Acute liver failure

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Episode based on:

Weingarten MA, Sande AA. Acute liver failure in dogs and cats. J Vet Emerg Crit Care 2015. 25(4):455-473.

Get in touch if you would like a copy of the paper.

1. Injury versus failure:

Acute liver injury: acute hepatocellular damage but liver function is retained; damage may resolve without any impact on function
Failure implies reduced liver function due to severe and extensive damage

2. More common causes:


Cycad Palms or Sago Palms:

  • Found throughout the USA, especially in the South; also in other countries but not native to the UK
  • Primary toxin is cycasin
  • No specific treatment or antidote

Blue-green algae*
Amanita mushrooms*

(* No specific antidotes or therapies)

Xylitol – see episode 6

Drug/Drug reactions:

Dose-dependent predictable hepatotoxic drugs versus idiosyncratic non-dose dependent hepatotoxicity
Paracetamol (acetaminophen):

  • Used therapeutically in dogs; wide safety margin in this species
  • Cats are very susceptible to its dose-dependent toxicity so it should not be used in this species

Infectious – especially leptospirosis
Hepatic lipidosis in cats
Fatal acute hepatic necrosis in cats due to oral administration of diazepam and zolazepam – idiosyncratic

3. Clinical findings and consequences:

Clinical signs:

Often non-specific, e.g. vomiting, diarrhoea, anorexia, lethargy etc.
May progress toward sepsis and multiple organ dysfunction
May be due to primary cause of ALF and/or consequences of ALF

Icterus/jaundice due to hyperbilirubinaemia:

  • Three types: pre-hepatic due to red cell haemolysis; hepatic and post-hepatic which often occur to some extent concurrently

“Due to the large reserve capacity of the liver, icterus due to intrahepatic cholestasis is only apparent when the liver is severely and diffusely affected.”


ALF has multifactorial and complex effects on coagulation

“Some patients with ALF may show no evidence of hemorrhage, others may hemorrhage only after invasive procedures including placement of IV catheters, while others may have spontaneous hemorrhage”

Both primary (thrombocytopenia, thrombopathia, endothelial dysfunction) and secondary (clotting factor deficiency) clotting abnormalities may be present

ALF may result in altered production of both procoagulant and anticoagulant factors
Patients with ALF often have functional defects in vitamin K-dependent coagulation factors
May have evidence of dysfibrinogenaemia or hyperfibrinolysis in the absence of DIC

“The end result of these alterations in primary hemostasis, secondary hemostasis, and fibrinolysis is a “rebalanced,” but often unstable, system that can result in either hemorrhage or thrombosis.”

Hepatic encephalopathy:

Neuropsychiatric disorder subdivided into 3 types based on chronicity, aetiology and presentation:

  • Type A: acute form, associated with acute liver failure
  • Type B: bypass form, associated with portal-systemic shunts
  • Type C: chronic form, associated with cirrhosis and portal hypertension

Signs of type A HE often manifest suddenly and progress rapidly; spectrum from mild to very severe neurological signs
Ammonia likely plays a crucial role in the development of type A HE; further complicated by cerebral oedema, intracranial hypertension, hypoglycaemia, hyponatraemia, and systemic inflammatory response syndrome (SIRS). 


In health, the liver plays a key role in the body's innate and acquired immune systems. Through the portal circulation, the liver is exposed to bacteria from the gastrointestinal tract and the liver also synthesises factors involved in the complement cascade. In ALF, the liver is unable to effectively remove or neutralise pathogens prior to the blood passing into systemic circulation, resulting in bacteraemia.

“In people with ALF, bacteremia has been reported in up to 80% of the patient population, most commonly with gram-negative enteric organisms, staphylococci species, and fungal organisms, such as Candida albicans. Iatrogenic sources of bacteremia are common and include indwelling intravenous and urinary catheters, as well as skin contamination.”

4. Diagnosis:

Clinical pathology:

Need to demonstrate hepatic dysfunction or insufficiency rather than just injury
Intracellular ‘leakage’ enzymes – ALT, AST – increase first signifying hepatocellular injury
Inducible membrane-bound ALP and GGT may also increase – typically to much less extent but depends on presence of concurrent biliary tract obstruction

“Increase in both ALT and AST activities are sensitive indicators of acute liver damage, but the degree of increase in these values above the reference interval does not necessarily correlate with the degree of hepatocellular damage.”

Subsequent evidence of dysfunction:

  • Hyperbilirubinaemia
  • Prolonged prothrombin time
  • Hypoglycaemia
  • Hypoalbuminaemia – typically end-stage

But sequence and development of these findings can vary.

“There are several electrolyte and acid-base derangements that either occur as a result of ALF or complicate management of ALF patients. These abnormalities include hypokalemia, hypophosphatemia, hyperphosphatemia, hyponatremia, hyperlactatemia, and refractory metabolic acidosis”.

“Patients with ALF often develop hyperlactatemia and an associated metabolic acidosis. Causes of hyperlactatemia include hypotension, poor tissue perfusion, and tissue hypoxia with subsequent anaerobic metabolism and lactate production at the level of the tissue…Hyperlactatemia has been associated with a poor prognosis in human patients with ALF and HE as well as people with ALF secondary to acetaminophen toxicity.”


“plasma ammonia concentrations remain difficult to interpret as it is the actual exposure of the brain to ammonia, not the concentration of ammonia in circulation, that leads to the development of HE. Therefore, the health of the blood–brain barrier, an immeasurable quantity, plays a significant role in the clinical interpretation of ammonia concentration and the development of HE….However, serum ammonia concentration may be useful for prognosis as hyperammonemia at presentation as well as persistent hyperammonemia in spite of treatment has been associated with both increased rates of cerebral herniation as well as an increased mortality rate” in people.

Performance of in-house point-of-care analysers can be very unpredictable/unreliable
Submitting samples to external laboratories is possible – must heed sample-handling guidelines including keeping on ice

Diagnostic imaging:

Routine imaging will not evaluate liver function but may demonstrate gross abnormalities in liver structure; these vary depending on the cause of the pathology, in particular between focal and diffuse conditions.
Ultrasonography will also allow guided samples to be obtained for histopathology

“when diagnosing ALF, sonography is a useful, but not definitive, tool and must be paired with appropriate history, physical examination findings, biochemistry results, and histopathology.”

5. Treatment:

“Aggressive treatment for ALF should be initiated as soon as possible. If the underlying cause is known, it should be removed and an antidote, if available, administered. Unfortunately, the inciting cause of ALF is often unknown and thus the cornerstone of therapy in veterinary patients remains supportive care while the liver is allowed time to recover. Generalized supportive care includes intravenous fluid therapy, liver supplemental medications, nutritional management, and management of any complications that may arise.”

Supportive care:

Fluid therapy:

Standard approach in terms of correcting hypovolaemia/hypoperfusion and dehydration and subsequent maintenance of fluid balance

Avoid lactate-containing fluids?

“Lactated Ringer's solution should be avoided as it contains lactate as a buffer, which requires a functioning liver for proper metabolism”; remember that this lactate would be converted by the liver to bicarbonate which according to the traditional model of acid-base is why Hartmann’s or lactated Ringer’s is considered an alkalinising solution.

“it seems to me that the recommendation to use 0.9% sodium chloride is based on theoretical reasoning to avoid the administration of lactate; the sodium concentration is higher than that in Hartmann’s which may be helpful because as I mentioned earlier these patients may be hyponatraemic, but this solution may also promote a metabolic acidosis in a patient that is potentially already acidaemic. What patient-centred clinical relevance all this has, well, I don’t think we can say for sure.” (Shailen)

“In patients who remain hypotensive (systolic blood pressure < 90 mm Hg, MAP < 65 mm Hg) despite correction of intravascular volume depletion with fluid therapy, vasopressor therapy may be required….In patients who are persistently hypotensive despite volume resuscitation and the use of vasopressors, relative adrenal insufficiency, and a trial of a supraphysiologic dose of a corticosteroid could be considered.”

For more on critical illness-induced corticosteroid insufficiency see “Steroids and Shock” episode, number 17

Maintain normoglycaemia – avoid hyperglycaemia – and normal electrolyte status
Avoid hyponatraemia


“Patients in ALF typically exist in a hypermetabolic state with a higher than normal energy requirement, leading to a catabolic state characterized by a negative nitrogen balance….Provision of adequate dietary protein is essential as catabolism of skeletal muscles leads to increased ammonia production, decreased capacity for muscle detoxification of ammonia, and increased potential for HE.”

Preferred protein sources may vary between patients with HE and those without in terms of keeping ammonia production low
Also consider carbohydrates, lipids, vitamins

“Hepatoprotective” medications:

“There are numerous “hepatoprotective” medications on the market, including SAMe, NAC, silymarin, and vitamins C and E, which decrease oxidative stress. In health, hepatocytes have potent intrinsic antioxidant systems including glutathione (GSH). In damaged livers, GSH may be less available, resulting in increased ROS concentrations leading to hepatocyte death.”

Lack of evidence in terms of efficacy (except for N-acetylcysteine in paracetamol toxicity)
Considerable uncertainty in terms of therapeutic dosing regimens

“I think the perspective with these agents in acute liver failure is that they may do some good, we don’t know for sure, but are unlikely to harm the patient. Of course we have to factor any patient stress caused by administration of oral medications and any financial costs into our risk and cost to benefit assessment.” (Shailen)

Management of complications:


“In human patients with ALF, the most common sites of infection are the lung, urinary tract, and blood and the most commonly isolated organisms include Staphylcocci, Streptococci, and enteric gram-negative bacilli…Infection prevention is crucial and cleanliness should be strictly maintained by doctors and nursing staff through thorough hand washing and barrier nursing protocols…The use of prophylactic antimicrobials in all ALF patients is controversial, as prophylactic parenteral and enteral antimicrobials have not been shown to improve outcome or survival in these patients….Empirical antimicrobial therapy is recommended when suspicion for infection or the likelihood of sepsis is high, such as when there is progression of HE, refractory hypotension, or the presence of SIRS…The choice for empiric antimicrobial therapy should include broad spectrum coverage for gram-positive and gram-negative bacteria, such as a third-generation cephalosporin.”

Coagulation disorders:

Spontaneous haemorrhage uncommon
Plasma therapy not recommended solely on the basis of a prolonged PT or aPTT
No clear benefits to the use of plasma in patients without evidence of haemorrhage; need to be cognoscente of potential risks (albeit less than with red cell administration)/costs

What about giving plasma before an invasive procedure?

“This recommendation is empirically derived, as there are no evidence-based data showing that the treatment of coagulopathies results in less risk of hemorrhage during invasive procedures, and there are no data showing an appropriate standard end-point of therapy.”

Treat all ALF patients with vitamin K1?
Consider H2 blockers or proton pump inhibitors as gastrointestinal bleeding is a potential complication?

Hepatic encephalopathy, cerebral oedema, and increased ICP:

“Unlike with patients with type C [chronic] HE, there are currently insufficient data to recommend therapy with lactulose or nonabsorbable antimicrobials such as rifaximin and neomycin in patients with ALF.” Not sure of the evidence base for this.

Correction of cerebral oedema via mannitol or hypertonic saline is a mainstay of therapy in acute liver failure patients with hepatic encephalopathy
For more on intracranial hypertension detection and management see traumatic brain injury episode, episode 22.

6. Prognosis:

Varies considerably depending on:

  • Underlying aetiology
  • Degree of hepatocellular damage
  • Capacity of liver to regenerate
  • Stage of disease when treatment is initiated
  • Presence and rapidity of development of disease sequelae such as HE
  • Response to therapy

“Unfortunately, the prognosis of ALF in dogs and cats is generally considered to be poor” 


Auzinger G, Wendon J. Intensive care management of acute liver failure. Curr Opin Crit Care 2008; 14(2):179–188.

Weingarten MA, Sande AA. Acute liver failure in dogs and cats. J Vet Emerg Crit Care 2015. 25(4):455-473.

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