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 expansion with triglyceride stores. In fewer cases, inappetence is caused by environmental stresses such as forced weight loss programs 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.
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. Diarrhea is common in HL cats with inflammatory bowel disease or enteric lymphoma as primary disease processes. Classic signs of HE are not observed 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 AP are common. In cats with a primary necroinflammatory process involving the pancreas, liver, bile ducts, or gallbladder, GGT activity will be markedly increased exceeding the fold increase in AP. In all other conditions causing HL, GGT activity is normal or only modestly increased. The GGT:AP relationship is useful in discerning underlying cholangitis/cholangiohepatitis and other diseases involving biliary structures. 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, TSBA are abnormal before overt 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. Kidneys also may appear hyperechoic due to tubular fat 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, urinary bladder, and scrutiny for renal or urocystoliths.
Definitive diagnosis is based on the history, physical examination findings, laboratory features, ultrasonographic appearance of the liver, and hepatic aspiration cytology. Liver biopsy is not necessary; however, underlying cholangitis/cholangiohepatitis syndrome or hepatic lymphoma may eventually require biopsy for definitive diagnosis. Cytology preparations show profound vacuolar distention of hepatocytes involving >80% of hepatocytes. Canalicular cholestasis is commonly observed.
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 as 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 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 restricted considering concurrent potassium phosphate supplements in order to avoid iatrogenic hyperkalemia.
A fortified water-soluble vitamin solution (2 mL/L of fluids, see
see Hepatic Disease in Small Animals: Formulation of a Fortified Water-Soluble Vitamin Supplement (2 mL/L of IV fluid) in Dogs and Cats with Liver Disease) should be added. 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 observed 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 μg/cat, SC). Cobalamin deficiency is common in HL cats and may predispose individuals to this syndrome. When present, B12 deficiency confounds intermediary metabolism. Treatment with N-acetylcysteine is initiated during the first 2–3 days (150 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, 3 doses given at 12-hr intervals), before procedures that might provoke bleeding.
Feeding is initiated once the cat is rehydrated and has reasonable electrolyte balance. Some cats may develop renal potassium wasting as a result of underlying renal disease or lipid accumulation in their renal tubules. 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 feeding 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 Hepatic Disease in Small Animals: Nutrition in Hepatic Disease in Small Animals). Because cats with HL are in metabolic liver failure, appetite stimulants are inappropriate; diazepam, oxazepam, cyproheptidine, and mirtazepine should not be used. 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. 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 esophageal tube (E-tube) is placed with the distal tip 2–4 cm craniad to the esophageal-gastric junction. This should be documented using 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 can optimize nitrogen tolerance on a normal feline diet by modifying enteric flora, substrate utilization, and colonic 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 resistant to repletion.
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, sid, no more than 5 days) may be used as antiemetics. Enteric motility may be stimulated by exercise during owner visits.
To avert development of refeeding-induced hypophosphatemia, which can cause weakness, hemolysis, encephalopathy, and other adverse effects, serum phosphorus concentrations should be serially monitored and supplemental potassium phosphate judiciously provided. 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 TSBA are extraordinarily high in these cats and bile acid profiles (by HPLC) 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. If symptomatic pancreatitis is concurrent and complicates food retention, feeding through a J-tube may be necessary. Feeding distal to the pancreas is done using a constant rate infusion of CliniCare® mixed with supplemental pancreatic enzymes through a J-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 the 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 AP of obese cats undergoing weight reduction may identify emerging HL that will allow suspension of the weight loss program and early treatment intervention. Recurrence is rare in recovered cats.
Last full review/revision March 2012 by Sharon A. Center, DVM, DACVIM