Hepatic encephalopathy - Veterinary Practice
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Hepatic encephalopathy

A guide to the pathogenesis, signalment, diagnosis and treatment of the condition, which is often associated with portosystemic shunts

Hepatic encephalopathy (HE) is described as a spectrum of neuropsychiatric abnormalities seen in patients with liver dysfunction after exclusion of other known brain disease (Ferenci et al., 2002). HE is most frequently found in association with some form of portosystemic shunt (PSS) in dogs and cats but may also occur in other hepatic disorders that lead to end-stage liver failure.


HE has a complex pathogenesis and is likely a culmination of multiple factors. While an increased blood concentration of ammonia is the most commonly cited cause (Bexfield and Watson, 2009), the clinical signs can also be associated with several other metabolites including mercaptan, amino acid imbalances and abnormalities of the GABA-benzodiazepine receptor.

The pathophysiology of HE can be divided into three different phases (Bexfield and Watson, 2009):

1. Ammonia and other waste products are generated from protein in the process of food digestion and absorption in the digestive tracts or the breakdown of endogenous protein (muscle) if an animal is in negative nitrogen balance. The blood concentration of these toxic metabolites increases due to impaired liver function or the direct entry into the systemic circulation in PSS.

2. Amino acid imbalance subsequently occurs and causes changes in the serum.

3. Brain cells are damaged by the toxic metabolites. Impaired cognition is also caused by changes of neurotransmitters, including monoamine and their receptors.

A number of concurrent factors may exacerbate the clinical signs of HE (Lidbury and Cook, 2016; Table 1). Management should be aimed at reducing these factors.

SepsisInflammatory mediators have a synergistic effect with ammonia
Gastrointestinal haemorrhageIncreased protein load and ammoniagenesis
Electrolyte abnormalities
Bacterial overgrowth and bacterial translocation
Excess proteinIncreased ammoniagenesis
DehydrationElectrolyte changes
Increased renal ammoniagenesis
DrugsOpioids and benzodiazepines lead to sedation
Diuretics lead to electrolyte imbal-ances, alkalosis and dehydration
HypokalaemiaMovement of intracellular potas-sium into the extracellular space leads to intracellular acidosis and trapping of ammonium ions within cells
HyponatraemiaEnhanced astrocyte swelling
AlkalosisIncreased access of ammonia to neurons
Poor compliance with lactulose therapyIncreased ammoniagenesis
Bowel obstructionDehydration
Electrolyte abnormalities
Bacterial overgrowth and bacterial translocation
Superimposed hepatic injuryDecreased hepatic conversion of ammonia to urea
TABLE (1) Precipitating factors for hepatic encephalopathy


PSS is the most common cause of HE in dogs and cats, with most cases more specifically due to a single congenital PSS (Lidbury et al., 2012). The signalment of dogs with HE naturally reflects this; 33 months is the median reported age of dogs displaying clinical signs of HE (Lidbury and Cook, 2016). While there are currently no studies showing breeds of dogs predisposed to HE, breeds most likely to have a congenital PSS include Havanese, Yorkshire Terrier, Maltese, Dandy Dinmont Terrier, Pug, Miniature Schnauzer, Standard Schnauzer and Shi Tzu (Tobias and Rohrbach, 2003). Several breeds of cats have been reported to be affected by congenital PSS, including domestic shorthair, Persian, British Shorthair, Ragdoll, domestic longhair, Birman, British Blue and Tonkinese. The median age at presentation is eight months (Scavelli et al., 1986).

Clinical signs

The syndrome of HE is well recognised in dogs and cats and typically results in intermittent, diffuse cerebral disease that varies in intensity from day to day, ranging from depression and lethargy to seizures and coma. Episodic signs of encephalopathy, which worsen after a meal, are particularly suggestive of HE. Clinical signs can be divided into four stages (Salgado and Cortes, 2013; Table 2). Cats in later stages may also present with golden or coppercoloured irises secondary to decreased hepatic metabolism (Lipscomb et al., 2007).

In all stages of the clinical syndrome, animals may show non-neurologic signs related to the underlying disease such as vomiting, diarrhoea, weight loss, ascites, insufficient growth, polyuria and polydipsia (Taboada and Dimski, 1995).

Stage IStage IIStage IIIStage IV
Mild confusion
Dull demeanour
Mild irritability
Markedly dull behaviour
Personality changes
Head pressing
Inactive but arousable
Severe ptyalism
Occasional aggression
Complete unresponsiveness
TABLE (2) Stages of hepatic encephalopathy


There is no definitive diagnostic test for HE, therefore a diagnosis is based on the presence of consistent clinical signs, the exclusion of other causes of encephalopathy, laboratory findings, imaging studies, and response to treatment (Lidbury and Cook, 2016). Portosystemic shunting is the most common cause of HE, so all affected patients should be evaluated for this.

Blood tests are useful in determining liver function; tests should include:

  • Total protein
  • Albumin
  • Blood urea nitrogen
  • Total cholesterol
  • Glucose
  • Total bilirubin
  • Ammonium
  • Total bile acids

Hyperammonaemia indicates PSS or hepatic insufficiency and the measurement of pre- and post-prandial bile acid concentration is a useful test for diagnosing hepatobiliary disease, including PSS (Salgado and Cortes, 2013).

In all stages of the clinical syndrome, animals may show non-neurologic signs related to the underlying disease such as vomiting, diarrhoea, weight loss, ascites, insufficient growth, polyuria and polydipsia

A definitive diagnosis of PSS requires diagnostic imaging or surgical exploration. Several imaging modalities are useful for this purpose, including angiography, abdominal ultrasonography, portal scintigraphy, computed tomography angiography and MRI angiography (Lidbury and Cook, 2016).


The underlying cause of the HE should be treated, including surgical ligation of congenital PSS. In the meantime, it should be managed medically with supportive management measures dependent on whether a patient has acute or chronic HE. A typical regime for management of an acute HE crisis involves the components outlined in Table 3 (Bexfield and Watson, 2009; Lidbury and Cook, 2016).

Identify, remove and treat any precipitating factors such as gastrointestinal bleeding, constipation, metabolic alkalosis, hypokalaemia, azotaemia or inflammatory disease.
Withhold food and water for 24 to 48 hours.
Administer intravenous crystalloid fluids taking into account the change in fluid volume and changes in fluid distribution (note that some authors recommend avoiding lactated Ringer’s solution).
Avoid/treat hypokalaemia – measure potassium levels regularly and supplement fluids as necessary.
Avoid/treat hypoglycaemia, as this can cause irreversi-ble brain damage and seizures – measure blood glucose frequently and supplement fluids as necessary.
Administer warm water enemas (10ml/kg q4-6 hours) to remove any source of ammonia from the faeces. Lactulose can be given per rectum after a cleansing warm water enema at a dose of 1-3ml/10kg body weight (diluted to 30 percent with warm water) q6-8 hours for dogs and cats. Oral lactulose may be administered once an animal is able to swallow.
Give antibiotics, eg ampicillin, intravenously at a dose of 20mg/kg q6-8 hours to protect against bacteraemias.
Administer a gastroprotectant (eg intravenous ranitidine) if there is evidence of gastrointestinal bleeding. Oral sucralfate should only be used once an animal is able to swallow. Cimetidine should be avoided as it is metabo-lised by the liver.
Use a low-dose propofol infusion if seizuring (1mg/kg bolus followed by 0.1-0.2mg/kg/minute infusion to effect). The use of diazepam to control seizures is controversial as it is hepatically metabolised.
Administer intravenous mannitol (0.5-1.5g/kg over 10-20 minutes) if clinical signs are suggestive of cerebral oedema.
TABLE (3) Treatment of an acute hepatic encephalopathy crisis

Traditionally, dietary management of HE patients has revolved around protein restriction to reduce ammonia absorption from the colon. More recently, it has been suggested that colonic ammonia absorption is really only significant in patients fed on poor-quality diets that contain poorly digestible protein (Bexfield and Watson, 2009). Moreover, it has been demonstrated that patients with chronic liver disease may develop severe muscle wasting from being in a long-term catabolic state and a low-protein diet can lead to increased muscle protein catabolism, promoting further hyperammonaemia (Center, 1998).

The current practice when reintroducing food to patients with HE is as much protein as they can tolerate, or to restrict protein to a level that is just enough to prevent HE. If protein restriction is necessary, a minimal intake of 2.1g protein/kg body weight/day is recommended for dogs; 4.0g/kg body weight/day is recommended for cats (Cordoba et al., 2004).

Selection of an appropriate dietary protein source should also be considered. Nonmeat protein-based diets are often recommended for dogs with HE (Proot et al., 2009). Due to the unique metabolic requirements of cats, the use of vegetable protein sources is not advised. A high quality, highly digestible protein should be fed little and often in normal amounts. A feeding tube should be considered in patients that are anorexic. Treatment should be monitored by

If protein restriction is necessary, a minimal intake of 2.1g protein/ kg body weight/day is recommended for dogs; 4.0g/kg body weight/day is recommended for cats

weighing the animal regularly, body condition scoring and checking blood albumin levels (Bexfield and Watson, 2009).

Protein levels in the diet should be increased if blood protein levels fall or the dog loses weight. A commercially prepared prescription diet (such as Royal Canin Hepatic) is appropriate for patients with HE (Cordoba et al., 2004; Proot et al., 2009). If the patient becomes neurologically asymptomatic, the level of protein in the diet can be slowly increased by 0.3 to 0.5g/kg at 7- to 10-day intervals using an additional dairy or vegetable protein (Cordoba et al., 2004).

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