Feline hepatic lipidosis (HL, fatty liver disease) is the most commonly encountered liver disease in cats, and results from accumulation of fat (triglyceride) within the majority of hepatocytes.
Feline hepatic lipidosis (HL, fatty liver disease) is the most commonly encountered liver disease in cats, and results from accumulation of fat (triglyceride) within the majority of hepatocytes. The end result is severe intrahepatic cholestasis which leads to a rapid decline in liver function. Many affected cats are middle-aged or older. Overweight cats that become anorectic are particularly at risk. Stressful events or another systemic disease that causes the cat to stop eating are common precipitating factors. Studies have documented a concurrent or inciting disease in 50-95% of cases. Common concurrent illnesses include pancreatitis, cholangiohepatitis, inflammatory bowel disease, extrahepatic bile duct obstruction, and neoplasia. However, any illness or event that causes a prolonged lack of food intake can put cats at risk for developing HL, even those that are not overweight.
The exact cause of HL is unknown. Catabolism due to inadequate caloric intake appears to play a central role in the development of the disease. Factors theorized to be involved in the pathogenesis include 1) increased breakdown of peripheral fat stores with resultant increased fatty acid delivery to the liver, 2) as a result, oxidation of fatty acids in the liver by mitochondria is overwhelmed (i.e., decreased oxidation of fatty acids; leads to lipid accumulation), and 2) impaired removal of triglycerides (as VLDL) from the liver.
History and physical exam
Patients typically present with prolonged anorexia, gastrointestinal signs, weight loss (often > 25% of body weight), and lethargy. Icterus is frequently present on initial examination (> 70% of cases). Other findings include hepatomegaly, dehydration, and muscle wasting.
Initial CBC may be normal or reveals a mild non-regenerative anemia (22% of cases) and poikilocytosis, but is otherwise unremarkable. A declining hematocrit is a common finding during treatment and is influenced by a number of factors including repeated blood draws, hemolysis (due to Heinz bodies or severe hypophosphatemia), and/or blood loss. Care should be taken to limit the amount drawn during daily blood sampling to the absolute minimal amount needed to run the desired test, to avoid exacerbation of anemia. Approximately 25 to 40% of HL cats will require blood products during hospitalization.
Biochemical abnormalities include moderate increases in ALP, mild to moderate increases in ALT, and increases in AST. In contrast to other feline hepatobiliary diseases where GGT is typically increased, GGT is often normal or only mildly elevated in patients with hepatic lipidosis. Hypokalemia (30%), hypophosphatemia (17%), and hypomagnesemia (28%) may develop during the course of the disease, particularly during the refeeding period. When present, hypoalbuminemia, hyperammonemia, and hypoglycemia, are indicators of severe hepatic dysfunction.
In a study of 22 cats with naturally occurring liver disease, coagulation abnormalities were found in 82% of cats. Vitamin K deficiency was the most common abnormality detected. Coagulopathy in HL cats can result from deficiency of active vitamin K (due to cholestasis) and from reduced production of clotting factors. Routine coagulation testing such as PT and PTT are appropriate, but proteins-induced-by-vitamin K absence may be a more sensitive test to detect vitamin K dependent coagulopathies.
On abdominal ultrasonography the liver is diffusely hyperechoic and may also be enlarged. Sonography also assists with documentation of concurrent diseases such as pancreatitis or other intra-abdominal conditions that may have led to the anorexia. All HL patients should be screened for the presence of concurrent or underlying diseases. One study found a decreased recovery rate in HL cats that had concurrent pancreatitis compared to those in whom HL was the only diagnosis.
Definitive diagnosis of HL is established by histologic examination of the liver, which reveals severe intrahepatic lipid accumulation. Hepatic lipidosis may be suggested on fine-needle aspiration of the liver, and many clinicians prefer this test during the initial phase of treatment to support a presumptive diagnosis of HL, and may postpone biopsy of the liver until the hospitalized patient is more stable.
Fine-needle aspiration of the liver can easily reach a diagnosis of HL by demonstration of a predominance of heavily vacuolated hepatocytes. It has the advantage of being much less invasive and may be a more appropriate means of arriving at a preliminary diagnosis during the early phase of treatment in the fragile liver cat. However, it has significant drawbacks, in that it may miss concurrent hepatic disorders and may on occasion incorrectly classify primary inflammatory or neoplastic diseases as HL.
Liver biopsy is required for definitive diagnosis and to rule out other concurrent hepatic conditions, and is usually obtained with ultrasound-guidance. Because of the high lipid content, biopsy specimens of HL cats may float when placed in formalin. Obtaining a biopsy is particularly important if suspicion for another primary hepatopathy exists. Aerobic and anaerobic bile or liver cultures are also obtained at this time. Histologic examination of biopsy specimens demonstrates severe vacuolization in the majority of hepatocytes. Inflammation and necrosis are absent unless another concurrent hepatic disorder is present. Vitamin K1 (0.5 mg/kg SC q 12h) is administered in an attempt to improve coagulation abnormalities prior to liver biopsy. This may resolve abnormalities resulting from vitamin K1 deficiency. Clotting factor deficiencies will not correct with this therapy. Therefore if coagulation parameters remain abnormal, fresh frozen plasma or fresh who blood may be required before liver biopsy to provide necessary clotting factors. Risk of complications is also increased if the platelet count is below 80,000. Hemorrhagic complications from liver biopsy can be reduced to 10% or less by careful patient selection. Most post-biopsy bleeding complications occur within the first 5 hours after biopsy but can be delayed up to 18 hours. Cats should be closely monitored for significant post-biopsy bleeding during this time.
The goals in treatment of the HL cat are to 1) provide nutritional support with adequate calorie and protein intake, 2) correct fluid and electrolyte imbalances, 3) monitor for and manage complications of liver disease (coagulopathy, nausea, refeeding syndrome, HE, etc.), and 4) identify and treat any underlying conditions.
Treatment centers around aggressive nutritional support and the management of concurrent or underlying conditions. Early diagnosis and nutritional intervention improve chances for a successful outcome. Failure to treat concurrent disorders may hinder the clinician's attempts at reversing lipidosis. Initial treatment involves correcting fluid and electrolyte deficits using an intravenous balanced electrolyte solution supplemented with 20 mEq KC/L. Hypokalemia is common, and if identified, will require more aggressive supplementation and monitoring. Many clinicians, including the author, avoid lactate-containing fluids (such as LRS) because of the concern for decreased metabolism of lactate that may accompany severe hepatic dysfunction. Further studies are needed to determine if lactate-containing fluids pose a true threat to our feline liver patients. Unless hypoglycemia is documented, avoid supplementing intravenous fluids with dextrose as this may encourage further hepatic TG accumulation. Vitamin depletion may occur in HL patients. B-Complex vitamins are therefore often added to fluids at 1-2 ml/L to prevent deficits in thiamine and other water-soluble vitamins. Cobalamin (Vitamin B12) deficiency has been documented in 40% of HL cases, and deficiency can be determined in many with a fasting cobalamin level. A single dose of 250 ug SC cyanocobalamin SC can be administered while awaiting results. If reduced vitamin B 12 concentrations are documented, ongoing supplementation may be required.
In critical patients, anesthesia can further decompensate the patient and may need to be postponed. A temporary nasogastric tube is an excellent route by which to initiate nutritional support (using liquid enteral diets) in these patients. This can be placed in the awake patient after applying a small amount of topical anesthetic into the nostril (avoid using large amounts which can drain down to and numb the larynx). Once the patient is more stable (1-2 days), anesthesia can be performed to place a more permanent and wider lumen feeding tube (e.g., 12 Fr esophagostomy tube, 18-20 Fr gastrostomy tube). This can often be accomplished at the time the patient is anesthetized for an ultrasound-guided liver biopsy. Because of the fragile nature of these patients post anesthesia, surgery is avoided unless indicated for the management of an underlying condition.
In order to ensure adequate energy and nutrient intake, feeding must occur through a feeding tube. The use of appetite stimulants and palatability enhancements of foods are usually insufficient to promote sufficient intake by the HL cat, and therefore risk delaying appropriate therapy which may in turn decrease chances for recovery. Relying on force-feeding and appetite stimulants is therefore discouraged. The nutritional target is to provide the cat with its maintenance energy needs by providing a complete and balanced diet that is protein rich (~30-40%), contains a moderate amount of lipids (~ 50%), and is low in carbohydrate (~20%). The formula 1.1 x (30 x kg body weight) + 70 provides a good initial estimate of total caloric need. Eukanuba Maximum-Calorie [2.1 kcal/ml] (The Iams Company, Dayton OH) and Feline a/d [1.0 kcal/ml] (Hill's Pet Products, Topeka KS) are a commonly used diets that fulfill these criteria and can be easily blenderized with some water for use through a tube. Protein must not be restricted, unless overt hepatic encephalopathy is noted. Feedings are divided over 4-6 meals per day, and one third of the daily requirement is fed on day one. The amount is gradually increased to the full daily requirement (by another 1/3 each day) over the next 2-3 days. At the same time IV fluid rates are gradually reduced by the amount of fluid now being provided through the feeding tube. At this point the daily feeding amount can be gradually switched to q8h feedings, which is easier for owners to manage at home.
It is unknown whether supplementation with taurine, carnitine or arginine hastens recovery. L-carnitine is a cofactor that permits conversion of fatty acids into energy via of beta oxidation. A 1990 AJVR study concluded that carnitine deficiency does not contribute to the pathogenesis of HL. An anecdotal report of improved survival in another group of cats with severe HL supports the need for further study. A dose of 250 to 500 mg of medical grade carnitine is used when supplementing cats. Taurine is required for bile acid conjugation and levels may be reduced in some HL cats. Supplementation can be provided at 200-250 mg PO q 24h for the first 7 to 10 days of treatment.
Glutathione is an important antioxidant within the liver and depletion is common in HL cats. Stores can be replenished by providing thiol donor substrates (N-acetylcysteine, S-adenosylmethionine [SAMe]). SAMe is enteric-coated and should therefore not be crushed and given through the tube.
Complications are commonly encountered during the first three days of refeeding and patients must be closely monitored during this time. Vomiting is common in HL cats that are being refed and can result from severe hepatic dysfunction and reduced stomach volume. Metoclopramide (1-2 mg/kg/day as a CRI) has antiemetic and prokinetic actions and should be used if vomiting develops. Additional antiemetics may need to be added if nausea persists (e.g., dolasetron 0.6-1.0 mg/kg IV q24h). If vomiting does not subside, consider looking for other contributing conditions and/or switching from bolus to CRI (‘trickle') feedings. With refractory nausea, temporarily switching to total parenteral nutrition may be necessary. Hypokalemia and hypophosphatemia may exacerbate GI signs and can cause weakness. Additionally, phosphorus levels below 1.5 mg/dl can induce hemolysis. Phosphorus should be supplemented if levels fall below 2.0 mg/dl (potassium phosphate at 0.01-0.03 mmol/kg/hr). Phosphorus levels should be monitored every 6 to 12 hours during supplementation. Reduce KCL in the IV fluids by the amount of potassium provided in the phosphate infusion. Hypokalemia carries a negative survival risk and decreased levels should therefore not be ignored. Hepatic encephalopathy (HE) is managed with antibiotics and lactulose to limit ammonia production and NH3 diffusion across the blood brain barrier. Stuporous patients require more aggressive measures. Protein restriction may be needed in severe cases of HE. Monitor HL patients for risk factors that can worsen or precipitate HE which include hypokalemia, alkalosis, gastrointestinal bleeding, constipation, infection, hypoglycemia, and azotemia. Overtranquilization and stored blood products (increased ammonia content) can also exacerbate HE. Hypotension may develop in some patients following anesthesia and blood pressures should be measured in patients who appear more depressed or have a slow recovery. Hepatic encephalopathy is another differential that can cause similar symptoms. Persistent hypotension should trigger aggressive supportive measures (IV crystalloids, +/- colloids, +/- pressors in fluid-replete patients) and a search for other contributing causes (e.g., sepsis).
Vital signs are closely monitored. A PCV/TP, blood glucose, and azostrip are checked every day. Evaluation of electrolytes may be required one or more times each day and should be tailored to the individual patient. A sudden dramatic decline in PCV should prompt investigations for hypophosphatemia and blood loss.
Once patients have reached their full caloric needs, are stable, and vomiting is controlled, care can be transitioned to the owner at home. Owners must be given detailed instructions on feeding tube care, how to detect tube site infections, and trouble-shooting when problems occur (e.g., tube clogging). Cats often require tube feedings for 3-8 weeks. Fresh food is offered each day throughout this period to encourage the patient to resume oral feeding. Once cats start consuming food orally, tube feedings can be gradually reduced each week as long as their weight remains stable during this time. The tube can be removed once the cat is completely off all supplemental feedings for at least one week and consuming a sufficient amount of food to maintain its weight during that ‘tube-feeding-free' time.
Survival rates in HL cats have been reported to range from 60-88%. Early aggressive treatment combined with diligent monitoring and supportive care offer the best chance at a successful outcome. Higher median potassium and hematocrit levels as well as young age were more favorably associated with survival in 1 study. Bilirubin levels often decline by 50% in the first 7-10 days in responders. Liver enzymes decline more slowly. Those with a poor prognosis often succumb during the first week of treatment. A lower survival rate has been reported with concurrent pancreatitis. Residual hepatic dysfunction does not persist following complete recovery and recurrence is unlikely unless the precipitating cause was not corrected.
Center SA. Feline Hepatic Lipidosis. Vet Clin Small Anim 2005;35 (1) 225-269.
Willard MD, Weeks BR, Johnson M. Fine-needle aspirate cytology suggesting hepatic lipidosis in four cats with infiltrative hepatic disease J Feline Med Surg. 1999;1(4):215-20.
Wang KY, Panciera DL, Al-Rukibat RK, et al. Accuracy of ultrasound-guided fineneedle aspiration of the liver and cytologic findings in dogs and cats: 97 cases (1990–2000). J Am Vet Med Assoc 2004;224(1):75–8.
Bigge LA, Brown DJ, Penninck DG. Correlation between coagulation profile findings and bleeding complications after ultrasound-guided biopsies: 434 cases (1993–1996). J Am Anim Hosp Assoc 2001;37(3):228–33.
Center SA, Warner K, Corbett J, et al. Proteins invoked by vitamin K absence and clotting times in clinically ill cats. J Vet Intern Med 2000;14(3):292–7.
Brown B, Mauldin GE. Metabolic and hormonal alterations in cats with hepatic lipidosis.J Vet Intern Med. 2000 Jan-Feb;14(1):20-6Am J Vet Res. 2000 May;61(5):566-72.
Zoran DL The carnivore connection to nutrition in cats. J Am Vet Med Assoc. 2002;221(11):1559-1567.
Justin RB, Hohenhosue AE. Hypophosphatemia associated with enteral alimentation in cats. J Vet Inter Med. 1995;9:228-233.
Center SA, Warner KL, Erb HN: Liver glutathione concentrations in dogs and cats with naturally occurring liver disease. Am J Vet Res 2002;63: 1187-97.