Definition

• Feline hepatic lipidosis->80% of hepatocytes accumulate substantial triglyceride vacuoles that distend the cytosolic compartment, causing canalicular compression, severe cholestasis, and liver dysfunction.
• Untreated-leads to progressive metabolic dysregulation and death.
• Develops secondary to a primary disease or condition causing anorexia or catabolism.

Pathophysiology

• Cats have a unique propensity to accumulate triglyceride filled hepatocellular vacuoles.
• Causal factors-energy and protein deficits; increased peripheral fat mobilization; increased hepatic triglyceride synthesis; impaired hepatic -oxidation of fatty acids; reduced hepatocellular triglyceride exportation.
• Cytosolic triglyceride vacuoles displace organelles to cell periphery, associate with organelle dysfunction, and canalicular compression.
• Hepatic failure-with rare overt HE.

Systems Affected

• Hepatobiliary-severe intrahepatic cholestasis, hepatic dysfunction or failure
• Gastrointestinal-anorexia; vomiting
• Musculoskeletal-peripheral tissue wasting
• Nervous-HE, ptyalism, moribund condition
• Hemic/Lymphatic/Immune-abnormal RBC shapes (poikilocytes), Heinz body hemolysis
• Renal/Urologic-potassium wasting; renal tubule triglyceride accumulation

Incidence/Prevalence

Most common severe feline hepatopathy in North America causing jaundice.

Geographic Distribution

Worldwide

Signalment

Signs

Causes

Risk Factors

• Obesity
• Anorexia, negative nitrogen balance
• Catabolism or rapid weight loss
• Vitamin B₁₂ deficiency

Differential Diagnosis

• Primary liver disease-CCHS, cholelithiasis, EHBDO, or neoplasia (esp. lymphosarcoma) important considerations differentiated by abdominal ultrasonography, liver aspiration, and liver biopsy.
• PSVA-rarely confused; diagnosis by ultrasound or colorectal scintigraphy, and lab testing.
• Hepatic toxoplasmosis or FIP-liver biopsy, serology, immunohistochemistry.
• Pancreatitis-differentiated by ultrasonography, serum tests (low fPLI rules down likelihood of pancreatic inflammation, high values with local inflammation or pancreatitis; inconsistent amylase, lipase), pancreatic aspiration cytology, gross inspection, biopsy.
• Gastrointestinal disease-IBD differentiated by endoscopic or full-thickness bowel biopsies; obstruction differentiated by abdominal survey or contrast radiography and ultrasonography.
• Toxicities-suspected based on history (e.g., oral diazepam, acetaminophen, methimazole).
• Hyperthyroidism-serum thyroid panel.

CBC/Biochemistry/Urinalysis

• Hematology-poikilocytes common; non-regenerative anemia; hemolytic anemia: severe hypophosphatemia or Heinz bodies (low GSH); leukogram reflects underlying disorder.
• Biochemistry-hyperbilirubinemia; high ALP, ALT activity; normal or mild increase in GGT if no primary necro-inflammatory disorder of biliary or pancreatic tissue; low BUN; normal creatinine; variable glucose (hypoglycemia rare); variable cholesterol, albumin, globulins (high globulins with inflammatory disease); hypokalemia (associated with failure to survive, refeeding phenomenon); severe hypophosphatemia (<2 mg/dL) complicates initial 72 h of feeding (refeeding syndrome).
• Urinalysis-lipiduria and unconcentrated urine common; ammonium biurate crystalluria not seen; renal potassium wasting (some cats).

Other Laboratory Tests

• Prolonged coagulation times-PT, APTT, ACT, esp. PIVKA in >50% tested cats; fibrinogen usually normal; abnormalities correct with parenteral vitamin K₁ therapy.
• Hyperammonemia-uncommon.
• Serum bile acids-high before hyperbili-rubinemic; redundant test if hepatobiliary jaundice.
• B₁₂ deficiency-may increase susceptibility to HL and appears to compromise recovery.

Imaging

Diagnostic Procedures

• Fine-needle liver aspiration cytology: >80% hepatocytes with severe cytosolic vacuolation; biopsy rarely needed to confirm HL
• Definitive diagnosis HL-based on history, clinical features, high ALP, diffuse hyperechoic hepatic parenchyma, severe hepatocyte lipid vacuolation on aspiration cytology; cannot rule out underlying primary hepatic disorders (e.g., CCHS, EHBDO, PSVA) with these tests.
• Liver biopsy-definitive diagnosis of under-lying “primary” liver disorders; done only if poor response to therapy or high GGT. Caution: stabilize cat before anesthesia and biopsy to reduce risk of death.
• Vitamin K₁ (0.5–1.5 mg/kg SC or IM) three doses at 12-h intervals, at least 12 h before: aspiration sampling, liver biopsy, jugular vein catheterization, or feeding appliance insertion to reduce risk of severe iatrogenic bleeding.

Pathologic Findings

• Gross-diffuse hepatomegaly, smooth surface; friable greasy consistency, yellow/pale color with reticulated appearance; sample floats in formalin.
• Microscopic-diffuse, severe hepatocellular vacuolation; large (macrovesicular) or small (microvesicular) vacuolation.
• Oil Red O-on frozen tissue confirms lipid; but not typically necessary.

Appropriate Health Care

• Inpatient-necessary for recumbent cats or those with neck ventriflexion (indicates severe electrolyte disturbance: potassium or phosphate, or thiamin deficiency).
• Discharge for home care after stabilization and enteral feeding route established, and demonstrated to be problem free.
• Frequent reevaluations-imperative.
• Outpatient-reduces stress and thereby facilitates recovery in some cats.

Nursing Care

• Balanced polyionic fluids-avoid lactate and dextrose supplementation. Acetate may not be metabolized quickly; 0.9% NaCl preferred.
• Potassium chloride supplementation is important, use sliding scale (see Hypokalemia).
• Phosphate supplements usually needed (see Hypophosphatemia) at initial feeding (refeeding syndrome).
• Magnesium supplements rarely needed; low Mg may rarely complicate potassium repletion.

Activity

Activity may augment gastric motility when gastroparesis complicates feeding (chronic vomiting); early recovery phase cats too weak.

Diet

• Nutritional support-cornerstone of recovery.
• High-protein, high-calorie feline diet essential.
• Energy-50–60 kcal/kg ideal weight/day; gradual transition to full energy requirement over 3–5 days; feed multiple small meals/day.
• Forced alimentation usually required.
• Forced oral feeding may cause food aversion.
• Tube feeding-initially by nasogastric tube transitioned to esophageal tube after hydration and electrolyte status improves, and vitamin K₁.
• Avoid laparotomy for gastric feeding tube insertion; cats with HL have high mortality.
• Cautiously offer PO food daily to assess interest in food.
• Human stress formula enteral diets (not recommended)-require supplemental arginine (or citrulline), and taurine.

Supplements

• Supplements improve survival in severely affected cats.
• Medical grade L-carnitine (250–500 mg/day). Carnitine supplements have wide variability in bioavailability; Carnitor (liquid medical grade carnitine) recommended. Carnitine has been confirmed to increase and sustain fatty acid oxidation in overweight cats undergoing weight loss, as in HL (see Suggested Readomg).
• Taurine (250–500 mg/day).
• Thiamin (50–100 mg/day).
• Vitamin B₁₂ (initially, 1 mg IM or SC once): determine chronic vitamin B₁₂ needs by sequential B₁₂ values (weekly intervals).
• Water-soluble vitamins in fluids (2 mL/L).
• Vitamin E (10 IU/kg/day) in food.
• Thiol donors (NAC, SAMe): as above.
• Potassium gluconate (for hypokalemia), reduces fluid potassium supplements.
• Marine oil in food (2000 mg q24h).

Client Education

• Warn client-sequential biochemical assays needed to assess recovery.
• Educate client about feeding tube use/care and may be retained for 4–6 months.
• Advise client-recurrence unlikely; liver function will not be chronically compromised.

Surgical Considerations

• Avoid surgical interventions until hydration, electrolyte depletions, Vit. K₁ deficiency, Heinz body anemia alleviated.
• Exploratory laparotomy and liver biopsy (if indicated)-inspect for underlying disorders; biopsy pancreas, stomach, and small bowel.

Drug(s)

• Vitamin K₁-recommended for all cats with suspected HL; see dose above, avoid overdosage: oxidant hemolysis and liver injury.
• Drugs to ameliorate HE (see Hepatic Encephalopathy) usually not needed.
• Emesis control-metoclopramide: for vomiting, nausea, and gastroparesis (0.2–0.5 mg/kg SC q8h, 30 min before feeding, or as a CRI IV drip at 0.01–0.02 mg/kg/h or 1–2 mg/kg/day); dolasetron (0.5–0.6 mg/kg q24h IV, SC, PO); or maropitant (1 mg/kg IV, SC, PO q24h, 5 days max); famotidine: to avert damage to lower esophagus if vomiting (0.5–1.0 mg/kg q12–24h).
• Systemic antibiotics-as appropriate for concurrent infections.

Contraindications/Precautions

• Adjust dosages of medications relying on hepatic metabolism or excretion.
• Avoid benzodiazepines and barbiturates-interact with neuroreceptors provoking HE.
• Appetite stimulants (e.g., diazepam, oxazepam, cyproheptadine, mirtazepine)-do not provide dependable energy intake; some produce sedation; diazepam rare fulminant hepatic failure.
• Avoid injectable medications with a propylene glycol carrier; may lead to hemolysis in cats with low GSH.
• Ursodeoxycholic acid-likely not beneficial; may be injurious in HL; may promote taurine deficiency due to conjugation.
• Dextrose supplements-may provoke hepatic triglyceride accumulation.
• Avoid tetracyclines or stanazolol-these promote triglyceride deposition leading to HL.
• Avoid propofol-(phenol derivative) may provoke hemolysis 12 h after infusion in cats with Heinz body anemia; some HL cats recover slowly; alternatively use gas anesthesia.

Patient Monitoring

• Body weight, condition, hydration, electrolytes; judicious adjustment of energy, fluid, and electrolyte provisions important.
• Serum bilirubin-declines within 2 weeks of adequate management; predicts recovery.
• Liver enzyme activity-slow to normalize; do not predict recovery.
• Discharge for home care-when vomiting is controlled, gastroparesis resolved, bilirubin declining, patient ambulatory, and tube-feeding apparatus is problem-free.
• Tube feeding-discontinued only after confirmed voluntary food consumption.

Prevention/Avoidance

• Obesity-prevent; weight reduction must not exceed 2.0% bodyweight per week.
• Caution owner to verify food intake during weight loss regimens and during at-home stress.

Possible Complications

• Feeding tube malfunction or obstruction-tube obstructions relieved with: papaya juice, carbonated soft drink, or pancreatic enzyme slurry; 15-min dwell time, warm water flush.
• Rare HE after dietary support introduced.
• Hepatic failure can lead to death.
• Untreatable underlying causal disorder.

Expected Course and Prognosis

• Optimal response to tube feeding and nutritional supplements-recovery in 3–6 weeks.
• Therapy as described-85% recovery of severely affected animals.
• Underlying disease influences outcome.
• HL rarely recurs.
• HL does not cause chronic liver dysfunction.

Associated Conditions

• Primary liver disorders
• Pancreatitis
• Malassimilation: various causes
• Diabetes mellitus
• Neoplasia-hepatic and systemic
• Hepatic encephalopathy (rare)
• Systemic illness limiting nutrition intake

Synonyms

• Fatty liver syndrome
• Hepatosteatosis
• Feline hepatic vacuolation
• Vacuolar hepatopathy
• Vacuolar degeneration

See Also

• Cholangitis/Cholangiohepatitis Syndrome
• Hepatic Encephalopathy

Abbreviations

• ALP = alkaline phosphatase
• ALT = alanine aminotransferase
• CCHS = cholangitis/cholangiohepatitis syndrome
• CIN = chronic interstitial nephritis
• EHBDO = extrahepatic bile duct obstruction
• fPLI = feline pancreatic lipase
• GGT = gamma glutamyltransferase
• GSH = glutathione
• HE = hepatic encephalopathy
• HL = hepatic lipidosis
• IBD = inflammatory bowel disease
• NAC = N-acetylcysteine
• PIVKA = proteins invoked by vitamin K absence or antagonism
• PSVA = portosystemic vascular anomaly
• SAMe = S-adenosylmethionine

Client Education Handout Available Online