Caballero B. (ed.) Encyclopaedia of Food Science, Food Technology and Nutrition. Ten-Volume Set

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their therapeutic efficacy. Thus, for example, the

enterohepatic circulation of morphine and of other

opiates may prolong their analgesic effect. On the

other hand, accumulation of the anticoagulant war-

farin, or of the tranquillizers benzodiazepines, or of

digitoxin may expose patients to the risk of drug

overdose. For most of these drugs, administration of

activated charcoal or ion-exchange resins (cholestyr-

amine, for example) is of proven value in the treat-

ment of overdose by interrupting their enterohepatic

circulation, thus favoring fecal excretion.

Colonic Bacteria and the Enterohepatic

Circulation

0051 Both endogenous and exogenous substances are ex-

creted in bile in conjugated forms. These are mainly

glucuronate and sulfate conjugates, with the notice-

able exception of bile acids which are conjugated

almost exclusively with glycine and taurine in

humans. Conjugation, on the one hand, makes these

substances sufficiently hydrophilic to be excreted in

bile and, on the other hand, makes them too hydro-

philic to be absorbed by passive diffusion in the gut.

Bile acids are unique in being actively absorbed in the

distal ileum in the conjugated form. For all other

substances, deconjugation is a necessary step to

increase their lipophilicity prior to passive colonic

diffusion The human colonic flora is capable of pro-

ducing glucuronidases and sulfatases, and passive dif-

fusion of the resulting hydrolyzed compounds is

usually quantitatively small, because of the relatively

small surface-to-volume ratio in the colon, and be-

cause binding to bacteria and to nonabsorbable diet-

ary components favors fecal excretion. This explains

why the enterohepatic circulation is quantitatively

small for all substances relying on a colonic deconju-

gation step to enter the enterohepatic circulation

following biliary excretion.

See also: Bile; Gallbladder; Liver: Structure and

Function; Mycotoxins: Classifications; Toxicology

Further Reading

Angelin B, Eriksson M and Rudling M (1999) Bile acids and

lipoprotein metabolism: a renaissance for bile acids in

the post-statin era? Current Opinion in Lipidology 10:

269–274.

Bahar RJ and Stolz A (1999) Bile acid transport. Gastro-

enterology Clinics of North America 28: 27–58.

Carey MC and Duane WC (1994) Enterohepatic circula-

tion. In: Arias IM, Boyer JL, Fausto N, Jakoby WB,

Schachter D and Shafritz DA (eds) The Liver: Biology

and Pathobiology, 3rd edn, pp. 769–786. New York:

Raven Press.

Cooper AD (1999) Role of the enterohepatic circulation of

bile salts in lipoprotein metabolism. Gastroenterology

Clinics of North America 28: 211–229.

Hofmann AF (1989) Enterohepatic circulation of bile

acids. In: Handbook of Physiology, section 6, vol. 111,

pp. 567–596. American Physiological Society.

Hofmann AF (1992) Bile acids in liver and biliary disease.

In: Millward-Sadler GH, Wright R and Arthur MJP (eds)

Wright’s Liver and Biliary Disease, 3rd edn, pp. 289–

316. London, UK: WB Saunders.

Hylemon PB and Harder J (1998) Biotransformation

of monoterpenes, bile acids, and other isoprenoids in

anaerobic ecosystems. FEMS Microbiology Reviews

22: 475–488.

Lanzini A and Northfield TC (1991) Biliary lipid secretion

in man. European Journal of Clinical Investigation 21:

259–272.

Love MW and Dawson PA (1998) New insights into bile

acid transport. Current Opinion in Lipidology 9:

225–229.

Mejer PJ, Hagenbuch B and Stieger B (1994) Properties of

two cloned basolateral bile acid uptake proteins of rat

and human liver. In: Hofmann AF, Paumgartner G and

Stiehl A (eds) Bile Acids in Gastroenterology. Basic and

Clinical Advances, pp. 139–146. Lancaster, UK: Kluwer

Academic.

Nutritional Management of

Liver and Biliary Disorders

E Medici, King’s College Hospital, London, UK

Background

0001Nutrition intervention in liver disease is both challen-

ging and well researched. Intervention will depend on

the individual patient needs and is related to symp-

toms rather than disease state. Hence, patients with

liver cirrhosis will suffer much the same range of

problems irrespective of the etiology. Preserving the

patient’s nutritional status is central to the treatment

of all liver patients. Liver transplantation is now well

established as the treatment for end-stage liver disease

and restores the patient’s nutritional status; however,

patients often develop different nutritional complica-

tions, predominantly excess weight gain and hyper-

lipidemias. This section will aim to give a brief

understanding of the current evidence-based nutrition

practice in liver disease and transplantation.

Type of Liver Disease

0002Acute or fulminant hepatic failure (FHF) refers to

massive hepatocellular necrosis resulting in hepatic

LIVER/Nutritional Management of Liver and Biliary Disorders 3603

encephalopathy and coma within 8 weeks from the

onset of symptoms and in the absence of previous

liver disease. Most common forms of FHF in the UK

are due to exogenous hepatotoxins such as paraceta-

mol (acetaminophen). FHF carries a mortality rate of

50–80%. Nutrition intervention is short-term until

the patient recovers, is transplanted, or dies. Diet

manipulation is rarely required, and standard ICU

feeding protocols will apply.

0003 Chronic liver failure refers to the progressive

damage and cirrhosis of the hepatocytes over a pro-

longed period. Complications are stage-dependent

and often reflect degree of damage to the liver. A

patient with cirrhosis can be asymptomatic for up to

40 years. Normally, the patient will alternate between

an asymptomatic or controlled symptoms state

(compensated liver disease) and a symptomatic state

(decompensated liver disease). A decompensated

state may result in any one or a combination of symp-

toms such as ascites, variceal bleeding, diabetes,

steatorrhea, and/or encephalopathy. All of these

symptoms will require dietary manipulation.

Protein Energy Malnutrition

0004 As the liver is central in the metabolism, assimilation,

and synthesis of protein, it is not surprising that pro-

tein-energy malnutrition (PEM) is common in pa-

tients with chronic liver disease. PEM refers to the

increased catabolism of muscle and other visceral

proteins for gluconeogenesis. PEM in chronic liver

disease has been well documented with a prevalence

of 27–100%. The severity of PEM is dependent on

etiology and length of disease, with alcoholic liver

disease patients being worst effected.

0005 PEM in chronic liver disease has been demon-

strated as an independent risk factor to clinical out-

come and, therefore, is always prioritized in the

treatment of cirrhotic patients. Protein energy malnu-

trition has been associated with:

0006 worsening encephalopathy;

0007 poor control of ascites;

0008 increased infection rate;

0009 increased hospital admissions;

0010 increased mortality.

The reasons for this gross PEM are multifactorial;

however, the imbalance of catabolic and anabolic

hormones plays a pivotal role. Factors associated

with PEM in chronic liver disease include:

0011 increased energy and protein requirements;

0012 increased levels of catabolic hormones, predomin-

antly catecholamines, but also corticosteriods and

glucagon;

0013resistance to the anabolic hormones, insulin and

growth hormone;

0014reduction of the anabolic hormones, growth factor 1

and its carrier proteins;

0015alteration in nutrient utilization;

0016reduced glycogenolysis;

0017increased gluconeogenesis;

0018increased lipolysis

PEM is exacerbated in cirrhotic patients by accom-

panying anorexia and malabsorption. Aggressive

nutrition support is often needed to meet increased

energy and protein requirements in order to attenuate

catabolism and PEM.

0019Dietary intervention commences with appropriate

assessment of the patient’s muscle status and not

simply body weight. The latter may be affected by

ascites and/or edema, and does not differentiate

between fat and muscle stores. Normal weight or

obesity may mask PEM, as normal or excessive fat

stores can be present in such patients. The patient’s

requirements will need to be calculated and met,

orally, nasoenterally or intravenously.

Elevated Energy and Protein

Requirements

0020Increased requirements for energy and protein have

been demonstrated in compensated as well as decom-

pensated liver disease, acute liver failure, and post-

liver transplantation by a number of authors. Basal

metabolic rate (BMR) has been found to be 40%

higher than in healthy individuals, and protein re-

quirements have been estimated at 1–1.8 g kg

1

day

1

(healthy individual requirements 0.8 g kg

1

day

1

). Energy and protein requirements have been

found to be closely associated with lean body mass;

hence, standard calculations should use dry body

weight, and adjustments have to be made for excess

fat stores, fluid overload, and ascites (see Table 1). It

has been suggested, that patients with a dry body

mass index (BMI) of 30 kg m

2

and 40 kg m

2

tbl0001Table 1 Estimating fluid weight

Estimated ascitic weight (kg)

Mild 2.2

Moderate 6.0

Severe 14.0

Estimated peripheral edema weight (kg)

Mild 1.0

Moderate 5.0

Severe 10.0

From Wicks C and Madden A (1994) A Practical Guide to Nutrition in Liver

Disease, 2nd edn. Birmingham, UK: The Liver Interest Group of the British

Dietetic Association.

3604 LIVER/Nutritional Management of Liver and Biliary Disorders

(see Table 2) should have their requirements calcu-

lated at 75 and 65%, respectively, of their actual body

weight.

0021 Some authors strongly recommend that resting

energy expenditure should be measured and not pre-

dicted. However, as indirect calorimetry carts are not

readily available and may be impractical, the use of

predictive equations and stress factors is inevitable.

Two validated equations for calculating requirements

are used in the UK and are shown with examples in

Tables 3–5.

Diabetes

0022The incidence of diabetes is higher in patients with

liver disease resulting from hepatitis C virus and alco-

hol. The prevalence has been quoted at 27–39%. It

is essential to maintain good glycemic control (i.e.,

4–8mmoll

1

). Hyperglycemia exacerbates muscle

catabolism and can increase infection risk. A stand-

ard diabetic diet should not be prescribed, as it en-

courages a low intake of protein and total energy and

will compromise the patient’s nutritional status. A

modified diet encouraging the avoidance of simple

carbohydrate whilst increasing fat and protein dense

foods should be followed. This will allow for normal

glycemic control whilst still meeting energy and pro-

tein requirements. Hypoglycemic agents (oral or in-

sulin) will often be required in conjunction with diet.

0023If the patient is anorectic and not meeting require-

ments, oral sip feeds and/or nasogastric feeding will

be indicated. As these feeds will contain maltodex-

trins, hypoglycemic agent therapy will need alteration

to compensate for the expected elevation in blood

sugar.

Ascites

0024This is the excessive accumulation of extracellular

fluid in the peritoneal cavity, usually as a late compli-

cation of cirrhosis. The development of ascites is a

complex multifactorial process of which the precise

mechanism is still unknown. It is probably due to

sodium retention (enhanced by secondary hyperaldos-

teronism), compounded by hypoalbuminemia and

portal hypertension. A diagrammatic representation

tbl0002 Table 2 Calculating body mass index

BMI kg m

2

Weight in kilograms

Height in meters

Interpretation of BMI values (kg m

2

15 ¼critically underweight – Increase weight

15.9–19.9 ¼underweight – increase weight

20–24.9 ¼ideal weight – grade 0 obesity – maintain weight

25–29.9 ¼overweight – grade I obesity – maintain or lose weight

30–39.9 ¼obese – grade II obesity – must reduce weight by at

least 10%

40 ¼grossly obese – grade III obesity – must lose weight by at

least 10%

tbl0004 Table 4 Estimating energy requirements using basal metabolic rate with activity and stress factors (estimated daily

requirements ¼BMR (% stress þ% activity) þBMR)

BMR kcal (kJ)

Age Men Women

15–18 years 17.6W þ 656 (74W þ 2742) 13.3W þ 690 (56W þ 2884)

18–30 years 15.0W þ 690 (63W þ 2884) 14.8W þ 485 (62W þ 2027)

30–60 years 11.4W þ 870 (48W þ 3637) 8.1W þ 842 (34W þ 3520)

> 60 years 11.7W þ 585 (49W þ 2445) 9.0W þ 656 (38W þ 2742)

Stress factors

Compensated liver disease 0–20%

Acute (fulminant hepatic failure)/ventilated/transplant 20–30%

Decompensated liver disease 30–40%

Activity factor

Bed-bound/immobile 10%

Bed-bound mobile/sitting 15–20%

Mobile on ward 25%

Protein requirements

Compensated liver disease 0.8–1.2 g kg

1

day

1

Decompensated liver disease/transplant 1.2–1.8 g kg

1

day

1

W, dry lean body weight.

tbl0003 Table 3 ESPEN guidelines recommendations

Protein g kg

1

day

1

Energy kcal kg

1

day

1

(kJ kg

1

day

1

)

Compensated liver

disease

1.0–1.2 25–30 (105–125)

Decompensated liver

disease

1.0–1.5 25 (if ventilated) – 40

(105–167)

LIVER/Nutritional Management of Liver and Biliary Disorders 3605

is shown in Figure 1. Ascites usually develops when

the patient has advanced ‘decompensated’ disease.

Ascites causes discomfort and shortness of breath,

reduced appetite, increased risk of infection (spontan-

eous bacterial peritonitis), and increased mortality. In

addition, ascitic patients will also display even higher

energy and protein requirements than nonascitic liver

patients.

0025Ascites is normally managed by a combination of

dietary sodium restriction and diuretic therapy. The

aim should be to achieve a net fluid loss of 500 ml

day

1

(equivalent to a weight loss of 0.5 kg), until the

ascites clears. Serum urea, creatinine, and electrolyte

concentration should be checked at least once a week

at the start of treatment. A rising serum urea or

creatinine and falling serum sodium concentration

indicate impending renal failure and should lead to

tbl0005 Table 5 Example for calculating requirements using both

methods

Subject: 36-year-old female with moderate ascites and hepatic

encephalopathy secondary to chronic liver disease; the patient is

bed-bound

Height ¼ 1.6 m

Weight ¼ 86 kg

(1) Estimate dry body weight: 86 kg  6kg ¼ 80 kg

(2) Calculate BMI: 80/(1.6)

¼ 31 kg m

2

(3) Estimate lean body weight: 75% of 80 kg ¼ 60 kg (the weight

to be used for requirement calculations is 60 kg)

Estimated daily requirements using the ESPEN guidelines:

1800–2400 kcal (7524–10032 kJ) per day

60–90 g of protein per day

Estimating daily requirements using BMR and stress factors

BMR ¼(8.1 60) þ842 ¼1328 kcal (5551 kJ)

Daily energy requirements ¼1328 (10% activity þ30%

stress) þBMR ¼1860 kcal (7771 kJ)

Daily protein requirements ¼70–108 g

Liver disease

Poor albumin synthesis

Low plasma albumin

Low plasma osomotic pressure

Intrahepatic vascular obstruction

Hepatic venous outflow block

Increased portal venous

pressure

Variation in peritoneal membrane

Increase in hepatic lymph

Ascites

Body fluids and sodium depleted

Theoretical path to developing ascites

Renal proximal and distal tubules

Sodium and water

retention

fig0001 Figure 1 Theoretical pathway to the development of ascites.

3606 LIVER/Nutritional Management of Liver and Biliary Disorders

a reduction in diuretic treatment. A combination of

frusemide and spironolactone diuretic therapy is

often used. The latter is potassium-sparing and may

result in hyperkalemia after prolonged use. Other

interventions include paracentesis (removal of large

volumes of ascitic fluid via a cannula).

0026 If a low-sodium/no-added-salt diet and diuretic

therapy do not work, the ascites is classified as refrac-

tory/resistant, and transplantation or surgical proced-

ures will be required to alleviate the symptoms.

Sodium Restriction

0027 These patients will be extremely catabolic, and dis-

play anorexia. Meeting their nutritional requirements

is paramount and also extremely difficult without

supplementary feeding. Reducing salt intake will

automatically result in reduced palatability and pos-

sibly further reduce the patient’s intake. During hos-

pitalization, it is much easier to impose a sodium

restriction on patients whilst ensuring that energy

and protein requirements are met. Once discharged,

this level of restriction is very difficult to maintain,

and a ‘realistic’ diet of no added salt must be

prescribed. An example of a no-added-salt diet is

shown in Table 6. This will depend on the patient’s

socio-economic background, motivation, mental

acuity and prognosis. Cutting down salt intake will

also help with adherence to the fluid restriction,

which is often imposed at 750–1500 ml day

1

0028Oral supplements and nasogastric feeds should be

chosen carefully. Feeds low in sodium and volume

(i.e., 2 kcal ml

1

) will be ideal.

0029Confusion often arises over serum sodium levels.

Irrespective of the serum levels (patients are normally

hyponatremic), no-added-salt diets should always be

prescribed/encouraged for all patients with ascites.

Varices

0030These are veins that have become grossly enlarged as a

consequence of portal hypertension. They are caused

by the development of venous back flow as a result of

portal vein obstruction by the cirrhotic liver. They are

more often seen in the lower 5 cm of the esophagus

and fundus of the stomach. The most significant com-

plication of varices is hemorrhage, which is fatal for

50% of patients.

tbl0006 Table 6 Low-sodium alternatives

Low-sodiumenergy and protein-dense foods High-sodium foods ^ to be avoided

Meat, fish, poultry

Fresh or frozen meat, fish, poultry (roast, fry, cook with

unsalted butter or oil), tinned fish in oil or water (not brine)

Sausages, tinned meat, tinned fish in brine, corned beef, bacon,

ham, gammon, burgers, pies, ready meals, smoked/pickled

meat/fish, fish in batter, pa

, sandwich spreads, salami, etc.

Dairy products

Full-cream milk, yogurt, fromage frais, all creams, cream

cheese, mozzarella, cottage cheese, ricotta cheese, eggs

Lassi, most cheeses not mentioned in the ‘USE’ list, all processed

cheeses, e.g., cheese spreads/slices

Fats and oils

All oils, unsalted butter Dressings, bottled sauces, mayonnaise

Cereals and breads

Shredded Wheat, Raisin Splitz, Sugar Puffs, puffed wheat,

porridge, unsalted muesli, all flours, bread, rolls, pasta

Most other breakfast cereals, rich breads, e.g., brioche, focaccia,

ciabatta, croissant, pot noodles

Fruit and vegetables

Fresh, frozen, tinned or dried fruit, fresh or frozen vegetables,

tinned tomatoes, tomato pure

e, tinned vegetables in water

only, all fruit juices

Dried, pickled, and most tinned vegetables, olives, gherkins, etc.

Savory snacks

Unsalted nuts, peanuts and raisins, Smiths ‘Shake þ Salt’

crisps (throw away the salt sachet), all butter popcorn

Salted nuts, crisps, Twiglets, salted popcorn and other salted

snacks

Biscuits

Most biscuits – especially Jaffa Cakes, wafers, Kit-kat, Malted

milk, Bourbon creams, Nice, plain Hobnobs, Matzo crackers

Digestives, shortbread cheese biscuits, Ryvita

Sweet snacks/condiments

All milky puddings, custard, cakes, gateaux, chocolate,

especially Smarties, Walnut whips, plain chocolate, Fry’s

chocolate cream, After Eights, fruit sweets – boiled sweets,

jelly babies, pastilles, Opal Fruits, marmalade, jam, honey,

chocolate spread

Fudge, toffees, Marmite, peanut butter, Vegemite

Drinks and miscellaneous

Whole milk, hot chocolate, milk shake, yogurt shakes,

Lucozade, cordials

Soup, stock cubes, Bovril, Marmite, Build Up Soup

LIVER/Nutritional Management of Liver and Biliary Disorders 3607

Diet

0031 The presence of varices is not necessarily a contra-

indication to nasogatric feeding. Two randomized

controlled trials investigating the benefit of aggressive

nutrition support via nasogastric feeding to full re-

quirements compared with no feeding found no in-

crease in variceal bleeds between the study and

control groups. Nasogastric feeding is often not ap-

propriate when a patient is actively bleeding or within

48 h of variceal treatment (banding/sclerotherapy).

0032 No dietary modifications are required for these

patients, except to reassure and encourage a normal

consistency diet. Many patients will self-regulate

their diet to soft/sloppy consistency, because of a

misconception that solid foods will rupture their vari-

ces. This would only be encouraged if the patient

finds swallowing painful, because of variceal treat-

ment such as sclerotherapy or banding.

Hepatic Encephalopathy

0033 Hepatic Encephalopathy (HE) in patients with

chronic liver disease (CLD) is a common complica-

tion, with a prevalence of 50–70%. HE as a result of

FHF is accompanied by intracerebral edema, and

intervention relies on the reduction of the cerebral

pressure and/or liver transplantation.

0034 HE is a neuropsychiatric condition as a result of

portal vein shunting away from the cirrhotic liver.

Toxins present in the portal vein shunted away from

the liver and hepatocytes without detoxification are

thought to be able to cross the blood–brain barrier,

with resultant alteration in the patient’s conscious-

ness, personality, intellectual capacity, and speech.

HE in chronic liver disease can be reversed with med-

ical and nutritional intervention.

0035 The pathogenesis for HE remains unknown but is

thought to be multifactorial. Several theories have

been proposed and researched. The more popular

theories to HE are those relating to the elevated am-

monia levels and disturbance in the branched chain

amino acid (BCAA) to aromatic amino acid (AAA)

ratio in the blood.

0036 The onset of HE in patients with CLD is often

precipitated by a number of factors, which, once

treated, alleviate the encephalopathy.

0037 Such factors include:

0038 constipation;

0039 sepsis;

0040 gastrointestinal bleed;

0041 alcohol binge;

0042 dehydration;

0043 enthusiastic use of diuretics;

0044 paracentesis;

0045electrolyte imbalance;

0046hypokalemia (increased renal NH

production);

0047protein-rich diet.

Ammonia Theory

0048Elevated circulating ammonia and ammoniagenic

substances are probably the result of portal vein

shunting and the inability of ammonia from the gas-

trointestinal tract to reach the hepatocytes for urea

production. Once ammonia diffuses across the blood–

brain barrier, neurotoxicity results, as the brain does

not have a urea cycle. Toxicity on the central nervous

system may be direct or indirect. The latter has been

suggested, as ammonia serum levels correlate very

poorly with the presence or level of encephalopathy.

It is now well established that the action on luminal

content by colonic gut flora and glutaminase in

the ileum are major contributors of ammonia in the

portal vein. The small and large intestine are there-

fore targeted for treatment.

0049This theory encouraged the use of low-protein diets

to try and reduce ammoniagenic compounds in the

portal vein. However, this practice has been proven to

be ineffective and, in many cases, detrimental to the

patient’s well-being.

False Neurotransmission Theory

0050The false neurotransmission theory in the 1970s was

based on the altered ratio of BCAA to AAA in the

serum seen in most cirrhotic patients. In healthy indi-

viduals, BCAA (leucine, isoleucine, and valine) serum

levels are three to four times greater than AAA (free

tryptophan, phenylalanine, and tysosine). The higher

BCAA concentration results in a greater affinity for

the receptor sites of the single carrier system and

transport across the blood–brain barrier for normal

neurotransmission. In cirrhotic patients and especially

encephalopathic patients, this level is altered to 1:1.

0051AAAs are predominantly utilized by the liver,

whereas BCAAs are predominantly utilized by per-

ipheral muscle. During liver disease, BCAAs continue

to be metabolized by the muscle for energy, but AAA

metabolism by the cirrhotic liver is heavily reduced

and results in the reduced ratio.

0052With this altered amino acid plasma ratio in the

blood, AAA can compete with more affinity to diffuse

across the blood–brain barrier. Elevated serum am-

monia indirectly favors the uptake of AAA into the

brain (see Figure 2).

0053The use of altered amino acid feeds with encepha-

lopathic patients was therefore encouraged. It was

hypothesized that altering the amino acid compos-

ition of these patients would lead to an improved

3608 LIVER/Nutritional Management of Liver and Biliary Disorders

BCAA:AAA serum ratio and improved encephalop-

athy. Unfortunately, the trials have not been conclu-

sive on the benefit of these expensive and less

palatable supplements. Improvement in HE has not

always been accompanied by an improvement in the

amino acid ratio.

0054 In the 1980s and 1990s, many metabolic and pro-

spective randomized trials investigating the effect of

dietary protein intake and use of BCAA feeds in en-

cephalopathy have concurred that:

0055 Treatment and elimination of precipitating factors

often lead to the improvement and elimination of

HE without manipulation of the diet.

0056 Spreading the protein loads throughout the day

results in more effective ammonia clearance.

0057 Endogenous ammonia production from muscle ca-

tabolism often exceeds oral protein intake. This is

due to the imbalance of anabolic and catabolic

hormones and push toward gluconeogenesis in cir-

rhotic patients. This picture is often exacerbated by

the patient’s inability to consume adequate nutri-

tion (owing to confusion and/or drowsiness).

0058 Protein requirements are elevated at 1.2–1.8 g kg

1

day

1

0059 Positive nitrogen balance is directly linked to im-

provement and/or elimination of encephalopathy.

0060 Negative nitrogen balance has been directly linked

to the presence and worsening of HE.

0061Positive nitrogen balance is achieved by meeting

protein requirements. Supplementary feeding with

oral sip feeds, nasoenteral, or intravenous nutrition

is often required. Similar outcomes have been

achieved from standard feeds or BCAA feeds.

0062Peripheral muscle is responsible for clearing 50%

of the circulating ammonia. Therefore, the more

muscle-wasted a patient is, the greater the circulat-

ing ammonia.

0063Peripheral muscle utilizes BCAA for energy and

preservation of muscle mass, and so BCAA feeds

have improved nitrogen balance quicker than

standard feeds.

0064BCAA (predominantly leucine) in cirrhotic patients

have been found to:

0065reduce the flux of AAA from muscle cells;

0066reduce proteolysis;

0067increase protein synthesis;

0068increase uptake of AAA by the liver;

0069increase uptake and metabolism of ammonia in

muscle cells.

Current Practice for Hepatic

Encephalopathy

Diet

0070Any precipitating factors must be dealt with before

dietary effectiveness can be of benefit.

Lactulose

Glucagon/catecholamines

low IGF/ insulin resistance

Catabolism/

proteolysis

Portal vein

shunting

Inadequate

oral intake

False neurotransmitters

increase in inhibitory transmitters

Ammonia and

amino acid pool

Colon

Gut flora

Ileum

Glutaminase

Oral

diet

Amino acids

BCAA

AAA

BCAA

Single carrier system

fig0002 Figure 2 Route of ammonia and amino acids during portal shunting. Ammonia and amino acids from gastrointestinal metabolism

enter the portal vein. As the portal vein is shunted away from the cirrhotic liver, ammonia and amino acids are in the systemic

circulation. BCAAs are rapidly taken up and utilized by peripheral muscle for energy and serum levels become reduced. AAAs cannot

be cleared from the circulation, as they require the urea cycle in the liver. In addition, gluconeogenesis and muscle catabolism

increase the release of ammonia and AAA in the circulation. Ammonia may diffuse across the blood–brain barrier, resulting in

neurotoxicity, and also increases the affinity of the single carrier system for AAA to cross into the brain and result in the production of

false neurotransmitters.

LIVER/Nutritional Management of Liver and Biliary Disorders 3609

0071 Meeting energy and protein requirements, which

often requires supplementation (oral and/or naso-

enteral), will normally resolve HE. The use of BCAA

feeds in HE is not established in the UK but may

benefit patients with particularly persistent encephal-

opathy. Low-protein diets are contraindicated and

should not be used. However, some patients with

persistent HE, good muscle mass who are exceeding

their protein requirements, may benefit from redu-

cing dietary protein intake to recommendations and

possibly using BCAA supplements.

Lactulose/lactitol

0072 The effectiveness of lactulose/lactitol is undisputed

and is one of the first-line treatments. This is not

surprising, as constipation is cited by many authors

as a common precipitating factor for HE. As men-

tioned earlier, colonic flora and glutaminase in the

ileum are responsible for the significant production

of free ammonia carried in the portal vein.

0073 It is desirable for a patient with a history of hepatic

encephalopathy to open their bowels two to four

times per day and the stools to be soft and acidic

(pH < 6). Lactulose/lactitol remove both dietary and

endogenous ammonia from the gut lumen by osmotic

cathartic action.

Antibiotics – Neomycin and Metronidazole

0074 Antibiotics work similarly to lactulose but can only

be used for a short time, owing to their ototoxicity

and nephrotoxicity.

Lactobacillus acidophilus

0075 Lactobacillus acidophilus populates the colonic

lumen with nonurease-producing bacteria, and the

research has been extremely controversial.

Ornithine Aspartate Treatment

0076 Ornithine is essential for converting NH

to urea,

whereas aspartate is essential for the conversion of

to glutamine in the urea cycle. Ornithine aspar-

tate via enteral or parenteral infusion has been found

to be effective in resolving mild encephalopathy in

small trials.

Zinc Supplementation

0077 It has been well documented that patients with

chronic liver disease have low serum zinc levels as a

result of increased urinary losses. In addition, two

out of the five urea cycle enzymes are zinc-

dependent. Trials investigating zinc supplementation

to increase the activity of the urea cycle have been

inconclusive.

Steatorrhea

0078Steatorrhea is a common complication as a result of a

mechanical block in the biliary tract or by intra-

hepatic lesions. When bile salt entry into the duode-

num is hindered, the emulsification of dietary fats is

incomplete. Steatorrhea is more frequently seen in

patients with cholestatic disease, e.g., primary biliary

cirrhosis (PBC) and primary sclerosing cholangitis

(PSC). The reduced absorption of fat results in

nausea, indigestion, and steatorrhea, with accom-

panying calcium and fat-soluble vitamin malabsorp-

tion. The patient’s nutrition status will obviously be

compromised if steatorrhea is profuse. However, stea-

torrhea varies from patient to patient.

0079The prescription of low-fat diets should only be

prescribed if the steatorrhea is socially unacceptable

for the patient or is causing muscle loss, or the patient

reports nausea and/or indigestion when consuming

fats. Blanket fat restrictions will compromise a pa-

tient’s intake of energy and make nutrition support

difficult. Therefore, fat restrictions should never be

applied to patients not experiencing any of the above

symptoms.

0080Malabsorption may also be caused or exacerbated

by concomitant inflammatory bowel disease. There is

a high prevalence of ulcerative colitis in patients

suffering from PSC, whereas celiac disease has been

associated with PBC patients. It is therefore import-

ant for bowel motions to be assessed carefully.

0081If fat restrictions are indicated, energy intake will

need to be manipulated and monitored. The level and

type of fat restriction required are extremely variable

from patient to patient. Increased use of carbohy-

drates and carbohydrate-only supplements is often

beneficial. There is also a vast range of fat-free oral

supplements. If energy requirements cannot be met

with increased carbohydrate alone, then medium-

chain triglyceride (MCT) emulsions and oils can be

utilized. MCTs are water-soluble and do not require

emulsification by bile salts. The emulsion can be

taken on its own at a maximum dose of 45 ml qds

or added to drinks such as milkshakes and low-fat

milk. The oil can be used in various recipes but has a

low smoking point, often making it unsuitable for

frying. If supplementary feeding is required, oral

and enteral feeds are available, containing MCT as

its predominant fat source.

0082Plasma levels of fat-soluble vitamins A, D, E, and

K should be routinely checked and supplementa-

tion given accordingly. Blanket supplementation

should not be encouraged, as excessive intake is

toxic.

0083Prevalence of osteoporosis is much higher in pa-

tients suffering from PSC and PBC. It is therefore

3610 LIVER/Nutritional Management of Liver and Biliary Disorders

advisable to use a calcium supplement with active

vitamin D.

0084 Patients suffering from celiac disease need further

adaptation to their diet to exclude gluten.

Liver Transplantation

Immediately Post-transplant

0085 Aggressive nutrition support immediately post-

transplant is essential to ensure quick and rapid

recovery. Initially, nasogastric feeding may not be

tolerated, as gastric stasis is common. In such in-

stances, nasojejunal feeding should be used. These

patients’ requirements have been estimated at 140%

BMR and protein up to 2 g kg

1

day

1

. Aggressive

nutrition support has been shown to reduce the pa-

tients’ ICU stay and time on the ventilator.

0086 Medication interaction Patients are placed on im-

munosuppressive drugs (Tacrolimus or Neoral), ster-

oids, and antibiotics. Immunosuppression drugs are

gradually reduced, and a minimal dose must be taken

daily for the rest of the patient’s life. The steroids are

used to reduce inflammation and are stopped within a

few months. The antibiotic therapy is prophylactic

and lasts for a few weeks only.

0087 Diet Once the patient is on the ward, elevated pro-

tein and energy requirements should continue to be

met. The patient’s appetite (usually) returns to normal

as a result of the steroids, the cessation of restrictive

diets, and a general feeling of well-being. Food-safety

advice is necessary for up to the first four months,

because of the initial high dose of immunosuppres-

sion medication. The patient should also be advised

to avoid grapefruit and grapefruit juice, as these have

been shown to interfere with the absorption of Tacro-

limus and neoral from the gut.

0088 Glucose intolerance and diabetes are also common

posttransplant. They may be short-lived until the pa-

tient stops prednisolone therapy. However, the inci-

dence of diabetes post liver transplantation is high

and thought to be related to immunosuppression

therapy. Hyperkalemia is also a common side-effect

seen with immunosuppression therapy but normally

resolves with a reduction in the dose. Low-dietary-

potassium advice may be required.

Long-term Post-transplant

0089 Unfortunately, up to 65% of transplant patients, at

one year post-transplant, become obese with hyper-

cholesterolemia and an increased risk of coronary

heart disease. This is more common in patients trans-

planted for chronic liver disease. Healthy eating

advice is therefore instigated once a normal BMI of

20–25 kgm

2

is achieved. The exact reason for

obesity is not known. However, it has been suggested

that the patient’s inactive lifestyle, increased appetite,

enjoyment of foods, and immunosuppression therapy

all play a role. Premorbid obesity has been found to

correlate with postransplant obesity. Therefore, such

patients should be encouraged to follow a healthy

eating and exercise plan as soon as possible post

transplantation.

0090Diabetes Diabetes in post liver transplant patients is

common, despite cessation of steroids from their ther-

apy. Once a patient achieves a good appetite and is

eating regularly, standard healthy eating diabetic

advice should be given.

See also: Amino Acids: Properties and Occurrence;

Diabetes Mellitus: Etiology; Energy: Intake and Energy

Requirements; Lactic Acid Bacteria; Malnutrition: The

Problem of Malnutrition; Malnutrition in Developed

Countries; Metabolic Rate; Protein: Requirements