Hepatic Encephalopathy (HE)

What is hepatic encephalopathy?

HE may be defined as a disturbance in central nervous system function because of hepatic insufficiency. It can be present in both acute and chronic liver failure. The neuropsychiatric manifestations are reversible.

Discuss the pathophysiology of HE?

  • A large body of work points at ammonia as a key factor in the pathogenesis of HE.
  • Portal ammonia is derived from both the urease activity of colonic bacteria and the deamidation of glutamine in the small bowel.
  • The intact liver clears almost all of the portal vein ammonia, converting it into glutamine and preventing entry into the systemic circulation.
  • Ammonia gain access to the systemic circulation as a result of decreased hepatic function or portal-systemic shunts.
  • Once in brain tissue, they produce alterations of neurotransmission that affect consciousness and behaviour.
  • In acute and chronic liver disease, increased arterial levels of ammonia are commonly seen. However, correlation of blood levels with mental state in cirrhosis is inaccurate.

Discuss the clinical presentation of HE?

  • HE is a diagnosis of exclusion. Other metabolic and cerebral structural causes can have a similar presentation.
  • Pre existing liver disease (acute or chronic), presence of a precipitating factor, and/or a prior history of HE are clinical elements needed for diagnosis.
  • Measurement of venous ammonia blood levels may be helpful
  • The most distinctive presentation is the development of an acute confusional state that can evolve into coma (acute encephalopathy).

Discuss the stages of HE?
West Haven criteria:
Stage 0. Lack of detectable changes in personality or behaviour. Asterixis absent.
Stage 1. Trivial lack of awareness. Shortened attention span. Impaired addition or subtraction. Hypersomnia, insomnia, or inversion of sleep pattern. Euphoria or
depression. Asterixis can be detected.
Stage 2. Lethargy or apathy. Disorientation. Inappropriate behaviour. Slurred speech. Obvious asterixis.
Stage 3. Gross disorientation. Bizarre behaviour. Semistupor to stupor. Asterixis generally absent.
Stage 4. Coma.

Discuss the management of HE?


In case of deep encephalopathy, oral intake is withheld for 24–48 h and i.v. glucose is provided until improvement. Enteral nutrition can be started if the patient appears unable to eat after this period. Protein intake begins at a dose of 0.5 g/kg/day, with progressive increase to 1–1.5 g/kg/day.

Precipitating factors

A precipitating factor can be found in most cases of cirrhosis with acute or chronic HE. These factors should be vigorously searched and eliminated. The precipitating factors are:

  • GI bleed
  • Infections- SBP or any other infection.
  • Renal and electrolyte disturbances- renal failure, metabolic alkalosis, hypokalaemia, dehydration, and diuretic effects.
  • Medication- benzodiazepines, narcotics, and other sedatives.
  • Constipation
  • Excessive dietary protein.
  • Acute deterioration of liver function in cirrhosis- like superimposed alcoholic hepatitis, portal vein thrombosis etc.

Lactulose is a first-line pharmacological treatment of HE.

  • Lactulose (galactosido-fructose) is not broken down by intestinal disaccharidases and thus reaches the colon, where bacteria will metabolize the lactulose to acetic acid and lactic acid. This lowers the colonic pH and thus favours the formation of the nonabsorbable NH4+ from NH3, trapping NH3 in the colon and effectively reducing plasma ammonia concentrations. Other effects like catharsis also contribute to the clinical effectiveness of lactulose.
  • An excessively sweet taste, flatulence, and abdominal cramping are the most frequent subjective complaints with this drug.
  • For acute encephalopathy, lactulose (ingested or via nasogastric tube), 45 ml p.o., is followed by dosing every hour until evacuation occurs. Then dosing is adjusted to an objective of two to three soft bowel movements per day (generally 15–45 ml every 8–12 h).
  • Lactitol is more palatable and can be used instead of lactulose. Both are equally efficacious.

Bowel cleansing is a rapid and effective method to remove ammoniagenic substrates.

The goal of antibiotic therapy in the treatment of HE is to reduce the mass o f enteric bacteria that produce ammonia. Antibiotics are reserved for patients who respond poorly to disaccharides. So antibiotics are added to lactulose after 48 hours, if the response has been poor. Options are

  • Neomycin (1-2 g/day) – concerns regarding oto and nephro toxicity limits its use.
  • Metronidazole (250 mg bd) – neurotoxicity limits its use
  • Rifaximin (400 mg t.i.d) is much better tolerated, but is expensive. The tolerability profile of rifaximin is comparable to placebo

Liver transplantation

The development of overt HE carries a poor prognosis with a 1-yr survival of 40%. Appropriate candidates should be referred to transplant centres after the first episode of overt encephalopathy of any type.

Blei AT, Córdoba J. Hepatic Encephalopathy. Am J Gastroenterol. 2001 Jul; 96(7):1968-76.

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