Liver: lipidosis in Cats (Felis) | Vetlexicon
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Liver: lipidosis

ISSN 2398-2950


Introduction

  • Accumulation of fat in >50% of hepatocytes.
  • Cause: idiopathic, secondary to systemic illness.
  • Signs: anorexia, jaundice, vomiting, diarrhea, constipation, weight loss.
  • Diagnosis: liver biopsy including fine needle aspiration (FNA).
  • Prognosis: fair-good, reversible if underlying disease controlled.
Print off the owner factsheet Fatty liver disease (hepatic lipidosis) in cats to give to your client.

Presenting signs

  • Due to hepatic dysfunction +/- underlying disease.
  • Jaundice  Jaundice .
  • Gastrointestinal signs:
    • Most commonly anorexia and vomiting.
    • Less often diarrhea or constipation.
  • Hepatic encephalopathy Hepatic encephalopathy - depression, ptyalism, weakness.
  • Period of anorexia 2-7 days +.
  • Often obese cats but can be seen in thin patients.

Geographic incidence

  • Common in USA.
  • Increasingly recognized in UK.

Age predisposition

  • Can develop in cats of any age but most commonly middle-aged (median age 7 years).

Cost considerations

  • Diagnostic tests to confirm hepatic lipidosis (biochemistry, hematology, imaging and tissue sampling of the liver).
  • Evaluation for underlying cause.
  • Supportive treatment including placement of enteral feeding tubes, fluid therapy and medications.

Pathogenesis

Etiology

  • Idiopathic - between 1-50% of reported cases.
  • 50-98% of cases reported secondary to systemic disease, eg neoplasia, diabetes mellitus  Diabetes mellitus, hyperthyroidism Hyperthyroidism, hyperadrenocorticism   Hyperadrenocorticism.
  • Syndrome characterized by hepatocellular lipid accumulation, intrahepatic cholestasis and abnormal hepatic function.
  • Pathophysiology incompletely understood and is likely due to multiple mechanisms including:
    • Chronic overnutrition and excess caloric intake leading to increased hepatic triglyceride content.
    • Increased mobilization of fat from peripheral stores Hyperlipidemia overwhelms hepatic fat utilization and/or mobilization capacity.
      • Increased hormone sensitive lipase activity (via increased levels of noradrenaline, adrenaline, cortisol, growth hormone, glucagon and thyroxine) promotes lipolysis.
      • Decreased rate of fatty acid oxidation.
      • Increased hepatic fat synthesis.
      • Decreased mobilization of fat from liver as lipoproteins.
    • Relative carnitine deficiency - carnitine is required for fatty acid transport into and out of hepatocytes.
    • Resistance to insulin activity (hence reduced lipoprotein lipase activity, which cause lipid uptake and reduced inhibition of hormone sensitive lipase).
    • Protein-calorie malnutrition.
    • Nutrient deficiencies (taurine, arginine, methionine, cysteine, vitamin K1 and B-vitamins).

Predisposing factors

General

  • Caused by illness, change in diet, environmental factors and stress (eg boarding cattery stay, introduction of new cats to household).

Diagnosis

Presenting problems

  • Anorexia.
  • Jaundice.
  • Vomiting Vomiting, diarrhea, constipation.
  • Hepatomegaly.
  • Hepatic encephalopathy - altered mentation, ptyalism, weakness.

Client history

  • Obesity Obese cat 01 (but remember can be seen in thin cats).
  • Anorexia for 2-7 days +.
  • Weight loss.
  • Signs related to an underlying disease process.
  • Recent change in diet or environment.

Diagnostic investigation

  • The aim of the investigation is three fold:
  • To confirm that the cat has HL.
  • To confirm metabolic complications associated with HL.
  • To search for an underlying cause of HL.

Hematology

Biochemistry

Urinalysis

Cytology

  • Hepatic parenchyma fine needle aspirate.

Histopathology

  • Liver biopsy Biopsy: hepatic - ultrasound-guided, laparoscopic or surgical at exploratory coeliotomy. 
    Coagulation times must be checked before biopsy, vitamin K1 supplementation frequently required before biopsy can be performed.
  • Biopsy will float in formalin.

2-D Ultrasonography

  • See liver ultrasonography Ultrasonography: liver.
  • Diffuse homogeneous hyperechogenicity of hepatic parenchyma and hepatomegaly Liver: normal - ultrasound .
    Changes are not specific for HL.
  • Assess all abdominal organs for evidence of underlying cause for HL.

Radiography

  • See abdominal radiography Radiography: abdomen.
  • Hepatomegaly  Liver: hepatomegaly - radiograph lateral .
  • Loss of muscle over lumbar region, retention of intra-abdominal fat.
  • Ancillary tests depending upon clinical signs and history, eg:

Confirmation of diagnosis

Discriminatory diagnostic features

  • Biochemistry.
  • Ultrasonography.

Definitive diagnostic features

  • Hepatic cytology and histopathology.

Gross autopsy findings

  • Examine other systems, (eg endocrine) to aid interpretation. Evidence of other primary disease?
  • Liver pale yellow and swollen.
  • If severe, liver friable and greasy.

Histopathology findings

  • Fat vacuoles within hepatocytes.
  • Two patterns of hepatic vacuolation observed - micro and macrovacuolation.
  • Absence of inflammatory, necrotizing or neoplastic lesions in idiopathic HL.
  • Biopsy of other abdominal organs may be indicated, eg to evaluate for inflammatory bowel disease.

Differential diagnosis

  • Other causes of intra-hepatic cholestasis:
  • Causes of post-heptatic cholestasis, ie biliary obstruction Bile duct: disease.
    • Cholelithiasis.
    • Biliary tract neoplasia.
    • Pancreatitis Pancreatitis.
    • Pancreatic neoplasia.
    • Duodenal pathology causing obstruction of duodenal papilla.
  • Causes of pre-hepatic jaundice: 
    • Hemolysis, eg immune-mediated, oxidant injury, inherited RBC membrane enzyme deficiency.
  • See Liver: chronic disease Liver: chronic disease.

Treatment

Standard treatment

  • Two stages:
  • Stabilize patient:
    • Address fluid and electrolyte deficits.
    • Treat hepatic encephalopathy.
    • Treat coagulopathies.
    • Initiate feeding via naso-esophageal tube.
  • Confirm diagnosis:
    • Search for underlying causes and treat as appropriate.
    • Place longer term feeding tube.
    • Introduce nutritional supplements.
  • Fluid and electrolyte support (may need potassium supplementation Fluid therapy: for electrolyte abnormality):
    • Rehydration with crystalloid fluids, eg Ringers, lactated Ringers.
    • Provide potassium chloride Potassium chloride / gluconate in fluids at levels to address any hypokalemia Hypokalemia and deliver maintenance requirements (maintenance = 20 mmol/l) - do not exceed 0.5 mEq/kg/hr.
    • If persistent hypokalemia check whether patient is hypomagnesemic Hypomagnesemia and provide magnesium supplementation if necessary.
    • Phosphate Hypophosphatemia may also need to be supplemented - administer as potassium phosphate (must not be given with calcium containing fluids due to risk of precipitation).
    • Dextrose supplemented fluids are contra-indicated.
    • Colloids occasionally used if hypoproteinemia Hypoproteinemia.

Nutrition

  • Cornerstone of therapy for HL.
  • Diet type:
    • High protein diet used to reverse fat and protein catabolism, eg Hill's a/d, enteral care formula or Royaal Canin Recovery.
    • Protein restriction is ONLY indicated if concurrent hepatic encephalopathy - use prescription renal formulas.
  • Food administration:
    • Calculate daily requirement (60-80 kCal/kg/day).
    • Voluntary oral intake is unlikely to be sufficient to meet calorie requirements.
    • Do not force feed - risk of aspiration pneumonia, development of food aversion and unlikely to be able to meet full daily energy requirement.
    • Most cats require tube feeding, as voluntary food intake often takes weeks to recover. Cats usually leave the hospital with tubes in place.
    • Parenteral nutrition very occasionally used in critical care setting during stabilization phase, however enteral feeding is preferred.
    • Feeding tubes:
      • Naso-esophageal Nasoesophageal intubation:
        • Suitable for short-term feeding (5-7 days).
        • Consider whilst stabilizing as can be placed without anesthesia.
        • Can only feed liquid formula.
      • Esophagostomy Esophagostomy feeding tube placement:
        • Requires short anesthesia for placement.
        • No special equipment required.
        • Suitable for canned formula (if homogenized).
        • Well-tolerated.
        • Can be maintained for weeks-months.
      • Gastrostomy Gastrostomy: percutaneous tube (endoscopic):
        • Can be placed endoscopically or at surgery.
        • Suitable for canned formula if homogenized.
        • Well-tolerated.
        • Can be maintained for weeks-months.
    • Food is delivered via tubes in 4-6 meals throughout day (fed 1/3 total ration day 1, 2/3 day 2 and complete ration day 3 onwards to minimize intestinal upset).
    • Bloodworks (PCV Hematology: packed cell volume and electrolytes) should ideally be monitored daily for 3-5 days for the development of 'refeeding syndrome' when feeding is instituted - hypophosphatemia, hypokalemia, hypomagnesemia and hepatic encephalopathy.
  • Appetite stimulants:
    • Unlikely to be effective in early stages of disease.
    • May be useful when cat starts to recover voluntary food intake however effective treatments (mirtazapine and cyproheptadine Cyproheptadine) require hepatic metabolism.
    • Avoid diazepam Diazepam (potential for hepatotoxicity).
  • Address nausea +/- intestinal ileus:
    • Maropitant Maropitant citrate. (Cerenia 1 mg/kg SC q24 h for 5 days) - anti-emetic.
    • Metoclopramide Metoclopramide - anti-emetic and pro-kinetic - useful if concurrent intestinal ileus:
      • Most effective.
      • As CRI 1-2 mg/kg/24 hrs.
    • Ondansetron Ondansetron if refractory vomiting (0.22 mg/kg IV q8-12 hrs) - central anti-emetic.
  • Manage hepatic encephalopathy Hepatic encephalopathy:
  • Nutritional supplements Nutrition: disease modulation: a variety of supplements have been used in HL, with only L-carnitine L-carnitine and cobalamin evaluated in experimental studies. Recommendations for nutritional supplements are therefore based on the known role of agents in lipid metabolism and the likelihood for development of deficiency:
  • B vitamins:
    • Cobalamin (B12) Blood biochemistry: vitamin B12:
      • Deficiency often associated with intestinal disease.
      • Required for synthesis of endogenous S-adenosylmethionine.
      • 250 µg/kg SQ weekly for 6 weeks.
    • B1-thiamine:
      • May be deficient due to anorexia or malabsorption.
      • Signs of deficiency - neuromuscular (including central vestibular signs, weakness, neck ventroflexion), hypothermia, hypotension.
      • 100 mg SQ q12-24 hrs until signs resolve and enteral feeding being delivered.
        Rarely SQ administration can cause anaphylaxis (observed often when given IV).
  • Fat soluble vitamins:
    • Vitamin K1:
      • Administer pre-hepatic biopsy.
      • 0.5-1.5 mg/kg SQ q12 hrs for three doses.
      • If persistent coagulation abnormalities consider transfusion of whole blood or plasma to replace clotting factors.
    • Vitamin E Vitamin E:
      • Hepatic anti-oxidant.
      • 10 units/kg/day PO.
  • Amino acids:
    • L-carnitine L-carnitine:
      • Required for hepatic mobilization of fats and fatty acid oxidation.
      • 250-500 mg/day PO.
    • Taurine Taurine:
      • Essential amino acid required for bile acid conjugation.
      • May be deficient due to anorexia.
      • 250-500 mg q24 hrs PO at least until feeding full calorie requirement of a feline veterinary formula.
  • Anti-oxidants:
    • SAMe S-adenosylmethionine:
      • Precursor for glutathione, a systemic anti-oxidant synthesized in the liver. In starvation hepatic stores of glutathione are reduced, increasing the risk of hepatic oxidant injury and Heinz body hemolytic anemia.
      • Starting dose 35-60 mg/kg q12-24 hrs.

Monitoring

Prevention

Outcomes

Prognosis

  • Good if idiopathic HL.
  • Fair if secondary HL, depends on underlying disease.
  • >60% cases improve if meticulous care and management.
  • Recurrence rare once recovered if idiopathic HL.
  • Positive prognostic factors:
    • Younger age (more likely idiopathic HL).
    • Higher initial serum potassium level.
    • Higher initial hematocrit.

Expected response to treatment

  • Recovery of voluntary food intake to sustain daily calories requirement may take several weeks - couple of months.
  • Hepatic enzymes and biochemistry return over weeks-months if idiopathic.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Armstrong P J, Blanchard G (2009) Hepatic lipidosis in cats. Vet Clin North Am Sm Anim 39 (3), 599-616 PubMed.
  • Centre S A (2005) Feline hepatic lipidosis. Vet Clin North Am Sm Anim 35 (1), 225-269 PubMed.
  • Chastain C B, Panciera D, Waters C (2000) Metabolic and hormonal alterations in cats with hepatic lipidosis. Sm Anim Clin Endocrinol Sept-Dec 10 (3), 10.
  • Griffin B (2000) Feline hepatic lipidosis: pathophysiology, clinical signs and diagnosis. Compend Contin Educ Pract Vet 22 (9), 847-858 VetMedResource.
  • Griffin B (2000) Feline hepatic lipidosis: treatment recommendations. Compend Contin Educ Pract Vet 22 (10), 910-922 VetMedResource.
  • Center S A (1999) Chronic liver disease - current concepts of disease mechanisms. JSAP 40 (3), 106-114 PubMed.
  • Willard M D, Weeks B R, Johnson M (1999) Fine needle aspirate cytology suggesting hepatic lipidosis in four cats with infiltrative hepatic disease. J Fel Med Surg (4), 215-220 PubMed.
  • Dimski D S (1997) Feline hepatic lipidosis. Semin Vet Med Surg (Small Anim) 12 (1), 28-33 PubMed.
  • Akol K G, Washabau R J, Saunders H M et al (1993) Acute pancreatitis in cats with hepatic lipidosis. JVIM (4), 205-9 PubMed.
  • Center S, Crawford M, Guida J et al (1993) A retrospective study of 77 cats with severe hepatic lipidosis: 1975-1990​. JVIM (6), 349-59 PubMed.

Other sources of information

  • Holan K M (2008) Feline hepatic lipidosis. In: Kirks's Current Veterinary Therapy XIV Small Animal Practice, Ed Bonagura J, Twedt D, Missouri, Elsevier Saunders. pp 570-575.