Hepatic Encephalopathy

---

DEFINITION

Complex, potentially reversible, neuropsychiatric syndrome in patients with cirrhosis or acute liver failure.

D E A B M I M

---

EPIDEMIOLOGY

Liver disease causes

Precipitating Factors
GI bleed
Sedatives, analgesics
Dehydration
Renal failure
Hypokalemia
Metabolic alkalosis
Infection (SBP, penumonia, UTI)
Excess dietary protein
Constipation
D E A B M I M  

---

AETIOLOGY

Liver disease causes

D E A B M I M  

---

BIOLOGICAL BEHAVIOUR

Pathophysiology
Multifactorial.

1. Brain exposed to toxic substances
- produced by gut by action of bacteria on nitrogenous compounds
- incompletely cleared from blood by compromised liver

2. Ammonia is implicated and most studied
- elevated plasma ammonia occurs in HE
- crosses BBB and enters CNS astrocytes
- combines with glutamate to form glutamine, enters mitochondria, converted back to ammonia
- causes reactive oxygen species and mitochondrial swelling

3. Adverse effects on cerebral perfusion
- also contribute to brain dysfunction.

4. GABA may also play a role.
- increased in liver injury and high ammonia
--> patients may respond to flumazenil.

5. Other roles possible for mercaptans, neurosteroids.
- individual factors may have varying influences, contributing to protean manifestations.


D E A B M I M  

---

MANIFESTATIONS

Encephalopathy	Consciousness	Cognitive	Behavior	Neuromuscular
Stage 1 (mild)	abnormal sleep	Short attention, mildly impaired	Euphoria, depression, irritable.	Tremor, incoordination
Stage 2 (mod)	lethargy / disorientation	Amnesia, grossly impaired	Personality change, inappropriate	Slurring, hypoactive reflexis, asterixis
Stage 3 (severe)	somnolece	Unable to compute	Paranoia	Hyperactive reflecxes, Babinski, rigidity
Stage 4 (coma)	stupor	None	None	Dilated pupils.

Notes
Deficits such as hemiplegia in <20%, seizures are rare
- so if focal neurology or seizures, consider alternative diagnoses.
D E A B M I M

---

INVESTIGATIONS

EEG
Always abnormal in overt HE, but changes are not specific.

Other tests
As per underlying cause and suspected precipitating factors.
D E A B M I M

---

MANAGEMENT

Classification
A
HE with Acute Liver Failure

B
HE with portosystemic bypass and no intrinsic liver disease

C
HE with cirrhosis and portal hypertension or portosystemic shunts
- may be episodic or persistent
- often there is a precipitating factor as above; look for it, most common is GI bleeding (elevates gut protein --> production of nitrogenous byproducts)
- often infective association; may be pathogenic link with cytokines / astrocytic swelling

Type C

1. Look for causes and occult infection.
- beware, may have neutropaenia, and may not mount a fever
- paracentesis for SBP
- antibiotics if high index of suspicion.

2. Correct dehydration and electrolyte imbalances
- uraemia will contribute to increased ammonia
- hypokalaemic alkalosis will enhance renal ammonia production and increase transport across the BBB.

3. Avoid sedatives and analgesics
- neurotoxins

4. Oral Disaccarides (lactulose)
- mainstay of therapy
- decreases ammonia absorption by trapping it in the acidic colonic lumen
- and cathartic action of flushing colon reduces available time for absorption
- lacks RCT evidence but most commonly used agent
--> maybe most effective in GI bleeding to flush colon.
- aim for 3-5 soft BMs / day, usually 30mL b.d. is about right.
Few adverse effects except occasional hypernatraemia

5. Restrict Dietary Protein
Theoretically reduces nitrogenous toxin production
Lack of CT evidence.
- in fact in alcoholic context, high-protein may have some benefits; and don't want excess catabolism if concomitant sepsis.
Usually pt is not eating much anyway to start with, then ca modestly restrict to 1.0 g/kg/day

6. Antibiotics
Suppression of toxin production by gut bacteria
Avoid aminoglycosides
Metronidazole and vanc = equivocal results
Some evidence for experimental agents, not widely available or practiced.

7. Other Therapies
Possibly flumazenil
Probiotics reduce substrate for other bacteria.

Type A

1. Cerebral oedema and intracranial hypertension can contribute.
- very low risk in stages I-II, but rises in III and IV
- perhaps due to liver damage / failure mediators
--> assess for ICP, e.g. pupils, reflexes; some places use invasive monitoring but that is intense and not recommended.
- treat as required e.g. avoiding hypotonic solutions, using mannitol and using hypertonic saline, temporary hyperventilation.

2. High Dependency
- ICU review for Grade 2 with intensive monitoring and support
- at grade III, may need intubation for airway

3. Lactulose is ~ineffective in acute liver failure.


D E A B M I M

---

REFERENCES

---