Presented by

Faten farid elsayed

Nutritional Management of Hepatic patients

Points will be covered

Background on Liver Dysfunction◦ Review of liver physiology◦ Diseases of the liver

Acute hepatic failure Chronic liver disease

◦ Historical Treatment Theories/Practice Protein Restriction & BCAA Supplementation

◦ Goals of MNT

Let’s Take It From The Top

A Physiology Review

Functions of the Liver:A Brief Overview

Largest organ in body, integral to most metabolic functions of body, performing over 500 tasks

Only 10-20% of functioning liver is required to sustain life

Removal of liver will result in death within 24 hours

Functions of the Liver

Main functions include: Metabolism of CHO, protein, fat Storage/activation vitamins and minerals Formation/excretion of bile Steroid metabolism, detoxifier of drugs/alcohol Action as (bacteria) filter and fluid chamber Conversion of ammonia to urea

Gastrointestinal tract significant source of ammonia Generated from ingested protein substances that are

deaminated by colonic bacteria Ammonia enters circulation via portal vein Converted to urea by liver for excretion

Alanine Transaminase (ALT)

Aspartate Transaminase(AST) The Urea Cycle

Liver Diseases

Duration Acute vs Chronic

Pathophysiology Hepatocellular vs

Cholestasic Etiology

Viral Alcohol Toxin Autoimmune

Stage/Severity ESLD Cirrhosis

Viral hepatitis A, B, C, D, E (and G)

Fulminant hepatitis

Alcoholic liver disease

Non-alcoholic liver disease

Cholestatic liver disease

Hepatocellular carcinoma

Inherited disorders

Classifications

Progression of Liver Diseases

Metabolic change in acute liver failure

These patients with hepatic failure have metabolic response=

Failing liver +stress response of critical ill patient

Nutritional support may aid in regeneration or wait for transplantation

These patients with hepatic failure have metabolic response=

Failing liver +stress response of critical ill patient

Nutritional support may aid in regeneration or wait for transplantation

Metabolic change………..continued

Energy expenditure

Increased resting energy expenditure by 20 -30%

Glucose metabolism

1 -decrese insulin sensitivity as glucagon secretion increased

2 -glucagon not suppressed by glucose infusion

Lipid metabolism Decreased hepatic ketogenesis -- -- --low conc of free fatty acids and ketone

bodies However they tolerate intravenous lipid emlusion contain (MCT/LCT)

Plasma amino acids

Increased its level 3 to 4 foldsDecreased( BCCA) and increased (Tryptophan, AAA and sulphur containing AANo elemination of AA in splanchnic areaIncreased rate of conversion of glutamine to ammonia +alanineMore glutamine production in brain and skeletal muscleNo urea formation

Treatment of ALF

Various measures in current treatment of ALF Strategies to lower ammonia

production/absorption Nutritional management

Protein restriction BCAA supplementation

Medical management Medications to counteract ammonia’s effect on

brain cell function Lactulose Antibiotics

Devices to compensate for liver dysfunction Liver transplantation

ProposedComplex

Feedback Mechanisms In Treatment

Of HE

Nutrition requirement in ALF

Nutrition requirement in ALF

Patient with ALF have glucose intoleranceHyperammoniaIncreased REE

Caloric requirement

Malnourished patients: begin nutrition at reduced calorie levels

Substrate requirements

-Potien requirement-----discussed belowCarbohdrate and lipid to supply calories Minerals and vitamines should be supplied

Route of nutrition feeding

-oral feeding -if patient not tolerate oral; entral is

recommended to ensure adequate intake of calories

Nutritional Management of ALF Historical treatment theories

Protein Restriction BCAA supplementation

Historical Treatment Theories:Protein Restriction Studies in early 1950’s showed cirrhotic pts

given “nitrogenous substances” developed hepatic “precoma”

Led to introduction of protein restriction Began with 20-40g protein/day regardless body

weight Increased by 10g increments q3-5 days as

tolerated with clinical recovery Upper limit of 0.8-1.0 g/kg Was thought sufficient to achieve positive

nitrogen balance Lack of Valid Evidence

Efficacy of restriction never proven within controlled trial

Protein restriction??Normal Protein Diet for Episodic Hepatic

Encephalopathy Cordoba et al. J Hepatol 2004; 41: 38-43

Objective: To test safety of normal-protein diets

Randomized, controlled trial in 20 cirrhotic patients with HE 10 patients subjected to protein restriction,

followed by progressive increments No protein first 3 days, increasing q3days until 1.2g/kg

daily for last 2 days 10 patients followed normal protein diet (1.2g/kg) Both groups received equal calories

Protein restriction??

Results On days 2 and 14:

Similar protein synthesis among both groups Protein breakdown higher in low-protein group

Conclusion No significant differences in course of

hepatic encephalopathy Greater protein breakdown in protein-

restricted subjects

Protein and HE Considerations

No valid clinical evidence supporting protein restriction in pts with acute ALF

Protein intake < 40g/day contributes to malnutrition and worsening ALF Increased endogenous protein breakdown

NH3 Susceptibiliy to infection increases under

such catabolic conditions

BCAA Supplementation Effective or Not?

Branched Chain Amino Acids (BCAA)

ValineLeucineIsoleucine

•Important fuel sources for skeletal muscle during periods of metabolic stress•Metabolized in muscle & brain, not liver-promote protein synthesis-suppress protein catabolism-substrates for gluconeogenesis

Catabolized to L-alanine and L-glutamine in skeletal muscle

Branched-Chain Amino Acids For Hepatic Encephalopathy

Als-Nielsen B, Koretz RI, Kjaergard LL, Gluud C. The Cochrane

Database of Systematic Reviews, 2003, 1-55

Branched-Chain Amino Acids For Hepatic Encephalopathy

Meta-Analysis of randomized-controlled trials on the treatment of HE with IV or oral BCAA

Objective To evaluate the beneficial and harmful effects of BCAA or BCAA-

enriched interventions for patients with hepatic encepalopathy Review Criteria

All randomized trials included, irrespective of blinding, publication status, or language

Data from first period of crossover trials and unpublished trials included if methodology and data accessible

Participants Patients with HE in connection with acute or chronic liver

disease or FHF Patients of either gender, any age and ethnicity included

irrespective of etiology of liver disease or precipitating factors of HE

Branched-Chain Amino Acids For Hepatic Encephalopathy

Types of Interventions Experimental Group

BCAA or BCAA-enriched solutions given in any mode, dose, or duration with or without other nutritive sources

Control Group No nutritional support, placebo support, isocaloric support,

isonitrogenous support, or other interventions with a potential effect on HE (ie., lactulose)

Outcome Measures Primary

Improvement of HE (number of patients improving from HE using definitions of individual trials)

Secondary Time to improvement of HE (number of hours/days with HE from the

time of randomization to improvement) Survival (number of patients surviving at end of treatment and at

max f/up according to trial) Adverse events (number and types of events defined as any

untoward medical occurrence in a patient, not necessarily causal with treatment)

Branched-Chain Amino Acids For Hepatic Encephalopathy

Data Collection and Analysis Trial inclusion and data extraction made independently

by two reviewers Statistical heterogeneity tested using random effects and

fixed effect models Binary outcomes reported as risk ratios (RR) based on

random effects model

Branched-Chain Amino Acids For Hepatic Encephalopathy: Results

Eleven randomized trials (556 patients) Trial types: BCAA versus carbohydrates,

neomycin/lactulose, or isonitrogenous controls Median number of patients in each trial: 55 (range 22 to

75) Follow-up after treatment reported in 4 trials

Median 17 days (range 6 to 30 days) Compared to control regimens, BCAA significantly

increased the number of patients improving from HE at end of treatment RR 1.31, 95% CI 1.04 to 1.66, 9 trials

No evidence of an effect of BCAA on survival RR 1.06, 95% CI 0.98 to 1.14, 8 trials No adverse events (RR 0.97, 95% CI 0.41 to 2.31, 3 trials)

Authors' conclusions : No convincing evidence that BCAA had a

significant beneficial effect on improvement of HE or survival in patients with HE Small trials with short and most of poor quality

Primary analysis showed a significant benefit of BCAA on HE, but significant statistical heterogeneity was present Low methodological quality source of heterogeneity

(=bias) Benefits of BCAA on HE only observed when lower

quality studies included Effect size and “small study bias”

No significant association between dose or duration and the effect of BCAA

How Much Protein: That is the Question??

Grade III to IV hepatic encephalopathy Usually no oral nutrition Upon improvement, individual protein tolerance can be

titrated by gradually increasing oral protein intake every three to five days from a baseline of 40 g/day

Oral protein not to exceed 70 g/day if pt has hx of hepatic encephalopathy

Below 70 g/day rarely necessary, minimum intake should not be lower than 40 g/day to avoid negative nitrogen balance.

1.0g/kg/day protein, depending on degree of muscle wasting

BCAA-enriched solutions may benefit protein intolerant (<1g/kg)

How Much Protein: That is the Question??

Up to 1.6g/kg/day protein as tolerated Low-grade HE (minimal, I, II) should not be

contraindication to adequate protein supply

In patients intolerant of a daily intake of 1 g protein/kg, oral BCAA up to 0.25 g/kg may be beneficial to create best possible nitrogen balance BCAA’s do not exacerbate encephalopathy It should consider in patients with transjagular

intrahepatic port systemic shunt( high incidence for HE)

L-ornithine L-asprtate(LOLA) in ALF

L-Ornithine L-asprtate(LOLA) acts to stimulate the urea cycle and glutamine synthesis which are important mechanisms in ammonia detoxification, and by that it is considered an ammonia lowering treatment. Many clinical trials found that LOLA improved hepatic encephalopathy better than placebo.

Chronic Liver Disease

Algorithm content developed by John Anderson, PhD, and Sanford C. Garner, PhD, 2000. Updated by Jeanette M. Hasse and Laura E. Matarese, 2002.

Clinical manifestation of cirrhosis

Severe damage to structure & function of normal cells

Inhibits normal blood flow

Decrease in # functional hepatocytes

Results in portal hypertension & ascites

Portal systemic shunting

Blood bypasses the liver via shunt, thus bypassing detoxification

Toxins remain in circulating blood

Neurtoxic substances can precipitate hepatic encephalopathy

Chronic liver disease —malnourished??

Decreased Absorption

• Inadequate bile flow • Bacterial overgrowth • Pancreatic insufficiency Iatrogenic Factors

• unecessary dietary restrictions

• Frequent Paracentesis • Diuresis (micronutrient

losses) • Lactulose therapy

Decreased Intake

• Anorexia(altered tast sensation)

• Early sensation of fullness (ascites)

• Ascites • Altered mental

status/encephalopathy • Frequent hospitalizations Metabolic Alterations Elevated leptin Increased cholecystokinin Elevated TNF-a

Metabolic change in chronic liver disease

energy Hypermetabolic state

carbohydrate metabolism

-Glucose intolerance in nearly 2/3 of patients with cirrhosis (10-37% develop diabetes)- Occurs because of insulin resistance in peripheral tissues and decreased in insuline like growth factor.- Hyperinsulinemia, possibly because insulin production increased, hepatic clearance decreased- Fasting hypoglycemia occur after 12 hours fasting due decreased glycogen stores; patients may need small, frequent meals

-diminished hepatic and muscle glycogen stores

Fat metabolism

In fasting state:Plasma level of free fatty acids, glycerol and ketone body IncreasedIncreased lipolysis and mobilization of lipid depositsAfter meal:

Lipid oxidation n’t uniformly impaired and plsma clearance not decrease so the patients can utilize fatEssential and polysaturated FA decreased in cirrhotic patients

Metabolic change in chronic liver disease

protein

-Increase breakdown and decrease synthesis -Depleted glycogen stores utilize increased fat and

muscleprotein for fuel even during short-term fasting lead to muscle wasting

-Protein catabolism may lead to hyper ammoniaStable cirrhotic patient:Keep positive nitrogenous balance and preserve their lean body mass from protein intake during oral feeding

Mineral and

vitamines

-Zinc deficiency is common with cirrhosis.Decreased dietary intake of meats, increased urinary excretion of zinc due to diuretic use, and increased zincneeds have been suggested as causes . Zinc is essentialfor the function of over 300 enzymes, including thoseof the urea cycle.

-Fat soluble deficiency in patient with cholestatic jaundice -Water soluble vitamine deficiency in alcoholic cirrohosis

MNT in chronic Liver Disease

Poor Dietary Intake Due to poor appetite, early satiety with ascites

Small frequent meals- Aggressive oral supplementation Zinc supplementation

Nutrient Malabsorption Due to bile, failure to convert to active forms

ADEK supplementation Calcium + D supplementation Folic Acid Supplementation early supplement of thiamine before glucose in

alcoholic hepatitis

MNT in chronic Liver Disease

CaloriesMost patients are malnourished so

supplementing full calories refeeding syndrome

Caloric requirement/kg of estimated euvolmic weight

Malnourished patients

Begin with reduced caloric level for the first 2 -3 day

Patients with ascites

We calculate calories according to euvolemic weight to prevent overestimated energy

Refeeding risk 15 to 20 kcl/kg

Maintainance 25 to 30 kcl /kg

anabolism 30 to 35 cal /kg

MNT in in chronic Liver Disease

Abnormal Fuel Metabolism Increased perioxidation, gluconeogenesis

Bedtime meal to decrease it Protein Deficiency

protein catabolism, repeat paracentesis High protein snacks/supplements 1.2-1.5 gms/day

MNT in in chronic Liver Disease

Standard Guidelines IV with minerals 2gm Na restriction in presence of ascites Do not restrict fluid unless serum Na

<120mmol NGT used in pts awaiting transplant TPN should be considered only if

contraindication for enteral feeding

Treatment of assosciated steatorrhea Fat restricted when steatorrhea is present Medium-chain triglycerides (MCT) can replace some

of the fats. They contain only 8-12 carbons:changes their physical characteristics.

They are much more water soluble; can be absorbed across the small intestine wall into the blood stream.

Mainly, they are transported direct to the liver via the portal vein.

They do not bind to fatty acid-binding proteins, are not reesterified to triglycerides, and are not packaged in chylomicrons

Nutrition in liver transplanted patients

- initiate entral or oral within 12 to 24 hours post operatively

In early postoperative phase suffer from hyperglycemia:

----Diabetogenic potential of tacrolimus----Disturbed glucose metabolism and presence of insulin

resistanceThese patients have negative nitrogen balance up to 28

days post op so they need increase supplementation of protien and amino acids upto 1 to 1.5 g/kg/day with no need for branched chain AA.

Postoperative magnesium should be monitored.

conclusion

Medical nutrition therapy is cornerstone in manging hepatic patients besides other medical treatments

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