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Acute Liver Failure – A review of recent publications
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Acute liver failure is a severe, often fatal condition of the liver, characterised by severe and widespread liver injury resulting in cellular necrosis, inflammation, and associated loss of liver function. The aim of this blog is to summarise findings from two recent literature reviews on acute liver failure in dogs and cats1,2, and a recent retrospective review of 49 clinical cases of acute liver failure in dogs3.
Acute liver failure is defined as acute liver injury that is severe enough that it compromises liver functions, including the following:
Protein synthesis
Glucose metabolism – glycogen production and glycogenolysis
Fat metabolism
Coagulation factor production
Immune function
Bile acid secretion
Bilirubin metabolism
Ammonia metabolism
In addition, further characterization of acute liver failure, based on recent human definitions may also include:
The absence of pre-existing liver disease
The presence of hepatic encephalopathy
Elevated bilirubin concentrations
The presence of coagulopathy
Aetiology1-3
Numerous causes of acute liver failure exist in dogs and cat, including toxins, drugs, infectious agents, and even some cancers.
Among the most common toxins associated with acute liver failure are
Cycads (Sago Palms)
Blue-green algae
Amanita phalloides
Aflatoxins
Xylitol
Drugs may cause acute liver failure in a dose-dependent manner (intrinsic toxins), or an idiosyncratic manner. Drugs that are known to cause acute live failure include
Carprofen
Acetaminophen (Paracetamol)
Phenazopyridine
Sulfonamides
Lomustine (CCNU)
Zonisamide
Stanozolol (cats)
Oral benzodiazepines (cats)4
Infectious agents such as leptospirosis and canine adenovirus-1 are known to cause acute liver failure in dogs
Leptospirosis
Canine adenovirus-1
Idiopathic hepatic lipidosis in cats
Trematodes
Platynosomum fastosum is a small liver fluke that invades the biliary ducts and gallbladder of cats after the cat ingests lizards containing the fluke. Infected cats may remain asymptomatic, or may present with biliary obstruction and liver failure
Neoplasia
Round cell tumours and lymphoma have been associated with development of acute liver failure in dogs
Clinical signs1-3
Clinical signs of acute liver failure reflect the important role of the liver in metabolism, protein synthesis and immune-function. Aside from non-specific symptoms, such as nausea, vomiting, diarrhoea, and anorexia, the following are key components of acute liver failure – both in terms of diagnostic value, and prognostic value.
Icterus
Coagulopathy
Hepatic encephalopathy
Hypoglycaemia
Sepsis
Diagnosis1
The diagnosis of acute liver failure is usually made based on documentation of elevations in transaminases (ALT, AST) and inducible enzymes (ALP, GGT), combined with elevations in ammonia, bilirubin and coagulation times.
Treatment1,2
Treatment of acute liver failure falls into three (3) categories:
Toxin decontamination and antidote therapy
Most hepatic toxins do not have specific antidotes available
Acetaminophen
N-acetylcysteine 140 mg/kg loading dose, followed by 100 mg/kg given over 16 hrs. as a CRI
Mushrooms
Penicillin G 300.000-1,000,000 units/kg/day IV
Silymarin 30-40 mg/kg/day PO for 3-4 days
Hepatic lipidosis
Nutritional support via feeding tube
Supportive care
Intravenous fluid therapy
Intravenous fluid therapy is used to correct hypovolaemia and hydration deficits.
Ringers acetate is preferred to lactated Ringer’s solution, as lactate requires hepatic metabolism to form the active buffer.
Synthetic colloid fluid therapy is relatively contraindicated in patient with acute liver failure
Vasopressors and positive inotropes
In patients who remain hypotensive, despite several boluses of crystalloid fluid therapy, the use of positive inotropes and vasopressors should be considered
Corticosteroids: in patients who are persistently hypotensive despite the aforementioned efforts, a physiological dose of corticosteroids may be trialed, on the assumption the patient may have critical-illness related corticosteroid insufficiency.
Maintain normoglycaemia
Monitor for, and correct hypoglycaemia using glucose bolus (5 ml/kg of 10% glucose IV over 5 minutes) +/- continuous infusion (1-2 ml/kg/hr of 5% glucose IV continuous infusion)
Correct electrolyte abnormalities as they arise
Nutrition:
Provide nutritional support early in disease, using enteral route (preferred) or parenteral route (if enteral route not possible)
50% of calories should be provided in the form of readily digestible, soluble carbohydrates
20-40% of the diet should be provided in the form of fats
Vitamin K1 should be supplemented at 1-2 mg/kg/day
Thiamine should be supplemented at a dose of 5-10 mg/kg q 12 hrs.
Hepatic anti-oxidants
Glutathione precursors and anti-oxidants such as N-acetylcysteine (NAC), S-adenyl L-methionine (SAMe), or Silibinin may be supplemented
Vitamin E is a free-radical scavenger that may be supplemented at a dose of100-400 UI/day (dog); 30-50 UI/day 9cat)
Management of complications
Infection
Routine use of antibiotics in non-septic patients is controversial
In septic patients, amoxycillin 20 mg/kg IV q 8 hrs.; +/- metronidazole 10 mg/kg IV q 12 hrs. may be recommended
Coagulation abnormalities
Patients with acute liver failure usually have coagulopathy resulting from reduced hepatic production of clotting factors, as well as increased total body consumption of clotting facts (DIC)
Evidence for survival benefit from transfusion of fresh frozen plasma in patients without occult bleeding is lacking
Fresh frozen plasma should be administered at a dose of 20-30 ml/kg in patients with clinical evidence of haemorrhage, or in those patients undergoing invasive procedures (hepatic biopsy, feeding tube placement etc.)
Hypoglycaemia
Hypoglycaemia should be managed as previously outlined
Hepatic encephalopathy
Hepatic encephalopathy resulting from acute liver failure results from vasogenic oedema, rather than accumulation of toxins such as ammonia, mercaptans, etc.
Maintain systolic arterial blood pressure at 100-120 mm Hg with intravenous fluids, inotropes and vasopressors as indicated
Ensure adequate respiratory function
In the euvolaemic patient with deteriorating HE, mannitol at 0.25 g/kg IV over 10-20 minutes may be considered
Control convulsions with propofol continuous infusions 6 mg/kg/hr IV CRI
Prognosis1-3
The prognosis for acute liver failure in dogs varies, depending on the cause – but may be as high as 86%3. Acute liver failure cause by infectious diseases, such as leptospirosis; and pharmacological toxicosis, such as NSAID and acetaminophen appear to carry a better prognosis than acute liver failure caused by environmental toxins such as algae, cycads and mushrooms.
In addition, negative prognostic indicators in dogs and cats include1
Higher elevations of ALT and bilirubin in dogs with cycad ingestion
Low albumin concentrations in dogs with cycad ingestion
Mushroom poisoning
Blue-green algae ingestion
Development of clinical bleeding or ascites during hospitalization
References:
Weingarten MA, Sande AA. Acute liver failure in dogs and cats. Journal of Veterinary Emergency and Critical Care. 2015 Jul;25(4):455-73.
Thawley V. Acute liver injury and failure. Veterinary Clinics: Small Animal Practice. 2017 May 1;47(3):617-30.
Lester C, Cooper J, Peters RM, Webster CR. Retrospective evaluation of acute liver failure in dogs (1995–2012): 49 cases. Journal of Veterinary Emergency and Critical Care. 2016 Jul;26(4):559-67.
Hughes D, Moreau RE, Overall KL, Winkle TV. Acute Hepatic Necrosis and Liver Failure Associated with Benzodiazepine Therapy in Six Cats, 1986–1995. Journal of Veterinary Emergency and Critical Care. 1996 Jan;6(1):13-20.
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