Hepatic Encephalopathy

What is it
-Reversible spectrum of physical and neurocognitive abnormalities seen in patients with liver
dysfunction or portosystemic shunting
-Elevated Ammonia plays a key role. There may also be a role for inhibitory neurotransmission through
gamma-aminobutyric acid (GABA) receptors in the central nervous system and changes in central
neurotransmitters and circulating amino acids.
-Ammonia normally metabolized in the liver to urea then excreted. If clearance decreased, it crosses
blood brain barrier and is coverted to glutamine and promotes cerebral edema
-Seen in about 30-40% of patients with cirrhosis

Risk Factors:
Usually have some extent of liver disease or portosystemic shunting. Precipiated by:
-Drugs – Benzos, Narcotics, Alcohol
-Increased Ammonia production/absorption or entry to brain – Increased protein intake, GI bleed,
infection, hypokalemia, constipation, metabolic alkalosis
-Dehydration – Vomiting, Diarrhea, Hemorrhage, Diuretics, Large paracentesis
-Vasular occlusion – hepatic or portal vein thrombosis
-GI bleeding, UTIs due to proteabus morabilis, hepatocellular carcinoma, renal failure

Symptoms
Primarily altered mental status but signs of liver cirrhosis support diagnosis
- Asterixis, jaundice, ascites, spider angiomata, palmar erythema, hepato/splenomegaly
- Altered mental status – mood changes, slow to respond, unsteadiness, slurred speech, muscle
rigidity, irritability, memory loss, impaired sleep

Diagnosis
-Primarily clinical so history and physical most important
-Elevated Ammonia (15-45 wnl) supports diagnosis but is not required. Elevated Ammonia alone is non
specific. Usually begins to correlate with HE once increase of 2fold above normal. The partial pressure of
gaseous ammonia that readily enters brain is most related but rarely calculated.
-Noncontrast CT of head helps to rule out other causes of altered mental status (trauma, edema,etc)

Grading/Categorization
4 factors for categorization: the underlying disease, the severity of manifestations, the time course, and
whether precipitating factors are present.
1.Underlying disease:
•Type A=acute: hepatic encephalopathy occurring in the setting of acute liver failure
•Type B=bypass: hepatic encephalopathy occurring in the setting of portal-systemic bypass with no
intrinsic hepatocellular disease
•Type C=cirrhosis: hepatic encephalopathy occurring in the setting of cirrhosis with portal hypertension
or systemic shunting
2.Severity of manifestations: Based on West Haven Criteria
•Minimal/0: Abnormal results on psychometric or neurophysiological testing without clinical
manifestations
•Grade I: Changes in behavior, mild confusion, slurred speech, disordered sleep
•Grade II: Lethargy, moderate confusion
•Grade III: Marked confusion (stupor), incoherent speech, sleeping but arousable
•Grade IV: Coma, unresponsive to pain
3.Time course: episodic, recurrent (bouts of hepatic encephalopathy that occur within a time interval of
six months or less), or persistent (a pattern of behavioral alterations that are always present,
interspersed with episodes of overt hepatic encephalopathy).
4.Precipitating factors: Episodes of hepatic encephalopathy are described as being either
nonprecipitated or precipitated.

Treatment:
Grade 1 and 2 can be treated outpatient if adherence to treatment is not an issue
Grade 3 and 4 require hospital admission
Treat the precipating cause if known
Provide nutritional support (no protein restrict), hydration and correct electrolyte abnormalities such as
hypokalemia as low K increases renal ammonia production.
Lower ammonia with Lactulose or Lacticol. Can add Refaximin if needed.
- Rifaximin – non absorbable antibiotic that decreased bacteria that produce ammonia
- Lactulose/ Lacticol – decreases ammonia absorption in GI tract, GI flora degrade it into lactic acid +
acetic acid.
Look out for agitation and manage with haloperidol over benzos. Restraints if needed

Complications:
Persistent neurocognitive abnormalities
Death

Differential for Hyperammonia

- GI bleed, Renal disease, UTI with proteus mirabilis, shock, parenteral nutrition

Differential for Hepatic Encephalopathy

- DKA – will see hyperglycemia with ketones and anion gap metabolic acidosis
- Uremic encephalopathy – will see elevated urea and normal ammonia
- Acute alcohol intoxication – will see elevated blood alcohol