Nutritional Management of Liver Disease. Review the functions of the liver Review diseases of the liver Major complications of liver disease Nutritional.

Nutritional Management of Liver Disease

• Review the functions of the liver• Review diseases of the liver• Major complications of liver disease• Nutritional features of end stage liver disease• Nutritional management of end stage liver disease• Nutritional response to hepatic transplantation• Nutritional management of non alcoholic fatty liver

disease (NAFLD)• Hepatitis C

Functions of the Liver

Major role of the liver is the regulation of solutes in the blood that affect the functions of other organs for example: the brain, heart, muscle and kidneys

Strategically placed such that all blood passing from the small intestine must travel through the liver

Functions of the Liver

Storage and metabolism of macronutrients such as protein, carbohydrates and lipids

Metabolism of micronutrients – vitamins and minerals

Metabolism and excretion of drugs and toxins – endogenous and exogenous

Role of the Liver in Nutrient Metabolism

Storage and metabolism of macronutrients such as protein, carbohydrates and lipids

Carbohydrate Storage of carbohydrate as

glycogen Gluconeogenesis Glycogenolysis


Protein Synthesis of serum proteins e.g. albumin Synthesis of blood clotting factors Formation of urea from ammonia Oxidation of amino acids Deamination or transamination of amino

acids


Fat Hydrolysis of triglycerides, cholesterol and

phospholipids to fatty acids and glycerol

Formation of lipoproteins

Ketogenesis


Fat Fat storage

Cholesterol synthesis

Production of bile necessary for digestion of dietary fat


Vitamins Site of the enzymatic steps in the activation of

vitamins : thiamine

pyridoxine

folic acid

vitamin D(25 hydroxycholecalciferol)

Site of the synthesis of carrier proteins for vitamins: A, B12, E


Storage site for fat soluble vitamins A, D,

E, K, B12

Minerals

Storage site for copper iron and zinc

Diseases of the Liver

Hepatitis Inflammation of hepatocytes Reversible Precipitants include:

Viral infections such as hepatitis A, B, C

Drugs such as paracetamolSome herbal preparationsAlcohol

Fatty Liver:Infiltration of the liver by fatPossible causes include:

alcoholobesitytype 2 diabetes mellitushyperlipidaemia

sudden rapid weight gain

hepatitis CTPN

NAFLD (Non Alcoholic Fatty Liver Disease)

Resembles alcohol induced fatty liver

Occurs in people who do not abuse alcohol

Has the potential to progress to cirrhosis and liver failure

Non Alcoholic Fatty Liver Disease (NAFLD)

Simple steatosis Steatohepatitis (NASH) Fibrosing steatohepatitis Cirrhosis


Risk Factors include: Overweight Obesity Central Obesity


Factors involved in the development of NAFLD:

Lifestyle : Weight gain Weight loss Reduced activity

Childhood and adult obesity Type 2 diabetes


The major underlying risk factor for the development of NAFLD is insulin resistance

NAFLD (Non Alcoholic Fatty Liver Disease)

Prevalence of obesity in patients with NAFLD reported between 30% and 100%

Prevalence of type 2 diabetes in patients with NAFLD reported between 10% and 75%

Prevalence of hyperlipidaemia in patients with NAFLD reported between 20% and 92%

NAFLD - Symptoms

Often asymptomatic of liver disease at time of diagnosis

Fatigue or malaise and/or a feeling of fullness or discomfort on the right side of the abdomen

NAFLD - Symptoms

Mild to moderate elevation of the enzymes:

aspartate amino transferase

alanine amino transferase

Diagnosis confirmed on biopsy

Cirrhosis Refers to chronic scarring of the liver

Clearly delineated nodules form within the liver which contain connective tissue

This leads to a significant reduction in liver function

Fulminant Hepatic Failure Sudden massive necrosis of hepatocytes

The patient rapidly becomes encephalopathic and comatosed

Causes may be viral or a reaction to a drug such as paracetamol, sulphathiazone or some herbal remedies

Autoimmune liver diseases Diseases of the biliary tract and include

primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC)

PSC often occurs in association with ulcerative colitis

Serum cholesterol levels may be elevated and unresponsive to medication or dietary manipulation

Alcoholic liver disease

Alcohol is toxic to the liver

Caused by chronic alcohol abuse

All stages of the disease process – hepatitis, fatty liver fibrosis and cirrhosis

Alcoholic liver disease

Cessation of alcohol may result in recovery in the early stages of liver disease

Cessation of alcohol in patient with cirrhosis may result in an improvement in liver function and may also result in a slowing down of the disease progression

Wilson’s Disease

Copper storage disease

May result in cirrhosis if untreated

First presentation often in adults who present with cirrhosis

Wilson’s Disease

If detected in childhood management involves penecillamine which acts to bind Cu in the GIT

Value of dietary Cu restriction debatable in children; of no value in adults in the presence of cirrhosis

Hepatic tumours Often occur in association with Hepatitis B

or Hepatitis C

Occur independently

Include hepatocellular carcinomas, cholangiosarcoma (bile duct tumours)

Portal Hypertension

Occurs as a result of fibrous infiltration of the liver which in turn causes increased pressure in the portal vein

This pressure continues back through the system to the abdominal capillaries which then leak serous fluid into the abdominal cavity due to this increased pressure and low serum albumin levels

Portal Hypertension

Surgical interventions may be undertaken to alleviate this pressure (TIPSS). There are risks associated with these procedures – infection, failed shunts, encephalopathy

Cirrhosis

Compensated i.e. well controlled

or Decompensated i.e. symptomatic

Decompensated cirrhosis

Symptoms of portal hypertension include: Ascites and/or peripheral oedema Jaundice Oesophageal and/or gastric varices Encephalopathy Hepatorenal failure Malnutrition

Ascites Refers to the accumulation of fluid in the

abdominal cavity

It contains protein, sodium and potassium

It is considered to be an active metabolic unit

Jaundice Refers to the yellow colour seen in

patients with liver disease

It is caused by high circulating levels of bilirubin

Severe itching may be present. May be alleviated by Questran/cholestyramine or by phenergan

Varices Distended/engorged veins that can occur at

any point in the venous system of the GIT

May bleed readily as patients with end stage liver disease (ESLD) have poor coagulation secondary to impaired synthesis of clotting factors

Encephalopathy Impaired mental state that results in impaired

mentation and coordination

May result in coma

Believed to be caused by increases in plasma ammonia and other nitrogenous waste products

These toxins cross the blood brain barrier and interfere with neuromuscular function and behaviour

Precipitants of encephalopathy include:

Peritoneal infection (subacute bacterial peritonitis – SBP)

GIT bleeding Poor compliance with lactulose (marketed

as Duphalac) therapy Nitrogen overload Fluid and electrolyte imbalance Medications Acid-base imbalance

There are four classifications of encephalopathy:

Grade1. foetor, impaired coordination, tremor, altered handwriting, reduced attention

span, mild confusion, mood swings and altered sleep

pattern

Grade 2. asterixis (impaired ability to draw a star), slurred speech, ataxia

inappropriate behaviour, lethargy, impaired memory and mild disorientation

Classifications of encephalopathy cont…

Grade3. bizarre behaviour, confusion, moderate to severe

disorientation, uncharacteristic anger, paranoia, somnolence, stupor and muscle rigidity

Grade 4. comatosed, dilated pupils

Nutritional Management of Liver Disease

Early Stages of Liver Disease: No specific dietary management

Healthy diet according to healthy eating guidelines

Beware of miracle cures

Acute Hepatitis:

High protein/high energy intake required to promote hepatocyte regeneration

• Fat restriction contraindicated• Nausea/anorexia• Consider oral supplementation such as

glucose polymers, fruit based high protein drinks, or high protein/ high energy drinks in the presence of nausea/anorexia

Caution against herbal remedies as some may be harmful and most have no scientific basis

Nutritional Features of End Stage Liver Disease

Look malnourished Low se protein levels

albumin, prealbumin, transferrin, retinol binding protein, insulin like growth factor-1

Vitamin deficienciesthiamine, vit A, D, E

Mineral deficienciesZn, Mg, Cu, Ca

Nutritional Features of Liver Disease

Weight and BMI do not reflect true nutritional status (ascites and/or oedema)

Oral intakes are not necessarily poor

Exhibit features of protein energy malnutrition

Nutritional Assessment of patients with ESLD

Weight? Weight history? Protein markers of nutritional status? Descriptive history of wasting? Skinfolds? Intake? Appetite?

Nutritional Assessment of patients with ESLD

SGA for patients with liver disease (Hasse) Anthropometry Food history Nausea Anorexia Taste changes Diarrhoea Early satiety Functional capacity

Grip strength

Malnutrition in End Stage Liver Disease

Changes in Macronutrient Metabolism:

Energy

Fat

Protein

Nutritional Management of End Stage Liver Disease

Energy Requirements: Patients with compensated cirrhosis do not

appear to need modification of their energy intakes

Patients with decompensated liver disease require 35 – 40 non protein kcals/kg/day*

Ascites is a viable metabolic unit

*Plauth M, Merlim, Kondrup J, Weimann A, Ferenci P, Muller MJ.ESPEN Guidelines for Nutrition in Liver Disease and Transplantation. Clinical Nutrition 1997; 16: 43-55


Energy Energy expenditure: currently there are no

metabolic equations which are able to estimate accurately the energy requirements of the patient with ESLD.

Harris-Benedict, Schofields and Muller all underestimate the energy requirements of this group

Indirect calorimetry


Glycogen storage Reduced glycogen storage capacity

Unable to tolerate periods of prolonged fasting – increased protein breakdown in periods of prolonged fasting


Fat Altered fat synthesis

Lipids are oxidised as a preferential substrate

Increased lipolysis

Active mobilisation of lipid stores

Decompensated Liver Disease

Fat restriction contraindicated in most patients

Symptoms of fat intolerance such as steatorrhoea, abdominal pain or nausea following a high fat intake are rare. If present fat modification may be necessary


Protein Protein turnover in cirrhotic patients is normal or

increased Stable cirrhotics have increased protein

requirements¹ ²׳ Stable cirrhotic patients are capable of achieving

positive nitrogen balance during aggressive nutritional support regime¹ ²׳

¹Kondrup J, Neilsen K et al. Effect of long term refeeding on protein metabolism in patients with cirrhosis of the liver. Br J Nutr 1997; 77: 197-212

²Swart, GR et all. Minimal protein requirements in liver cirrhosis determined by nitrogen balance measurements at three levels of protein intake. Clin Nutr 1989; 8: 329-336


Protein Protein turnover in cirrhotic patients is normal or

increased Stable cirrhotics have increased protein

requirements¹ ²׳ Stable cirrhotic patients are capable of achieving

positive nitrogen balance during aggressive nutritional support regime¹ ²׳

¹Kondrup J, Neilsen K et al. Effect of long term refeeding on protein metabolism in patients with cirrhosis of the liver. Br J Nutr 1997; 77: 197-212

²Swart, GR et all. Minimal protein requirements in liver cirrhosis determined by nitrogen balance measurements at three levels of protein intake. Clin Nutr 1989; 8: 329-336


Protein Protein refeeding showed a 30% increase

in protein synthesis*

Protein refeeding did not show a significant increase in protein degradation*

*Kondrup J, Neilsen, K,and Anders J. Effect of long term refeeding on protein metabolism in patients with cirrhosis of the liver. Br J Nutrition (1997), 77, 197-212


Protein Patients with cirrhosis have been shown to

have high protein requirements to maintain positive nitrogen balance*

*Konrup J, Nielsen K, Juul A. Effect of long-term refeeding on protein metabolism in patients with cirrhosis of the liver. Br. J. Nutr. 1997; 77: 197-212


Protein The protein restricted diets used

traditionally have probably arisen historically from the response to a dietary protein load seen in cirrhotic patients who have some form of portocaval shunt surgery


Protein requirements in episodic hepatic encephalopathy

62 patients with acute encephalopathy assessed – 32 excluded

30 patients randomised into two groups

All patients received lactulose enema and then identical oral neomycin dosage

Cordoba J, Lopez-Hellin J et al. Normal protein diet for episodic hepatic encephalopathy: results of a randomised study. J of Hepatology 41 2004) 38-43


20 patients completed study

5 patients in each arm dropped out – 4 deaths in each. Group A: additional variceal bleed; group B: additional voluntary abandon


2 groups – 15 in each group

14 days

Group A: 0g protein/day for 3 days. Protein increased incrementally to 1.2g protein/kg/day

Group B: 1.2g protein/kg/day

Protein synthesis and breakdown studied at day 2 and day 14


Day 2: Increased protein breakdown in protein

restricted group

No statistically significant difference in protein synthesis



Restricting protein intake did not have any positive effect on the evolution of episodic hepatic encephalopathy


Protein Protein restriction is contra - indicated for

patients with decompensated cirrhosis Recommended protein intake for cirrhotics

is 1.0 – 1.5g protein/kg/day¹ Dietary protein restriction does not appear

to be of any benefit in episodic hepatic encephalopathy²

¹Plauth M, Merlim, Kondrup J, Weimann A, Ferenci P, Muller MJ.ESPEN Guidelines for nutrition in Liver Disease and Transplantation. Clinical Nutrition 1997; 16: 43-55²

²Cordoba J, Lopez-Hellin J et al. Normal protein diet for episodic hepatic encephalopathy: results of a randomised study. J of Hepatology 41 2004) 38-43


Does the type of protein matter?


Amino Acids in Encephalopathy Patients with advanced liver disease have an

altered ratio of branched chain amino (leucine valine, isoleucine) acids to aromatic amino acids (phenylalanine, tyrosine)

Aromatic amino acids are catabolised in the liver and their metabolism is impaired in cirrhosis resulting in an increase in circulating levels of AAAs


Amino Acids in Encephalopathy Branched chain amino acids (BCAA) are

metabolised predominantly in the skeletal muscle and fat

Plasma BCAA levels fall due to their utilisation as an energy substrate and a substrate in gluconeogenesis


Amino Acids in Encephalopathy The alteration in the ratio of BCAA:AAA

has been proposed as an aetiological factor in the development of encephalopathy*

*Fischer JE, Rosen HM, Ebeid AM et al. The effect of normalisation of plasma amino acids on hepatic encephalopathy in man. Surgery. 1976 Jul. 80 (1): 77-91.


Amino Acids in Encephalopathy Marchesini et al carried out a multicentre

double blind randomised trial in which BCAA supplementation was compared with an isocaloric casein supplementation in 64 patients with encephalopathy*

*G Marchesini, FS Dioguardi, GP Bianchi et al. Long- term oral branched chain amino acid treatment in chronic hepatic encephalopathy. J of Hepatol, 1990; 11:92-101


16/34 patients in the BCAA group regained normal mental state compared with 9/30 in the casein treated group (p<0.05)

After 6 months on BCAA treatment nitrogen balance improved and was suggestive of decreased nitrogen catabolism in the BCAA treated group

G Marchesini, FS Dioguardi, GP Bianchi et al. Long- term oral branched chain amino acid treatment in chronic hepatic encephalopathy. J of Hepatol, 1990; 11:92-101


Long-term oral BCAA supplementation(6 months) resulted in an increase in body weight

G Marchesini, FS Dioguardi, GP Bianchi et al. Long- term oral branched chain amino acid treatment in chronic hepatic encephalopathy. J of Hepatol, 1990; 11:92-101


15 centres over up to 15.5 months* 174 patients with Childs B or C cirrhosis

*Marchesini G, Bianchi G, Merli M et al. Nutritional supplementation with branched chain amino acids in advanced cirrhosis: a double blind randomised trial.

Gastroenterology 2003;124:1792-1801


Methods: Three types of nutritional supplements.

Each 10g package supplied: 14.4g BCAA/day (leucine, isoleucine, valine

and saccharose providing 37.5 kcal) 2.1g lacto-albumin/day (lacto-albumin,

saccharose and mannitol providing 33.6 kcal) 2.4g maltodextrose/day (maltodextrose,

saccharose providing 34.9 kcal)


Methods: All subjects were instructed to take 2

packets three times daily dissolved in 200ml water half an hour before meals

Patients were maintained on self selected diet. No new dietary restrictions were recommended or prescribed

Standard therapies (albumin, diuretics, lactulose) were allowed but registered


Results: 115 patients remained in the study 59 patients were withdrawn for a variety

reasons:• Death• Deterioration in liver function• Non-compliance (palatability, nausea,

gastrointestinal discomfort and diarrhoea)• Psychiatric disease


Results: Patients treated with BCAAs were admitted to

hospital less frequently:195 days in BCAA group; 327days in L-ALB group and 520days in M-DXT group

Length of stay varied within the treated groups: 0-24 days in BCAA group 0-31 days in the L-ALB group 0-77 days in the M-DXT group


Results: Improved triceps skinfold thickness in the BCAA

group Improved midarm fat area in the BCAA group Reduction in the prevalence and severity of

ascites in the BCAA group Shift towards better scoring of health only in the

BCAA group M-DXT supplementation therapy did not require

increase in insulin therapy


Results: Total bilirubin levels decreased in the BCAA

group and increased in the M-DXT group Improvement in the CTP score in the BCAA

group CTP was stable in the L-Alb group and M-DXT

group Reduced prevalence of anorexia in the BCAA

group


To summarise: There are benefits to routinely supplement

patients with advanced cirrhosis with branched chain amino acids

Patient compliance


Current Criteria for use of Oral BCAA Supplementation at RPAH:

chronic encephalopathy frequent hospital admissions due to

encephalopathysevere depletion of fat and muscle

storeselevated blood sugar levels


Does the timing or frequency of meals of meals matter?


• Reduced glycogen storage capacity


Eating Pattern Swart and Zillikens demonstrated that

spreading food intake and inclusion of a late evening meal significantly improved nitrogen balance in cirrhotics*

*Swart G, Zillikens M. Effect of a late evening meal on nitrogen balance in patients with cirrhosis of the liver Med J 1989;299: 1202-3


Eating Pattern A modified eating pattern should be

recommended to all patients with ESLD.

This would include eating at regular intervals – perhaps 5-7 small HP/HE meals/snacks per day

Include a pre-bedtime HP/HE snack to provide substrate for the liver to work with during sleep (supplements)

Ascites Patients with ascites usually have a high total

body sodium but often have a low se sodium

Generally have a poor intake secondary to abdominal distension

Early Satiety

Delayed gastric emptying

Frequent snacking important to achieve high energy intake

Ascites

Sodium restricted diet. Most common restriction is a no added salt diet which can range between 50Mm Na and 100Mm Na

Diuretics. Most commonly used are Lasix and Aldactone.

Salt substitutes contraindicated due to potassium sparing effect of aldactone

Ascites

Fluid restriction

Moderate (1500ml )to severe (≤ 800ml)

≤800ml used to treat intractable ascites unresponsive to diuretic therapy or when diuretic therapy no longer possible due to compromised renal function

• Don’t measure: custards, ice cream

Oesophageal Varices

Varices can occur at any point along the GIT

Oesophageal varices may bleed easily and bleeding further compromises the patient's nutritional status

Oesophageal Varices

Varices can occur at any point along the GIT

Oesophageal varices may bleed easily and bleeding further compromises the patient's nutritional status

Oesophageal Varices

Following an oesophageal bleed the patient will be nil by mouth

Varices will be banded

Oral intake recommenced when patient’s condition stabilises

Oesophageal Varices

When allowed to eat patients should be advise to:

Eat carefully and avoid large bolus of food which might dislodge a clot

Avoid over distension of the stomach which might lead to regurgitation or vomiting

Avoid foods with sharp bones that might be accidentally swallowed

Diabetes in Liver Disease

Patients with ESLD may present with impaired glucose tolerance. This may be due to a number of factors: Depleted hepatic glycogen stores

Impaired glucose tolerance

Hyperinsulinaemia

Insulin resistance

Diabetes in Liver Disease

Management involves diabetic education without restriction of energy intake

Insulin therapy

BCAA supplementation has been shown to facilitate control of blood sugar levels in patients with ESLD


Achieve and maintain high energy intake(35-40 non protein kcal/kg/day)

Achieve and maintain a high protein intake(1.0-1.5g/kg/day)

Avoid unnecessary fat restriction

Encourage frequent snacking


Restrict dietary sodium intake in the presence of ascites and/or oedema

Restrict fluid intake to assist in the management of ascites/oedema associated with hyponatraemia


Consider branched chain amino acid supplementation

Significant pre-bedtime snack

Nutritional Response to Hepatic Transplantation

Hepatotoxicity of Herbal Remedies

Herbs are potent medicines

The community is increasingly seeking out alternative or “natural” therapies

Patients with hepatitis C frequently seek out alternative therapies

Hepatotoxicity of Herbal Remedies

Important to be aware of the possible harmful effects of herbs

Some herbs are hepatotoxic and patients with known liver disease should avoid using them

Nutritional Management of NAFLD

Treatment centres around reducing insulin resistance Dietary intervention

Increased physical activity

Metformin


Weight loss strategies in presence of overweight/obesity. Weight loss results in improved lipid and carbohydrate metabolism.

Weight loss must be slow. Rapid weight loss results in worsening liver function tests and hepatomegaly

Rapid weight loss may promote or worsen NAFLD, NASH and may result in liver failure


• Normal weight subjects: dietary and pharmacological treatment of altered lipid and /or carbohydrate metabolism

• In overweight individuals with elevated aminotransferase levels weight loss of 10% or more corrects aminotransferase levels and decreases hepatomegaly


Modification in lifestyle which involves weight reduction and regular exercise are the mainstay of treatment and prevention of NAFLD


SummaryThere is no quick fix and there are no gimmicks for the consumer – Weight control– Increased exercise/physical activity– Good Diabetic control– Manage lipid abnormalities

Nutritional Management of Liver Disease. Review the functions of the liver Review diseases of the liver Major complications of liver disease Nutritional.

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