Liver: acute disease

• Cause: overwhelming toxic or metabolic (eg lipidosis) insult, neoplasia or infection; acute on chronic liver disease.
• Signs: non-specific; anorexia, vomiting, depression +/- polydipsia/polyuria; signs of hepatic encephalopathy.
• Diagnosis: biochemistry, ultrasonography, hepatic biopsy.
• Treatment: underlying cause if recognized; otherwise supportive and symptomatic.
• Prognosis: depends on etiology, severity and treatment of inciting factor.
• See also Liver: chronic disease Liver: chronic disease.

• Collapse/coma.
• Seizures.

Infection

• Viral: FeLV Feline leukemia virus disease, FIP Feline infectious peritoniti , (usually chronic presentation).
• Bacterial: extension of neutrophilic cholangitis* (previously suppurative cholangiohepatitis) Liver: cholangitis, or hematogenous.
• Mycotic: eg, histoplasmosis Histoplasma capsulatum, if associated with pulmonary disease.
• Protozoal, ie toxoplasma Toxoplasmosis.
• Parasitic: liver flukes (not in UK).
• * Based on WSAVA recommendations the classification of feline liver disease has been clarified and is now:
  • Neutrophilic cholangitis (acute and chronic).
  • Lymphocytic cholangitis (acute and chronic).
  • Chronic cholangitis (fluke infestation in endemic areas).

Immune mediated

• Lymphocytic cholangitis (acute and chronic, previously cholangiohepatitis).

Hepatotoxins

Cats have a relative sensitivity to many drugs due to low levels of glucuronyl transferase delaying metabolism.

• Drugs: anticonvulsants, azathioprine Azathioprine, ketoconazole Ketoconazole, methoxyflurane Methoxyflurane, sulfonamides Trimethoprim, tetracycline Tetracycline .
• Chemicals: carbon tetrachloride, heavy metals, selenium, tannic acid.
• Biological substances: aflatoxin, blue-green algae.

Metabolic

• Acute pancreatitis Pancreatitis, acute hemolytic anemia Anemia: immune-mediated hemolytic, hepatic lipidosis Liver: lipidosis, trauma Trauma: overview, heat stroke Hyperthermia.

Specific

• Unvaccinated animals.

• Overwhelming hepatic insult   →   functional reserve capacity exceeded   →   failure to perform diverse metabolic functions   →   clinical signs.

• Hepatic functional reserve large   →   75% damage before exhausted   →   periacinar zonal necrosis, infiltration of inflammatory cells due to toxins, living agents and metabolic disease will cause extensive damage.
• Decreased production of clotting factors   →  bleeding tendency.
• Hepatic cellular damage   →   cellular release of bilirubin   →  icterus.
• Inflammation of biliary system   →   partial obstruction to biliary flow   →  icterus.
• Inadequate bile delivery to intestine   →   impairment of fat digestion   →  diarrhea.
• Failure to maintain euglycemia   →  hypoglycemia.
• Decreased production of albumin   →  hypoalbuminemia.
• Failure to detoxify ammonia and other mercaptans from intestine   →  hepatic encephalopathy Hepatic encephalopathy.

• Dependent on etiology, within days of ingestion of toxin, infection.

• Lethargy.
• Anorexia.  
• Icterus.
• Vomiting Vomiting.
• Diarrhea.
• Coma.
• Polydipsia/polyuria.

• Anorexia.
• Depression.
• Vomiting Vomiting.

• Diarrhea Diarrhea: dietary.
• Polydipsia/polyuria.
• Icterus.
• Altered mentation.
• Excessive salivation.

• Behavioral changes.
• Seizures Seizures.
• Coma.
• Bleeding tendency.

• Icterus.
• Abdominal pain.
• Depression.

• Pyrexia.
• Signs of hepatic encephalopathy Hepatic encephalopathy.

• Neurological dysfunction related to cerebrum.
• Petechial hemorrhages.

Biochemistry

• Serum enzymes - activity may be first indicator of hepatic disease.
  Extent of increased activity does not reflect severity of damage; cannot be used for prognosis.
• Alanine aminotransferase Blood biochemistry: alanine aminotransferase (SGPT, ALT) - intracellular enzyme released when hepatocellular necrosis occurs - ie indicates acute or active hepatocellular damage.
• Alkaline phosphatase Blood biochemistry: alkaline phosphatase, and gamma glutamyl transferase Blood biochemistry: gamma glutamyl transferase - increased production due to intrahepatic or biliary cholestasis.
  Sensitive and specific in the cat as no steroid-induced isoenzyme of ALP - as in the dog.
• Ammonia  Blood biochemistry: ammonia: produced by intestinal bacteria degraded in liver; increased levels due to hepatic failure or porto-systemic shunt.
  Samples should be taken into heparin container and stored on ice until analyzed.
• Bilirubin  Blood biochemistry: total bilirubin: elevated bilirubin.
• Bile acids  Blood biochemistry: bile acid: increased fasting and 2 hrs post prandial levels; good test of hepatic function.
• Albumin  Blood biochemistry: albumin: rarely see significant decrease. Albumin is a negative acute phase protein, non-specific decrease of 10-20% with inflammation.

Bacteriology

• Blood culture to identify bacteremia.
• Gall bladder aspirate and culture (surgical or by ultrasound guided percutaneous aspirate).
• Check for possible coagulopathy.

2-D Ultrasonography

• Abdominal examination to identify pancreatic/gall bladder disease.
• Evaluation of hepatic parenchyma/identification of diffuse or focal lesions.

Histopathology

• Liver biopsy Biopsy: hepatic to determine etiology if initial tests non-diagnostic - may perform at laparotomy Laparotomy: midline, or by ultrasound guided percutaneous biopsy Biopsy: ultrasound-guided.
  Check for possible coagulopathy.

Radiography

• Liver usually normal size or enlarged in acute hepatic failure.

• Liver occasionally looks normal in acute disease - histology essential.
• Examine firstin situto rule out portosystemic shunts Congenital portosystemic shunt (CPSS). Remove brain and fix whole if neurological signs accompany.
• Bacteriological sample where indicated - swab through incised seared surface.

• Consider fresh samples for toxicology, (liver, kidney, fat, stomach contents, urine - consult lab).
• Consider frozen sections for fatty liver.

Primary liver diseases

• Cholangitis (neutrophilic or lymphocytic) Liver: cholangitis.
• Neoplasia, eg lymphosarcoma, bile duct carcinoma, systemic mastocytosis.
• Portosystemic shunts Congenital portosystemic shunt (CPSS).
• Toxic hepatopathy.

Secondary liver diseases

• Feline infectious peritonitis (FIP Feline infectious peritonitis).
• Toxoplasmosis Toxoplasmosis.
• Neoplasia - metastatic.
• Hepatic lipidosis Liver: lipidosis - idiopathic, endocrine disorders.
• Feline 'triaditis'.

Causes of jaundice

• Causes of hemolytic anemia: Hemobartonella felis Mycoplasma haemofelis, 'Candidatus Mycoplasma haemominutum' and 'Candidatus Mycoplasma turicensis'  , autoimmune hemolytic anemia Anemia: immune-mediated hemolytic, FeLV Feline leukemia virus disease.
• Hepatocellular disease, (see primary and systemic causes of liver disease).
• Obstructive: intrahepatic, eg neoplasia, inflammation; extrahepatic, eg pancreatic neoplasia Pancreas: neoplasia, or inflammation, bile stones.

• Cage rest and nutritional support to optimize conditions for hepatic regeneration and prevent scarring.
• Intravenous fluids Fluid therapy: overview, to maintain fluid and electrolyte balance.
• Intravenous diazepam Diazepam, if seizures, avoid repeated use.

• Antibiotics, if indicated, to counter primary and secondary infections and reduce gut ammonia production (ampicillin Ampicillin, neomycin Neomycin).
• Sucralfate Sucralfate (500mg SID), if gastrointestinal bleeding.

• Dextrose added to intravenous fluids if hypoglycemia.
• If encephalopathy, may use enemas to remove substrates for bacterial metabolism and lactulose Lactulose, to minimize ammonia Blood biochemistry: ammonia, and mercaptan production.
• Discontinue any suspect drugs.
• Feed high quality protein diet.
  Cottage cheese alone is inadequate as a protein source in cats. It is deficient in arginine which is essential in the urea cycle and therefore very important in liver disease.
• Protein reduction only indicated if there is encephalopathy.
  Protein restriction can seriously impair liver's ability to regenerate and indiscriminate restriction may reduce or prevent recovery since cats have a high protein requirement.

• Vitamin K Vitamin K, if coagulopathy.

• Watch for development of coagulopathy, encephalopathy.
• Check serum glucose Blood biochemistry: glucose, in case hypoglycemia develops.
• Serum potassium Blood biochemistry: potassium, since hypokalemia may worsen encephalopathy.

Treatment

• Maintain reduced protein, low fat, high carbohydrate diet Dietetic diet: for liver insufficiency.
• Minimize exercise.

Monitoring

• Serum biochemistry every 2-3 weeks.
• If persistent abnormalities, follow-up liver biopsy.

• Depends on severity and elimination of underlying insult.
• Poor if coagulopathy and/or hepatic encephalopathy present.
• Less severe forms may result in complete regeneration.
• Persistent inflammation may result in chronic hepatitis Liver: chronic disease.

• Resolution of vomiting, depression, anorexia, etc. within days of treatment initiation.
• Serum biochemistry returns to normal within 3 weeks.

• Failure to identify and treat underlying disease/inciting factor.
• Failure to maintain rest may lead to fibrosis of liver and permanent damage.

Refereed papers

• Recent references from PubMed and VetMedResource.
• Center S A, Warner K, Corbett J et al (2000) Proteins invoked by vitamin K absence and clotting times in clinically ill cats. JVIM 14 (3), 292-297 PubMed.
• Center S A (1999) Chronic liver disease - current concepts of disease mechanisms. JSAP 40 (3), 106-114 PubMed.

Other sources of information

• Marks S L (2008) Feline hepatic disorders: update on diagnosis and management. Proceedings of the 51st BSAVA Congress, pp 201-205.
• Rothuzien J, Bunch S E, Cullen J M, Charles J A, Desmet V J, Twedt D C, van den Ingh T, van Winkle T, Washabua J (eds) (2006) WSAVA Liver Standardization Group. Standards for Clinical and Histological Diagnosis of Canine and Feline Liver diseases. Saunders/Elsevier, Edinburgh.
• Michel R (1995) Nutritional management of liver disease. Veterinary Clinics North America (SA) 25, 485.