Diagnostic and Therapeutic Approach to Acute Liver Failure

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 (ultrasound-guided 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: S-adenosylmethionine, 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.