Post on 26-Mar-2015
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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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