Undergrad Handout 2008

Nutritional Management of Liver Disease

Review the functions of the liverReview diseases of the liverMajor complications of liver diseaseNutritional features of end stage liver diseaseNutritional management of end stage liver diseaseNutritional response to hepatic transplantationNutritional 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 LiverStorage 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 lipidsCarbohydrate Storage of carbohydrate as glycogenGluconeogenesisGlycogenolysis

Role of the Liver in Nutrient MetabolismProteinSynthesis of serum proteins e.g. albumin Synthesis of blood clotting factorsFormation of urea from ammoniaOxidation of amino acidsDeamination or transamination of amino acids

Role of the Liver in Nutrient MetabolismFatHydrolysis of triglycerides, cholesterol and phospholipids to fatty acids and glycerol

Formation of lipoproteins

Ketogenesis

Role of the Liver in Nutrient MetabolismFat Fat storage

Cholesterol synthesis

Production of bile necessary for digestion of dietary fat

Role of the Liver in Nutrient MetabolismVitaminsSite 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

Role of the Liver in Nutrient Metabolism Storage site for fat soluble vitamins A, D, E, K, B12

MineralsStorage site for copper iron and zinc

Diseases of the LiverHepatitis 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 gainhepatitis 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 steatosisSteatohepatitis (NASH)Fibrosing steatohepatitisCirrhosis

Non Alcoholic Fatty Liver Disease (NAFLD)

Risk Factors include:OverweightObesityCentral Obesity

Non Alcoholic Fatty Liver Disease (NAFLD)Factors involved in the development of NAFLD:Lifestyle :Weight gainWeight lossReduced activityChildhood and adult obesityType 2 diabetes

Non Alcoholic Fatty Liver Disease (NAFLD)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 - SymptomsOften 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 - SymptomsMild to moderate elevation of the enzymes: aspartate amino transferase alanine amino transferase

Diagnosis confirmed on biopsy

CirrhosisRefers 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 diseasesDiseases 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 diseaseAlcohol is toxic to the liver

Caused by chronic alcohol abuse

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

Alcoholic liver diseaseCessation 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

Wilsons DiseaseCopper storage disease

May result in cirrhosis if untreated

First presentation often in adults who present with cirrhosis

Wilsons 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 tumoursOften occur in association with Hepatitis B or Hepatitis C

Occur independently

Include hepatocellular carcinomas, cholangiosarcoma (bile duct tumours)

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

CirrhosisCompensated i.e. well controlled orDecompensated i.e. symptomatic

Decompensated cirrhosisSymptoms of portal hypertension include:Ascites and/or peripheral oedemaJaundiceOesophageal and/or gastric varicesEncephalopathy Hepatorenal failureMalnutrition

AscitesRefers to the accumulation of fluid in the abdominal cavity

It contains protein, sodium and potassium

It is considered to be an active metabolic unit

JaundiceRefers 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

VaricesDistended/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

EncephalopathyImpaired 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 bleedingPoor compliance with lactulose (marketed as Duphalac) therapyNitrogen overloadFluid and electrolyte imbalanceMedicationsAcid-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, ataxiainappropriate 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 DiseaseEarly 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 regenerationFat restriction contraindicatedNausea/anorexiaConsider oral supplementation such as glucose polymers, fruit based high protein drinks, or high protein/ high energy drinks in the presence of nausea/anorexiaCaution against herbal remedies as some may be harmful and most have no scientific basis

Nutritional Features of End Stage Liver DiseaseLook malnourishedLow se protein levelsalbumin, prealbumin, transferrin, retinol binding protein, insulin like growth factor-1Vitamin deficienciesthiamine, vit A, D, E Mineral deficienciesZn, Mg, Cu, Ca

Nutritional Features of Liver DiseaseWeight 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 ESLDWeight?Weight history? Protein markers of nutritional status?Descriptive history of wasting?Skinfolds?Intake?Appetite?

Nutritional Assessment of patients with ESLDSGA for patients with liver disease (Hasse) AnthropometryFood historyNauseaAnorexiaTaste changesDiarrhoeaEarly satietyFunctional capacity

Grip strength

Malnutrition in End Stage Liver Disease

Changes in Macronutrient Metabolism:

Energy

Fat

Protein

Nutritional Management of End Stage Liver DiseaseEnergy Requirements:Patients with compensated cirrhosis do not appear to need modification of their energy intakesPatients 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

Nutritional Management of End Stage Liver DiseaseEnergyEnergy 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 groupIndirect calorimetry

Nutritional Management of End Stage Liver Disease

Glycogen storageReduced glycogen storage capacity

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

Nutritional Management of End Stage Liver DiseaseFatAltered fat synthesis

Lipids are oxidised as a preferential substrate

Increased lipolysis

Active mobilisation of lipid stores

Decompensated Liver DiseaseFat 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


ProteinProtein turnover in cirrhotic patients is normal or increasedStable cirrhotics have increased protein requirements Stable cirrhotic patients are capable of achieving positive nitrogen balance during aggressive nutritional support regime

Kondrup 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: 197-212Swart, 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


ProteinProtein 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


ProteinPatients 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 encephalopathy62 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

Nutritional Management of End Stage Liver Disease Restricting protein intake did not have any positive effect on the evolution of episodic hepatic encephalopathy

Nutritional Management of End Stage Liver DiseaseProteinProtein restriction is contra - indicated for patients with decompensated cirrhosis Recommended protein intake for cirrhotics is 1.0 1.5g protein/kg/dayDietary protein restriction does not appear to be of any benefit in episodic hepatic encephalopathy

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

Nutritional Management of End Stage Liver DiseaseAmino Acids in EncephalopathyPatients 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

Nutritional Management of End Stage Liver DiseaseAmino Acids in EncephalopathyBranched 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

Nutritional Management of End Stage Liver DiseaseAmino Acids in EncephalopathyThe 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.

Nutritional Management of End Stage Liver DiseaseAmino Acids in EncephalopathyMarchesini 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

Nutritional Management of End Stage Liver Disease16/34 patients in the BCAA group regained normal mental state compared with 9/30 in the casein treated group (p

Nutritional Management of End Stage Liver DiseaseLong-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

Nutritional Management of End Stage Liver DiseaseMethods: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)

Nutritional Management of End Stage Liver DiseaseMethods:All subjects were instructed to take 2 packets three times daily dissolved in 200ml water half an hour before mealsPatients were maintained on self selected diet. No new dietary restrictions were recommended or prescribedStandard therapies (albumin, diuretics, lactulose) were allowed but registered

Nutritional Management of End Stage Liver DiseaseResults:115 patients remained in the study59 patients were withdrawn for a variety reasons:DeathDeterioration in liver functionNon-compliance (palatability, nausea, gastrointestinal discomfort and diarrhoea)Psychiatric disease

Nutritional Management of End Stage Liver DiseaseResults: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 groupLength 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

Nutritional Management of End Stage Liver DiseaseResults:Improved triceps skinfold thickness in the BCAA groupImproved midarm fat area in the BCAA groupReduction in the prevalence and severity of ascites in the BCAA groupShift towards better scoring of health only in the BCAA groupM-DXT supplementation therapy did not require increase in insulin therapy

Nutritional Management of End Stage Liver DiseaseResults:Total bilirubin levels decreased in the BCAA group and increased in the M-DXT groupImprovement in the CTP score in the BCAA groupCTP was stable in the L-Alb group and M-DXT groupReduced 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

Nutritional Management of End Stage Liver Disease Current Criteria for use of Oral BCAA Supplementation at RPAH:chronic encephalopathyfrequent 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

Nutritional Management of End Stage Liver DiseaseEating PatternSwart 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

Nutritional Management of End Stage Liver DiseaseEating PatternA 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)

AscitesPatients 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

AscitesSodium 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

AscitesFluid 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

Dont measure: custards, ice cream

Oesophageal VaricesVarices can occur at any point along the GIT

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

Oesophageal VaricesFollowing an oesophageal bleed the patient will be nil by mouth

Varices will be banded

Oral intake recommenced when patients condition stabilises

Oesophageal VaricesWhen 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 DiseasePatients 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

Nutritional Management of End Stage Liver DiseaseAchieve 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

Nutritional Management of End Stage Liver DiseaseRestrict 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

Nutritional Management of End Stage Liver DiseaseConsider branched chain amino acid supplementation

Significant pre-bedtime snack

Nutritional Response to Hepatic Transplantation

Hepatotoxicity of Herbal RemediesHerbs 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 RemediesImportant 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 NAFLDTreatment centres around reducing insulin resistance Dietary intervention

Increased physical activity

Metformin

Nutritional Management of NAFLDWeight 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

Nutritional Management of NAFLDNormal 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

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

Nutritional Management of NAFLDSummaryThere is no quick fix and there are no gimmicks for the consumer Weight controlIncreased exercise/physical activityGood Diabetic controlManage lipid abnormalities

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Undergrad Handout 2008