20 hepatic enchephalopathy

HEPATIC ENCEPHALOPATHY

GAO XIANGDepartment of Gastroenterology

The First Affiliated Hospital

DEFINITION

Hepatic encephalopathy is a reversible neuro-psychiatric state that complicates severe liver disease(HE).

AETIOLOGY

Encephalopathy associated with Cirrhosis and portal hypertension

Encephalopathy associated with portal-systemic Bypass without hepatocellular disease

Encephalopathy associated with Acute liver failure

Concensus in Hepatic Encephalopathy, WCOG, 2001; in press

Hepatic encephalopathy-A complication of cirrhosis of the liver

0 20 40 60 80 100 120 140 1600

20

40

60

80

100Pr

obab

ility

of c

ompl

icat

ions

(%)

Gines et al. Hepatology (1987) 7, 1:122-128

Months

Key questions Mechanism: clearance of toxins central system --- treatment

Clinical manifestation: neuro-psychiatric changes --- diagnosis and clinical grading

PATHOGENETIC MECHANISM

Ammonia toxicity theory False neurotransmitters theory & amino acid imbalance theory Gama-aminobutyric aicd and endogenou

s benzodiazepines (GABA/BZ ) receptor complex theory

Others

intestinal Precipitating factors bacteria/protein GI bleeding

infection

liver removed hypokalemia and/or alkalosis

portal-systemic shunt hypovolemia and/or hypoxia

large protein meal

blood-brain barrier constipation drugs(sedatives )

cerebral toxicity hypoglycemia

Ammonia intoxication theoryNH3 NH4

urea&

H+

Branched-chain amino acid /Aromatic amino acids 3-3.5 :1 (normal)

<1 : 1 (cirrhosis)------ the use of branched-chain amino acid

Amino acid metabolic imbalance

Tyrosine intestinal bacterial decarboxylase

L-dopa Tyrosine Phenylalanine

Dopamine (Liver)

Noradrenaline Octopamine -phenylethanolamine true false Sympathetic transmitter

Brain function disturbed

False neurotransmitterColon: protein

x(Brain)

GABA/BZ receptor complex theory

•GABA (from intestine produced by bacteria)

•Endogenous BZ

--- the use of benzodiazepine antagonist

CLINICAL MANIFESTATION

DIAGNOSIS AND

DIFFERENTIAL DIAGNOSIS

• Severe liver disease or portal-systemic shunt

• Neuropsychiatric manifestation• Precipitants that induce HE• Obvious impaired liver function tests, eleva

ted blood ammonia level, flapping tremor and typical EEG change indicate the possible diagnosis

Diagnosis

Coma induced by other causes

Differential diagnosis

TREATMENT

1. Identification & correction of the precipitating cause: Precipitating factors Drugs! Electrolyte imbalance – hypokalemia/metabolic alkalosis (diuretics, vomiting, diarrhea, infusion) GI Bleeding Infection Constipation Large protein meal …….

2. Intervention to reduce the production & absorption of gut-derived ammonia & other toxins:

1) Diet: reduce and modify dietary protein and maintain Calorie intake

2) Enemas (mild acid) and/or purgation3) Lactulose or lactitol4) Inhibition of gut bacteria: Antibiotics: neomycin(oral), metronidazone?5) Modification of colonic flora: probiotics?

Modify colonic flora, resulting in displacement of urease-containing bacteria with lactobacillus

Cathartic effect

Lower the colonic pH, resulting in the formation of nonabsorbable NH4 from NH3 in the colon

3. Stimulation of metabolic ammonia metabolism: 1) Ornithine-aspartate: enhancing the metabolism

of ammonia to glutamine 2) Sodium glutamate or potassium glutamate,

Arginine? 3) Sodium benzoate(oral): acting with glycine in

the colon to form hippurate which can be excreted in the urine

- applied in chronic HE, particularly in those with elevated blood ammonia

4. Correct amino acid metabolic imbalance: infusion or oral administration of BCAA (branched-chain amino acid)

5. GABA/BZ complex antagonist: flumazenil ( particularly if patient has been given

banzodiazepines )

6. Other drugs

7. Miscellaneous treatment

Prevention and treatment of cerebral edema

8. Temporary hepatic support

9. Liver transplantation

PROGNOSIS

Acute hepatic failure (+++) Cirrhosis - with precipitant (++) Cirrhosis - portal-systemic shunt (+) Cirrhosis - end stage (++++)