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Feline Hepatic Lipidosis


Sharon A. Center

, BS, DVM, DACVIM, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University

Last full review/revision May 2015 | Content last modified May 2015

Hepatic lipidosis (HL), the most common acquired and potentially lethal feline liver disease, is a multifactorial syndrome. In most cases, a primary disease process causing anorexia sets the stage for HL in overconditioned cats. Peripheral fat mobilization exceeding the hepatic capacity to either redistribute or use fat for β-oxidation (producing energy) leads to profound hepatocyte cytosolic expansion with triglyceride (fat) stores. In fewer cases, inappetence is caused by environmental stresses (eg, forced weight loss with unacceptable food substitutions, moving to a new household, newly introduced or loss of pets or family members, boarding, accidental confinement [eg, locked in a garage, basement, or attic], or an inside-only cat being lost outside). The term “idiopathic HL” is appropriate only when an underlying disease condition or event leading to inappetence cannot be identified.

HL has no necroinflammatory component, and the severe cholestasis is caused by canalicular compression secondary to hepatocyte triglyceride vacuolar distention. The syndrome is associated with a number of metabolic deficits, including low hepatic and RBC glutathione, low plasma taurine, low vitamin K1 causing coagulopathies in some cats, thiamine and/or cobalamin deficiency and likely other B vitamin depletions, and electrolyte aberrations (especially low potassium and low phosphorus).

Clinical signs vary but usually include dramatic weight loss (>25%, may include dehydration deficits), lethargy, vomiting, ptyalism, pallor, neck ventroflexion, hepatomegaly, jaundice, gastroparesis and intestinal ileus (due to electrolyte aberrations), and retention of omental and falciform fat despite diminished peripheral fat stores. Diarrhea is common in HL cats with inflammatory bowel disease or enteric lymphoma as primary disease processes. Classic signs of HE are not seen, and ammonium biurate crystalluria is unusual, although bleeding tendencies may develop. Vitamin K1 deficiency has been confirmed in numerous HL cats by observation that bleeding tendencies and coagulation test abnormalities resolve with vitamin K1 therapy.

Laboratory results reflect the HL syndrome as well as the primary underlying disease. A nonregenerative anemia, poikilocytosis, increased RBC Heinz bodies, variable WBC count, hyperbilirubinemia and bilirubinuria, mild to marked increases in ALT and AST, and marked increases in ALP are common. In cats with a primary necroinflammatory process involving the pancreas, liver, bile ducts, or gallbladder, GGT activity will be increased, usually exceeding the fold increase in ALP. In all other conditions causing HL, GGT activity is normal or only modestly increased. The GGT:ALP relationship is useful in discerning underlying cholangitis/cholangiohepatitis and other diseases involving biliary structures (including pancreatitis). Finding a high GGT also predicts whether a liver or pancreatic biopsy is indicated. Depending on underlying disorders, hypoalbuminemia and hyperglobulinemia may be found. Prolonged PT or APTT may develop; the PIVKA clotting time is more sensitive for detection of vitamin K1 sufficiency. In the earliest stages of the HL syndrome, TSBAs are abnormal before onset of jaundice (this circumstance is rarely encountered). Peritoneal effusion is rare but when found represents the primary disease process or iatrogenic fluid overload.

Ultrasonographic evaluation reveals homogeneous hyperechoic hepatic parenchyma and subjective hepatomegaly. Hyperechogenicity is determined by comparing hepatic parenchyma to falciform fat and the spleen (liver is normally hypoechoic vs spleen). Kidneys also may appear hyperechoic because of increased renal tubular fatty vacuolation. Ultrasonographic examination should carefully assess the entire abdomen for evidence of an underlying disease process and include evaluation of the biliary tree, gallbladder, pancreas, intestinal wall thickness, hepatic and mesenteric lymph nodes, kidneys, and urinary bladder, and scrutiny for uroliths in the kidneys, ureters, or bladder.

Definitive diagnosis is based on the history, physical examination findings, laboratory features, ultrasonographic appearance of the liver, and ultrasound-guided hepatic aspiration cytology. Liver biopsy is not necessary to diagnose HL; however, underlying cholangitis/cholangiohepatitis or hepatic lymphoma may eventually require biopsy for definitive diagnosis. Cytology preparations show profound vacuolar distention of hepatocytes involving >80% of hepatocytes aspirated. Canalicular cholestasis is commonly seen. Mistaken aspiration of omental fat rather than liver is easily deduced by the absence of hepatocytes.

Treatment of HL is aimed at correcting fluid, electrolyte, and metabolic deficits and initiating food intake. Because cats with HL may have high lactate concentrations and may not be able to metabolize acetate, 0.9% NaCl is the fluid of choice. Fluids should not be supplemented with dextrose, because this will reduce utilization of intrahepatic fatty acids for β-oxidation. Because affected cats are usually overconditioned, fluid therapy must be based on ideal body weight. Overhydration is common when fluid dosage is based on total overconditioned body weight and can lead to pleural and abdominal effusion and pulmonary edema.

Fluids should be appropriately supplemented with potassium (using the sliding scale) based on electrolyte status. If initial serum phosphate concentration is low (<2 mg/dL), potassium phosphate should be added at a rate of 0.01–0.03 mmol/kg/hr. Potassium chloride supplementation must be judiciously adjusted, considering concurrent potassium phosphate supplements to avoid iatrogenic hyperkalemia. Potassium phosphate supplements (up to 0.06 mmol/kg/hr) are commonly initiated when feeding is started to guard against development of severe hypophosphatemia associated with the "refeeding syndrome."

A fortified water-soluble vitamin solution (2 mL/L of fluids, see Table: Formulation of a Fortified, Water-Soluble Vitamin Supplement a for Dogs and Cats with Liver Disease) should be added to the IV fluids. Thiamine supplements (50–100 mg/day) are specifically indicated in HL and provided in water-soluble fluid supplements or by the oral route. Rare anaphylactoid reactions and neuromuscular paralysis have been seen in a few cats treated with thiamine by SC or IM injection.

A diagnostic blood sample should be collected for B12 determination followed by empirical B12 administration (250–1,000 mcg/cat, SC). Cobalamin deficiency is seemingly common in HL cats and may predispose individuals to this syndrome. When present, B12 deficiency confounds intermediary metabolism; however, this is confirmed only by assessment of methylmalonic acid, which confirms functional B12 insufficiency. Unfortunately, this assessment cannot be promptly completed. Consequently, B12 supplementation (which has no adverse effects) is routinely supplemented with the less exacting measurement of plasma B12 used to determine propriety of longterm supplementation. Treatment with N-acetylcysteine is initiated during the first 2–3 days (140 mg/kg, IV, administered through a 0.25-μm filter over 20 min, then 70 mg/kg, IV, tid-qid; diluted to a 10% solution). N-acetylcysteine should not be given as a prolonged (>1 hr) constant-rate infusion, because it may induce hyperammonemia by deviating substrates from the urea cycle.

Vitamin K1 is given with a small needle (0.5–1.5 mg/kg, SC or IM, three doses given at 12-hr intervals) before procedures that might provoke bleeding (eg, insertion of a jugular catheter, esophageal feeding tube, cystocentesis, or hepatic aspiration sampling).

Some cats may develop renal potassium wasting as a result of underlying renal disease or lipid accumulation in their renal tubules. The fractional excretion of potassium can be estimated by measuring potassium and creatinine in simultaneously collected baseline serum and urine samples: fractional potassium excretion = ([urine potassium/urine creatinine] × [serum creatinine/serum potassium]) × 100%. In a hypokalemic cat, a value <1% is expected. Values >20% represent marked renal potassium wasting and indicate the need for aggressive potassium supplementation. Cats with prodigious potassium needs should have potassium gluconate added to their food as soon as oral intake is established. This will reduce the concentrations of potassium needed in the IV fluids and associated risk of iatrogenic hyperkalemia.

Nutritional support is the cornerstone of recovery (see Nutrition in Hepatic Disease in Small Animals). Feeding is initiated after the cat is rehydrated and has reasonable electrolyte balance, because these are requisite factors enabling normal enteric motility. Because cats with HL are in metabolic liver failure, appetite stimulants are inappropriate; diazepam, oxazepam, cyproheptidine, and mirtazepine should not be used and will not recover an affected cat. Occasionally, an appetite stimulant may help initiate feeding early in syndrome development.

A palatable odiferous food should be offered initially. If the cat salivates or objects, all food should be removed because of the risk of inducing a "food aversion syndrome." If oral feeding is not tolerated, feeding a liquid diet (eg, CliniCare®) with supplements via a nasoesophageal tube is cautiously initiated as a first step. A 5–10 mL volume of tepid water is administered first to assess the cat’s tolerance and response. If no vomiting or signs of discomfort are noted, the process is repeated with liquefied food. After a few days of nasoesophageal feeding, if the cat is judged to be a reasonable anesthetic risk, an esophagostomy tube (E-tube) is placed with the distal tip 2–4 cm craniad to the esophageal-gastric junction. This should be documented with a lateral thoracic radiograph.

A high-protein, calorie-dense, balanced feline diet is recommended for E-tube feeding. Only rarely should a protein-restricted diet be used, because protein restriction can aggravate hepatic lipid accumulation. Rather, use of lactulose and oral amoxicillin or low-dose metronidazole (7.5 mg/kg, bid) can optimize nitrogen tolerance to allow feeding of a normal feline diet (these measures modify enteric flora, substrate utilization, and increase colonic catharsis or cleansing). A number of metabolic supplements have improved recovery of affected cats: taurine (250–500 mg/cat/day), medical grade liquid oral l-carnitine (250–500 mg/cat/day), vitamin E (10 IU/kg/day), and potassium gluconate (if hypokalemia is persistent).

Initial feedings are small and given frequently or by constant-rate infusion. On the first day, one-third to one-half of the cat’s energy requirements are fed; the amount fed is then gradually increased over the next 2–4 days to the ideal intake. If vomiting occurs, electrolytes must be rechecked, feeding tube position verified, and factors relevant to the underlying disease process considered. Metoclopramide (0.05–0.1 mg/kg, IM, up to tid, or 0.25–0.5 mg/kg divided per day as a constant-rate infusion), ondansetron (0.025 mg/kg, IV, up to bid), or maropitant (1 mg/kg/day, no more than 5 days) may be used as antiemetics. Enteric motility may be stimulated by exercise during owner visits.

To avert development of hypophosphatemia induced by re-feeding, which can cause weakness, hemolysis, encephalopathy, and other adverse effects, serum phosphorus concentrations should be serially monitored and supplemental potassium phosphate judiciously provided. Routine IV potassium phosphate supplementation is administered when feeding is initiated to obviate persistent or feeding-induced hypophosphatemia. If gastritis is suspected, an H2-blocker (eg, famotidine or ranitidine) may be used, and carafate administered PO (but not via E-tube). If the cat tolerates oral medications, SAMe at 40 mg/kg/day is given between meals once N-acetylcysteine treatment is completed. SAMe supplementation must be accompanied by sufficient B12, folate, and other water-soluble vitamins to ensure optimal metabolic benefit (metabolism to glutathione and methyl group donation for transmethylation reactions). Use of ursodeoxycholate in HL may be detrimental because TSBAs are extraordinarily high in these cats and because bile acid profiles resemble those associated with EHBDO (increased secondary bile acids). All bile acids are toxic to cells in high concentrations and, in HL, bile acids are seemingly trapped by canalicular compression.

In the rare circumstance that signs of HE are encountered, lactulose, amoxicillin, or low-dose metronidazole (≤7.5 mg/kg, PO, bid) may be useful. In symptomatic pancreatitis, feeding distal to the pancreas is done using a constant-rate infusion of CliniCare® mixed with supplemental pancreatic enzymes through a jejunostomy tube. Alternatively, parenteral nutrition can be provided, although this may delay recovery and provoke hepatic triglyceride retention.

Prognosis for cats with HL is good with early diagnosis, full treatment support, and control of underlying disease. Monitoring liver enzymes has no value in predicting recovery. However, a decline in total bilirubin by 50% within the first 7–10 days portends an excellent chance of full recovery. Concurrent pancreatitis is a poor prognostic indicator. Monitoring ALP of obese cats undergoing weight reduction may identify emerging HL that will allow suspension of the weight loss program and early treatment intervention. Recurrence of HL is rare in recovered cats.

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