• Syndrome characterized by abnormal mentation due to toxins and metabolites crossing the blood-brain barrier in severe hepatic dysfunction and leading to diffuse cerebral impairment.
• Cause: severe hepatic insufficiency; course may be acute, eg Theiler’s disease, or chronic, eg pyrrolizidine alkaloid toxicity (ragwort poisoning); rarely congenital portosystemic shunts (foals).
• Signs: abnormal mentation, from depression, dementia → coma.
• Diagnosis: history and clinical signs suggestive; confirmation is by presence of laboratory findings indicative of liver failure.
• Treatment: supportive.
• Prognosis: very poor – hepatic damage is usually irreversible.

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• Early stage: depression and inappetence.
• Later stages: may see head pressing, visual impairment, circling; terminally generalized seizures or coma.

• Worldwide.

• Cost associated with treatment of hepatic encephalopathy and underlying hepatic disease.

• Horses with hepatic encephalopathy are not suitable for general anesthesia.
• Use benzodiazepines with caution as these drugs will induce astrocyte swelling and worsen HE.
• Ideally, sedatives should be avoided in HE as that might cause excessive lowering of the head in the standing horse and promote cerebral edema, in addition to the potential negative effects on the brain, liver, and other organ perfusion.

• Any disorder that results in diffuse hepatocellular dysfunction:
  • Ragwort poisoning Toxicity: pyrrolizidine alkaloid.
  • Other causes of liver damage, eg Theiler’s disease Liver: hepatitis – acute (Theiler’s disease).
• Congenital portosystemic shunts (rare).

• Incompletely understood.
• The pathophysiology of HE is complex and likely involves several gut‐derived neurotoxins, cerebral and systemic inflammation, cerebral vascular dysfunction, and neuroendocrine abnormalities.
• Multiple theories – systemic ammonia accumulation secondary to liver dysfunction occurs:
  • Ammonia crosses the blood brain barrier (BBB) and accumulates in the brain, acting as a neurotoxin.
  • Glutamate, NMDA (N‐methyl‐d‐aspartate) receptor activity and increased glutamine all play a central role in ammonia metabolism and HE.
  • Increased ammonia in the brain results in increased metabolism of ammonia by astrocytes and the resulting accumulation of glutamine which is known to disrupt water balance in the brain leading to cytotoxic edema.
  • Inflammation and ammonia‐induced free radical production in the brain may also cause vasogenic edema.
• Increased BBB permeability for ammonia may also play an integral role in HE. Changes in BBB permeability may be due to both structural alterations in tight junctions and inflammatory vascular effects and functional changes. Increases in blood ammonia, metalloproteinase activity, and endotoxin may increase permeability of the BBB in liver failure permitting transport of other neurotoxins to the brain.
• Other theories: alteration in amino acid metabolism due to liver dysfunction results in imbalance between aromatic amino acids (AAA) and branched chain amino acids (BCAA). AAA preferentially cross blood brain barrier and act as precursor for serotonin, an inhibitory neurotransmitter.
• Other neurotransmitters are frequently discussed as playing a role in HE, but their association has not been well documented. These neurotransmitters include endogenous benzodiazepine‐like compounds, mercaptans, and monoamines.
• End result is diffuse cerebral impairment.

Refereed papers

• Recent references from PubMed and VetMedResource.
• Oliveira-Filho J P, Cagnini D Q, Badial P R et al (2013) Hepatoencephalopathy syndrome due to Cassia occidentalis (Leguminosae, Caesalpinioideae) seed ingestion in horses. Equine Vet J 45 (2), 240-244 PubMed.
• Muller J M V, Herder V, Feige K et al (2011) Ataxia and weakness as uncommon primary manifestations of hepatic encephalopathy in a 15-year-old trotter gelding. Equine Vet Educ 23 (1), 5-10 VetMedResource.
• Nout Y S (2011) Gait deficits in liver disease: Hepatic encephalopathy and hepatic myelopathy. Equine Vet Educ 23 (1), 11-13 VetMedResource.
• Hughes K J, McGorum B C, Love S et al (2009) Bilateral laryngeal paralysis associated with hepatic dysfunction and hepatic encephalopathy in six ponies and four horses. Vet Rec 164 (5), 142-147 PubMed.
• Johns I C, del Piero F & Wilkins P A (2009) Hepatic encephalopathy in a pregnant mare: identification of histopathological changes in the brain of a mare and fetus. Aust Vet J 85, 337-340 PubMed.

Other sources of information

• Divers T (2015) Equine Hepatic Encephalopathy. In: Equine Neurology. 2nd edn. Ed: Furr M & Reed S. pp 343-348.