Transcript Nutritional Management of Hepatic Encephalopathy

Nutritional Management of Hepatic patients
Presented by
Faten farid elsayed
Points will be covered
Background on Liver Dysfunction
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Review of liver physiology
Diseases of the liver
Acute hepatic failure
Chronic liver disease
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Historical Treatment Theories/Practice
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Protein Restriction & BCAA Supplementation
Goals of MNT
Let’s Take It From The Top
A Physiology Review
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Functions of the Liver:
A Brief Overview
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
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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
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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
The Urea Cycle
Aspartate Transaminase(AST)
Alanine Transaminase (ALT)
Liver Diseases
Classifications
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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
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
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 folds
Decreased( BCCA) and increased (Tryptophan, AAA and
sulphur containing AA
No elemination of AA in splanchnic area
Increased rate of conversion of glutamine to ammonia +alanine
More glutamine production in brain and skeletal muscle
No urea formation
Treatment of ALF
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Various measures in current treatment of ALF
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Strategies to lower ammonia production/absorption
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Nutritional management
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Protein restriction
BCAA supplementation
Medical management
Medications to counteract ammonia’s effect on brain cell
function
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Lactulose
Antibiotics
Devices to compensate for liver dysfunction
 Liver transplantation
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Proposed
Complex
Feedback
Mechanisms
In Treatment
Of HE
Nutrition requirement in ALF
Nutrition requirement in ALF
Patient with ALF have
glucose intolerance
Hyperammonia
Increased 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
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Historical treatment theories
 Protein
Restriction
 BCAA supplementation
Historical Treatment Theories:Protein Restriction
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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
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Lack of Valid Evidence
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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
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Objective: To test safety of normal-protein diets
Randomized, controlled trial in 20 cirrhotic patients
with HE
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10 patients subjected to protein restriction, followed by
progressive increments
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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
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Protein restriction??
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Results
 On
days 2 and 14:
 Similar
protein synthesis among both groups
 Protein breakdown higher in low-protein group
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Conclusion
 No
significant differences in course of hepatic
encephalopathy
 Greater protein breakdown in protein-restricted subjects
Protein and HE Considerations
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No valid clinical evidence supporting protein
restriction in pts with acute ALF
Protein intake < 40g/day contributes to malnutrition
and worsening ALF
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Increased endogenous protein breakdown
NH3
Susceptibiliy to infection increases under such
catabolic conditions
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BCAA Supplementation
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Effective or Not?
Branched Chain
Amino Acids (BCAA)
Valine
Leucine
Isoleucine
•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 Lglutamine 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
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Meta-Analysis of randomized-controlled trials on the treatment of HE with IV
or oral BCAA
Objective
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Review Criteria
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To evaluate the beneficial and harmful effects of BCAA or BCAA-enriched
interventions for patients with hepatic encepalopathy
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
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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
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Types of Interventions
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Experimental Group
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Control Group
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BCAA or BCAA-enriched solutions given in any mode, dose, or duration with or without
other nutritive sources
No nutritional support, placebo support, isocaloric support, isonitrogenous support, or
other interventions with a potential effect on HE (ie., lactulose)
Outcome Measures
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Primary
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Improvement of HE (number of patients improving from HE using definitions of individual
trials)
Secondary
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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
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Data Collection and Analysis
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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
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Eleven randomized trials (556 patients)
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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
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Compared to control regimens, BCAA significantly increased the number
of patients improving from HE at end of treatment
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Median 17 days (range 6 to 30 days)
RR 1.31, 95% CI 1.04 to 1.66, 9 trials
No evidence of an effect of BCAA on survival
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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:
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No convincing evidence that BCAA had a significant beneficial
effect on improvement of HE or survival in patients with HE
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Primary analysis showed a significant benefit of BCAA on HE,
but significant statistical heterogeneity was present
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Low methodological quality source of heterogeneity (=bias)
Benefits of BCAA on HE only observed when lower quality
studies included
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Small trials with short and most of poor quality
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??
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Grade III to IV hepatic encephalopathy
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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??
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Up to 1.6g/kg/day protein as tolerated
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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)
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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
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Inhibits normal blood flow
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Decrease in # functional hepatocytes
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Results in portal hypertension & ascites
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Portal systemic shunting
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Blood bypasses the liver via shunt, thus
bypassing detoxification
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Toxins remain in circulating blood
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Neurtoxic substances can precipitate
hepatic encephalopathy
Chronic liver disease —malnourished??
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Decreased Intake
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Decreased Absorption
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• Anorexia(altered tast sensation)
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• Inadequate bile flow
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• Early sensation of fullness (ascites)
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• Bacterial overgrowth
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• Ascites
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• Pancreatic insufficiency
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Iatrogenic Factors
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• unecessary dietary restrictions
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• Frequent hospitalizations
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• Frequent Paracentesis
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Metabolic Alterations
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• Diuresis (micronutrient losses)
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Elevated leptin
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• Lactulose therapy
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Increased cholecystokinin
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Elevated TNF-a
• Altered mental
status/encephalopathy
Metabolic change in chronic liver disease
energy
Hypermetabolic state
carbohydrate
metabolism
-Glucose intolerance in nearly 2/3 of patients with cirrhosis (1037% 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
Increased
Increased lipolysis and mobilization of lipid deposits
After meal:
Lipid oxidation n’t uniformly impaired and plsma clearance not
decrease so the patients can utilize fat
Essential 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 muscle
protein for fuel even during short-term fasting lead to muscle wasting
- Protein catabolism may lead to hyper ammonia
Stable cirrhotic patient:
Keep positive nitrogenous balance and preserve their lean body mass
from protein intake during oral feeding
Mineral - Zinc deficiency is common with cirrhosis.
and Decreased dietary intake of meats, increased urinary
vitamines excretion of zinc due to diuretic use, and increased zinc
needs have been suggested as causes . Zinc is essential
for the function of over 300 enzymes, including those
of 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
 ADEK
bile, failure to convert to active forms
supplementation
 Calcium + D supplementation
 Folic Acid Supplementation
 early supplement of thiamine before glucose in alcoholic
hepatitis
MNT in chronic Liver Disease
Calories
Most patients are malnourished so supplementing full calories
refeeding syndrome
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Malnourished
patients
Patients with
ascites
Begin with reduced caloric level for the first 2 -3
day
We calculate calories according to euvolemic weight to
prevent overestimated energy
Caloric requirement/kg of estimated euvolmic weight
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
 Bedtime

perioxidation, gluconeogenesis
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
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- 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 resistance
These 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
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Medical nutrition therapy is cornerstone in manging hepatic patients besides
other medical treatments
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