expression of energy expenditure in relation to either
body weight (ideal, actual, or 'dry' weight), fat free massor body cell mass and this is discussed in detail elsewhere(52, 153). When related to predicted energy expenditureamong stable cirrhotics a subgroup of 15-20% may beconsidered as hypermetabolic, 25-30% as hypometabolicand the large majority as normometabolic (9, 152). Hypemetabolism may be an indicator of a high risk population
characterized by more severe malnutrition, greater hemodynamic abnormalities and a poorer outcome after transplantation (52, 135) and, therefore, the diagnosis should
be based on a sound assessment of body cell mass as a

CLINICAL NUTRITION

major determinant of energy expenditure (153). Increased
resting energy expenditure has also been observed during
complications of liver disease, such as acute hepatic failure(154), high volume ascites (39), or presence of hepatoellular
carcinoma (155).
Total energy expenditure in cirrhosis has been determined only occasionally and increased requirements appear
to be offset by reduced physical activity. Diet-induced
thermogenesis has been found normal in cirrhotics (15, 17,156) and energy requirements for physical activity do notseem to be increased (157, 158).
Although resting energy expenditure is difficult to predictin patients with clinically stable liver cirrhosis, for practical
purposes energy requirement may be calculated from theHarris and Benedict equation (52).
Protein. In clinical intervention trials protein or aminoacids were given in amounts of 0.6-1.2 g.kg-l.d -1 inpatients with cirrhosis and severe encephalopathy (129) and
0.5-1.6 g.kg-l.d-1 in patients with alcoholic hepatitis or
cirrhosis with or without low grade encephalopathy (32-34,
57, 58, 66-68, 71, 72, 117, 118). In only a few studies,
however, were protein requirements assessed systematically. From these findings, patients with stable cirrhosis
appear to have increased protein requirements of
1.2 g.kg-kd -~ to maintain nitrogen homeostasis as opposed
to 0.8 g-kg-l.d-1 in normal individuals (29, 36, 106). The
reasons for this phenomenon are not yet clear, but theincreased protein requirement seems to be due to increased
whole body protein degradation which may be due to low
plasma levels of IGF-1 (159, 160).
Micronutrients. Deficiency of fat-soluble vitamins is ob-

served in patients with steatorrhea due to cholestasis andbile salt deficiency und in alcohol abusers (112, 161). A
depletion in water soluble vitamins is not uncommon
in cirrhosis, particularly in alcohol induced cirrhosis(162, 163).
Zinc and selenium deficiency has been observed inboth alcoholic and non-alcoholic liver disease (164-166)
and may be associated with neurological symptoms (167).
The causes are multiple: reduced dietary intake, malabsorption, increased metabolic demands, impaired conversionof vitamins into their active forms and reduced hepatic
storage.
Conclusions. In patients with clinically stable chronic liverdisease energy requirements are similar to healthy subjects.
Energy expenditure is increased in patients with cirrhosis
and complications. Protein requirements are increased inpatients with cirrhosis. Micronutrient deficiencies are notuncommon in cirrhosis, but no data on requirements areavailable in this patient group.
Recommendations

In patients with chronic liver disease nutritional therapy
is of documented value in those with malnutrition who

51

are failing to maintain an adequate oral nutrient intake.
Generally, nutrition should be provided by the oral or
the enteral route. Parenteral nutrition should only be used
when enteral feeding is not possible or impractable. For
parenteral nutrition energy should be provided by glucose
and fat in a ratio of 65-50 : 35-50% of non-protein calories.
Parenterally administered fat is cleared from the blood andutilized efficiently by the majority of patients with cirrhosis(23, 24); MCT/LCT emulsions are well tolerated in transplanted patients (168). As a standard, nitrogen should be
provided by conventional amino acid solutions for parenteral nutrition or high quality protein for enteral feedingin amounts to meet requirements as outlined above.
Recommendations for various clinical conditions are
summarized in the Table. In patients with clinically stablecirrhosis, available data on energy and nitrogen balancesuggest a recommended intake for maintaining body composition of 1.3 x REE or 25-30 kcal.kg-l.d-1 non-protein
energy plus 1.0-1.2 g.kg-l-d-1 of protein. In malnourishedpatients requiring repletion, intakes should be higher.
According to the intervention studies available, malnourished patients who have an inadequate dietary intake
and are at risk of fatal complications of liver cirrhosis(infection, bleeding, etc) should receive nutritional support.
In the studies suggesting a positive effect on liver function and clinical outcome, non-protein energy was given
in amounts of 35-40 kcal-kg-l-d-1 plus protein of up to
1.6 g.kg-l.d -J. In these patients, low grade encephalopathy(I-II) should not be considered a contraindication to
nutritional support including an adequate protein supply.
In patients with encephalopathy as their main problem,
other precipitating causes should be excluded before
considering the patient protein-intolerant. Transient protein
restriction can be instituted, but after a few days adequate
nutrition should be reinstituted. In proven protein-intolerant
patients, oral BCAA-supplementation may be helpful inTable Nutrition in chronic liver disease - recommendations of the 1997
ESPEN consensus group
Clinical condition

Non-protein energy
kcal.kgl-d 1

Protein or amino acids
g.kg-l.d -I

Compensated cirrhosis

25-35

1.0-1.2

35-40

1.5

25-35

Transiently 0.5,
then 1.0-1.5 if protein
intolerant: vegetable
protein or BCAA
supplement25-35

0.5-1.2
BCAA-enrichedamino-acid solution

Complications
Inadequate intake
Malnutrition
Encephalopathy I-II

Encephalopathy III-I¥

Generally, the oral or enteral routes are preferred.
Parenteral nutrition should only be used when enteral feeding is notpossible or impractable. For parenteral nutrition energy should be
provided by glucose and fat with fat constituting 35-50% of non-protein
calories. Nitrogen should be provided using conventional amino acidsolutions unless indicated otherwise. For calculations ideal body weightshould be used.

52 ESPENGUIDELINESFOR NUTRITIONIN LIVERDISEASEAND TRANSPLANTATIONa c h i e v i n g an a d e q u a t e n i t r o g e n intake. V e g e t a b l e p r o t e i ncanalso b e tried, but the risk o f i n a d e q u a t e p r o t e i n

a s s i m i l a t i o n s h o u l d b e k e p t in m i n d .
P a t i e n t s in c o m a ( e n c e p h a l o p a t h y I I I - I V °) can safelyb e g i v e n T P N r e g i m e n s p r o v i d i n g 2 5 - 3 0 k c a l - k g - t . d -1 n o n p r o t e i n e n e r g y plus 1.0 g . k g - l . d 1 u s i n g B C A A - e n r i c h e d
a m i n o acid solutions.
In a d d i t i o n to the clinical c o n d i t i o n s g i v e n in the Table, italso s e e m s a d v a n t a g e o u s to a d m i n i s t e r p o s t o p e r a t i v e nutrition to p a t i e n t s u n d e r g o i n g m a j o r surgery, i n c l u d i n g transplantation. F a s t i n g p e r i o d s s h o u l d n o t e x c e e d 6 h due to thel i m i t e d g l y c o g e n stores in m a l n o u r i s h e d cirrhotic patients.

References
t. Patek A J Jr, Post J. Treatment of cirrhosis of the liver by a nutritious
diet and supplements rich in vitamin B complex. J Clin Invest 1941;
20:481-505
2. Child C G, Turcotte J G. Surgery and portal hypertension. In: ChildC G, ed. The Liver and Portal Hypertension. Philadelphia: Saunders,
1964:50-51
3. Mendenhall C L, Anderson S, Weesner R E, Goldberg S J, Crolic
K A. Protein calorie malnutrition associated with alcoholic hepatitis.
Am J Med 1984; 76:211-221
4. Lautz H U, Selberg O, Ktrber J, Btirger M, Mt~llerM J. Protein
calorie malnutrition in liver cirrhosis. Clin Invest 1992, 70:478.486
5. Italian Multicentre Cooperative Project on nutrition in liver cirrhosis.
Nutritional status in cirrhosis. J Hepatol 1994; 21:317-325
6. Crawford D H G, Shepherd R W, Halliday J Wet al. Body
composition in nonalcoholic cirrhosis: the effect of disease etiology
and severity on nutritional compartment. Gastroenterology 1994;
106:1611-1617
7. Merli M, Riggio O, Dally L, P I N C. What is the impact ofmalnutrition on survival in liver cirrhosis. Hepatology 1996;
23:1041-1046
8. Orloff M J, Charters A C, Chandler J G et al. Portocaval shunt asemergency procedure in unselected patients with alcoholic cirrhosis.
Surg Gynecol Obstet 1975; 141:59-68
9. Mtiller M J, Lautz H U, Plogmann B, Burger M, KiSrberJ, Schmidt
F W. Energy expenditure and substrate oxidation in patients withcirrhosis: the impact of cause, clinical staging and nutritional state.
Hepatology 1992; 15:782-794
10. Owen O E, Trapp, V E, Reichard J Aet al. Nature and quantity offuels consumed in patients with alcoholic cirrhosis. J Clin Invest
1983; 72:1821-1832
11. Merli M, Riggio O, Romiti Aet al. Basal energy production rateand substrate use in stable cirrhotic patients. Hepatology 1990;
12:106-112
12. Bianchi G, Marchesini G, Zoli M, Bugianesi E, Fabbri A, Pisi E.
Prognostic significance of diabetes in patients with cirrhosis.
Hepatology 1994; 20:119-125
13. Mfiller M J, Pirlich M, Balks H J, Selberg O. Glucose intolerance inliver cirrhosis: Role of hepatic and non-hepatic influences. Eur J Clin
Chem Clin Biochem 1994; 32:749-758
14. Petrides A S, De Fronzo R A. Glucose and insulin metabolism incirrhosis. J Hepatol 1989; 8:107-114
15. Mtiller M J, Willmann O, Rieger A et al. Mechanism of insulin
resistance associated with liver cirrhosis. Gastroenterology 1992;
102:2033-2041
16. Selberg O, Burchert W, van der Hoff Jet al. Insulin resistance in
cirrhosis. Positronemission tomography scan analysis of skeletal
muscle glucose metabolism. J Clin Invest 1993; 91: 1897-1902.
17. Riggio O, Merli M, Romiti Aet al. Early post prandial energy
expenditure and macronutrient use after a mixed meal in cirrhotic
patients. J Parent Enteral Nutr 1992; 16:445-450
18. Kruszynska Y, Williams N, Perry M, Home P. The relationshipbetween insulin sensitivity and skeletal muscle enzyme activity inhepatic cirrhosis. Hepatology 1988; 8:1615-1619
19. Selberg O, Radoch E, Walter G F, Mtiller M J. Skeletal muscle
glycogen content in patients with cirrhosis. Hepatology 1994;
20:135-141

20. Merli M, Erikson S L, Hagenfeldt H, Wahren J. Splanchnic andperipheral exchange of FFA in patients with liver cirrhosis. J Hepatol
1986; 3:348-355
21. Petrides S A, Groop L C, Riely C A, De Fronzo R A. Effect ofphysiologic hyperinsulinemia on glucose and lipid metabolism incirrhosis. J Clin Invest 1991; 88:561-570
22. Miiller M J, Fenk A, Lautz H U et al. Energy expenditure andsubstrate metabolism in ethanol-induced liver cirrhosis. Am J
Physiol 1991; 260:E338-E344
23. Miiller M J, Rieger A, Willmann Oet al. Metabolic responses tolipid infusions in patients with liver cirrhosis. Clin Nutr 1992;
11:193-206
24. Druml W, Fischer M, Pidlich J, Lenz K. Fat elimination in chronic
hepatic failure: long-chain vs medium-chain triglycerides. Am J Clin
Nutr 1995; 61:812-817
25. Cabr6 E, Nunez M C, Gonzalez-Huix F et al. Clinical and nutritional
factors predictive of plasma lipid unsaturation deficiency inadvanced liver cirrhosis: a logistic regression analysis. Am J
Gastroenterol 1993; 88:1738-1743
26. Cabr6 E, Abad-Lacmz A, Nunez M C et al. The relationship ofplasma polyunsaturated fatty acid deficiency with survival inadvanced liver cirrhosis: Multivariate analysis. Am J Gastroenterol
1993; 88:718-722
27. Petrides A S, Luzi L, Reuben A, Riely C, DeFronzo R A. Effect of
insulin and plasma amino acid concentration on teucine metabolism
in cirrhosis. Hepatology 1991; 14:432M41
28. McCullough A J, Tavill A S. Disordered Energy and protein
metabolism in liver disease. Semin Liver Dis 1991; 11:265-273
29. Nielsen K, Kondrup J, Martinsen Let al. Long-term oral refeedingof patients with cirrhosis of the liver. Br J Nutr 1995; 74:557-567
30. Ballmer P E, Walshe D, McNurlan M A, Watson H, Brunt P W,
Garlick P J. Albumin synthesis rates incirrhosis: correlation withChild-Turcotte Classification. Hepatology 1993; 18:292-297
31. Ballmer P E, Reichen J, McNurlan M A, Sterchi A-B, Anderson S E,
Garlick P J. Albumin but not fibrinogen synthesis correlates withgalactose elimination capacity in patients with liver cirrhosis.
Hepatology 1996; 24:53-59
32. Bunout D, Aicardi V, Hirsch Set al. Nutritional support in
hospitalized patients with alcoholic liver disease. Eur J Clin Nutr
1989; 43: 615-621.
33. Cabr6 E, Gonzalez-Huix F, Abad-Lacruz Aet al. Effect of total
enteral nutrition on the short-term outcome of severely malnourishedcirrhotics. A randomized controlled trial. Gastroenterology 1990;
98:715-720
34. Kearns P J, Young H, Garcia G et al. Accelerated improvement of
alcoholic liver disease with enteral nutrition. Gastroenterology 1992;
102:200-205
35. Mendenhall C L, Moritz T E, Roselle G Aet al. A study of oral
nutrititional support with oxandrolone in malnourished patients withalcoholic hepatitis: results of a department of veterans affairs
cooperative study. Hepatology 1993; 17:564-576
36. Nielsen K, Kondmp J, Martinsen L, Stilling B, Vikman B.
Nutritional assessment and adequacy of dietary intake in hospitalized
patients with alcoholic liver cirrhosis. Br J Nutr 1993; 69:665-679
37. Harris J A, Benedict F G. A biometric study of basal metabolism inman. Publication n ° 270. Carnegie Institute of Washington DC, 1919
38. Schneeweiss B, Graninger W, Ferenci Pet al. Energy metabolism
in patients with acute and chronic liver disease. Hepatology 1990;
11: 387-393
39. Dolz C, Raurich J M, Ibanez J, Obrador A, Mars~ P, Gay~tJ. Ascites
increases the resting energy expenditure in liver cirrhosis.
Gastroenterology 1991; 100:738-744
40. Prijatmoko D, Strauss B J G, Lambert J R et al. Early detection ofprotein depletion in alcoholic cirrhosis: role of body composition
analysis. Gastroenterology 1993; 105:1839-1845
41. Mclntyre N. Undernutrition and malnutrition in cirrhosis. In:
Tygstmp N, Orlandi F, eds. Cirrhosis of the Liver: Methods andFields of Research. Amsterdam: Elsevier, 1987:225-234
42. Mason J B, Roubenoff R. The unbearable lightness of being acirrhotic Gastroenterology 1993; 105:1911-1914
43. Bramley P, Oldroyd B, Stewart Set al. Body composition analysis inliver cirrhosis. The measurement of body fat by dual energy X-ray
absorptiometry in comparison to skinfold anthropometry,bioelectrical impedance and total body potassium. In: Ellis K J,
Eastman J D, eds. Human Body Composition. New York: Plenum
Press, 1993:11-214
44. Heymsfield S B, Arteaga C, McManus C, Smith J, Moffitt S.

CLINICAL NUTRITION

Measurement of muscle mass in humans: validity of the 24-hoururinary creatinine method. Am J Clin Nutr 1983; 37:478-494
45. PMich M, Selberg O, Brker K, Schwarze M, Mtiller M J. The
validity of the creatinine approach to estimate skeletal muscle massin patients with liver cirrhosis. Hepatology 1996; 24:1422-1427
46. Roubenoff R, Kehayias J J. The meaning and measurement of leanbody mass. Nutr Rev 1991; 46:163-175
47. Forbes G B, Braining G J. Urinary creatinine excretion and leanbody mass. Am J Clin Nutr 1976; 29:1359-1366
48. Guglielmi F W, Contento F, Laddaga L, Panella C, Francavilla A.
Bioelectric impedance analysis: experience with male patients withcirrhosis. Hepatology 1991; 13:892-895
49. Zillikens M C, van den Berg J W O, Wilson J H P, Swart G R.
Whole body and segmental bioelectrical impedance analysis inpatients with cirrhosis of the liver: changes after treatment of ascites.
Am J Clin Nutr 1992; 55:621-625
50. McCullough A J, Mullen K D, Kalhan S C. Measurements of total
body and extracellular water in cirrhotic patients with and without
ascites. Hepatology 1991; 14:1102-1108
51. Zillikens M C, van den Berg J W O, Wilson J H P, Rietveld T, Swart
G R. The validity of bioelectrical impedance analysis in estimating
total body water in patients with cirrhosis. J Hepatol 1992; 16:59~55
52. Miiller M J, Brker K H W, Selberg O. Are patients with livercirrhosis hypermetabolic? Clin Nutr 1994; 13:131-144
53. Merli M, Romiti A, Riggio O, Capocaccia L. Optimal nutritional
indexes in chronic liver disease. J Parenter Enteral Nutr 1987;
11: 130S-134S
54. Crawford D H G, Cuneo R C, Shepherd R W. Pathogenesis andassessment of malnutrition in liver disease. J Gastroenterol Hepatol
1993; 8:89-94
55. Mendenhall C L, Moritz T E, Roselle G A e t al. Protein energy
malnutrition in severe alcoholic hepatitis: diagnosis and response totreatment. J Parenter Enteral Nutr 1995; 19:258-265
56. Fan S-T, Lo C-M, Lai E C S, Chu K-M, Liu C-L, Wong J.
Perioperative nutritional support in patients undergoing hepatectomy
for hepatocellular carcinoma. N Engl J Med 1994; 331:1547-1552
57. Mendenhall C, Bongiovanni G, Goldberg S e t al. VA cooperative
study on alcoholic hepatitis III: changes in protein-calorie
malnutrition associated with 30 days of hospitalization with andwithout enteral nutritional therapy. J Parent Ent Nutr 1985;
9:590-596
58. Naveau S, Pelletier G, Poynard T et al. A randomized clinical trial of
supplementary parenteral nutrition in jaundiced alcoholic cirrhotic
patients. Hepatology 1986; 6: 270-274.
59. Hill G L. Impact of nutritional support on the clinical outcome of thesurgical patient. Clin Nutr 1994; 13:331-340
60. Blackburn G L, Bistrian B R, Maini B S, Sclamm B A, Smith M F.
Nutritional and metabolic assessment of the hospitalized patient. J
Parenter Enteral Nutr 1977; 1:11-22
61. Mullen J I, Buzby G P, Matthews D C, Smale B F, Rosato E F.
Reduction of operative morbidity and mortality by combined
preoperative and postoperative nutritional support. Ann Surg 1980;
192:604-613
62. Di Cecco S R, Wieners E J, Wiesner R H, Southom P A, Plevak D J,
Krom R A F. Assessment of nutritional status of patients with endstage liver disease undergoing liver transplantation. Mayo Clin Proc
1989; 64:95-102
63. Conn, H O. Cirrhosis. In: Schiff L, Schiff E, eds. Diseases of theLiver. Philadelphia: Lippincott, 1982:864-865
64. Drenick E J, Simmons F, Murphy J F. Effect on hepatic morphologyof treatment of obesity by fasting, reducing diets and small-bowel
bypass. N Engl J Med 1970; 282:829-834
65. O'Keefe S J, E1-Zayadi A R, Carraher T E, Davis M, Williams R.
Malnutrition and immunoincompetence in patients with liverdisease. Lancet 1980; ii: 615-617
66. Mezey E, CabaUeria J, Mitchell M C, Parrs A, Herlong H F, Rod6s
J. Effect of parenteral amino acid supplementation on short-term andlong-term outcomes in severe alcoholic hepatitis: a randomized
controlled trial. Hepatology 1991; 14:1090-1096
67. Achord J L. A prospective randomized clinical trial of peripheralamino acid-glucose supplementation in acute alcoholic hepatitis. Am
J Gastroenterol 1987; 82:871-875
68. Bonkovsky H L, FieUin D A, Smith G S, Slaker D P, Simon D,
Gaiambos J T. A randomized controlled trial of treatment of
alcoholic hepatitis with parenteral nutrition and oxandrolone. 1.
Short-term effects on liver function. Am J Gastroenterol 1991;
86:1200-1208

53

69. M¢ller S, Bendtsen F, Christensen E, Heuriksen J H. Prognostic
variables in patients with cirrhosis and oesophageal varices without
prior bleeding. J Hepatol 1994; 21:940-946
70. Helton W S. Nutritional issues in hepatobiliary surgery. Semin Liver
Dis 1994; 14:140-157
71. Nasrallah S M, Galambos J T. Amino acid therapy of alcoholic
hepatitis. Lancet 1980 ii: 1276-1277
72. Diehl A M, Boinott J K, Herlong H F et al. Effect of parenteralamino acid supplementation in alcoholic hepatitis. Hepatology
1985; 5:57-63
73. Swart G R, Zillikens M C, van Vuure J K, van den Berg J W O.
Effect of late evening meal on nitrogen balance in patients withcirrhosis of the liver. Br Med J 1989; 299:1202-1203
74. Holdsworth J D, Dionigi P, Clague M B, James O F W, Wright P D.
Body protein metabolism and plasma amino acids in cirrhosis of theliver. The effect of varying the branched chain amino acid content of
intravenous amino acid solutions. Clin Nutr 1984; 3:153-162
75. Millikan W J, Henderson J M, Galloway J R et al. In vivo
measurement of leucine metabolism with stable isotopes innormal subjects and in those with cirrhosis fed conventionaland branched-chain amino acid-enriched diets. Surgery 1985;
98:405-413
76. Weber F L, Bagby B S, Licate L, Kelsen S G. Effects of branchedchain amino acids on nitrogen metabolism in patients with ch:rhosis.
Hepatology 1990; 11: 942-950
77. Swart G R, van den Berg J W O, Wattinema D L, Rietveld T, vanVuure J K, Frenkel M. Elevated protein requirements in cirrhosis of
the liver investigated by whole body protein turnover studies. Clin
Sci 1988; 75:101-107
78. Verboeket-van de Venne W P H G, Westerp K R, van Hoek ]3,
Swart G R. Energy expenditure and substrate metabolism in patientswith cirrhosis of the liver: effects of the pattern of food intake. Gut
1995, 36:110-116
79. Campillo B, Bories P N, Leluan M, Pornin B, Devanlay M, Fouet P.
Short-term changes in energy metabolism after 1 month of a :regularoral diet in severely malnourished cirrhotic patients. Metabolism
1995; 44:765-70
80. Horst D, Grace N D, Conn H O et al. Comparison of dietary ]proteinwith an oral, branched chain-enriched aminoacid supplement inchronic portal-systemic encephalopathy: a randomized controlled
trial. Hepatology 1984; 4:279-287
81. Egberts E-H, Schomerns H, Hamster W, Jtirgens. Branched chainamino acids in the treatment of latent portosystemic encephaiopathy.
A double blind placebo-controlled crossover study. Gastroenterology
1985; 88: 887-895.
82. Marchesini G, Dioguardi F S, Bianchi G P e t al. Long-term oral
branched-chain amino acid treatment in chronic hepatic
encephalopathy. J Hepatol 1990; 11: 92-101
83. Plauth M, Egberts E-H, Hamster W e t al. Long-term treatment oflatent portosystemic encephalopathy with branched chain aminoacids. A double-blind placebo-controlled crossover trial. J Hepatol
1993; 17:308-314
84. Weber F L, Minco D, Fresard K M, Banwell J G. Effects ofvegetable diets on nitrogen metabolism in cirrhotic subjects.
Gastroenterology 1985; 89:538-544
85. Morgan T R, Moritz T E, Mendenhall C L, Haas R, and V A.
Cooperative study group. Protein consumption and hepatic
encephalopathy in alcoholic hepatitis. J Am Coil Nutr 1995;
14:152-158
86. Freund H, Dienstag J, Lehrich J et al. Infusion of branched-chainenriched amino acid solution in patients with hepatic
encephalopathy. Ann Surg 1982; 196:209-220
87. Weismann K, Christensen E, Dreyer V. Zinc supplementation inalcoholic cirrhosis. A double-blind clinical trial. Acta Meal Scand
1979; 205:361-366
88. Garrett-Laster M, Russell R M, Jacques P F. Impairment of taste andolfaction in patients with cirrhosis: the role of vitamin A. Hum Nutr
Clin Nutr 1984; 38: 203-214.
89. Marchesini G, Fabbri A, Bianchi G, Brizi M, Zoli M. Zinc
supplementation and amino acid-nitrogen metabolism in patientswith advanced cirrhosis. Hepatology 1996; 23:1084-1092
90. Sokol R J, Butler-Simon N, Conner C et al. Multicenter trial ofd-c~-tocopheryl polyethylene glycol 1000 succinate for treatment ofvitamin E deficiency in children with chronic cholestasis.
Gastroenterology 1993; 104:1727-1735
91. Argao E A, Heubi J E, Hollis B W, Tsang R C. d-c~-tocopheryl
polyethylene glycol-1000 succinate enhances the absorption of

54 ESPENGUIDELINESFOR NUTRITION IN LIVER DISEASE AND TRANSPLANTATION
vitamin D in chronic cholestatic liver disease of infancy andchildhood. Pediatr Res 1992; 31: 146-150
92. Suchner U, Rothkopf M M, Stanislaus G, Elwyn D H, Kvetan V,
Askanazi J. Growth hormone and pulmonary disease. Metabolic
effects in patients receiving parenteral nutrition. Arch Intern Med
1990; 150:1225-1230
93. Gatzen C, Scheltinga M R, Kimbrough T D, Jacobs D O, Wilmore
D W. Growth hormone attenuates the abnormal distribution of body
water in critically ill surgical patients. Surgery 1992; 112:181-187
94. Ziegler T R, Rombeau J L, Young L S e t al. Recombinant human
growth hormone enhances the metabolic efficacy of parenteralnutrition: a double blind, randomized controlled study. Clin J
Endocrinol Metab 1992; 74:865-873
95. Byrne T A, Morrissey T B, Nattakom T V, Scheltinga M R, Ziegler
T R, Wilmore D W. Growth hormone, glutamine, and a modified
diet enhance nutrient absorpti-on in patients with severe short bowel
syndrome. J Parent Enteral Nutr 1995; 19:296-302
96. MOiler S, Junl A, Becker U, Flyvbjerg A, Skakkebaek N E,
Henriksen J H. Concentrations, release, and disposal of insulin-likegrowth factor (IGF)-binding proteins (IGFBP), IGF-I, and growth
hormone in different vascular beds in patients with cirrhosis. J Clin
Endocrinol Metab 1995; 80:1148-1157
97. Donaghy A, Ross R, Gimson A, Hughes S C, Holly J, Williams R.
Growth hormone, insulinlike growth factor- 1, and insulinlike growth
factor binding proteins 1 and 3 in chronic liver disease. Hepatology
1995; 21:680-688
98. Scharf J-G, Schmitz F, Frystyk Jet al. Insulin-like growth factor-1
serum concentrations and patterns of insulin-like growth factor
binding proteins in patients with chronic liver disease. J Hepatol
1996; 25:689-699
99. Bucuvalas J C, Cntfield W, Horn Jet al. Resistance to the growthpromoting and metabolic effects of growth hormone in children withchronic liver disease. J Pediatr 1990; 117:397-402
100. MOiler S, Becker U, Gronbaek M, Juul A, Winkler K, Skakkebaek
N E. Short-term effect of recombinant human growth hormone inpatients with alcoholic cirrho sis. J Hepatol 1994; 21: 710-717
101. Clemmons D R. Use of growth hormone and insulin-like growth
factor I in catabolism that is induced by negative energy balance.
Horm Res 1993; 40:62-67
102. Greenberger N J, Carley J, Schenker S, Bettinger I, Stamnes C,
Beyer P. Effect of vegetable and animal protein diets in chronic
hepatic encephalopathy. Dig Dis 1977; 22:845-855
103. Uribe M, Marquez M A, Ramos G Get al. Treatment of chronic
portal-systemic encephalopathy with vegetable and animal protein
diets. Dig Dis Sci 1982; 27:1109-1116
104. Zillikens M C, van den Berg J W, Wattimena J L, Rietveld T, Swart
G R. Nocturnal oral glucose supplementation. The effects on protein
metabolism in cirrhotic patients and in healthy controls. J Hepatol
1993; 17:377-383
105. Srivastava A, Mehta R, Rothke S P e t al. Fitness to drive in patientswith cirrhosis and portacaval shunting: a pilot study evaluating
driving performance. J Hepatol 1994; 21:1023-1028
106. Swart G R, van den Berg J W O, van Vuure J K, Tietveld T,
Wattimena D L, Frenkel M. Minimum protein requirements in livercirrhosis determined by nitrogen balance measurements at threelevels of protein intake. Clin Nutr 1989; 8:329-336
107. Grtingreif K, Abicht K, Kluge M e t al. Clinical studies on zinc inchronic liver diseases. Z Gastroenterol 1988; 26:409-415
108. van der Rijt C C D, Schalm S W, Schat H, Foeken K, DeJong G.
Overt hepatic encephalopathy precipitated by zinc deficiency.
Gastroenterology 1991; 100:1114-1118
109. Reding P, Duchateau J, Bataille C. Oral zinc supplementation
improves hepatic encephalopathy. Results of a randomized
controlled trial. Lancet II 1984:493-495
110. Bresci G, Parisi G, Banti S. Management of hepatic encephalopathy
with oral zinc supplementation: a long-term treatment. Eur J Med
1993; 2:414-416
111. Riggio O, Ariosto F, Merli M e t al. Short-term oral zinc
supplementation does not improve chronic hepatic encephalopathy.
Results of a double-blind crossover trial. Dig Dis Sci 1991;
6:1204-1208
112. Lindor K D. Management of osteopenia of liver disease with special
emphasis on primary biliary cirrhosis. Semin Liver Dis 1993;
13:367-373
113. Crippin J S, Jorgensen R A, Dickson E R, Lindor K D. Hepatic
osteodystrophy in primary biliary cirrhosis: effects of medical
treatment. Am J Gastroenterol 1994; 89:47-50

114. Hirsch S, Bunout C, de la Maza P e t al. Controlled trial on nutrition
supplementation in outpatients with symptomatic alcoholic cirrhosis.
J Parenter Enter Nutr 1993; 17:119-124
115. Soberon S, Pauley M P, Duplantier R, Fan A, Halsted C H.
Metabolic effects of enteral formula feeding in alcoholic hepatits,
Hepatology 1987; 7:1204-1209
116. Calvey H, Davis M, Williams R. Controlled trial of nutritional
supplementation, with or without branched chain amino acidenrichement, in the treatment of acute alcoholic hepatitis. J Hepatol
1985; 1:141-151
117. Simon D, Galambos J T. A randomized controlled study of
peripheral parenteral nutrition in moderate and severe alcoholic
hepatitis. J Hepatol 1987; 7:200-207
118. Bonkovsky H L, Singh R H, Jafri I H et al. A randomized controlled
trial of the treatment of alcoholic hepatitis with parenteral nutritionand oxandrolon. II: short-term effects on nitrogen metabolism,
metabolic balance and nutrition. Am J Gastro 1991; 86:1209-1218
119. Garrison R N, Cryer H M, Howard D A, Polk H C. Clarification ofrisk factors for abdominal operations in patients with hepatic
cirrhosis. Ann Surg 1984; 199:648-655
120. Kanematsu T, Koyanagi N, Matsumata T, Kitano S, Takenaka K,
Sugimachi K. Lack of preventive effect of branched-chain aminoacid solution on postoperative hepatic encephalopatby in patientswith cirrhosis: a randomized, prospective trial. Surgery 1988;
104:482-488
121. Rossi-Fanelli F, Riggio O, Cascino A et al. Branched-chain aminoacids vs lactulose in the treatment of hepatic coma. A controlled
study. Dig Dis Sci 1982; 27:929-935
122. Wahren J, Denis J, Desnrmont P et al. Is intravenous administrationof branched chain amino acids effective in the treatment of hepatic
encephalopathy? A multicentre study. Hepatology 1983; 3:475-480
123. Cerra F B, Cheung N K, Fischer J E et al. Disease-specific aminoacid infusion in hepatic encephalopathy: a prospective randomized,
double-blind controlled trial. J Parent Enteral Nutr 1985; 9:288-295
124. Michel H, Bories P, Aubin J P, Pomier-Layrargues G, Bauret P,
Bellet-Herman H. Treatment of acute hepatic encephalopathy incirrhotics with a branched-chain amino acids enriched versus a
conventional amino acid mixture. A controlled study in 70 patients.
Liver 1985; 5:282-289
125. Fiaccadori F, Ginelli F, Pedretti Get al. Branched-chain enrichedamino acid solutions in the treatment of hepatic encephalopathy:
A controlled trial. Ital J Gastroenterol 1985; 17:5-10
126. Strauss E, Dos Santos W R, Da Silva E C et al. Treatment of hepatic
encephalopathy: a randomized clinical trial comparing a branchedchain enriched amino acid solution to oral neomycin. Nutr Supp
Svcs 1986; 6:18-21
127. Vilsmap H, Gluud C, Hardt F et al. Branched-chain enriched aminoacid versus glucose treatment of hepatic encephalopathy. A double
blind study of 65 patients with cirrhosis. J Hepatol 1990; 10:291-296128. Ferenci P. Critical evaluation of the role of branched chain aminoacids in liver disease. In: Thomas J C, Jones E S, eds. Recent
Advances in Hepatology. Edinburgh: Churchill Livingstone,
1986; 137-154
129. Naylor C D, O'Rourke K, Detsky A S, Baker J P. Parenteralnutrition with branched chain amino acids in Hepatic
encephalophathy: a metaanalysis. Gastroenterology 1989;
97:1033-1042
130. Shaw B W, Wood R P, Gordon R D, Iwatsnki S, Gillquist W P,
Starzl T E. Influence of selected patient variables and operative
blood loss on six-month survival following liver transplantation.
Semin Liv Dis 1985; 5:385-393
131. Akerman P A, Jenkins R L, Bistrian B R. Preoperative nutritionassessment in liver transplantation. Nutrition 1993; 9:350-356
132. Hasse J, Strong S, Gorman M A, Liepa G. Subjective global
assessment: alternative nutrition-assessment technique for livertransplant candidates. Nutrition 1993; 9:339-343
133. Pikul J, Sharpe M D, Lowndes R, Ghent C N. Degree ofpreoperative malnutrition is predictive of postoperative morbidity
and mortality in liver transplant recipients. Transplantation 1994;
57:469-472
134. Moukarzel A A, Najm I, Vargas J, McDiarmid V S, Busuttil R W,
Ament M E. Effect of nutritional status on outcome of orthotopic
liver transplantation in pediatric patients. Transplant Proceed 1990;
22:1560-1563
135. Mtiller M J, Loyal S, Schwarze M, Lobers J, Selberg O, Ringe B.
Resting energy expenditure and nutritional state in patients with

CLINICAL NUTRITION

liver cirrhosis before and after liver transplantation. Clin Nutr 1994;
13:145-152
136. Chin S E, Shepherd R W, Thomas B Jet al. Nutritional support inchildren with end-stage liver disease: a randomized crossover trialof a branched-chain amino acid supplement. Am J Clin Nutr 1992;
56:158-163
137. Reilly J, Metha R, Teperman L et al. Nutritional support after livertransplantation. A randomized prospective study. J Parent Enteral
Nutr 1990; 14:386-391
138. Hasse J M, Blue L S, Liepa G U et al. Early enteral nutrition support
in patients undergoing liver transplantation. J Parent Enteral Nutr
1995; 19:437-443
139. Pescovitz M D, Mehta P L, Leapman S B, Milgrom M L, Jindal
R M, Filo R S. Tube jejunostomy in liver transplant recipients.
Surgery 1995; 117:642-647
140. Wicks C, Somasundaram S, Bjarnason I e t al. Comparison of enteralfeeding and total parenteral nutrition after liver transplantation.
Lancet 1994; 344:837-840
141. Kuse E, Weimann A. Besonderheiten im Rahmen derTransplantationschirnrgie. In: Hartig W, ed. Moderne
Infusionstherapie- Kiinstliche Ern~ihrung. Mtinchen: W.
Zuckschwerdt, 1993:529-534
142. Swart G R, Metselaar H J, Hesselink E J, van den Berg J W O.
Whole body protein turnover rates and body composition before andafter liver transplantation. In: Capoeaccia L, Merli M, Riggio O, eds.
Advances in Hepatic Encephalopathy and Metabolic Nitrogen
Exchange. Boca Raton: CRC Press; 1995, 76-80
143. Palmer M, Schaffner F, Thung S N. Excessive weight gain after livertransplantation. Transplantation 1991; 51: 797-800.
144. Munoz S J, Deems R O, Moritz M J, Martin P, Jarrell B E, Maddrey
W C. Hyperlipidemia and obesity after orthotopic livertransplantation. Transplant Proceed 1991; 23:1480-1483
145. Italian Society of Parenteral and Enteral Nutrition. Consensus
statement - Perioperative nutrition: the rationale for nutritional
support. Clin Nutr 1996; 15:155-156
146. Plevak D J, DiCecco S R, Wiesner R J H et al. Nutritional support
for liver transplantation: Identifying caloric and protein
requirements. Mayo Clin Proc 1994; 69: 225-230.
147. Wolfe R R, Allsop J R, Burke J F. Glucose metabolism in man:responses to intravenous glucose infusion. Metabolism 1979;
28:210-220148. Lundbom N, Laurila S. Central pontine myelinolysis after correctionof chronic hyponatremia. Lancet 1993; 342:247-248
149. McDiarmid S V, Colonna J O 2d, Shaked A, Ament M E, Busuttil
R W. A comparison of renal function in cyclosporine and FK-506treated patients after primary orthotopic liver transplantation.
Transplantation 1993; 56:847-853
150. Shanbhogue R L K, Bistrian B R, Jenkins R L, Jones C, Benotti P,
Blackburn G L. Resting energy expenditure in patients with end
stage liver disease and in normal population. J Parent Enteral Nutr
1987; 11:305-308
151. Green H J, Bramley P N, Losowsky M S. Are patients with primarybiliary cirrhosis hypermetabolic? Hepatology 1991; 14:464-472
152. Bosari S, Marradi C, Chiara O, Bevilacqua G, Nespoli A. Energy
expenditure in cirrhotic patients. In: Kleinberger G, Ferenci P,
Riederer P, Thaler H, eds. Advances in Hepatic Encephalopathy and
Urea Cycle Diseases. Basel: Karger, 1984:674-681
153. Heymsfield S B, Waki M, Reinus J. Are patients with chronic liverdisease hypermetabolic? Hepatology 1990; 11:502-505
154. Schneeweiss B, Pammer J, Ratheiser K et al. Energy metabolism inacute hepatic failure. Gastroenterology 1993; 105:1515-1521
155. Merli M, Riggio O, Servi R et al. Increased energy expenditure incirrhotic patients with hepatocellular carcinoma. Nutrition 1992;
8:321-325

55

156. Campillo B, Bories P N, Sommer F, Wirquin E, Fouet P. The
thermogenic and metabolic effects of food in liver cirrhosis:
consequences on the storage of nutrients and the hormonalcounterregulatory response. Metabolism 1992; 41:476-482
157. Campillo B, Fouet P, Bonnet C, Arian G. Submaximal oxygen
consumption in liver cirrhosis. Evidence of severe functional aerobic
impairment. J Hepatol 1990; 10:163-167
158. De Lissio M, Goodyear L J, Fuller S, Krawitt E L, Devlin J T.
Effects of treadmill exercise on fuel metabolism in hepatic cirrhosis.
J Appl Physiol 1991; 70:210-215
159. Kondrnp J, Nielsen K, Juul A. Effect of long-term refeeding onprotein metabolism in patients with cirrhosis of the liver. Br J Nutr
1996; in press
160. Kondrup J, Nielsen K. Protein requirement and utilization in patientswith cirrhosis of the liver. Z Gastroenterol 1996; 34 (Suppl 5): 26-31
161. Lieber C S. Alcohol, liver, and nutrition. J Am Coll Nutr 1991;
10:602-632
162. Shenker S, Halff G A. Nutritional therapy in alcoholic fiver disease.
Sem Liver Dis 1993; 13:196-209
163. Mills P R, Shenkin A, Anthony R S e t al. Assessment of nutritional
status and in vivo immune responses in alcoholic liver disease. Am J
Clin Nutr 1983; 38:849-859
164. Aggett P J. Severe zinc defiency. In: Mills C F, ed. Zinc in Human
Biology. Berlin: Springer, 1989:259-274
165. Barry M, Keeling P W N, Feely J. Tissue zinc status and drug
elimination in patients with liver disease. Clin Sei 1990;
78:547-552
166. Thuluvath P J, Triger D R. Selenium in chronic liver disease.
J Hepatol 1992; 14:176-182
167. Halsted J A, Hackley B, Rudszi C, Smith J C. Plasma zincconcentration in liver diseases. Comparison with normal controls
and certain other chronic diseases. Gastroenterology 1968;
54:1098-1105
168. Kuse E, Kemnitz J, Kotzerke Jet al. Fat emulsions in parenteralnutrition after liver transplantation: The recovery of the allog:rafts
RES function and histological observations. Clin Nutr 1990;
9:331-336

Appendix*ESPEN Consensus Group Liver/Transplantation
P. E. Ballmer, Departement Innere Medizin, Inselspital, Universit~it Bern,
Switzerland
W. O. Bechstein, Virchow-Klinikum, Humboldt-Universit~it Berlin,
Germany
P. Ferenci, Allgemeines Krankenhaus, Vienna, Austria
M. A. Gassull, Hospital Universitari Germans Trias i Pujol, Badalona,
Spain
E. Holm, Medizinische Klinik, Mannheim, Germany
N. Mclntyre, Royal Free Hospital, London, U.K.
J. Kondrup, Rigshospitalet, Copenhagen, Denmark
E. R. Kuse, Medizinische Hochschule, Hannover, Germany
G. Marchesini, Policlinico S. Orsola, Bologna, Italy
M. Merli, II Cattedra di Gastroenterologia, Rome, Italy
M. Y. Morgan, Royal Free Hospital, London, U.K.
M. J. Mtiller, Institut ftir Humanern~hrnng und Lebensmittelkunde, Kiel,
Germany
J. Neuberger, Queen Elisabeth Hospital, Birmingham, U.K.
M. Planth, Klinikum Charit6, Humboldt-Universit~it, Berlin, Germany
G. R. Swart, Academisch Ziekenhuis, Rotterdam, Netherlands
A. Weimann, Medizinische Hochschule, Hannover, Germany
H. Vilstrup. University Hospital. Aarhus, Denmark