Feline hepatic lipidosis (FHL), the most common acquired and potentially lethal feline liver disease, is a multifactorial syndrome.
A primary disease process causing anorexia or food deprivation sets the stage for HL in overconditioned cats. Peripheral fat mobilization exceeding the hepatic capacity to either redistribute or use fat for beta-oxidation (producing energy) leads to profound hepatocyte cytosolic expansion with triglyceride (fat) stores.
In fewer cases, inappetence is due to environmental stresses (eg, forced weight loss with unacceptable food substitutions, moving to a new household, newly introduced pets, 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 or food deprivation cannot be identified after due consideration; typically, this occurs in < 10% of cases.
HL has no necroinflammatory component. Severe cholestasis is thought to reflect canalicular compression secondary to extreme hepatocyte distention with triglyceride-laden vacuoles. It also may reflect downregulation/expression of bile membrane transporters.
As a syndrome, HL is associated with a number of metabolic aberrations, including low hepatic and RBC glutathione (GSH) concentrations, low plasma taurine concentrations, vitamin K1 insufficiency driving coagulopathies, severe electrolyte imbalances, thiamine and cobalamin deficiencies causing metabolic encephalopathies, and the refeeding syndrome (causing clinically relevant electrolyte aberrations and lactic acidosis), as well as ketoacidosis. Ketone body formation reflects increased beta-oxidation and impaired dissipation of acetyl coenzyme A (CoA) from mitochondria. Insulin resistance is not a pathogenic feature.
Clinical Signs of Feline Hepatic Lipidosis
Clinical signs vary but usually include dramatic weight loss (> 25%, may include dehydration deficits) and variable lethargy, vomiting, ptyalism, pallor, neck ventriflexion, hepatomegaly, jaundice, gastroparesis, and intestinal ileus (due to electrolyte aberrations), with retention of omental and falciform fat despite wasting of peripheral fat stores (centripetal adiposity). Diarrhea is usually a historic complaint in cats with inflammatory bowel disease or enteric lymphoma. Ptyalism may reflect nausea or metabolic encephalopathy or be a manifestation of hepatic encephalopathy (HE).
Cats with severe electrolyte derangements (marked hypokalemia or hypophosphatemia) or severe thiamine (vitamin B1) deficiency may demonstrate extreme weakness and dramatic head and neck ventriflexion. These cats have limited stress tolerance and may become dyspneic (ventilatory muscle weakness) or collapse during routine procedures or restraint or in response to environmental stress.
Seizure activity is uncommon unless there is severe thiamine deficiency. Classic clinical signs of HE are not evident, ammonium biurate crystalluria is not documented, and hyperammonemia is rarely characterized.
Bleeding tendencies may be overt or covert, reflecting vitamin K1 insufficiency rather than hepatic synthetic failure. Vitamin K1 insufficiency reflects disrupted enterohepatic bile acid circulation secondary to severe canalicular compression. This complication is equivalent in effect to macroscopic extrahepatic bile duct obstruction.
Clinicopathologic features reflect impact of the HL syndrome as well as the primary underlying disease leading to inappetence and weight loss.
Nonregenerative anemia, poikilocytosis, increased RBC Heinz bodies, variable WBC count, and jaundiced plasma are typical.
Biochemical Profile and Urinalysis
Hyperbilirubinemia and mild to marked increases in ALT and AST activity with a marked increase in ALP activity are common.
In cats with an underlying necroinflammatory process involving the pancreas, liver, bile ducts, or gallbladder, the GGT activity will be notably increased, achieving a fold increase usually exceeding that of ALP. In all other conditions causing HL, GGT activity is normal or only modestly increased. This GGT-ALP relationship helps discern underlying cholangitis/cholangiohepatitis and other diseases involving ductal structures (including pancreatitis that has numerous ductal elements).
Finding a high GGT also predicts whether liver or pancreatic biopsies are indicated.
Depending on underlying disorders, hypoalbuminemia and hyperglobulinemia may be noted. In the earliest stages of HL syndrome, total serum bile acid concentrations are abnormal before onset of jaundice; however, this is rarely witnessed.
Serious electrolyte imbalances are common and are an important cause of patient morbidity and death. Hypokalemia, hypophosphatemia, and hypomagnesemia exist on presentation in ~28%, ~14%, ~20% of patients, respectively, with complicating “depletions” appearing after initial fluid administration or subsequent to development of refeeding syndrome. Severe hypokalemia and hypophosphatemia variably increase risk for RBC hemolysis (hypophosphatemia), muscle weakness, enteric atony, vomiting, head and neck ventroflexion, and neurobehavioral changes confused with HE. Prolonged hypokalemia substantially increases risk for death.
Urinalysis demonstrates expected bilirubinuria, with other abnormalities reflecting a primary illness. Ammonium biurate crystalluria is not documented. Urine sediment often discloses lipiduria (refractile fat microglobules) that occasionally form a buoyant lipid layer after urine centrifugation. Tiny lipid droplets in urine may be confused with coccoid bacteria by a naive observer. Hematuria is common with cystocentesis (should be avoided before vitamin K1 administration).
Fecal examinations help rule out hepatobiliary fluke infection that may masquerade as HL (similar clinicopathologic features).
Prolonged prothrombin time (PT) or activated partial thromboplastin time (aPTT) may be demonstrable; however, bleeding tendencies may exist despite normal test results. The most sensitive test for coagulopathy in HL is a thrombotest (PIVKA assay), clotting time that sensitively detects vitamin K1 sufficiency. Unfortunately, reagent availability has declined use of this testing method. Development of vitamin K1 deficiency is common and reflects disrupted enterohepatic bile acid circulation. As such, parenteral vitamin K administration is a standard of care when HL is a considered possibility.
Rare peritoneal effusion represents either primary disease causing HL or iatrogenic fluid overload due to fluid administration, based on an overconditioned body weight reflecting impact of the HL syndrome as well as the primary underlying disease leading to inappetence and/or weight loss.
Thoracic radiographs may disclose abnormalities reflecting a primary disease process (eg, prominent sternal lymph node reflects inflammatory disease in the abdomen or lymphoma).
Abdominal radiographs usually demonstrate hepatomegaly but may also provide clues to underlying pathologies.
Abdominal ultrasonography typically demonstrates homogeneous hyperechoic hepatic parenchyma (fat being hyperechoic) and subjective hepatomegaly. Hyperechogenicity is judged by comparing hepatic parenchyma to falciform fat and to the spleen (liver is normally hypoechoic compared to spleen). Kidneys may appear hyperechoic because of increased renal tubular fatty vacuolation.
Ultrasound examination should carefully assess the entire abdomen, inspecting for evidence of an underlying disease process. This should include careful inspection of the biliary tree, gallbladder; sphincter of Oddi (duodenal bile duct papilla); pancreas; intestinal wall thickness; hepatic, peripancreatic, and mesenteric lymph nodes; kidneys; and urinary bladder, with scrutiny for urolithiasis involving kidneys, ureters, bladder, and the urethral outflow tract.
Diagnosis of Feline Hepatic Lipidosis
Physical examination findings (jaundice, hepatomegaly)
Definitive diagnosis of HL is based on the following:
clinicopathologic features (especially hyperbilirubinemia and increased liver enzymes)
ultrasonographic confirmation of hepatic parenchymal hyperechogenicity and hepatomegaly
cytology of a US-guided hepatic aspirate (after vitamin K1 administration)
Liver biopsy is not necessary to diagnose HL; however, underlying cholangitis/cholangiohepatitis, hepatic lymphoma, or inflammatory bowel disease may eventually require biopsy for definitive diagnosis. On cytology, hepatocytes display profound lipid vacuolar distention involving > 80% of aspirated hepatocytes. It is important to note the cellularity of the inspected sample to determine confidence of this interpretation; there should be numerous hepatocytes in the sample.
Vacuolation may be microvesicular (many small vacuoles) or macrovesicular (large vacuoles); this has no bearing on survival or underlying cause. Canalicular cholestasis is commonly seen as thin elongate black to dark blue "casts" between adjacent hepatocytes or marginating hepatocytes. Mistaken aspiration of omental fat rather than liver is easily deduced by the absence of hepatocyte.
Treatment of Feline Hepatic Lipidosis
Management of HL is aimed at correcting fluid, electrolyte, and metabolic aberrations and initiating food intake.
Because cats with HL may have high lactate concentrations and may not be able to metabolize acetate, saline (0.9% NaCl) solution is the fluid of choice. Fluids should not be supplemented with dextrose, because this will decrease utilization of intrahepatic fatty acids for beta-oxidation. Because affected cats are usually overconditioned, calculation of rehydration and maintenance fluids must be based on ideal body weight. Overhydration, common when fluid dosage is based on total overconditioned body weight, can cause iatrogenic pleural and abdominal effusion and pulmonary edema.
Potassium and Phosphate Supplementation
Judicious KCl supplementation based on serum potassium concentrations is initially planned according to the conventionally used sliding scale. Concurrent hypophosphatemia must also be addressed with potassium-phosphate. This requires reconsideration of supplemental KCl to avoid cardiotoxic hyperkalemia (ie, potassium infusion > 0.5 mEq/kg/h).
Treatment guidelines for potassium-phosphate are tailored to the individual, metabolic circumstance, and primary disease process provoking FHL. Rapid transcellular phosphate shifts make it impossible to accurately predict the total dose for an individual. Consequently, sequential phosphate measurements are requisite.
Most HL cats are initially supplemented with IV potassium-phosphate if their phosphate is at the low end of the normal range or subnormal (< 2.0 mg/dL). K-phosphate supplementation should be preemptively used when enteral feeding is initiated because of risk for acute critical hypophosphatemia secondary to the refeeding phenomenon (commercial parenteral phosphate solution: 3 mmol/mL of phosphate = 93 mg/mL of elemental phosphorus).
Initial dosing ranges from 0.01 to 0.03, up to 0.06 mmol/kg/h. Potassium phosphate supplements (up to 0.06 mmol/kg/h) are often initiated when feeding is started to guard against "midnight" development of severe hypophosphatemia (associated with refeeding syndrome). Subsequently, serum phosphate is measured every 3 to 8 hours during, and immediately after, discontinued supplementation. Phosphate infusions are discontinued when serum phosphate is consistently > 2 mg/dL, or more abruptly adjusted if hyperphosphatemia is encountered.
Awareness for complications includes monitoring for hyperphosphatemia, iatrogenic hypocalcemia, avoidance of calcium-phosphate product > 58 mg/dL that may provoke tissue mineralization, and iatrogenic hyperkalemia (from failure to adequately adjust [decrease] the KCl infusion rate).
Once enteral feeding is established for several days, requirements for parenteral electrolyte supplements typically diminish. If continued potassium supplementation is required, oral K-gluconate usually suffices and the status of magnesium should be evaluated (hypomagnesemia can cause refractory hypokalemia).
Rarely, some cats develop renal potassium wasting as a result of underlying renal disease or perhaps lipid vacuolation of renal tubules. Fractional excretion of potassium can be estimated by measuring potassium and creatinine in simultaneously collected 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 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 decrease the concentrations of potassium needed in the IV fluids, which carry risk for lethal iatrogenic hyperkalemia (ie, with accidental flushing of a hyperkalemic fluid line).
Concomitant magnesium deficiency has long been appreciated to aggravate clinical effects of hypokalemia and renal tubular potassium wasting. In the rare cat with refractory hypokalemia, magnesium should be measured to determine need for supplementation. Unfortunately, there is no consensus recommending optimum magnesium supplementation. Most magnesium (99%) is intracellular, with < 1% in extracellular distribution. complicating dosing regimens. Intercompartmental shifts of magnesium affect measured values.
Dosing is complicated by available forms of magnesium. One gram of magnesium sulfate hexahydrate contains 8.1 mEq of magnesium; 1 mg magnesium sulfate injection contains 0.0081 mEq of magnesium. Magnesium chloride contains 9.25 mEq of magnesium per gram.
Conventional magnesium dosing ranges from 0.30–0.75 mEq/kg/d (or 0.185–0.375 mmol/kg/d) as a slowly administered constant-rate infusion (CRI), IV. Dosage recommendations vary; most clinicians recommend administering a loading dose of 0.15–0.3 mEq/kg (equivalent to 18.5–37 mg/kg of magnesium sulfate), IV, slowly over 10–20 minutes, followed by a CRI of 0.75–1 mEq/kg/d (equivalent to 92–123 mg/kg/d of magnesium sulfate), IV. Daily dose can be administered over 12–24 hours with dose decreases necessary in animals with renal insufficiency. Some clinicians decrease the daily dosage after the first day. Monitoring for clinical signs of hypermagnesemia is important (ie, muscle weakness, decreased respiratory effort).
A fortified water-soluble vitamin solution (2 mL/L of fluids, as shown in the , should be added to IV fluids.
Vitamin B12 deficiency is common in HL, presumably reflecting inappetence, underlying inflammatory bowel disease, chronic diarrhea, dysbiosis due to enteric disease or chronic antibiotic administration, malassimilation, pancreatic disease, or concurrent hyperthyroidism. A baseline blood sample should be collected for B12 determination followed by empiric B12 administration (250–500 mcg/cat, SC).
When present, B12 deficiency impairs mitochondrial metabolism; this can only be confirmed by detection of methylmalonic acidemia or aciduria using mass spectroscopy. Mechanistically, B12 insufficiency impairs mitochondrial conversion of methylmalonyl CoA to succinyl CoA, due to dysfunction of B12 -dependent methylmalonyl CoA mutase. Concentrations of B12 measured by routine analytic methods measure both the administered B12 supplement (cyanocobalamin) and relevant metabolically activated B12 (methyl- and adenosyl-cobalamin).
Vitamin K1 supplementation is critical as an immediate intervention in all cats with suspected HL. Prolonged PIVKA clotting times in severe HL are rectified after three dose administrations of 0.5–1.5 mg/kg, IM or SC (not IV), every 12 hours, given with a small needle. Treatment should be completed before invasive procedures (eg, insertion of jugular catheter, esophageal feeding tube, cystocentesis, or hepatic aspiration sampling). Too high a vitamin K dose repeated too frequently can provoke Heinz body hemolysis.
Vitamin E supplementation is initially provided using a water-soluble form (10 U/kg, PO, every 24 hours) once enteral feeding is established. Too much vitamin E can be deleterious because it may accumulate as the tocopheroxyl radical that provokes oxidative injury. This complication reflects metabolic inability to rejuvenate protective tocopherol because of insufficient GSH and other factors. In addition to oxidative injury, excessive vitamin E dosing can interfere with activity of vitamin K reductase, compromising activation of vitamin K-dependent coagulation factors.
Additional Therapeutic Considerations
Cats with HL have low circulating and low hepatic GSH, with high risk for Heinz body hemolysis. They likely also have a primary disease process associated with oxidative injury or an oxidative systemic redox imbalance. On acute presentation, N-acetylcysteine (NAC) is used IV as a thiol donor.
NAC, an acetylated variant of L-cysteine, is also converted to additional antioxidant metabolites, increases GSH synthesis (cysteine donor), and functions as a direct circulating free-radical scavenger. Treatment with NAC is recommended during the first 2–3 days (140 mg/kg, IV, via a 0.25 mcm filter if not the intravenous form of drug, though the IV form is preferred), administered over 20 minutes, then 70 mg/kg, every 6–8 hours, diluted to a 10% solution.
NAC should not be given as a prolonged (> 1 hour) constant-rate infusion because it may provoke hyperammonemia by deviating substrates from the urea cycle (impairs carbamyl phosphate synthetase 1 activity, limiting formation of carbamyl phosphate, which is essential for ammonia entrance into the urea cycle). Intravenous dosing is continued until oral SAMe administration is possible. Oral NAC is not advised as it has a terrible taste that can provoke nausea and vomiting. NAC rarely causes urticaria and hyperemia, considered an allergic reaction and necessitating discontinuation.
When oral medications can be accommodated (after correction of electrolyte and hydration deficits), bioavailable SAMe (20–40 mg/kg, PO, every 24 hours, administered on an empty stomach) is started. Using NAC is not equivalent to administering SAMe. NAC only supplements immediate cysteine availability, the limiting amino acid for GSH synthesis. SAMe has numerous important and irreplaceable metabolic roles including its functions as a thiol donor; methyl donor orchestrating a myriad of essential metabolic, synthetic, and detoxification processes as well as nucleoprotein synthesis and function (ie, gene transcription) and B12 activation; and generating methylthioadenosine and polyamines.
Methylthioadenosine drives regeneration of adenosine and methionine; it modulates gene expression, cell proliferation, and cellular differentiation and apoptosis. It also modifies protein and DNA methylation (competing for methyltransferases) impacting gene expression, has immunomodulatory effects, and suppresses proinflammatory cytokines while enhancing production of anti-inflammatory cytokines (interaction with nuclear factor kappa B pathway). Treatment with 20 mg/kg, PO, every 24 hours improved hepatic and circulating antioxidant GSH status in healthy cats; therapeutic response in HL has not been studied specifically.
Nutritional support Nutrition in Hepatic Disease in Small Animals Nutritional support has a pivotal influence in cats with hepatic lipidosis (HL) and is an important husbandry consideration for home management of animals with progressive hepatobiliary disease... read more is the cornerstone of recovery. Feeding is initiated after the cat is rehydrated and has reasonable electrolyte balance. A palatable odiferous food should be physically offered initially to entice patient interest. If the cat salivates, withdraws, repeatedly turns its head away from offered food, then all food should be removed from the patient's proximity to decrease risk of an induced food aversion syndrome. Initial feeding can also be explored with syringe offerings of a palatable liquid calorie-rich feline formula or chicken (other meats) baby food. Insertion of a feeding tube IS NOT a critical initial action.
Electrolyte adjustments must precede initial feeding attempts. It often takes 1–2 days to re-establish hydration and reasonable electrolyte balance before making feeding attempts. Gastric hypomotility develops in hypokalemia and increases risk for vomiting and aspiration pneumonia.
If oral feeding is refused or not tolerated, feeding a liquid diet 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 clinical signs of discomfort are noted over a 4-hour observational interval, 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. Position should be documented with a lateral thoracic radiograph.
E-tube feeding is the preferred method of provisioning nutritional support. Feedings are given over 20 minutes, and the tube is flushed well to remove residual material.
It is essential to avoid protein restriction. High-energy/high-calorie diets with balanced feline protein content are optimal for these patients. Calculated resting energy requirement (RER) ([BW(kg) x 30 + 70] or [BW (kg)0.75 x 70]) is the general goal for nutritional support but is initiated with 25% calculated RER, gradually increased over 3–5 days to full RER. Actual energy needs vary; some cats require less and some cats require more. In some cases, a trickle feeding regimen is needed (infusion pump propelled trickle) or frequent small feedings need to be given manually every 2–4 hours.
Tolerance of feeding must be monitored. In some cases tolerance is aided by physical activity (walking) that may increase peristaltic and gastric contractions. This should be tried before introducing metoclopramide or other motility modifiers (because of concern regarding hepatic drug metabolism).
Only rarely should a protein-restricted diet be used if a cat demonstrates clinical signs of hyperammonemia, because protein restriction can aggravate hepatic lipid accumulation. Rather, use of lactulose and oral amoxicillin or low-dose metronidazole (7.5 mg/kg, every 12 hours) can optimize nitrogen tolerance to allow feeding of a normal feline diet. Use of these measures variably modifies enteric flora and substrate utilization and increases colonic catharsis or cleansing that helps control hyperammonemia.
If vomiting is recurrent, 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 every 8 hours, or 0.25–0.5 mg/kg/d as a constant-rate infusion), ondansetron (0.025 mg/kg, IV, up to every 12 hours), or maropitant (1 mg/kg, PO, every 24 hours) may be used as antiemetics. Exercise (walking) during owner visits also may stimulate enteric motility that will decrease episodic vomiting.
Because cats with HL are in metabolic liver failure, appetite stimulants may not be normally metabolized and/or may increase risk for accumulation of noxious metabolites. Hence, diazepam, oxazepam, alprazolam, and cyproheptadine should be avoided. Appetite stimulants will not recover cats with severe HL. These cats usually need esophageal tube-assisted feeding to ensure adequate energy and protein intake. Early in onset of HL, appetite stimulants occasionally improve food intake; however, the underlying cause of inappetence must be addressed.
To avoid development of refeeding syndrome, correction of hypokalemia, initiation of an IV phosphate infusion, and thiamine supplementation should be initiated before feeding starts. Thiamine is necessary for normal pyruvate metabolism and function of the citric acid cycle; activities surge when feeding follows a prolonged fast. Lactic acidosis in HL is thought to at least partially reflect thiamine deficiency and rapidly resolves with thiamine supplementation and normalized hydration.
Phosphate supplementation provisions phosphate for the expected surge in ATP utilization and synthesis driven by food intake after chronic deprivation. Hypophosphatemia induced by refeeding syndrome causes weakness, hemolysis, metabolic encephalopathy, and numerous other adverse effects. Serum phosphorus concentrations should be serially monitored and supplemental potassium phosphate judiciously adjusted. Intravenous potassium phosphate supplementation is routinely administered just before feeding to obviate persistent or feeding-induced hypophosphatemia.
Plasma potassium concentrations also must be serially monitored. Water-soluble vitamins also are essential at onset of food intake. In the absence of potassium, phosphate, and thiamine supplementations, refeeding syndrome rapidly progresses these deficiencies, causing patient weakness and collapse, metabolic encephalopathy, hemolytic anemia, enteric atony, and even bleeding tendencies (hyperphosphatemia impacting platelet aggregation), along with numerous other adverse effects that can culminate in death.
L-carnitine (L-CN) is a conditionally essential vitamin-like nutrient, synthesized in the liver and kidneys from SAMe, lysine, vitamin C, vitamin B6 (pyridoxine), and iron. Three investigational studies in cats substantiate the benefit of supplemental L-CN for optimizing fatty acid oxidation in overconditioned cats while conserving lean body mass. Observational clinical data demonstrate improved recovery in HL cats supplemented with L-CN (in combination with appropriate nutritional support and electrolyte and vitamin supplements) compared to cats merely receiving fluids and nutritional support. Supplementation of L-CN either provides a beneficial supraphysiologic effect or pet cats maintain a narrow L-CN surplus and have limited on-demand synthetic capacity.
A further consideration supporting use of supplemental L-CN is that natural prey of cats contain substantially more L-CN than many feline diets (150–3,000 mg L-CN/kg animal tissue). Dosing of L-CN in HL cats is recommended at 250–500 mg/cat, every 24 hours, using medical grade liquid L-CN that can be administered via E-tube. A study of many over-the-counter L-CN products demonstrated lack of bioavailability.
Taurine, an essential amino acid, is depleted in cats with even short-term fasting. Among the functions of taurine is its obligatory use for bile acid conjugation. Conjugation of bile acids is essential for their water solubility, increasing renal and enteric disposal and mitigating their cytotoxicity, to some extent. Cats with HL have extreme increases in serum bile acid concentrations. Taurine supplementation at a dose of 250–500 mg/cat, PO, is given as soon as possible, at least during the first week of management.
There are three strong reasons to avoid ursodeoxycholic acid (UDCA) treatment in cats with HL.
Bile acids accumulate to extreme concentrations in cats with HL similar in magnitude and accumulated moieties to cats with extrahepatic bile duct obstruction Extrahepatic Bile Duct Obstruction in Small Animals Extrahepatic bile duct obstruction is the blockage of the normal flow of bile from the liver to the intestinal tract. Obstruction of the common bile duct is associated with a number of diverse... read more (EHBDO). In models of EHBDO, UDCA escalates liver injury to hepatocytes and small bile ductule cells.
Children with kwashiorkor (protein and energy malnutrition) who develop HL, a syndrome resembling feline HL, obese children with HL, and obese rat models of HL do not benefit from UDCA administration.
UDCA supplementation increases risk for further decline in plasma taurine concentrations (consumptive utilization) if dietary taurine intake is insufficient.
To calculate drug dosages for overconditioned cats, use estimated ideal body weight or lean body mass to avoid inadvertent overdosage.
Drugs to avoid:
Stanozolol (17-alpha alkylated steroid): proven to increase risk for FHL, especially in cats with renal dysfunction
Glucocorticoids: facilitate HL onset in some cats; speculated to reflect the inhibitory influence of glucocorticoids on mitochondrial matrix acyl-CoA dehydrogenases and beta-oxidation of medium- and short-chain fatty acids and decreased hepatic triglyceride exportation
Tetracyclines: concentration-dependent inhibition of mitochondrial beta-oxidation, leading to accumulation of free fatty acids, converted to microvesicular triglycerides in hepatocytes
Appetite stimulants: unreliable in provision of adequate nutritional intake. Some drugs generate potent hepatotoxic metabolites (benzodiazepines: diazepam, oxazepam, alprazolam). Cats with HL have increased risk for accumulation of metabolites that undergo glucuronidation, with delayed detoxification and slow biliary elimination. Mirtazapine has first-pass hepatic extraction and undergoes hepatic biotransformation and glucuronidation and therefore likely has a prolonged residence time.
Propofol: caution with repeated use of propofol in cats with HL. Even healthy cats develop Heinz bodies after propofol anesthesia. Slow recovery (hours to days) and delayed onset (6–12 hours) Heinz body hemolysis requiring blood transfusion is documented in cats with HL. It is unknown whether apparent toxicity relates to the phenol derivative status of propofol (cats generally do not metabolize phenol derivatives well) or mitochondrial toxicity and oxidative stress associated with the propofol infusion syndrome characterized in critically ill humans.
Hepatic lipidosis either resolves within 14–21 days or the patient dies; chronic survival does not occur. Recurrence after recovery is rare. Follow-up liver biopsy in recovered cats shows no residual lesions, architectural remodeling, fibrosis, or lipogranulomas.
Decline in total bilirubin by 50% within the first 7–10 days and declining serum beta-hydroxybutyrate concentrations are positive predictors of survival. Monitoring liver enzymes has no value in predicting recovery. Worsening or sustained hyperbilirubinemia, hypokalemia, hypoalbuminemia, hypotension, and concurrent pancreatitis are negative prognostic indicators.
Recovery of cats from HL in the author's hospital confirms efficacy of customized critical care, including appropriate nutritional support (rich in calories with feline-appropriate protein and fat) and metabolic supplements including L-CN. Survival ~75%–80% in severely affected cats is demonstrated compared to 50% in cats given only nutritional support.
Management of the underlying cause or primary disease process leading to HL is essential. Prognosis is best for cats presented early in syndrome onset that receive supportive care described herein, along with identification and control of the underlying cause of HL. Monitoring ALP in obese cats undergoing weight reduction may identify emerging HL that will allow suspension of the weight loss program and early treatment intervention.