Hepatic

Encephalopathy

Hepatic encephalopathy (HE)

a reversible neuro-psychiatric state
a complication of liver failure
pathogenesis is not understood fully
derangement of neurotransmitter
system and metabolic system

Pathogenesis
No

single metabolic derangement accounts for HE.

Failure of hepatic clearance of gut derived
substances.
Hepatocellular failure or shunting.
Altered aminoacid metabolism.
Accumulation of unmetabolized ammonia 2ry to
poor hepatic function or shunt.
Production of false neurotransmitters.
Activation of GABA-Benzo receptors by
endogenous ligands.
Altered cerebral metabolism.
Disturbed activity of Na/K ATPase.

Scarring of liver( cirrhosis)

Pathogenesis

Obstruction of the passage of blood (liver)

portal hypertension
Portal-systemic anastomoses ("shunts)

Bypasses liver

Return to heart
Toxic substances enters brain
Impending hepatic coma

Classification of hepatic
encephalopathy

(World Congress of Gastroenterology

1998 in Vienna )
1. Type A (=acute) describes hepatic
encephalopathy associated with
acute liver failure;
2. Type B (=bypass) is caused by
portal-systemic shunting without
associated intrinsic liver disease;
3. Type C (=cirrhosis) occurs in
patients with cirrhosis .

Classification of hepatic
encephalopathy
Type
Aetiological factors
A(20%)

Viral hepatitis,
Alcoholichepatitis,
Drug reacns &overdose.

B(100%)

Portal systemic shunt,

Dietary protein intake,
Intestinal bacteria.

C(75%)

Diuresis,
Haemorrhage,Paracentesis,
Diarrhoea,Surgery,Sedatives,
Sepsis,Constipation.

Neurotansmitters implicated in
HE

Ammonia and Glutamate

Manganese, Mercaptans,Phenols,
False neurotransmitters
GABA and Endogenous BZD
Others :Serotonin,Nitric oxide

Ammonia and Glutamate

Ammonia

is produced from breakdown of

proteins, amino acids, purines, pyrimidines.
Liver converts ammonia to urea and
glutamate by urea cycle
In HE, blood NH3 by 90% also brain levels
There is no urea cycle in the brain & NH3 is
removed by diff pathway

NH3 leads to CMR and BBB

permeability to NH3

Ammonia and Glutamate

contd
Hepatic
encephalopathy
increase in cerebral
ammonia
astrocyte damage
reduced glutamate
receptors
glutamine
accumulates

Ammonia and Glutamate

contd
SOURCE :

intestinal protein/bacteria
reduced hepatic removal
reduced muscle metabolism

NH3

EFFECTS:

Astrocyte damage
glutamine accumulates
BBB permeability (ICP)

Manganese &
false neurotransmitters
Blood

& Brain Mn levels increased in CLF

Normally produced dopamine &
catecholamines mediated neuroamines
are inhibited by false neurotransmitters
(tyramine,octopamine)
Plasma levels of aromatic a.a
&
branched chain a.a

GABA & Endogenous BZD

GABA

is principal inhibitory amine

It binds to specific GABA receptor in
postsynaptic memb
Receptor also has binding site for
BZD &barbiturates
GABA & Endogenous BZD are high in
plasma &CSF of liver failure pts
These leads to hyperpolarisation
&neuroinhibition

Symptoms & Signs

1.
2.
3.
4.
5.

Earliest manifestations of hepatic

encephalopathy is 'day-night Reversal
Impairment in spatial perception
Changed cognitive function mild
confusion to coma
Flapping tremor (asterixis )
Exaggerated deep tendon reflexes
&sustained ankle clonus

Acute liver failure

(Depending on onset of encephalopathy
& onset of jaundice)
Hyperacute - less than 7days
Acute
- 7 to 28 days
Subacute
- 28days to 6months
Chronic
- more than 6 months

Investigations
CSF

analysis

:cell count,protein,
glutamatic acid
Electroencephalogram :b/l synchronous
slowing of waves
Evoked potentials
Brain scans
Magnetic resonance spectroscopy
Neuropathology

Treatment of Hepatic
encephalopathy
Broadly divided into 3 areas
1. Identification & treatment of ppt
factors
2. Interventions to reduce the
production of & absorption of gut
derived ammonia & other toxins
3. Prescription of agents to modify
neurotransmitters

Reduction of absorption and production of

ammonia

Protein restriction to 20g/day then increase 10g /3-5 days and

evaluate tolerance.
Supplementation with vegetable protein is important in patients
with low tolerance.(Related to fiber/protein ratio)
Reduction of endogenous (intestinal cells shedding) and dietary
ammoniagenics by cathartics (Lactulose and Lactitol).
Dose titrated to 2-4 loose/acidic stools/day generally requiring 3060grams/day.
Lactulose (10-30ml tid):
1- Decreases Intestinal PH. Favors growth of non-urease
producing bacteria.
2- Promotes movement of ammonia from blood to bowel
and decreased absorption.
Lactilol (0.3-0.5g/kg/day)responds more quickly,less diarrhoea &
flatulence

Reduction of absorption and production of

ammonia

Antibiotics :
Neomycin (4-6 gr /day )for 5-7 days in acute cases
reduces ammonia formation in GIT
(careful in RF)
Metronidazole(200 mg Qid )
Rifaximin, or brand name Xifaxan, a derivative of rifamycin at a dose of 400
mg taken orally 3 times a day was as effective as lactulose or lactilol at
improving hepatic encephalopathy symptoms. Similarly, rifaximin was as
effective as neomycin and paromomycin. Rifaximin was better tolerated
than both the cathartics and the other nonabsorbable antibiotics. . There are
also concerns regarding the cost-effectiveness of the medication.
Purgation by enemas esp phosphate

Repopulation of bowel with non urease producing bacteria.

Erradication of H. pylori.

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