Hepatic coma

Dr.dr. I Gede Arinton,SpPD-KGEH

PAPDI Purwokerto

Purwokerto

2016
Hepatic Encephalopathy
in Chronic Liver Disease

2014 Practice Guideline

by AASLD and EASL

Classification

• Def = a brain dysfunction

• E/ : liver insufficiency and/or PSS;

• Manifest = a wide spectrum of

neurological or psychiatric
abnormalities ranging from
subclinical alterations to coma.
Classification

1. the underlying disease :

• Type A - from ALF

• Type B - from PS bypass or

shunting

• Type C -from cirrhosis

Classification

2. the severity of manifestations :

• Unimpaired

• Minimal

• Grade I-IV
Classification

• 3. its time course :

• Episodic HE

• Recurrent HE

• Persistent HE
Classification

• 4. existence of precipitating
factors :
• Nonprecipitated

• Precipitated
Precipitating Factors

• GI bleeding

• Infection

• SBP

• Paracentesis >>>>

• Dietary intake of protein >>>

• Portal or hepatic vein thrombosis

• Benzodiazepines, Narcotics, Alcohol

• Hypokalemia

• Constipation
Source: Bajaj JS, et al. Hepatology. 2012;55:1164-71.
Epidemiology

• 30-45% of patients with decompensated

Cirrhosis have HE

• 20% annual risk of development in of

patient with compensated cirrhosis.

• 60-80% of patients with compensated

cirrhosis have evidence of minimal
hepatic encephalopathy

Source: Bajaj JS. Aliment Pharmacol Ther. 2010;31:537-47.

 Pathogenesis

• Ammonia intoxication hypothesis

• False neurotransmitter hypothesis

• Amino acid imbalance hypothesis

• The gamma-aminobutyric acid

hypothesis
Pathophysiology

NH3

Glutamine NH3
NH3
Urea Glutamine

Glutamine
NH3 NH4+ Urea

Feces Urine
Ammonia intoxication hypothesis

Causes for elevated ammonia

Decreased ammonia clearance

impaired Krebs-Henseleit urea cycle
Increased ammonia production
urea in the blood is emitted into intestinal
lumen and degraded by urease in bacteria to
produce ammonia
ammonia is produced in the kidneys and
muscles
gastrointestinal hemorrhage and
absorption dysfunction
Intoxication of ammonia on the brain

Impairment of energy metabolism in brain

ammonia reacts with α-ketoglutatrate to
produce glutamate and glutamine
consumption of α-ketoglutatrate, NADH and ATP,
inhibition of pyruvate decarboxylase leading to the
reduction of acetyl CoA and acetylcholine
Alteration of neurotransmitters
decreased excitatory neurotransmitters
glutamate and acetylcholine
increased inhibitory neurotransmitters
glutamine and gamma-aminobutyric acid
Inhibiting action on nerve cell membrane
False neurotransmitter
hypothesis

phenylalanine → phenylethanolamine

tyrosine →
octopamine

Dopamine and norepinephrine

Amino acid imbalance hypothesis

BCAA/AAA
Insulin↑, glucagon ↑ ↑, insulin/glucagon ↓
Increased production of aromatic AA and
increased uptake and utilization of branch
chain AA
Inhibiting the production of normal
neurotransmitters
Promoting the production of false
neurotransmitters
Increased production of 5-
hydroxytryptophan(5-HT)
The gamma-aminobutyric acid
hypothesis GABA

Inhibitory neurotransmitters

Decarboxylase
↓
Glutamate →GABA
Number Connection Test
• Used for > 50 years to assess Number Connection Test
Patient’s Name
mental performance Date
Completion Time

• Simple, readily available Testers Initials

Patient’s Signature

• Results influenced by age and

level of education

Time required HE Grade

≤30 seconds None-

Minimal
31-50 seconds Minimal - I

51 to 80 I - II
seconds
81 – 120 II - III
seconds
Forced III
termination
Source: Weissenborn et al. J Hepatology May 2011
Rifaximin

• Semisynthetic antibiotic based on rifamycin

• Poor bioavailability - confined to the gut
• Mechanism thought be through intestinal flora
alteration
• Similar efficacy to nonabsorbable disaccharides
• Due to cost, reserved for patients who cannot
tolerate or do not respond to disaccharides
• Neomycin is a less costly alternative, but
association with ototoxicity and nephrotoxicity
limit use
BCAA

• Setiap 1000 mL Aminoleban Infus, mengandung :

• Asam Amino : 7,99 %

• Asam Amino Rantai Cabang : 35,5 %

• Arginin : 7,3 g

• Rasio Fischer : 37,05

• Rasio E/N : 1,09

• Total Nitrogen : 12,2 g/L

• Na+ : kurang lebih 14 mEq/L

• Cl- : kurang lebih 94 mEq/L

• Osmolaritas : 768 mOsm/L

Summary

• HE is commonly seen in patients with cirrhosis

• Reduced ammonia detoxification due to liver
dysfunction and/or porto-systemic shunting
• HE is a clinical diagnosis
• Protein restriction is not recommend
• Any acute episode of HE warrants a thorough
evaluation for precipitating factors
• Nonabsorbable disaccharides and antibiotics
are mainstays of treatment