DIAGNOSTIC AND THERAPEUTIC APPROACH TO ACUTE LIVER FAILURE
Romy M. Heilmann, med.vet., Dr.med.vet.
Texas A&M University, College Station, TX
Introduction
Acute liver failure (ALF) is a serious, rapidly progressive, and often lethal condition in dogs and
cats. Because the liver has a large reserve capacity, ALF reflects a state of severe hepatocyte
damage and/or dysfunction. The liver is highly susceptible to toxicity due to its central role in
metabolism and detoxification, and toxins can be further potentiated due to biotransformation
in the liver. Genetic factors likely also influence the individual susceptibility to ALF. Causes of
ALF include drugs (e.g., acetaminophen, diazepam, lomustine), environmental and plant toxins
(e.g., cycad, aflatoxins, blue-green algae, heavy metals), infectious diseases (e.g., Leptospira
spp., fungal infections), neoplasia (e.g., lymphoma, histiocytic sarcoma, hepatocellular
carcinoma), and other conditions (e.g., severe hepatic lipidosis in cats). Liver toxicity associated
with environmental or plant toxins occurs more frequently in dogs than in cats due to an often
indiscriminant appetite.
Presentation of patients with ALF
Patients with ALF often present with a peracute to acute onset of lethargy, weakness, and/or
vomiting. Physical examination often reveals marked dehydration, hypotension, icterus,
bleeding tendency, and in severe cases also neurological signs (severe lethargy, confusion,
recumbency, seizures, and/or coma) consistent with hepatic encephalopathy.
Diagnostics
Bloodwork of patients presenting in ALF often shows an increased bilirubin, increased liver
enzyme activities (hepatocellular pattern of injury: ALT and AST higher than ALKP and GGT;
cholestatic enzyme pattern: ALKP and GGT higher), and evidence of synthetic failure (decreased
cholesterol, total protein, albumin, and BUN). Ammonia is elevated in patients with hepatic
encephalopathy. Coagulation testing typically reveals prolonged clotting times and a decrease
in antithrombin, protein C, and coagulation factors. Abdominal ultrasound may indicate
echogenicity changes of the liver, but finding a normal liver on ultrasound does not rule out
ALF. Abdominal effusion can be seen with acute intrahepatic and splanchnic hypertension.
Infectious disease testing (Leptospira spp. serology and/or PCR) should be initiated in dogs with
ALF that are not current on the Leptospira spp. vaccine and those that have an unknown
vaccination history.
Some underlying causes (neoplasia such as lymphoma or histiocytic sarcoma) can be diagnosed
on fine-needle aspirates of the liver after the patient has been stabilized. A liver biopsy for
histopathologic evaluation, aerobic/anaerobic culture, and copper quantification (ultrasoundguided core needle biopsy, laparoscopic biopsy, or surgical biopsy) with cholecystocentesis
(aspiration of the gallbladder) for culture and cytology can be more definitive for predicting the
chance of recovery. However, toxic etiologies are seldom identified. Biopsy of the liver in
patients with ALF is associated with a significant risk of bleeding and requires treatment with
vitamin K1, desmopressin, cryoprecipitate and/or fresh-frozen plasma (FFP) prior to the
procedure.
Treatment
Patients with ALF should be treated and monitored in a 24-hour hospital care facility. An
intravenous catheter is essential for administration of fluids, medications, and (if indicated)
blood products. A 3-port jugular catheter (central line) is preferred in our hospital as it can be
used for intravenous administration but also for repeated blood sampling and monitoring of the
central venous pressure (if indicated).
Treatment of patients with ALF is mostly supportive. Activated charcoal or enemas can be given
if a known toxin was ingested and is suspected to still be contained in the gastrointestinal tract.
Supportive care should include administration of an antiemetic (ondansetron, metoclopramide,
maropitant) and liver protectant medication (intravenous: N-acetylcysteine; oral: Sadenosylmethionine, silibinin, vitamin E). Vitamin K1 (1 mg/kg q12h) should be administered
subcutaneously.
Intravenous crystalloids (LRS, Normosol-R, 0.9% NaCl) are an important aspect of ALF treatment
but require close monitoring for third space fluid transudation (development of edema and
abdominal effusion). Dextrose should be supplemented (2.5% or 5%) in patients with
hypoglycemia. The use of colloids (hetastarch, Vetstarch) in patients with ALF is controversial
due to the potential anticoagulant effects. Cryoprecipitate and/or fresh-frozen plasma (FFP) are
used to replace fibrinogen and coagulation factors. Antibiotics are given if bacterial
translocation from the intestine (metronidazole, amoxicillin, enrofloxacin) or if leptospirosis
(doxycycline, ampicillin) is a potential concern. Hepatic encephalopathy warrants oral
treatment with a non-absorbable antibiotic (neomycin, metronidazole, rifaximin) and the stool
softener lactulose. Patients with severe hepatic encephalopathy may require a lactulose enema
followed by cleansing water enemas.
Good nursing care and nutritional support are very important. Adequate protein should be
provided except for patients with severe hepatic encephalopathy. Hyporexic or anorexic
patients require placing a feeding tube (esophageal, nasoesophageal, or nasogastric).
Parenteral nutrition (partial or total) may be needed in patients with severe hepatic
encephalopathy.
Monitoring and Prognosis
Prognostication is limited with non-invasive tests. Sequential blood work (liver enzymes, total
protein, albumin, glucose, BUN, cholesterol, bilirubin, fibrinogen, antithrombin-III, electrolytes,
and ammonia) and urinalyses (to looks for ammonium biurate crystals, glucose, and casts) can
be helpful and should be performed. Patient parameters (attitude, temperature, heart rate,
pulse quality, respiratory rate, respiratory sounds, mucous membrane color, and capillary refill
time) and systemic blood pressure (Doppler or oscillometric) should also be closely monitored.
Despite the high potential of the liver for tissue regeneration, ALF is rapidly progressive and
often fatal. Poor prognostic indicators are hepatic encephalopathy and persistent
hypoglycemia. Patients that survive ALF can develop acquired portosystemic shunts and may
require life-long medical management.