1. Nutritional Management of Hepatic patients
Presented by
Faten farid elsayed

2. 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

3. Let’s Take It From The Top
A Physiology Review

4. 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

5. 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
CHO metabolism: glycogenesis, glycogenolysis, gluconeogenesis
Protein metabolism: deamination and transamination, synthesis of serum protein, blood clotting protein, lipoprotein
Fat: converts fatty acids from diet and adipose tissue Acetyl-CoA, also synthesis of cholesterol and phospholipids
Storage: fat soluble vitamins, B12, and other minerals
Conversion of Vit. D to active form, carotenes to vit. A, vit. K to prothrombin

6. Aspartate Transaminase(AST)
The Urea Cycle
Alanine Transaminase (ALT)

7. Liver Diseases Classifications Viral hepatitis A, B, C, D, E (and G)
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

8. Progression of Liver Diseases

9. 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

10. Metabolic change………..continued
Increased resting energy expenditure by %
Energy expenditure
1- decrese insulin sensitivity as glucagon secretion increased
2- glucagon not suppressed by glucose infusion
Glucose metabolism
Decreased hepatic ketogenesis
low conc of free fatty acids and ketone bodies
However they tolerate intravenous lipid emlusion contain (MCT/LCT)
Lipid metabolism
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
Plasma amino acids

11. 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

12. Proposed Complex Feedback Mechanisms In Treatment Of HE

13. Nutrition requirement in ALF

14. Nutrition requirement in ALF
Patient with ALF have
glucose intolerance
Hyperammonia
Increased REE
Malnourished patients:
begin nutrition at reduced calorie levels
Caloric requirement
Potien requirement-----discussed below
Carbohdrate and lipid to supply calories
Minerals and vitamines should be supplied
Substrate requirements
-oral feeding
-if patient not tolerate oral; entral is recommended to
ensure adequate intake of calories
Route of nutrition feeding

15. Nutritional Management of ALF
Historical treatment theories
Protein Restriction
BCAA supplementation

16. 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 g/kg
Was thought sufficient to achieve positive nitrogen balance
Lack of Valid Evidence
Efficacy of restriction never proven within controlled trial

17. Normal Protein Diet for Episodic Hepatic Encephalopathy
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

18. Protein restriction?? Results Conclusion 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

19. 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

20. BCAA Supplementation
Effective or Not?

21. 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 L-glutamine in skeletal muscle

22. 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

23. 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

24. 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)

25. 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

26. 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)

27. 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

28. 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)

29. 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)

30. 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.

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

32. 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

33. 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

34. Metabolic change in chronic liver disease
Hypermetabolic state
energy
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
carbohydrate 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
Fat metabolism

35. Metabolic change in chronic liver disease
- 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
protein
- Zinc deficiency is common with cirrhosis.
Decreased dietary intake of meats, increased urinary
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
Mineral and vitamines

37. 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

38. MNT in chronic Liver Disease
Calories
Most patients are malnourished so supplementing full calories
refeeding syndrome
Caloric requirement/kg of estimated euvolmic weight
Begin with reduced caloric level for the first 2 -3 day
Malnourished patients
We calculate calories according to euvolemic weight to prevent overestimated energy
Patients with ascites
15 to 20 kcl/kg
Refeeding risk
25 to 30 kcl /kg
Maintainance
30 to 35 cal /kg
anabolism

39. 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
gms/day

40. 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

41. 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

42. 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 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.

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

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47. Thank you