591058

research-article2015
NCPXXX10.1177/0884533615591058Nutrition in Clinical PracticeHasse and DiCecco

Invited Review
Nutrition in Clinical Practice
Volume XX Number X
Enteral Nutrition in Chronic Liver Disease: Translating Month 201X 1­–14
© 2015 American Society
Evidence Into Practice for Parenteral and Enteral Nutrition
DOI: 10.1177/0884533615591058
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hosted at
online.sagepub.com
Jeanette M. Hasse, PhD, RD, LD, FADA, CNSC1; and Sara R. DiCecco, MS, RD, LD2

Abstract
Malnutrition is prevalent in individuals with chronic liver disease and occurs as a result of inadequate nutrient intake, altered metabolism,
and malabsorption. Although limited data show benefits of enteral nutrition (EN) in this population, patients with chronic liver disease
often have inadequate oral intake and are potential candidates for EN. The goals of the EN, type and severity of liver disease, and access
for EN will influence the decision to initiate EN. This paper summarizes EN studies in patients with liver disease and provides practical
tips regarding patient selection, EN access, and EN formula choices. Two case studies illustrate the principles and challenges of providing
EN to patients with cirrhosis. The paper concludes with suggested parameters for an EN feeding protocol and recommendations for future
research. (Nutr Clin Pract. XXXX;xx:xx-xx)

Keywords
liver diseases; end-stage liver disease; liver cirrhosis; malnutrition; nutrition therapy; enteral nutrition

Introduction with chronic liver disease, who is an appropriate EN candidate,

how to deliver EN, and what EN formula to use. The principles
It is generally accepted that nutrition deficiencies and malnu- of providing EN to patients with chronic liver disease are illus-
trition will develop in the course of progressive liver disease. trated in 2 case studies.
Mendenhall et al,1 in some of the earliest work on nutrition
assessment in liver disease, found that overall worsening of
nutrition status correlated with both the severity and the pro- What Parameters Should Be Used to
gression of liver disease. The authors also noted that patients Assess Nutrition Status?
who were able to improve their nutrition status lowered their
The liver’s complex role in bodily functions, with >500 vital
6-month mortality rate, while those who continued to deterio-
functions, has a wide-ranging effect on nutrition status.
rate nutritionally continued on a trajectory toward increased
Functions of the liver include digestion (bile production); met-
mortality.1 Since this time, numerous other groups have tried to
abolic, synthetic, and storage functions (glucose, protein,
determine how to best prevent and treat the malnutrition of
fat, cholesterol, hormones, clotting and immune factors, vita-
liver disease. Three recent meta-analyses2-4 found that neither
min, minerals); and detoxification (ammonia, toxins, medica-
oral feeding nor enteral nutrition (EN) has been conclusively
tions). Table 2 summarizes the role of the liver in nutrient
shown to improve outcomes in patients with liver disease.
metabolism.
However, all authors noted that additional studies are needed
Nutrition assessment of patients with liver disease is com-
that entail better quality to avoid bias, randomization using
plicated, as no one indictor has been determined to be entirely
control groups, stratification for liver disease, and adequate
accurate and predictive in determining degree of nutrition
treatments and duration of therapy.
compromise. The goal of nutrition screening and assessment is
Many patients with chronic liver disease either are at nutri-
tion risk or have already developed malnutrition and are not
able to eat or drink adequate nutrients to meet their needs. From 1Annette C. and Harold C. Simmons Transplant Institute, Baylor
These patients may be candidates for EN. While literature is University Medical Center, Dallas, Texas; and 2Mayo Clinic Rochester,
Department of Dietetics, Rochester, Minnesota.
sparse regarding the best type and route of EN specific for
patients with liver disease, many professional organizations Financial disclosure: None declared.
have provided recommendations for use of EN in patients with
Corresponding Author:
liver disease in their guidelines5-9 (Table 1).
Jeanette M. Hasse, PhD, RD, LD, FADA, CNSC, Annette C. and Harold
This paper aims to provide practical advice regarding EN in C. Simmons Transplant Institute, Baylor University Medical Center, 3410
patients with chronic liver disease, specifically why EN may Worth Street, Suite 950, Dallas, TX 75246, USA.
be necessary, what we currently know about EN for patients Email: jm.hasse@baylorhealth.edu

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2 Nutrition in Clinical Practice XX(X)
Table 1.  Summary of Society Guidelines on Enteral Nutrition for Patients With Liver Disease.
Society
American Society for
Parenteral and Enteral
Nutrition and Society for
Critical Care Medicine
(2009)
European Society of
Parenteral and Enteral
Nutrition (2006)
American Association
for the Study of Liver
Diseases and the
American College of
Gastroenterology (2010)
Scottish Intercollegiate
Guidelines Network
(2013)
National Clinical Guideline
Centre for Acute and
Chronic Conditions
(NCGC-ACC) on behalf
of the National Institute
for Health and Clinical
Excellence (NICE) (2010)
BCAA, branched-chain amino acid; EN, enteral nutrition; ICU, intensive care unit; PEG, percutaneous endoscopic gastrostomy.
Guideline Statements Specific to EN or
Nutrition Support Reference
•• EN is the preferred route of nutrition therapy McClave SA, Martindale RG, Vanek VW, et al.
in ICU patients with acute and/or chronic Guidelines for the provision and assessment
liver disease. Nutrition regimens should avoid of nutrition support therapy in the adult
restricting protein in patients with liver failure. critically ill patient. JPEN J Parenter Enteral
•• Standard enteral formulations should be used in Nutr. 2009;33:277-316.
ICU patients with acute and chronic liver disease.
BCAA formulations should be reserved for the
rare encephalopathic patient who is refractory to
standard treatment with luminal acting antibiotics
and lactulose.
•• Use supplemental EN when patients cannot meet Plauth M, Cabré E, Riggio O, et al. ESPEN
their caloric requirements through oral food guidelines on enteral nutrition: liver disease.
despite adequate individualized nutrition advice. Clin Nutr. 2006;25(2):285-294.
•• If patients are not able to maintain adequate oral
intake from normal food, use
  -  oral nutrition supplements or
  - tube feeding (even in the presence of
esophageal varices).
•• PEG placement is associated with a higher risk of
complications and is not recommended.
•• Whole protein formulas are generally
recommended.
•• Consider using more concentrated high-energy
formulas in patients with ascites.
•• Use BCAA-enriched formulas in patients with
hepatic encephalopathy arising during EN.
•• The use of oral BCAA supplementation can
improve clinical outcome in advanced cirrhosis.
•• Patients with mild-moderate alcoholic hepatitis— O’Shea RS, Dasarathy S, McCullough
defined as a Maddrey score of <32, without AJ; Practice Guideline Committee of the
hepatic encephalopathy, and with improvement American Association for the Study of
in serum bilirubin or decline in the Maddrey Liver. Alcoholic liver disease. Hepatology.
Discriminant Function during the first week of 2010;51(1):307-328.
hospitalization—should be monitored closely but
will likely not require or benefit from specific
medical interventions other than nutrition support
and abstinence.
•• Patients with alcoholic cirrhosis should receive
frequent interval feedings, emphasizing a
nighttime snack and morning feeding, to improve
nitrogen balance.
•• Patients with advanced liver disease should be Scottish Intercollegiate Guidelines Network
given nutrition support to minimize malnutrition. (SIGN). Management of Hepatitis C.
A National Clinical Guideline (SIGN
Publication No. 133). Edinburgh, Scotland:
SIGN; 2013.
•• Assess the nutrition requirements of people with National Clinical Guideline Centre for
acute alcohol-related hepatitis. Offer nutrition Acute and Chronic Conditions. Alcohol-
support if needed, and consider using nasogastric Use Disorders: Diagnosis and Clinical
tube feeding. Management of Alcohol-Related Physical
Complications (Clinical Guideline No. 100).
London, UK: National Institute for Health
and Clinical Excellence; 2010.
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Hasse and DiCecco 3
Table 2.  Role of the Liver in Nutrient Metabolism.a
Nutrient Role of Liver
Protein Synthesis of serum proteins such as albumin
Synthesis of blood-clotting factors
Formation of urea from ammonia
Deamination/transamination of amino acids
Formation of creatine
Oxidation of the amino acids arginine,
histidine, lysine, methionine, alanine,
tryptophan, and tyrosine
Carbohydrate Glycogenesis
Gluconeogenesis
Glycogenolysis
Fat Hydrolysis of triglycerides, cholesterol, and
phospholipids to fatty acids and glycerol
Fat storage
Cholesterol synthesis
Ketogenesis
Formation of lipoproteins
Production of bile necessary for digestion of
dietary fat
Vitamins Site of enzymatic steps in the activation of
vitamins
Thiamine (thiamine pyrophosphate)
Pyridoxine (pyridoxal phosphate)
Folic acid (tetrahydrofolic acid)
Vitamin D (25-hydroxycholecalciferol)
Site of synthesis of carrier proteins for vitamins
such as A and B12
Vitamin E is transported in lipoproteins
synthesized by the liver
Storage site for vitamins A, D, E, K, B12
Minerals Storage site for copper, iron, zinc
a
Reprinted with permission from Elsevier from Hasse J. Nutritional
aspects of transplantation in adults. In: Bussutil RW, Klintmalm GB, eds.
Transplantation of the Liver. 3rd ed. Philadelphia, PA: Elsevier Books;
2015:494-510.10
to identify patients who are either at nutrition risk or already
compromised so that the providers can determine and imple-
ment an appropriate nutrition care plan. For patients with com-
pensated liver disease, traditional nutrition assessment
techniques should still be reasonably accurate and applicable.
Once a patient begins to decompensate (eg, develops ascites or
edema, has reduced liver synthetic function, develops gastroin-
testinal [GI] bleeding), traditional nutrition assessment meth-
ods become more difficult to interpret. Serum protein
concentrations are not considered valid nutrition assessment
parameters. In addition, they are affected by the altered syn-
thetic function of the liver and reflect the degree of synthetic
function, losses from paracentesis, provision of exogenous
albumin infusions, acute illness, and inflammation.
Subjective global assessment (SGA), with its multifactorial
approach to nutrition assessment, is often used for patients
with liver disease to ameliorate the effect of the disease process
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itself. SGA typically uses a combination of weight history, diet
history, GI symptoms, and physical assessment to determine a
composite sense of the current nutrition state.11
In an individual with liver disease, obtaining an accurate
weight history is imperative but challenging due to the fluc-
tuation of weight and body mass index due to fluid shifts.
Often, it is difficult to determine a “dry weight” to be used for
estimating nutrition needs and monitoring nutrition status.
Assessment of dietary intake, including food selection and
adequacy, provides critical information before deciding on the
plan of care. It is also imperative to evaluate the frequency and
chronicity of GI symptoms (nausea, vomiting, abdominal
pain, diarrhea, constipation, etc) to determine issues of inad-
equate intake versus excessive losses. A nutrition-focused
physical examination of a patient with liver disease is usually
most telling: clinicians should look for signs of muscle wast-
ing; loss of fat stores; skin changes with vitamin or mineral
deficiencies; and presence of ascites, edema, or sarcopenia.
Anthropometric measurements, hand grip strength, and more
advanced techniques such as dual-energy x-ray absorptiome-
try and computed tomography scans have all been used in a
comprehensive nutrition assessment, and while not perfect
predictors, they can be useful in determining general results
and trends over time.
When Should EN Be Considered?
The factors that contribute to the development of malnutrition
in liver disease (poor oral intake, maldigestion, and altered
metabolic processes) also contribute to the difficulty in pre-
venting and treating malnutrition. Patients are challenged to
eat and drink enough calories and protein to meet their
increased nutrition needs, as each day of inadequate nutrition
contributes to the progression of malnutrition. Table 3 sum-
marizes the many factors that contribute to the development of
malnutrition in patients with chronic liver disease.
According to the American Society for Parenteral and Enteral
(A.S.P.E.N.) Enteral Nutrition Practice Recommendations,14
“the principal indication for EN is a functional GI tract with
sufficient length and absorptive capacity and the inability to
take nutrients through the oral route either totally or in part” (p.
124). While groups have shown that nutrition counseling and
oral nutrition supplementation for patients with chronic liver
disease can be successful in alleviating nutrition deteriora-
tion,1,15-17 not all patients will be able to improve their oral
intake enough to meet their increased need for calories and pro-
tein. These are the patients who should be considered for EN.
What Do We Know About EN in Liver
Disease?
We conducted a search of PubMed using the MeSH terms
“end-stage liver disease” OR “liver disease” AND “enteral
nutrition” with the filters “humans,” “adult,” and “English
4 Nutrition in Clinical Practice XX(X)

Table 3.  Factors Contributing to Malnutrition in Patients With In 1990, Cabré et al20 published their results comparing EN
Chronic Liver Disease.a with oral diet in 35 malnourished patients with cirrhosis.
Factor Mechanisms
Patients received EN for a mean of 23.3 days. EN appeared to
offer a trend in improvement in survival, increased serum albu-
Inadequate ↑ levels of tumor necrosis factor-α and min level, and reduced rates of sepsis, which the investigators
nutrient intake leptin → loss of appetite theorized was due to a lowering of the catabolic rate. Kearns et
Ascites → impaired gastric expansion → al21 also compared EN (Isocal HCN, formerly manufactured by
early satiety, delayed gastric emptying,
Mead Johnson, Evansville, IN) with oral intake in a group of
bloating, abdominal distention
31 patients with alcoholic liver disease over 4 weeks. While
Hepatic encephalopathy → altered
consciousness with decreased oral intake patients required frequent feeding tube replacement during this
Alcohol intake replaces nutrition time (mean 3 times) and 6 patients dropped out, the patients
Nausea and vomiting receiving EN had a much higher calorie intake (170% of rest-
Restrictive diets (low-sodium, low-protein, ing energy expenditure [REE]) versus controls receiving oral
fluid restriction) diet (80% REE). The EN group also had improvement in serum
Altered taste perception (zinc deficiency) levels of liver function tests as well as hepatic encephalopathy.
Socioeconomic constraints However, no significant trends were seen in survival during the
Metabolic Altered glucose, lipid, and protein study period.
alterations metabolism The De Lédinghen22 group published a prospective trial
Altered pattern of energy consumption looking at early, short-term (mean 8.6 days) EN versus oral
Decreased glycogen levels and reduced intake (started 3 days post-GI bleed) in patients after an acute
ability to store nutrients
GI bleed. The investigators found that there was no significant
Insulin resistance
benefit of early short-term EN in this particular group as the
Malabsorption Bile salt deficiency in cholestatic liver
disease and cholestasis orally fed patients were able to resume and eat adequately like
Small bowel bacterial overgrowth the EN patients. There were 4 patients with rebleeds in the EN
Portal hypertensive enteropathy group (not all attributed to the NGT) versus 1 in the oral group
(not statistically different). The authors’ recommendation
a
Data from Juakiem et al12 and Johnson et al.13 included promoting early oral feeding in this population when
possible.
version available” on February 4, 2015. In addition, articles In 2000, Cabré et al23 compared treatment of EN versus cor-
were hand-searched to identify other relevant studies. ticosteroids and an oral diet for patients with alcoholic hepati-
Table 4 includes 13 studies that evaluated EN in patients tis. Patients were given either a BCAA-supplemented formula
with liver disease, either as a treatment of the disease itself or (Hepatic-Aid) or 40 mg of prednisolone and diet for 4 weeks;
as a means to improve nutrition status. In the first and longest the researchers followed these groups for 1 year. They noted
treatment study, Smith et al18 completed a prospective study of trends in survival differences between the groups; while the
10 patients to determine whether EN was feasible, what might EN group had more deaths in the first month, their 1-year sur-
be the best formula, and whether EN would be beneficial in vival trend was better than that of the corticosteroid/oral diet
malnourished, cirrhotic patients. In these patients fed for up to group. Deaths in the corticosteroid/oral diet group tended to
60 days, researchers did not find a difference in outcomes occur after the treatment was completed and were related to
based on the 3 formulas used, which differed in protein source. infections. The investigators did not see a meaningful differ-
Interestingly, they described nutrition recovery taking place in ence between the treatments with regard to 1-year death or
2 stages. The first phase lasted 20–40 days and consisted of infection rates or changes in nutrition status. They theorized
mobilizing fluid and starting to replete body mass. The second that treatment with corticosteroids and EN may be comple-
phase started about 30 days into feeding and was a continua- mentary or may have a synergistic effect and should be studied
tion of the improvement in body cell mass and serum liver further.
function tests concentrations. Campillo and colleagues24 also studied the effect of EN in a
Keohane et al19 followed in 1983 with their preliminary large clinical setting of patients with alcoholic cirrhosis. EN was
study of 10 patients with cirrhosis in stage 1–3 hepatic coma, provided to 24 patients (of 396 enrolled) who had had poor oral
fed with Hepatic-Aid (formerly manufactured by B Braun/ intake for >15 days of hospitalization (theorizing that it takes up
McGaw, Irvine, CA) for a mean of 7.3 days (range, 2–23 days). to 2 weeks to determine whether the patient is going to improve
The researchers demonstrated that EN was safe, ratios of and eat well enough). Ultimately, 8 patients were fed for >21
branched-chain amino acids (BCAA) and aromatic amino days while the remaining 16 were fed for <21 days. Two patients
acids (AAA) were improved, and positive nitrogen balance died of aspiration pneumonia. The investigators noted that com-
was achieved. However, other nutrition parameters were not pared with patients who did not receive EN, those who required
affected given the relatively brief feeding program. EN tended to be older, sicker, and more malnourished by the

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 Table 4.  Summary of Studies Evaluating Enteral Nutrition in Patients With Liver Disease.
Reference Type of Study Patient Population N Treatment EN Formula Duration of EN EN Tolerance Adverse EN Events Non-EN Group Adverse Outcomes Conclusions

18 a
Smith 1982 Prospective Malnourished 10 EN (3 formula options) Phase I: Magnacal (2.0 kcal/ 10–60 d Overall well 1 patient had constipation, 2 1 patient died early due to liver EN was tolerated.
  patients with via NDT mL, 70 g protein, 250 g tolerated mild diarrhea, 2 vomiting, failure. Increased protein did not worsen
  cirrhosis or carb, 80 g fat). 1 transient encephalopathy, hepatic encephalopathy.
  alcoholic Phase IIA: Osmolite plus and 2 mild hyperglycemia. Nutrition recovery took part in
hepatitis modularsb (1.67 kcal/mL, 2 stages. Phase I: 20–40 d,
70 g whey-based protein, extracellular fluid mobilized/
250 carb, 80 g fat). protoplasma mass repleting. Phase
Phase IIB: Isocalc plus II: ≥30 d, continued gain of body
modulars (1.74 kcal/mL, 70 weight as muscle, bone and fat
g casein-based protein, 250 stores.
g carb, 80 g fat). Liver function tests improved.
Keohane Prospective, Patients with 10 EN via NGT Hepatic-aidd (1.8 kcal/mL, 70 Mean 7.3 d (3–23 Well tolerated 8 of 10 patients had diarrhea, There was no control group. EN safe.
198319 clinical setting cirrhosis with g protein) d) until hepatic but 6 cases were related to BCAA:AAA ratios improved.
  grade 1–3 encephalopathy neomycin and lactulose. Positive nitrogen balance achieved but
  encephalopathy cleared for 3–5 d nutrition parameters unchanged.
Cabré 199020 Prospective Severely 35 EN (16) vs oral diet (19) Specialty product made by Mean 23.3 d EN Well tolerated 2 patients had mild heartburn 1 patient in each group died in the Serum albumin levels improved with
malnourished Uniasae (2115 kcal, 71 g vs 25.3 d oral and 2 experienced tube first week. nutrition.
patients with protein/BCAA, 48 g fat, diet intolerance (on days 12 2 EN patients died while 9 of 10 EN patients had better survival than
cirrhosis 367 g carb) and 16). oral diet patients died during patients on oral diet.
  admission (significantly Continuous EN may have decreased
  different). catabolic response and caused
improved sepsis tolerance.
There was a trend for fewer infections
in the EN group.
Kearns 199221 Prospective Patients with 31 EN via NDT (16) vs oral Isocal HNc (167 kJ/kg, 1.5 g 4 wk Well tolerated Several patients required 3 patients dropped out from each EN group met 170% resting energy
alcoholic liver diet (15) protein/kg IBW) replacement of NDT (mean group. expenditure vs 80% in oral group.
disease 3 times). EN accelerated improvement in serum
  liver function tests and hepatic
encephalopathy.
  No influence on survival.
De Lédinghen Prospective Patients with liver 22 Early EN via NGT (12) Dripac Sondalisf (1665 kcal, Day 1 through Well tolerated 1 patient had pneumonia, 1 patient had SBP, 1 rebled, and No benefit of short-term, early EN in
199722 disease and vs oral diet (10) (NPO 71 g protein) second 1 SBP, 4 experienced 2 died. patients with GI bleed.
  acute GI bleed ×3 d then graduated to sclerotherapy rebleed, and there were 3 EN patients rebled sooner than oral
  oral diet) session (mean deaths. No diarrhea was diet patients (NS).
8.6 d) reported. Encouraged early oral intake in this
population.
Cabré 200023 Prospective, Patients with 71 EN (35) vs Hepaticalg (2000 kcal, 72 g 4 wk 8 (23%) withdrew 5 patients required insulin. 5 patients receiving corticosteroids Deaths occurred earlier in EN
  randomized alcoholic corticosteroids plus protein/31% BCAA, 36 g (3 due to 3 patients had transient required insulin. patients, but there was no significant
  to treat acute hepatitis (57 oral diet (36) fat, 345 g carb) complications, diarrhea, 2 nausea and Oral intake was >80% prescribed difference between groups for

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hepatitis with cirrhosis) 5 due to tube vomiting, 1 aspiration,
intolerance) 1 GI bleed, and 1 severe
epistaxis. Eleven of 35 9 of 36 patients (25%) died during 1-year survival trend better for EN
patients receiving EN
(31%) died during the trial
(NS). Patients receiving
EN who completed the
study received 80–100% of
prescribed feeding.
amount for 21 of 28 days except death, infection rates, or changes in
in patients who died. nutrition status initially.
the trial. group.
Corticosteroids and EN may be
complementary/synergistic
treatments for severe alcoholic
hepatitis.

(continued)

5
 6
Table 4. (continued)
Reference Type of Study Patient Population N Treatment EN Formula Duration of EN EN Tolerance Adverse EN Events Non-EN Group Adverse Outcomes Conclusions

Campillo Prospective, Patients with 396 (315 alcohol; 24 patients (EN when 3 formulas, options to meet 8 patients >21 Few patients 12 (50%) of EN patients died EN patients tended to be older, sicker,
200324 clinical setting alcoholic 38 alcohol + oral intake inadequate needs d; 16 patients actually (trend for higher death rate more malnourished by time they
cirrhosis HCV; 22 HCV; for >15 d) via NGT <21 d received EN in patients fed a shorter were given EN.
21 other) (24/396) duration). Ascites was primary link to decreased
  6 (25%) of EN patients nutrition status.
  had severe septic Intake and nutrition status declined
complications, 2 (8%) with severity of liver disease and
 
aspiration pneumonia were independently associated with
 
leading to death, 2 mortality.
repeated vomiting, and EN should be started earlier in
1 experienced tube hospitalization. 
intolerance.
Hu 200325 Prospective, Postoperative 135 30 controls, 40 CPN, 65 Nutrison Fibreg (1500 mL 10 d All completed 32 of 65 patients had mild 1 control patient died due to EN patients reached positive nitrogen
  clinical setting patients with CPN plus EN (NJT goal) postoperatively study abdominal distension and multisystem organ failure on balance.
  Childs B or C placed during surgery) (EN started diarrhea that resolved with day 26. Ascites and liver function tests
  cirrhosis day 3) treatment. improved first in EN patients.
No worsening of hepatic
encephalopathy with EN.
EN protected gut barrier with lowest
and shortest fever.
Alvarez 200426 Prospective Patients with 13 (6 with 40 mg prednisone (rapid Hepaticalg (2000 kcal, 1.3 Mean 22 d 10/13 tolerated 3 patients died (2 while There was no control group. EN works differently than
  severe alcoholic cirrhosis) taper) plus EN via NGT kcal/mL, 72 g protein/ hospitalization hospitalized, 1 within 2 corticosteroids but may have
  hepatitis BCAA, 35 g fat, 345 g months). complementary effect with
  carb) No aspiration was noted and corticosteroids.
there was minimal diarrhea.   
4 patients had GI bleed,  
3 experienced tube
intolerance, 8 had an
infection, 5 experienced
hepatic encephalopathy
(1 at baseline), and 12 of
13 had hyperglycemia
requiring insulin.
Clarke 200427 Prospective Patients in ICU 137 (64 with Standard vs immune 49 Standard Median 9 d No comment Impact-fed patients received No significant differences reported. No significant differences between
  with chronic chronic liver formula 40 Standard Impacth (range, 4–15 d) higher protein. groups in early or late infections or
  and acute liver disease, 73 48 glycine-supplemented Impact-fed patients who ICU outcomes.
failure with acute liver Impacth survived had longer ICU Arginine-supplemented formula did
failure) stays. not reduce infections.
Higher protein loads were associated

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with increased ammonia levels and
prolonged ICU stay.
Campillo Prospective, Malnourished 63 (28 survivors, EN when oral intake Megareal,i Nutrodrip Survived (28) for Well tolerated Expired patients had more Sepsis was more prevalent in EN was tolerated.
200528 clinical setting patients with 35 deaths) suboptimal after 2–3 Energie,i or Inkodietj mean of 42.2 + side effects than survivors. expired group vs. survivors. Severity of liver disease, sepsis, and
  cirrhosis wk of hospitalization 30.9 d; expired Survivors received more 7 patients had pneumopathy/ length of EN were independent
  (35) at mean of calories and protein than aspiration (including 5 who died prognostic factors.
  15.2 ± 33.1 d. non-survivors and were due to aspiration pneumonia), EN patients had improved serum liver
  fed longer. 2 GI bleed, 2 vomiting, 2 function tests and dietary intake.
  3 patients had vomiting, 1 experienced tube intolerance, EN should be started earlier in
pneumopathy/aspiration; 0 and 5 had grade 3 hepatic hospitalization.
tube intolerances, 1 hepatic encephalopathy.  
encephalopathy grade 3,  
and 0 GI bleeds.

(continued)
 Table 4. (continued)
Reference Type of Study Patient Population N Treatment EN Formula Duration of EN EN Tolerance Adverse EN Events Non-EN Group Adverse Outcomes Conclusions

29 b
Tai 2011 Randomized Patients with 52 28 EN via NGT vs 24 Osmolite 1.5 + BCAA vs 14 d 12/28 (42.9%) 2 patients withdrew due to Rates of GI bleed and sepsis were EN patients had higher calorie intake,
  controlled decompensated oral diet oral diet plus Ensure Plusb had poor acute pancreatitis and GI comparable between groups. but nutrition and clinical parameters
cirrhosis tolerance); 2 bleed (patient died). were similar between groups at 2
withdrew and 6 wk.
EN trended to lower mortality at 6 wk.
Dupont 201230 Multicenter, Patients with 99 30–35 kcal/kg EN × 4 Isosource Energyh (1.6 kcal/ 3–4 wk EN (mean Goal achieved 5 (11%) patients experienced 13 complications occurred in 9 No difference between malnourished
  prospective, alcohol wk, then oral support mL) plus variety of oral 2.8 ± 1.2 wk) in 29/44 tube placement failure/ patients (16.4%). and nonmalnourished patients.
  randomized cirrhosis and for 2 mo (44) vs oral supplements (66%) patients intolerance. Short-term EN did not improve
  jaundice (no diet (1800 kcal, 60 g (minimum 30 12 complications occurred in 1-y survival or liver or nutrition
  severe acute protein, 3 g sodium) kcal/kg × 3 wk) 10 patients (22.7%). parameters in jaundiced cirrhotic
hepatitis) (35). 2 cases of EN were thought patients.
to precipitate hepatic Failure to show response due to better
encephalopathy. than expected oral intake.
Malabsorption causes resistance to EN
and/or insulin resistance.
EN may have more impact earlier in
disease process.

AAA, aromatic amino acids; BCAA branched chain amino acids; CPN, central parenteral nutrition; EN, enteral nutrition; GI, gastrointestinal; HCV, hepatitis C virus; IBW, ideal body weight; ICU, intensive care unit; NDT, nasoduodenal
tube; NGT, nasogastric tube; NJT, nasojejunal tube; NPO, nil per os; NS, not significant; SBP, spontaneous bacterial peritonitis.
a
Formerly made by Organon Nutritional Products, West Orange, NJ, USA.
b
Abbott Nutrition, Columbus, OH, USA.
c
Formerly made by Mead Johnson, Evansville, IN, USA.
d
Formerly made by B. Braun McGaw, Irvine, CA, USA.
e
Made specifically for study by UNIASA, Granada, Spain.
f
Dripac Sondalis, Sopharga, France.
g

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Nutricia, Schiphol Airport, The Netherlands.
h
Nestle Nutrition, Florham Park, NJ, USA.
i
Laboratoire Novartis, Paris, France.
j
Laboratoire Fresenius Kabi, Bad Homburg, Germany.

7
8 Nutrition in Clinical Practice XX(X)
time they started EN, and the authors also noted a sepsis rate of
25% (6/24 patients). Ascites was the primary driver of decreased
nutrition intake; oral intake and nutrition status declined in rela-
tionship to the proportion of the severity of liver disease and
were independently associated with mortality. The authors’ rec-
ommendations included that EN should be considered earlier
than 2 weeks into the hospitalization.
Hu et al25 compared oral diet with parenteral nutrition (PN)
and PN+EN for 10 days in a group of 135 patients with Child’s
B and C cirrhosis undergoing various surgical procedures. EN
was started on day 3 postoperatively (with PN coverage until
EN reached goal). Patients receiving EN were the first group to
reach nitrogen balance as well as have their ascites and serum
liver function tests improve. In addition, EN may have pro-
vided some gut barrier benefit, as this group also had the low-
est and shortest fevers, indicating some potential benefit in
preventing infection.
Alvarez et al26 followed in 2004 with a different approach,
comparing EN with a rapid taper of corticosteroids in the treat-
ment of alcoholic hepatitis. The patients were fed with a
BCAA-supplemented product (Hepatic-Aid) for a mean of 22
days, showing a good tolerance but with a common complica-
tion of hyperglycemia. The result of this study concurred with
that of Cabré et al,20 in speculation that EN helps to treat alco-
holic hepatitis and complements the effects of corticosteroids.
An abstract was published in Hepatology in 2004 regarding
the use of immunonutrition in critically ill liver disease
patients. Clarke et al27 compared a standard formula with a
standard immune-enhancing formula (Impact supplemented
with glycine, Nestle Health Science, Florham Park, NJ) and an
arginine-supplemented immune-enhancing formula (Impact
supplemented with arginine). The various groups were fed for
about 9 days (4–15 days). The investigators did not see a sig-
nificant difference in the infection rates or ICU outcomes,
implying that immunonutrition did not provide any benefit to
this population with short-term feeding. While the amounts of
calories that both groups received were similar, the immunonu-
trition-fed patients received significantly more protein and had
an increased blood ammonia level at day 4 corresponding to the
increased protein intake but did not have an increase in hepatic
encephalopathy symptoms. Those patients who received immu-
nonutrition and survived had the longest ICU stays.
Campillo et al,28 in 2005, published an update of their previ-
ous research24 with a larger patient population, now 63 patients,
who received EN after suboptimal intake for at least 2 weeks.
Overall feeding tolerance was acceptable with minimal compli-
cations. The results reaffirmed that the severity of liver disease,
sepsis, and duration of EN were important prognostic factors,
so that EN should be started early in the hospitalization.
Tai et al,29 in 2011, tried to determine whether oral feeding
versus short-term EN was better for advanced cirrhotic
patients hospitalized for any reason. Patients were fed a 1.5-
kcal/mL intact protein formula (Osmolite 1.5, Abbott
Nutrition, Columbus, OH) via nasogastric tube for up to 2
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weeks, and the authors compared these results with those of
patients consuming an oral diet and a standard oral supple-
ment (Ensure Plus, Abbott Nutrition, Columbus, OH), with
clinical parameters assessed at 2 and 6 weeks. Like several
other studies, tube intolerance was a limiting factor (2 of 30
failed to tolerate placement, 12 of 28 had documented tube
intolerance, yet 24 of 28 completed the 2 weeks of feeding).
Patients who received EN had a significant calorie intake ben-
efit and a trend toward increased midarm muscle circumfer-
ence. None of the other nutrition or clinical parameters were
significantly different. Their authors’ recommendation was to
continue to be aggressive with oral supplementation in short-
term feeding situations.
Most recently, Dupont et al30 published a multicenter nutri-
tion trial in 99 cirrhotic and jaundiced patients. Patients were
randomized to receive either EN for 4 weeks followed by oral
supplements for 8 weeks or a standard treatment in which
patients were encouraged to eat an adequate oral diet. The
investigators were able to achieve EN goal feedings in two-
thirds of the patients (29 of 44 patients received a minimum of
30 kcal/kg for at least 3 weeks). However, short-term EN did
not seem to have an effect on patients’ 1-year survival or liver
and nutrition parameters. The oral-fed group ate better than
expected, so the difference in nutrition consumed was not
large, which is one possible explanation for failure to see the
benefit of EN. These researchers agreed with previous authors,
that EN may have a more significant impact if provided earlier
in the disease process.
Who Is an Appropriate EN Candidate?
Candidacy for EN involves several considerations. The obvi-
ous conditions for initiating EN are that (1) a patient has a
functional GI tract and (2) a patient is unable to consume
enough oral nutrition despite maximal efforts with supplemen-
tation and perhaps even appetite stimulants. It is not uncom-
mon for patients with chronic liver disease to have poor
intake.31 Ferreira and colleagues32 assessed energy balance
(total caloric intake minus total energy expenditure) in 73
patients awaiting liver transplantation. Energy balance was
negative in all patients but was significantly worse in patients
with Child-Pugh Class C liver disease. The median energy bal-
ance was −749 kcal and −612 kcal in patients with Child-Pugh
Class A and B liver disease, respectively. However, those with
Class C liver disease had an energy balance of −1210 kcal (P <
.001).The same group analyzed energy balance according to
nutrition status.32 Patients waiting for liver transplantation who
were considered nourished had a median energy balance of
−590 kcal while those considered malnourished had an energy
balance of −922 kcal; this was not found to be statistically sig-
nificant (P = .167). Patients such as these who have negative
energy balance meet the first 2 criteria for EN. However, there
are secondary considerations in determining who is an appro-
priate EN candidate, including the type and stage of liver
Hasse and DiCecco 9
disease, the goal of EN, expected outcomes of EN, availability
of EN, and the patient’s desires.33,34
The type and stage of liver disease can influence decisions
about initiating EN. As a general rule, there is a greater preva-
lence of malnutrition in patients with more severe versus less
severe liver disease.24 In addition, reduced oral nutrient intake
tends to parallel worsening degree of liver failure.24 Those with
decompensated liver disease are more likely than those with
compensated liver disease to have stigmata of liver disease
including ascites, portal hypertension with varices, and hepatic
encephalopathy. Ascites has been associated with worsening in
nutrition status24 as it often results in early satiety and depressed
appetite as well as nutrient losses associated with paracentesis.
The presence of complications of end-stage liver disease such
as thrombocytopenia, esophageal varices, hepatic encephalop-
athy, and electrolyte imbalances can also influence decisions
regarding choices of feeding tube placement, formula, and
duration of treatment. These are discussed in subsequent
sections.
The goal of the EN is important to consider when selecting
appropriate EN candidates. Is the goal of EN to support the
patient until recovery from an acute illness or surgery? Is the
goal to replete nutrition status enough to allow a patient to be a
candidate for liver transplant? Or, is the goal to prolong sur-
vival without a transplant? As discussed earlier, only 2 studies
found that EN improved survival in patients with liver dis-
ease,20,23 while a more recent study found that EN did not
improve 1-year survival.30 Since EN was provided a relatively
short time (≤1 month) in all of these studies, it is difficult to
make any conclusions about the effect EN could have if given
over a longer period of time or to determine whether EN can
improve complications and outcomes other than mortality. It is
also unknown how pretransplant EN in transplant candidates
could affect posttransplant operative outcomes. Recent studies
have evaluated oral nutrition supplementation but not EN in
patients waiting for liver transplantation.35,36
Another consideration in determining candidacy for EN is
the access to a medical center and team that can provide and
monitor nutrition support in patients with ESLD. Iwasa et al37
showed that when patients with cirrhosis were followed by a
dietitian and received regular counseling, they had an
improved survival rate compared with those who did not
receive regular counseling by a dietitian. In addition, close
follow-up and support are often needed for tube complications
(such as expedited replacement of clogged or dislodged
tubes). Insurance coverage for EN as well as ability of family
and caregivers to provide adequate supervision must be veri-
fied if patients are considered for home EN therapy. Gravity
feeds via a nasogastric tube often cost less (since a pump is not
needed) compared with feedings via a nasoduodenal or naso-
jejunal tube and may be worth a trial in those without insur-
ance coverage for home EN.
Finally, the patient should be an active participant in the
decision whether to initiate EN. If improvement in nutrition
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status is required to become a transplant candidate, then
patients may opt for EN more readily than if they are not facing
transplantation. In many of the studies cited previously, tube
intolerance was a significant issue, with a number of patients
requiring multiple tubes over the course of the study.20,29 In our
experience, most people do not want a tube placed for nutri-
tion, but once the tube is placed and the patient starts to feel
better from adequate nutrition, the resistance lessens. In addi-
tion, they may appreciate the relief from the pressure to eat
adequately when they really cannot make themselves consume
enough food and fluids. Patients with significant hepatic
encephalopathy may not be cognizant enough to make an
informed decision about their care, and designated family or
care providers will have to provide direction.
How Is EN Delivered?
Historically, nasal feeding tubes were considered to be contra-
indicated in patients with varices or a history of GI bleeding.
The De Ledinghen22 group in 1997 noted an insignificantly
increased rate of rebleeding in patients receiving EN via naso-
gastric tube following a GI bleed; however, the investigators
felt that some of the circumstances of the bleeds were not
directly related or increased due to the feeding tube. The 2006
ESPEN Guidelines on Enteral Nutrition: Liver Disease pro-
voked additional debate regarding the safety of feeding tubes
in this population and their risk for bleeding. Currently, EN is
recommended when oral intake is inadequate; however, it is
suggested that practitioners wait for 24–48 hours after endos-
copy or GI bleed before placing a feeding tube.6,38 New tube
materials and placement techniques may help minimize the
risk of rebleed. Tubes that are smaller and more flexible theo-
retically could be safer than stiff, large tubes. Endoscopic
placement of a nasogastric or nasoenteric tube (duodenal or
jejunal) in patients with varices may reduce risk as well,
although no studies have tested this hypothesis.34
Placement of EN tubes with assistance of an electromag-
netic placement device is an option for many patients. Most
nasal tubes can remain in place for at least 4–6 weeks if well
maintained. If EN is required for additional time, it is generally
recommended that the tube be replaced in the other nostril.39
When prolonged EN is needed, a percutaneous endoscopic
gastrostomy (PEG) is often considered; however, PEGs are
generally considered to be contraindicated in cases of com-
pensated liver disease and are absolutely contraindicated in
cases of decompensated cirrhosis. Risks of PEG placement
include leakage of moderate to severe ascites, puncture of
varices, bleeding from coagulopathy, peritonitis, and poor
tract healing.34,40-45 In 1995, in a letter to the editor, Kynci
et al46 reported 1 successful case in which a PEG was placed
in a patient with varices and ascites. Baltz et al40,47 reported
their experience in 26 decompensated cirrhotic patients who
had undergone PEG placement over the course of 10 years.
While 2 of the 26 patients died from PEG-related
10 Nutrition in Clinical Practice XX(X)

Table 5.  Enteral Nutrition Formula Options for Patients with Chronic Liver Disease.

Enteral Nutrition Formula

Category Indications and Comments Relative Cost
Standard intact protein •• Require normal digestion. $
formulas •• Available in a variety of protein and calorie concentrations.
Nutrient-dense formulas •• Require normal digestion $
•• Generally available as 1.5–2 kcal/mL concentrations.
•• Useful in patients in whom fluid restriction is needed (eg, hypervolemic
hyponatremia, fluid retention, reduced urine output, early satiety, high
nutrition requirements).
Semi-elemental or partially •• Useful for patients who have impaired digestion. $$
hydrolyzed formulas •• Available in a variety of protein and calorie concentrations.
•• Often contain peptides and/or medium-chain triglycerides.
Elemental formulas •• Useful when digestion is impaired or a very-low-fat formula is preferred. $$$
•• Contain amino acids and dextrose (vs whole proteins and starches).
•• Usually high in carbohydrate, which could contribute to hyperglycemia in
patients with insulin impairment.
•• Usually hypertonic, which can reduce tolerance
Renal formulas •• Require normal digestion. $$
•• Useful for patients with renal dysfunction and hyperkalemia or
hyperphosphatemia.
•• Usually fluid-restricted with reduced amounts of potassium and phosphorus.
Immune-enhancing formulas •• Require normal digestion. $$$
•• Have not been shown to be beneficial in patients with liver disease.26,35
•• Usually contain immune-enhancing nutrients such as fish oil, arginine, RNA.
•• May affect insulin sensitivity and satiety.
•• May temporarily increase serum ammonia levels but do not worsen
symptoms of hepatic encephalopathy.50
BCAA formulas •• Controversial as to benefit, but American and European guidelines suggest $$$
consideration of BCAA formulas in patients with encephalopathy refractory
to other treatments or with a protein intolerance.
•• Contain higher proportion of BCAAs and reduced amounts of aromatic amino
acids and methionine.
•• Usually have reduced electrolyte content.

$, low cost; $$, moderate cost; $$$ high cost; BCAA, branched-chain amino acid.

complications and 9 others died within 90 days, the authors
still recommended that the benefit to risk ratio of PEG place-
ment be considered on an individual basis in cirrhotic patients.
For patients with mild to moderate ascites, paracentesis
before and after PEG placement until the tract is healed has
been suggested as an approach to allow for EN.48 However,
based on the opinion of many liver specialists and in the
authors’ experience, PEG tubes are rarely if ever considered
for patients with chronic liver disease.
Prior to any feeding tube placement, a patient should be
evaluated for relative contraindications including risk of coag-
ulation. General recommendations would be to ensure an inter-
national normalized ratio (INR) of <2 and/or a platelet count
<50,000/µL. While these are the usual criteria, many patients
with liver disease will not be able to meet these parameters
without infusion of platelets, fresh frozen plasma, or vitamin K
supplementation.34 In some cases, even with supportive mea-
sures, these levels will not be achieved, so the patient, nutrition
staff, primary services, and gastroenterology physicians should
discuss risk and benefit to determine whether the procedure
should be performed.
What Type of EN Formula Should Be
Used?
The type of EN formula selected for a patient depends on nutri-
ent needs or restrictions, ability to digest nutrients, and cost.49,50
Table 5 summarizes some common EN formula categories and
their indications.
Are There Other Considerations Specific
to Patients With Chronic Liver Disease?
Finally, some other considerations unique to patients with
chronic liver disease should be evaluated when providing EN.
Common nutrition assessment parameters are often invalid in
patients with liver disease. For example, body weight changes
in patients who have edema or ascites usually reflect fluid

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Hasse and DiCecco 11
rather than lean body mass changes. Therefore, one of the dif-
ficulties when providing EN to patients with liver disease is
trying to determine whether EN is improving nutrition status
since valid objective measures of nutrition status in this popu-
lation are lacking.
Some changes in the metabolism of nutrient substrates are
somewhat unique to patients with chronic liver disease.
Patients can experience fasting hypoglycemia related to the
limited ability of the liver to store glycogen. In addition,
patients with cirrhosis have been found to have an increased
metabolism of fat mimicking that seen in starvation.51 Protein
accrual has been found to be superior with nighttime versus
daytime nutrition supplementation.52 A study in which 103
patients with cirrhosis were randomized to daytime versus
nighttime supplementation with an oral nutrition drink resulted
in improved energy and protein intake in both groups. However,
the nocturnal supplement group had a significant increase in
lean tissue.52 Therefore, if a cyclic infusion of EN is being con-
sidered, a nocturnal infusion could be helpful in both prevent-
ing morning hypoglycemia and achieving protein accrual.
There are concerns that high protein intake could worsen
hepatic encephalopathy. However, published data do not sup-
port this concern. Córdoba and colleagues53 randomized 30
patients with cirrhosis who were admitted through the emer-
gency department to receive EN via a nasogastric tube provid-
ing 1.2 g/kg protein from the onset or a progressively increasing
protein diet from 0 g to 1.2 g/kg over 14 days. There were no
differences in encephalopathy between the groups, but the low-
protein diet group had increased protein breakdown. In an ear-
lier study looking at protein intake in patients with alcoholic
hepatitis, higher protein intake was actually associated with
improved encephalopathy.54
How Can These Principles Be Applied?
The previously discussed principles are illustrated in the fol-
lowing case studies. The reader is invited to identify indica-
tions for EN, selection of EN route and formula, and specific
problems that had to be overcome to deliver EN.
Case Study 1
A 66-year-old woman with cirrhosis due to primary biliary cir-
rhosis/autoimmune overlap syndrome was evaluated for trans-
plantation. Her liver disease was complicated by ascites
(paracentesis on a monthly basis) and hepatic hydrothorax. At
the time of initial transplant evaluation, she presented as mildly
malnourished with some loss of muscle mass over the previous
6 months despite a good effort to maintain an appropriate
intake. The patient was listed for transplantation but had a low
MELD score (the Model of End-Stage Liver Disease score is a
number calculated from INR, serum creatinine, and total bili-
rubin levels that assesses severity of liver disease). The patient
was seen by the transplant team every 3 months for follow-up.
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She contracted influenza A and experienced a rapid deteriora-
tion of intake (nausea, anorexia, severe early satiety, and
altered respiratory status) with resulting acute overall decline
in nutrition status. She became significantly debilitated over a
period of 3 weeks (she had dry weight loss of 6 kg or 10% body
weight and became nonambulatory) and developed ascites that
required paracentesis once a week as well as thoracentesis on
opposite sides every other day (despite aggressive manage-
ment with diuretics and albumin infusion within mild chronic
kidney dysfunction allowance). Handgrip strength measures
had decreased from 22 kg to 16 kg of force (27% decline) on
her right hand and from 26 kg to 18 kg of force (31% decline)
on her left hand.
Upon transfer from the patient’s local hospital to the trans-
plant center, a nasojejunal tube was placed and a nutrition plan
for 4–6 weeks of EN was made, to determine her ability to be
nutritionally rehabilitated enough to proceed with transplanta-
tion. Feedings were initiated and increased to a goal of 5 cans
over several days (1200 mL) of a 1.5-kcal/mL formula that
provided about 1800 kcal (estimated basal energy require-
ments +20% + 300 kcal for weight gain or about 30 kcal/kg of
dry weight) and 75 g of protein (1.2 g/kg of dry weight). She
tolerated the feedings well overall, started to eat small amounts
of foods in addition to the EN, and was able to resume physical
and occupational therapy enough be dismissed to the outpa-
tient arena in the care of her son on home EN. By the end of
week 3 of EN, she was ambulatory enough to walk >700 feet
on a 6-minute walk examination, and her dry weight loss had
stabilized. On day 28 of pretransplant nutrition, a deceased
donor organ became available for her and she was successfully
transplanted. Unfortunately, her feeding tube was dislodged in
the extubation process and access was lost, so she resumed oral
intake alone on day 1 post transplant. She made slow progress
with oral intake and was dismissed on hospital day 7 consum-
ing about one-third of her calorie, protein, and fluid needs.
Case Study 2
A 49-year-old patient with alcoholic cirrhosis and end-stage
renal disease (ESRD) requiring hemodialysis presented to the
hepatology clinic for a follow-up visit. Her medical history
included esophageal varices with GI bleed, hepatic encepha-
lopathy, type 2 diabetes mellitus, and severe ascites requiring
frequent large-volume paracenteses. The patient was 5 feet 6
inches tall with a usual body weight of 140 lb. Over a 12- to
18-month period, the patient lost about 40 lb, with the majority
of the weight loss (25–30 lb) occurring over the last 4 months to
a nadir (after paracentesis) of 99 lb. The patient had been able
over the last year to maintain adequate intake by eating a 2-g
Na, low-sugar diet and drinking an oral low-carbohydrate com-
mercial nutrition supplement 3 times daily (per calorie count of
2300 kcal and >100 g of protein per day). However, her appetite
deteriorated, early satiety worsened related to the ascites, and
she experienced intermittent periods of encephalopathy. All of
12 Nutrition in Clinical Practice XX(X)
these complications resulted in reduced nutrient intake and sub-
sequent weight loss. In addition, the patient’s ascites had
become so severe that she was requiring weekly large-volume
paracenteses, which contributed to further nutrient losses. The
patient had become cachectic with temporal wasting, prominent
clavicles and scapulae, distended abdomen, and thin extremi-
ties. The patient’s MELD score had reached 26, and the trans-
plant selection committee approved the patient for combined
liver and kidney transplantation. However, the committee
elected to make the patient inactive on the transplant waiting
list because of her severe malnutrition and deconditioning. The
patient was admitted to the hospital to initiate EN. Despite a
recent endoscopy that revealed medium-size varices and severe
portal hypertensive gastropathy and platelet count of 49,000/
µL, a nasojejunal feeding tube was safely placed under fluoros-
copy and secured with a bridle. The patient reported to the care
team, “I should have let them place a feeding tube earlier” refer-
ring to other admissions when her care team had recommended
EN. EN was initiated very slowly with a 2-kcal/mL formula that
was chosen due to her volume overload and ESRD. Goal EN
was set at a minimum of 1600 kcal (150% of Mifflin-St Jeor
calculation) and 68 g of protein (1.5 g/kg of dry weight). Oral
intake of a low-sodium diet and oral supplements were encour-
aged in addition to EN. Serum levels of potassium, magnesium,
and phosphorus were checked for 3 consecutive days to moni-
tor for refeeding syndrome. In addition, serum sodium levels
were monitored for hyponatremia (due to volume overload).
Long- and short-acting insulin was prescribed for diabetes mel-
litus, and glucose levels were checked 4 times daily with goal of
keeping serum glucose <180 mg/dL (nonfasting levels). The
EN infusion reached goal rate, laboratory tests were normal-
ized, and the patient was discharged to home several days later
where she continued her outpatient dialysis treatments and
weekly paracentesis. Approximately 2 weeks after discharge to
home, follow-up laboratory tests revealed an elevated potas-
sium level (6.2 mEq/L) so the EN formula was changed to a
renal formula reduced in potassium and phosphorus. The EN
provided about 1700 kcal and 76 g of protein per day in addition
to an oral diet (~1000 calories per diet recall).. The patient came
to the transplant center monthly for follow-up appointments. At
the first follow-up appointment, the patient’s weight was 117 lb
with a postparacentesis weight of 98 lb. Her triceps skinfold and
midarm muscle circumference measurements were <5th per-
centile. By the third month of home EN, her postparacentesis
weight and anthropometric measurements had not improved
and patient continued to appear emaciated. It was shortly after
this that the patient was admitted to the hospital, and continued
to deteriorate such that the transplant committee withdrew the
patient from consideration for transplantation with recommen-
dation for a palliative care consult.
This unfortunate case illustrates that nutrition support may
not always be able to change the trajectory of a patient’s course.
Although adequate EN was provided for a period of 2–3
months, the patient’s nutrition status did not improve. The
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question that is raised is whether provision of adequate nutri-
tion in the face of severe and decompensated organ failure can
improve nutrition status or change course of the disease.
Summary and Recommendations
Why do some patients with liver disease benefit from EN while
others do not? The current body of research does not provide any
answers to this question and really only seeds more questions.
While no conclusive evidence shows benefit of EN in liver dis-
ease, the provision of EN to patients with inadequate oral intake
may be in the patient’s best interest, with limited risk of doing
harm. Therefore, it seems reasonable to initially provide nutri-
tion intervention as oral diet and supplements; however, waiting
to escalate treatment to EN only after a period of weeks has
passed is likely too long.22,24 Once failure to meet nutrition goals
by the oral route has occurred in a limited timeframe, we would
recommend consideration of EN support.55 Waiting for at least
24–48 hours after a GI bleed seems reasonable to determine
whether the patient is at risk for rebleeding and is able to resume
an adequate oral intake. Conversely, it may be reasonable to start
EN very quickly in the case of a patient in the intensive care unit
with a critical illness or hepatic coma. Data remain unclear
whether nasogastric or nasal–small bowel feeding is better toler-
ated. Which type of tube to be placed may be better determined
based on the patient’s situation, ease of placement, comfort of
tube, concern for altered gastric emptying, and aspiration risk.
For most patients, an intact formula, often fluid restricted, seems
to be an appropriate way to start with feedings and would gener-
ally be the most economical product for home intake as well.13
In cases where refeeding may occur, the initiation of feedings at
a low rate for 24 hours, then increasing as tolerated to goal over
several days, would be sensible.
Based on the available literature, we offer the following
recommendations for an EN feeding protocol:
•• Maximize oral intake with nutrient-dense food, fluids,
and supplements.
•• Consider EN after 1 week of failure of adequate oral
intake.
|| Consider earlier EN initiation in critical care situ-
ations.
•• Place feeding tube (nasogastric, nasoduodenal, or
nasojejunal).
|| Wait at least 24–48 hours after GI bleed.
|| PEG tubes are generally contraindicated due to
ascites and varices.
•• Start EN at low rate (especially if the patient is at
refeeding risk), increasing to goal over several days.
|| Choose an intact-protein formula considering a
nutrient-dense product depending on nutrition
needs and fluid status.
|| Specialty formulas may be used in cases of signif-
icant malabsorption (semi-elemental, elemental)
Hasse and DiCecco 13
or renal insufficiency (renal formula); data are
lacking for use of immune-enhancing or BCAA
formulas.
•• Reassess weekly for tolerance, achievement of goal
feedings, and improvement in nutrition and functional
parameters.
We submit that this is a prime example of just how chal-
lenging it is to conduct evidence-based nutrition research. With
regard to providing EN to patients with chronic liver disease,
we are left with many unanswered questions. Currently, it is
unclear who might best benefit from EN, and following are
some of the many questions with regard to EN and chronic
liver disease yet to be answered:
•• Who might best benefit from EN?
•• Is it beneficial to provide EN sooner rather than later in
the course of liver disease?56,57 When is the appropriate
time?
•• Do some patients become too sick to be able to nutri-
tionally rehabilitate?
•• How long do you need provide EN to someone to obtain
real benefit? Is 4 weeks long enough?
•• What is the right formula? Does one type of product fit
all? Is intact protein better than BCAA?
•• Should EN goals be adapted to the degree of malnutri-
tion and severity of liver disease?
•• What are the right markers of nutrition to monitor?
•• Does the type of liver disease affect decisions about EN
or EN formulas?
•• Is malnutrition a symptom or sign of liver disease? Is
malnutrition a cause or effect of outcomes?
•• Is there a difference in EN results between the clinical
setting and controlled study?28
Thus far, there have been challenges in accumulating
enough patients to have the statistical power to answer these
questions, including a control group, and avoiding any types of
bias. With the increasing population of people with liver dis-
ease and the lengthy wait for transplantation, this (unfortu-
nately) may not be a problem in the future.
Statement of Authorship
Jeanette M. Hasse and Sara R. DiCecco equally contributed to the
conception/design of the work; contributed to the acquisition,
analysis, and interpretation of the data; drafted the manuscript;
critically revised the manuscript; and agree to be fully accountable
for ensuring the integrity and accuracy of the work. All authors
read and approved the final manuscript.
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