The document discusses liver disease and nutrition. It begins by reviewing the functions of the liver and various liver diseases. It then discusses nutritional features of end-stage liver disease and nutritional assessment and management guidelines. Specific topics covered include neurological symptoms associated with liver disease, nutritional assessment tools for patients with end-stage liver disease, daily energy expenditure calculation methods, progression of liver disease, and ESPEN guidelines on enteral and parenteral nutrition for various liver diseases.

1. LIVER DISEASE AND
NUTRITION

2. • Review the functions of the liver
• Review diseases of the liver
• Understanding neuro-psychological
symptoms associated with liver disease
• Nutritional features of end stage liver
disease
• Nutritional assement of end stage liver
disease
• Nutritional management –ESPEN
GUIDELINES IN LIVER DISEASE

3. Functions of the Liver:
• Largest organ in body, integral to most
metabolic functions of body,
• Only 10-20% of functioning liver is
required to sustain life
• Removal of liver will result in death within
24 hours

4. • Main functions include:
– Metabolism of CARBOHYDRATE, 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

5. (L)UREA CYCLE—TRANSAMINASE IN LIVER

6. REVIEW OF DISEASE OF LIVER
CLASSIFICATION.
• Duration
– Acute vs Chronic
• Pathophysiology
– Hepatocellular vs Cholestasic
• Etiology
– Viral
– Alcohol
– Toxin
– Autoimmune
• Stage/Severity
– ESLD
– Cirrhosis

7.  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 DISEASE

9. Understanding neuro-psychological symptoms
associated with liver disease
All neurological and psychological symptoms in patients with liver
disease that cannot be explained by presence of other
pathologies
• Brain and nervous system damage secondary to severe
liver dysfunction (most often chronic disease) resulting
from failure of liver to remove toxins
• Multifactorial pathogenesis with exact cause unknown
• Symptoms vary from nearly undetectable, to coma with
decerebration
– Characterized by various neurologic symptoms
• Cognitive impairment
• Neuromuscular disturbance
• Altered consciousness
• Reversible syndrome

10. Pathogenesis Theories
• Endogenous Neurotoxins
– Ammonia
– Mercaptans
– Phenols
• Increased Permeability of Blood-Brain Barrier
• Change in Neurotransmitters and Receptors
– GABA
– Altered BCAA/AAA ratio
• Other
– Zinc defficiency

11. Neurotoxic Action of Ammonia
• Readily crosses blood-brain barrier
• Increased NH3 = increased glutamate
– α-ketoglutarate+NH3+NADH→glutamate+NAD
– glutamate+NH3+ATP→glutamine+ADP+Pi
• As a-ketoglutarate is depleted TCA cycle activity halted
• Increased glutamine formation depletes glutamate stores
which are needed by neural tissue
– Irrepairable cell damage and neural cell death ensue.
– In liver disease, conversion of ammonia to urea and
glutamine can be reduced up to 80%

12. False Neurotransmitter Hypothesis
• Liver cirrhosis characterized by altered
amino acid metabolism
• Increased Aromatic Amino Acids in plasma and
influx in brain
• Decrease in plasma Branched Chain Amino Acids
• Share a common carrier at blood-brain barrier
• DECREASE BCAAs in blood may result in
INCREASE AAA transport to brain

13. • AAA are precursors to neurotransmitters
and elevated levels result in shunting to
secondary pathways

14. Change In Neurotransmitters and Receptors
• BRANCH CHAIN AMINOACID.
• Fischer and colleagues, published their
‘‘unifiedhypothesis on the pathogenesis of
HE’’ based on the observation that during
hepatic failure, plasma levels of BCAA
decreased and the AAA increased, DUE
TO increased BCAA catabolism in muscle
and decreased AAA breakdown in the
failing liver.

15. • A reduction in the insulin/glucagon ratio
was hypothesized to play a key role in
disturbing the balance between anabolism
and catabolism.
• Give rise to a decrease in the BCAA/AAA
ratio, which was called the Fischer-ratio
(BCAA/AAA ratio).

16. The increase in plasma AAA incombination
with an increased blood brain barrier
permeability for neutral amino acids has
been suggested to contribute to an
increased influx of AAA in the brain,
because they compete for the same
transporter (large neutral amino acid
transporter). This, inturn, would lead to
imbalances in neurotransmitter synthesis
and accumulation of falsneurotransmitters,
such as octopamine in thebrain, which
may contribute to HE

17. • hyperammonemia during liverfailure, ammonia is
detoxified by alternative pathways, the most
important of which, although essentially
temporary, is the formation of glutamine from
ammonia and glutamate maInly in muscle &
brain.
• In muscle BCAA transaminate with a-
ketoglutarate in the BCAA transferasereactions ,
yielding glutamate, explaining why
hyperammonemia may contribute to low plasma
BCAA

18. • coupling of ammonia to glutamate in the
glutaminsynthetase reaction as an alternative
ammonia detoxification route,
• glutamine is exported from muscle and
brain.The increased cerebral release of
glutamine in this hypothesis was thought to
facilitate the rapid exchange of glutamine for
neutral amino acids, notably the AAA, by the
large neutral amino acid carrier- This increased
influx of AAA in the brain would raise the
availability of precursors for neutrotransmitters.

19. • BCAA levels are crucially determined by
nutritional factors, whereas AAA levels
appear to depend much more upon intact
hepatic metabolism.

20. Increase Permeability of Blood-
Brain Barrier
• Astrocyte (glial cell) volume is controlled by
intracellular organic osmolyte
• Organic osmolyte is glutamine.
• glutamine levels in the brain result in volume
of fluid within astrocytes resulting in cerebral
edema (enlarged glial cells)
• Neurological impairment
– N=Normal Astrocytes
– A=Alzheimer type II astrocytes
– Pale, enlarged nuclei
– characterisic of HE

21. Nutritional Assessment of
patients with ESLD
 Weight?
 Weight history?
 Protein markers of nutritional status?
 Descriptive history of wasting?
 Skinfolds?
 Intake?
 Appetite?

22. Assement…
SGA for patients with liver disease ..
 Anthropometry
 Food history
 Nausea
 Anorexia
 Taste changes
 Diarrhoea
 Early satiety
 Functional capacity
 Grip strength

23. Daily energy expenditure
1) predictive equation;-harris benedict
equation( based on sex,ideal body wt,
height).
• Men: BMR = 66 + ( 13.7 x wt,kg ) + ( 5 x ht inch ) - ( 6.7
x age in year )
• Women: BMR = 655 + ( 9.6 x wt,kg ) + ( 1.8 x ht inch )
- ( 4.7 x age in years )

24. • BEE(KCAL/DAY)- 25 x WT IN KG
• To allow the thermal effect of food intake
the BEE multiplied by 1.2 to derive the
resting energy expenditure-is in resting
tate but not on fasted state.
• In hypermetabolic condition –
• Mild stress-BEEx1.2
• Mod stress-BEEx1.4
• Severe stress –BEEx1.6

25. • 2) indirect calorimetry.
It is impossibel to mesure metabolic heat
production in clinical practise, the
metabolic energy expenditure is mesured
indirectly by mesuring whole body vo2 and
vco2,technique called indirect calorimetry.

26. • ESPEN Guidelines on Enteral Nutrition:
Liver disease

27. ;NUTRION IN ALCOHOLIC HEPATITIS
subject recommendation grade
general Use simple bedside methods such as the
SubjectiveGlobal Assessment (SGA) or anthropometry
to identify patients at risk of undernutrition.
Recommended energy intake: 35–40 kcal/kg BW/d
Recommended protein intake: 1.2–1.5 g/kgBW/d
C
c
c
application Use supplementary enteral nutrition when patients
cannot meet their caloric requirements through
normal food.
In general, oral nutritional supplements are
recommended.
A

28. subject recommendation gerad
route Use tube feeding if patients are not able to maintain
adequate oral intake (even when oesophageal
varices are present)
PEG placement is associated with a higher risk of
complications and is not recommended
A
C
Type of
formula
Whole protein formulae are generally
Recommended.
Consider using more concentrated high-energy
formulae in patients with ascites.
Use BCAA-enriched formulae in patients with
hepatic encephalopathy arising during enteral
nutrition.
C
C
A

29. nutrition in liver cirrhosis
subject recommendation grade
General Use simple bedside methods such as the Subjective
Global Assessment (SGA) or anthropometry to
identify patients at risk of undernutrition.
Recommended energy intake: 35–40 kcal/kgBW/d
Recommended protein intake: 1.2–1.5 g/kgBW/d
C
C
C
application Use supplementary enteral nutrition when patients
cannot meet their caloric requirements through
normal food.
In general, oral nutritional supplements are
recommended.
A
A

30. route Use tube feeding if patients are not able to maintain
adequate oral intake (even when oesophageal
varices are present)
PEG placement is associated with a higher risk of
complications and is not recommended
A
c
Type of
formula
Whole protein formulae are generally
recommended.
Consider using more concentrated high-energy
formulae in patients with ascites.
Use BCAA-enriched formulae in patients with
hepatic encephalopathy arising during enteral
nutrition.
The use of oral BCAA supplementation can improve
clinical outcome in advanced cirrhosis
C
C
A
B

31. Nutrition in transplantation AND
SURGERY .surgerySUBJ RECOMME.. GRADE
preoperative Follow recommendations for cirrhosis. B
postoperative Initiate normal food/enteral nutrition within
12–24 h postoperatively.
Initiate early normal food or enteral nutrition after
other surgical procedures
B
route
preop Follow recommendations for cirrhosis.
postop Use nasogastric tubes or catheter jejunostomy for
early enteral nutrition.
b
FORMULA-
PREOP
Follow recommendations for cirrhosis.
POSTOP Whole protein formulae are generally
recommended.
In patients with ascites prefer concentrated high
energy formulae for reasons of fluid balance.
Use BCAA-enriched formulae in patients with
hepatic encephalopathy arising during enteral
nutrition.
C
C
A

32. OUTCOME-
PREOP
An improvement of perioperative mortality or
complication rate by preoperative tube feeding or
oral nutritional supplements has not yet been
showN.
OUTCOME-
POSTOP
Early normal food or enteral nutrition is
recommended for transplant and surgery patients
with LC in order to minimise perioperative—in
particular infectious—complications.

33. ESPEN GUIDELINES ON
PARENTRAL NUTRITION

34. NUTRTION IN ALCOHOLIC
STETOHEPATITIS
SUBJECT RECOMMEN.. GRADE
GENERAL Use simple bedside methods such as the Subjective
Global Assessment (SGA) or anthropometry to identify
patients at risk of undernutrition.
Start PN immediately in moderately or severely
malnourished ASH patients, who cannot be fed
sufficiently either orally or enterally.
Give i.v. glucose (2–3 g kg1 d1) when patients have to
abstain from food for more than 12 h.
Give PN when the fasting period lasts longer than 72 h.
C
A
C
C
ENERGY Provide energy to cover 1.3REE .
Give glucose to cover 50–60 % of non-protein energy
requirements.
Use lipid emulsions with a content of n-6 unsaturated
fatty acids ..
C
C
C

35. AMINOACID
S
Provide amino acids at 1.2–1.5 g kg1 d C
MICRONUTR
IENT
Give water soluble vitamins and trace elements daily
from the first day of PN.
Administer vitamin B1 prior to starting glucose infusion
to reduce the risk of Wernicke’s encephalopathy
C
C
MONITORIN
G
Employ repeat blood sugar determinations in order to
detect hypoglycemia and to avoid PN related
hyperglycemia.
Monitor phosphate, potassium and magnesium levels
when refeeding malnourished patients.
C
C

36. IN LIVER CIRRHOSIS
SUBJECT RECOMMEN.. GRAD
E
GENERAL Start PN immediately in moderately or severely
malnourished cirrhotic patients, who cannot be fed
sufficiently eitherorally or enterally.
Give i.v. glucose (2–3 g kg1 d1) when patients have
to abstain from food for more than 12 h.
Give PN when the fasting period lasts longer than
72 h.
Consider PN in patients with unprotected airways
and encephalopathy when cough and swallow
reflexes are compromised.
Use early postoperative PN if patients cannot be
nourished sufficiently by either oral or enteral route.
After liver transplantation, use early postoperative
nutrition; PN is second choice to EN.
C
A
C
C
C
A

37. ENERGY Provide energy to cover 1.3 x REE
Give glucose to cover 50 % - 60 % of non-protein
energy requirements.
Reduce glucose infusion rate to 2–3 g kg1 d1 in case
of hyperglycemia and use consider the use of i.v.
insulin.
Use lipid emulsions with a content of n-6 unsaturated
fatty acids lower than in traditional pure soybean oil
emulsions
C
C
C
AMINOACID
S
Provide amino acids at 1.2–1.5 g kg
In encephalopathy III or IV, consider the use of
solutions rich in BCAA and low in AAA, methionine
and tryptophane
C
A

38. MICRONUTR
IENT
Give water soluble vitamins and trace elements daily
from the first day of PN.
In alcoholic liver disease, administer vitamin B1 prior
to starting glucose infusion to reduce the risk of
Wernicke’sencephalopathy
C
C
MONITORIN
G
Employ repeat blood sugar determinations in order to
avoid PN related hyperglycemia.
Monitor phosphate, potassium and magnesium levels
when refeeding malnourished patients
A
C

39. IN ACUTE LIVER FAILURE
GENERAL Commence artificial nutrition when patient is unlikely to
resume normal oral nutrition within the next 5–7 days.
Use PN when patients cannot be fed adequately by
EN.
C
C
ENERGY Provide energy to cover 1.3 REE.
Consider using indirect calorimetry to measure
individual energy expenditure.
Give i.v. glucose (2–3 g kg1 d1) for prophylaxis or
treatment of hypoglycaemia.
In case of hyperglycaemia, reduce glucose infusion
rate to 2–3 g kg1 d1 and consider the use of i.v.
insulin.
Consider using lipid (0.8 – 1.2 g kg1 d1) together with
glucose to cover energy needs in the presence of
insulin resistance
C
C
C
C
C

40. IN ACUTE LIVER FAILURE
SUBJ RECOMMEN GRAD
E
AMINOACID In acute or subacute liver failure, provide amino acids
at 0.8–1.2 g kg1 d1.
C
MONITORIN
G
Employ repeat blood sugar determinations in order to
detect hypoglycaemia and to avoid PN related
hyperglycaemia.
Employ repeat blood ammonia determinations in order
to adjust amino acid provision.
C
C

41. References
• Cornelis H. C. Dejong,4* Marcel C. G. van de Poll,4
Peter B. Soeters,4 Rajiv Jalan,5and Steven W. M. Olde
Damink4, Aromatic Amino Acid Metabolism duringLiver
Failure1–3.
• ESPEN Guidelines on Parenteral Nutrition:
Hepatology,Mathias Plauth a, Eduard Cabre´ b, Bernard
Campillo c, Jens Kondrup d, Giulio Marchesini e,Tatjana
Schu¨ tz f, Alan Shenkin g, Julia Wendon h.
• Current Theories on the Pathogenesis ofHepatic
Encephalopathy (43770)DARRELDL. MOUSSEAUA ND
ROGERF . BUTTERWORT…

42. • Branched-chain amino acids increase arterial blood
ammonia in spite ofenhanced intrinsic muscle ammonia
metabolism in patients with cirrhosisand healthy
subjects,Gitte Dam,1 Susanne Keiding,1,2 Ole Lajord
Munk…
• ESPEN Guidelines on Parenteral Nutrition: Intensive
care,Pierre Singer a, Mette M….
• ESPEN Guidelines on Enteral Nutrition: Liver
disease$M. Plautha,, E. Cabre´b, O. Riggioc, M. Assis-
Camilod,

43. • NEUROTRANSMITTERS IN HEPATIC
ENCEPHALOPATHY,W. Agnieszka FOGEL, Wojciech
ANDRZEJEWSKIand Czeslaw MASLITSSKI..
Thank you.