Malnutrition is common in 50-90% of patients with liver cirrhosis and is an independent risk factor for poor clinical outcomes. The causes of malnutrition are multifactorial and include decreased oral intake due to anorexia and gastrointestinal symptoms, increased resting energy expenditure leading to hypermetabolism, impaired liver function causing metabolic alterations, and malabsorption of fats. Supplementation with branched chain amino acids can help correct imbalances in amino acid levels, improve outcomes such as survival rates, and prevent disease progression in advanced cirrhosis. Nutritional guidelines recommend patients with cirrhosis consume 25-40 kcal/kg/day and 1-1.5 g/kg/day of protein.

1. Protein-Energy
Malnutrition
The optimum BCAA for pharmaco-
nutritional solution…”

2. Malnutrition in Liver Cirrhosis
• Occurs in 50-90% of patients with liver cirrhosis
• Commonly undiagnosed due to liver disease
complications such as edema and ascites
• Independent risk factor for predicting clinical
outcomes
ES, et al. Middle east Journal of Digestive Diseases Vol 5 No 2, April 2013

3. Malnutrition in Liver Cirrhosis
• Associated with an increased risk of
morbidity/mortality, biochemical dysfunction,
compromised immune and respiratory functions,
decreased muscle mass, increased recovery time
and delayed wound healing
• Higher rates of refractory ascites, SBP, HRS, variceal
hemorrhage and post-transplant mortality in patients
with PCM
ES, et al. Middle east Journal of Digestive Diseases Vol 5 No 2, April 2013

4. Malnutrition is
present in 80%
of cirrhotics
Poor oral
intake
(anorexia, GI
symptoms, zinc
deficiency)
Increased
resting energy
expenditure
(REE)
“hypermetabolic
state”
Poor liver
synthetic
capacity
Malabsorption of
fats
(inadequate bile
production)
Kalaitzakis, et al. World J Gastro 2014
Cause of PEM in cirrhosis is
multifactorial

5. Pathogenesis of Protein Calorie
Malnutrition (PCM) in Liver Disease
• Multifactorial
• Changes that are known to affect nutrition status
include
1. Decreased intake
2. Metabolic alterations
3. Increased B-adrenergic activity
4. Malabsorption of fats due to inadequate
production of bile
ES, et al. Middle east Journal of Digestive Diseases Vol 5 No 2, April 2013

6. Decreased intake
• Anorexia secondary to changes in the liver’s control
of appetite
• GI symptoms such as early satiety, nausea,
vomiting, diarrhea, constipation, indigestion,
abdominal pain/distention, ascites and reflux
• Zinc deficieny that leads to anorexia and dysgeusia
or taste or smell changes or both
ES, et al. Middle east Journal of Digestive Diseases Vol 5 No 2, April 2013

7. Metabolic changes
• Early occurrence of ‘fasting state’ which uses
glycerol and amino acids and other
non-carbohydrate sources for the synthesis of
glucose
• Constant breakdown of fat and muscle
• Insulin resistance
ES, et al. Middle east Journal of Digestive Diseases Vol 5 No 2, April 2013

8. Increased B-adrenergic activity
• “Hypermetabolism” attributed to increased B-
adrenergic activity by 25% which leads to muscle
breakdown
• Increased plasma catecholamines and activation of
sympathetic nervous system (SNS) in cirrhosis
ES, et al. Middle east Journal of Digestive Diseases Vol 5 No 2, April 2013

9. Metabolic Alterations in Cirrhosis result
in Protein Depletion
Impaired hepatic glycogen synthesis & storage
AASLD guidelines on nutrition in HE: Hepatology 2013
ESPEN guidelines on nutrition in Liver disease: Nutrition 2006
Early & excessive lipolysis
Switch from glycogenolysis to gluconeogenesis
Loss of amino acids
Increase in protein requirements & ammonia production
Proteolysis to support splanchnic glucose
Response to fasting similar to
STARVED individuals for 2-3
days
ESPEN/AASLD = 35-40
kcal/kg/d
ESPEN/AASLD
1.2-1.5 G Protein/kg/d

10. Oxidation Ratio of Energy
Substrates
0
50%
100%
Liver Cirrhosis
(n=98)
Healthy Subjects
(n=20)
*** : p<0.001 Student’s t-test
25.7 Fats
Carbohydrates
***
***
58.332.0
49.5
13.5 Proteins16.0
Moriwaki,H et al.: Gastroenterology, 26 (5): 518-525, 1988

11. Moriwaki,H et al.: Gastroenterology, 26 (5): 518-525, 1988
REE: Resting Energy Expenditure
npRQ: Non-protein Respiratory Quotient BMR: Basal Metabolic Rate
:p<0.001***
: p<0.01**
Student’s t-test
REE/BMR npRQ
Liver
Cirrhosis
(n=98)
Healthy
Subjects
(n=20)
Liver
Cirrhosis
(n=98)
Healthy
Subjects
(n=20)
1.3
1.2
1.1
1.0
0
1.0
0.9
0.8
0.7
0
* * * * *
Energy Metabolism of Cirrhotics

12. Okita, K.: Nutrition-Assessment & Treatment, 8 (3), 317-323, 1991
Amount of Protein Intake (g/kg/day)0.5 1.0 1.5 2.0 2.5
NitrogenBalance(g/day)
6
4
2
0
-2
-4
-6
Amount of Protein needed to
maintain Nitrogen Balance
Normal
Cirrhosis
Cirrhosis + HCC
：1.0g/kg/day
：1.3g/kg/day
：1.5g/kg/day
Normal
Cirrhosis
Cirrhosis + HCC
Normal
Cirrhosis + HCC
Cirrhosis
Correlation Between Protein Intake
and Nitrogen Balance

13. Liver disease and BCAA
• Higher levels of aromatic amino acids (AAA) and
lower branched chain amino acids (BCAA) (reversal
of Fischer’s ratio)
• Supplementation of BCAA has been used to
normalize this ratio
• ASPEN recommends the use of BCAA for HE,
improvement of muscle cramps, immune function
and inhibition of hepatocarcinogenesis.

14. Inoue, Y. et. al. J. Iwate Med. Assoc., 40 (3), 351, 1988
Fischer’s Ratio 0 1.0 2.0 3.0 4.0
Normal (20)
Liver Cirrhosis (20)
Hepatocellular Carcinoma (10)
Liver Cirrhosis with HCC (30)
Fischer’s Ratio is the ratio of BCAA over AAA
Fischer’s ratio in Chronic liver
disease

15. 10
0
50
0
CumulativeSurvivalRates(%)
years10 32 4 5
1.8≦FR
FR＜1.0
1.0≦FR＜1.8
Yoshida, T. et.al. Gastroenterologica Japonica, Vol 24, No. 6, 1989
(Poverall<0.05 by the log rank test)
Plasma Fischer’s ratio (BCAA/AAA)
Determines Survival Rate in Cirrhotics

16. Matsuzaki, S. et. al., Hepatology. Vol.38 (5), 809,1999
50
100
0
0 1 2 3 4 5
BCAA (45 cases)
Control
(39 cases)
P<0.05
Years
Survivalrate(%)
Liver CirrhosisBCAA 59.4 ± 10.3 2.8 ± 0.4
Control 59.2 ± 10.7 2.9 ± 0.4
Age Albumin (g/ dL)
Effects of BCAA on Survival Rate
in Decompensated Liver Cirrhosis

17. Nutritional supplementation with branched-chain
amino acids in advanced cirrhosis: a double-blind,
randomized trial.
BACKGROUND & AIMS:
The role of oral supplementation with branched-chain amino acids (BCAA) in
advanced cirrhosis is far from settled.
A nutritional approach might prevent progressive liver failure and improve
nutritional parameters and quality of life.
Giulio Marchesini et al. Gastroenterology 2003;124;1792-1801

18. METHODS:
A multicenter, randomized study comparing 1-year nutritional supplementation
with BCAA against lactoalbumin or maltodextrins was performed in 174 patients
with advanced cirrhosis.
Primary outcomes were the prevention of a combined end point (death and
deterioration to exclusion criteria), the need for hospital admission, and the
duration of hospital stay.
Secondary outcomes were nutritional parameters, laboratory data and Child-Pugh
score, anorexia, health-related quality of life, and need for therapy.
Giulio Marchesini et al. Gastroenterology 2003;124;1792-1801
Nutritional supplementation with BCAAs in
advanced cirrhosis: a double-blind randomized
trial

19. RESULTS:
Treatment with BCAA significantly reduced the combined event rates compared
with lactoalbumin (odds ratio, 0.43; 95% confidence interval, 0.19-0.96; P = 0.039)
and nonsignificantly compared with maltodextrins (odds ratio, 0.51; 95%
confidence interval, 0.23-1.17; P = 0.108).
The average hospital admission rate was lower in the BCAA arm compared with
control treatments (P = 0.006 and P = 0.003, respectively). In patients who
remained in the study, nutritional parameters and liver function tests were, on
average, stable or improved during treatment with BCAA and the Child-Pugh
score decreased (P = 0.013). Also, anorexia and health-related quality of life (SF-
36 questionnaire) improved. Long-term compliance with BCAA was poor.
Giulio Marchesini et al. Gastroenterology 2003;124;1792-1801
Nutritional supplementation with BCAAs in
advanced cirrhosis: a double-blind randomized
trial

20. CONCLUSIONS:
In advanced cirrhosis, long-term nutritional supplementation with oral
BCAA is useful to prevent progressive hepatic failure and to improve
surrogate markers and perceived health status.
New formulas are needed to increase compliance.
Nutritional supplementation with BCAAs in
advanced cirrhosis: a double-blind randomized
trial
Giulio Marchesini et al. Gastroenterology 2003;124;1792-1801

21. Months
1.0
0.9
0.8
0.7
0.6
0.5
0 3 6 9 12 15
BCAA
M-DXT; P = 0.108
L-ALB; P = 0.038
CumulativeEvent-freeRates
Giulio Marchesini et al. Gastroenterology 2003;124;1792-1801
Cumulative event-free rate of
Aminoleban

22. Take Home Messages
• Malnutrition is very common among patients with
liver cirrhosis and is commonly undiagnosed.
• Malnutrition is an independent risk factor for
predicting clinical outcomes.
• Addition of a carbohydrate and protein-rich evening
snack with use of BCAA may help nitrogen balance
and improve survival.
• Longterm use of BCAA may improve survival and
prevent decompensation among cirrhotic patients.

23. Objectives of dietary intervention in
decompensated liver cirrhosis
1. Support residual liver function
2. Provide supportive treatment for ascites and liver
failure
3. Promote liver regeneration and healing
4. Prevent fat stasis and fatty stools
5. Correct nutritional deficiencies
6. Prevent or correct protein intolerance, by
supplementing with BCAA preparation
7. Provide adequate glucose for brain metabolism

24. Nutritional intervention in patients
with cirrhosis
• ASPEN and ESPEN Recommendations: 25-
40 kcal/kg/day based on dry weight; 1-1.5 g/kg
protein to prevent muscle catabolism
• Patients with acute episodes of HE: 0.6-0.8g/kg/day
until cause of HE is determined and eliminated
• Advised to consume small frequent meals
throughout the day
• Addition of a carbohydrate and protein-rich evening
snack (LES) may help nitrogen balance

25. ESPEN 2006 Guidelines on Enteral
Nutrition : Liver Cirrhosis
Subject Recommendations Grade
General Use simple bedsisde methods such as the Subjective
Global Assessment (SGA) or anthropometry to identify
at risk of nutrition.
Use phase angle or Body cell mass measured by
bioelectric impedance analysis to quantitate
undernutrition, despite some limitations in patients
with ascites.
Recommended energy intake: 35-40 kcal/kgBW/day
(147-168kJ/kgBW/day)
Recommended protein intake: 1.2-1.5g/kgBW/day
C
B
C
Application Use supplemental EN when patients cannot meet their
caloric requirements through oral food despite
individualized nutritional advise.
A

26. ESPEN 2006 Guidelines on Enteral
Nutrition : Liver Cirrhosis
Subject Recommendations Grade
Route If patients are not able to maintain adequate oral intake
from normal food, use
Oral nutritional supplements or
Tube feeding (even in the presence of esophageal
varices)
PEG placement is not recommended since it is
associated with a higher risk of complications
C
A
C
Type of
Formula
Generally recommended: Whole protein formula
Patients with ascites: consider more concentrated
high-energy formula
Patients with hepatic encephalopathy arising during
EN: use BCAA-enriched formula
BCAA can improve clinical outcomes in advanced
cirrhosis
C
C
A
B

28. AMINOLEBAN LIVAMIN
50 g sachet 4.15 g sachet
Oral Powder Oral Granules
Indication
Improvement of the nutritional state
of chronic hepatic insufficiency
patients including those with hepatic
encephalopathy.
Improvement of
hypoalbuminemia in patients with
decompensated hepatic cirrhosis
Aminoleban acts on
improving patients’ total
nutritional status
L-Isoleucine 1.9225 g L-Isoleucine 952 mg
Higher BCAA content of
Aminoleban
L-Leucine 2.037 g L-Leucine 1.904 g
High Fisher’s Ratio content
of Aminoleban (38) Vs
Livamin (0)
L-Valine 1.602 g L-Valine 1.144 g
Aromatic Amino Acids
Other Amino Acids
TOTAL Protein: 13.5 grams
Carbohydrate
Fats
Vitamins
Mineral
361.00/sachet 79.25/sachet
Proven efficacy made
affordable because of
ONEQUEST program
240.00/sachet (Compliance Pack)
237.75 (3 sachets need to equate
protein level of Amino)
Aminoleban have 3x more
protein than Livamin and
have necessary nutrients
Dosage TID TID Same
Preparation Constitute with water
To be taken with water , not to be
reconstituted with water or other
fluids
Can be mixed with Juice
for improve palatability
Registration Medical Food Drug
Does not require Rx when
purchased
VANTAGE POINT
Price
Contents
TOTAL Protein: 4 grams
Transformation of dietary
energy sources such as
carbohydrates, protein and
fats into cellular energy in
the form of ATP requires
micronutrients as co
enzymes and factors of
enzymatic reactions