Liver: chronic disease

• Cause: malformation, toxicity, neoplasia, endocrinopathy, metabolic (lipidosis), auto-immune (lymphocytic cholangitis), infection.
• Signs: non-specific - lethargy, anorexia, vomiting. Signs of hepatic encephalopathy.
• Diagnosis: biochemistry, hepatic function tests, ultrasonography, hepatic biopsy.
• Treatment: elimination of cause, supportive.
• Prognosis: depends on severity and treatment of inciting factor.
• See also Liver: acute disease Liver: acute disease.
  Print off the owner factsheet Liver problems in your cat  Liver problems in your cat  to give to your client.

• Insidious onset when reserve functional capacity is lost (>60%).

• Anorexia Anorexia, depression.
• Vomiting, diarrhea.

• Abdominal distension (ascites).

• End-stage liver failure.

• <5 yrs - lymphocytic cholangitis and feline infectious peritonitis.
• >6 yrs - hyperthyroidism.
• >10 yrs - neoplasia.

• Middle aged - hepatic lipidosis.

• Long-term therapy can be expensive.

• Expenses incurred in establishing a diagnosis.

• Anesthesia - as many commonly used drugs are metabolized in liver.
  Warn owner of increased risk of anesthesia.

• Idiopathic chronic hepatitis.
• Drugs - cats have a relative sensitivity to many drugs due to low levels of glucuronyl transferase delaying metabolism, eg acetaminophen, griseofulvin, megestrol acetate, ketoconazole.
• Infectious, eg FeLV Feline leukemia virus, FIP Feline sarcoma virus; bacterial, fungal and parasitic.
• Portosystemic shunt (congenital) Congenital portosystemic shunt (CPSS).
• Neoplasia, lymphoma Lymphoma or metastatic.
• Endocrinopathies.

• Cumulative 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 massive 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 Hypoglycemia.
• Decreased production of albumin   →  hypoalbuminemia.
• Failure to detoxify ammonia and other mercaptans from intestine   →  hepatic encephalopathy Hepatic encephalopathy.

• Lethargy.
• Anorexia.
• Vomiting Vomiting.
• Diarrhea.
• Polydipsia/polyuria.
• Icterus.
• Neurological signs.

• Lethargy.
• Decreased appetite.
• Behavioral changes.

• Nausea.
• Vomiting.
• Diarrhea.
• Polydipsia/polyuria.

• Abdominal distension (ascites).

• Unkempt hair coat.

• Ascites      .
• Icterus.

Signs of hepatic encephalopathy

• May occur with portosystemic shunt Congenital portosystemic shunt (CPSS), acute or end-stage liver disease.
• Behavior changes - dementia, dullness, aggression.
• Neurological abnormalities - circling, ataxia, head pressing, aimless pacing, seizures.
• Ptyalism  .
• Coma.

Biochemistry

• ALT  Blood biochemistry: gamma glutamyl transferase, AST, ALP Blood biochemistry: alkaline phosphatase, GGT   Blood biochemistry: gamma glutamyl transferase  - abnormalities indicate liver disease or injury (not a measure of liver function).
  May be reactive elevations, eg hyperthyroidism Hyperthyroidism.
• Increased ALP Blood biochemistry: alkaline phosphatase, is a sensitive indicator of cholestasis and a specific indicator of hepatobiliary disease in cats as there is no steroid-induced isoenzyme in this species.
• Bilirubin Blood biochemistry: total bilirubin, not sensitive guide but an increase >3 g/dl suggests liver disease.
• Serum bile acids (SBA Blood biochemistry: bile acid - supercedes BSP clearance test) for hepatobiliary function and portosystemic shunts.
• Ammonia Blood biochemistry: ammonia for hepatobiliary function and portosystemic shunts.

Hematology

• To check for hemolytic disease.

Histopathology

Exclude systemic causes of enzyme elevation, eg hyperthyroidism, before undertaking invasive diagnostic procedures.

• Fine needle aspiration (FNA Fine-needle aspirate).
• Percutaneous blind or ultrasound guided needle biopsy.
• Laparoscopy-guided biopsy.
• Laparotomy Laparotomy: midline (evaluate clotting function before biopsy).

2-D Ultrasonography

• Doppler ultrasound  - ascites    , portosystemic shunt.
• Evaluate parenchyma and biliary system.
• Multifocal radiolucencies - neoplasia or infection/abscessation.
• Identify focal lesions.
• Guide needle biopsy.
  If there is no dilation of the extrahepatic biliary tract, and no hemolytic disease in the presence of jaundice, hepatocellular disease is likely   →   take liver biopsy.
• Diffuse echogenicity - hepatic lipidosis.

Radiography

• Liver size is often normal.
• Hepatomegaly.
• Small (microhepatica     ) - portosystemic shunt.
• Focal masses.
• Choleliths.
• Contrast study - to identify portosystemic shunt   .

• Systematic examination of other organ systems helps interpretation of chronic disease.
• If history consistent, consider samples for toxicology (liver, kidney, fat, urine etc - consult lab).
• Remove brain and fix whole if likely hepatic encephalopathy.

• Swollen, pale, nodular liver.
• Shrunken liver late in disease process.
• Variable-sized regenerative nodules.

• Focal/multifocal masses.

• Frozen sections best demonstrate lipidosis, but formalin fixation acceptable.

• Varies with cause, eg:
  • Moderate to severe inflammation associated with 'piece-meal' necrosis of hepatocytes; begins in portal triad and extends into parenchyma.
  • Small islands of hepatocytes surrounded by inflammatory cells (lymphocytes, plasma cells, sometimes neutrophils)   →   bridging necrosis   →   active cirrhosis.
  • Special stains for copper accumulation (Rubeanic acid, Rhodamine).
  • Fibrosis and parenchymal nodules that disrupt normal hepatic architecture.
  • Presence of specific neoplastic cells, especially metastatic.

Primary liver diseases

• Cholangiohepatitis and lymphocytic cholangitis Liver: cholangitis.
• Neoplasia, eg lymphosarcoma Lymphoma, bile duct carcinoma, systemic mastocytosis.
• Portosystemic shunts Congenital portosystemic shunt (CPSS).
• Toxic hepatopathy (see Liver: acute disease Liver: acute disease).

Secondary liver diseases

• Feline infectious peritonitis (FIP) Feline infectious peritonitis.
• Toxoplasmosis Toxoplasmosis.
• Hyperthyroidism Hyperthyroidism.
• Neoplasia - metastatic.
• Hepatic lipidosis Liver: lipidosis - idiopathic, secondary to obesity Obesity, endocrine disorders.

Causes of jaundice

• Jaundice  .
• Causes of hemolytic anemia: Hemobartonella felis  Mycoplasma haemofelis, 'Candidatus Mycoplasma haemominutum' and 'Candidatus Mycoplasma turicensis' , auto-immune 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 or inflammation Pancreatitis, bile stones.

Causes of ascites

• Primary hepatic disease.
• FIP Feline infectious peritonitis.
• Bacterial peritonitis  Peritonitis.
• Glomerulonephritis (nephrotic syndrome) Glomerulonephritis.
• Congestive heart failure Heart: congestive heart failure.
• Chylous ascites.
• Other fluids (hemorrhage, bladder Bladder: trauma rupture, or biliary rupture).

• Antibiotics Therapeutics: antimicrobial drug  Therapeutics: gastrointestinal system to prevent secondary infections and to reduce gut ammonia production.
• H2 receptor blockers, eg ranitidine Ranitidine or cimetidine Cimetidine.
• Sucralfate Sucralfateif gastrointestinal bleeding.
• Spironolactone Spironolactone if ascites; if refractory, try furosemide Furosemide.
• Lactulose Lactulose and antibiotics for hepatic encephalopathy.
• Feed high quality protein diet Dietetic diet: for liver insufficiency.
  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 restriction 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 and zinc Zinc supplementation may be required.
• Cage rest.
• Ursodeoxycholic acid Ursodeoxycholic acid to displace toxic bile acids, stimulate bile flow and modulate immune response.

Treatment

• Repeat hepatic function tests and hepatic biopsy.

• Depends on underlying cause and degree of hepatic damage.

• Clinical improvement.
• Resolution of hepatic pathology.

• Development of hepatic cirrhosis Liver: cirrhosis.

Refereed papers

• Recent references from PubMed and VetMedResource.
• Godfrey D R & Rest J R (2000) Suspected necrolytic migratory erythema associated with chronic hepatopathy in a cat. JSAP 41 (7), 324-328 PubMed.
• Center S A (1999) Chronic liver disease - current concepts of disease mechanisms. JSAP 40 (3), 106-114 PubMed.

Other sources of information

• Johnson S E (2000) Chronic hepatic disorders. In:Textbook of Veterinary Internal Medicine.5th edn. Ettinger S J & Feldman E C (eds). W B Saunders, Philadelphia. pp 1298-1325.
• Laflamme D P (2000) Nutritional management of liver disease. In:Kirk's Current Veterinary therapy XIII.Bonagura J D (ed). W B Saunders, Philadelphia. pp 693-697.
• Center S A (1996) Feline hepatic disease - Current therapeutic concepts. Proceedings of BSAVA Waltham Symposium on liver disease. pp 56-63.
• Watson T (1996) Nutritional management of canine liver disease. Proceedings of BSAVA Waltham Symposium on liver disease.pp 42-46.
• Michel R (1995) Nutritional management of liver disease. Vet Clin North Am Small Anim Pract 25, 485.