Feline Hepatic Lipidosis

Bradley Turner, DVM; Bruce E. LeRoy, DVM, PhD; Heather L. Tarpley, DVM; Holly Moore, DVM; Kenneth S. Latimer, DVM, PhD; and Perry J. Bain, DVM, PhD

Class of 2005 (Turner) and Department of Pathology (Tarpley, Moore, Latimer, LeRoy, Bain) College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7388

Introduction

Feline hepatic lipidosis (HL) is the most common form of liver disease in cats. This disease is characterized by excessive lipid accumulation in hepatocytes, which in turn leads to hepatocellular and biliary tract dysfunction. There is no breed predilection and affected cats are primarily middle aged (4-12 years); however, HL can occur at any age. It is important for veterinarians to recognize HL in its early stages, because the damage to the liver may be reversible.

Pathogenesis

In normal hepatocytes, lipid is delivered from dietary sources or body fat stores in the form of free fatty acids (FFAs). Most of the intracellular FFAs are esterified to triglycerides. Once triglycerides are produced, they must be complexed to a lipid acceptor protein (or apoprotein) prior to export from the cell as lipoproteins. Triglycerides may accumulate if the balance between the synthesis of triglycerides and their utilization or mobilization is upset. When intracellular triglycerides accumulate in hepatocytes, they are stored in cytoplasmic vacuoles. Hepatic lipidosis occurs when this accumulation becomes severe and interferes with normal hepatocellular function.

The classical presentation of the idiopathic form of HL is a middle aged, obese housecat with a recent history of stress or starvation of over two weeks duration. During starvation, there is widespread mobilization of body fat, resulting in increased delivery of FFAs into hepatocytes and increased synthesis of triglycerides. In addition, protein synthesis, including the synthesis of apoprotein needed for triglyceride export from hepatocytes, is decreased as the supply of amino acids normally derived from the diet is lacking. Thus, along with increased synthesis of triglycerides in the liver there is also decreased fat export from hepatocytes secondary to dysregulated apoprotein synthesis. Both of these factors contribute to the resulting pathologic hepatocellular lipid accumulation that is the hallmark of hepatic lipidosis.

The pathogenesis of feline HL is not well understood. Obesity and anorexia are the primary risk factors for HL, however they may not be the only factors involved with this disease, as cats that are neither obese nor stressed occasionally develop HL. Hepatic lipidosis can be characterized as either idiopathic or secondary to other diseases such as inflammatory bowel disease, pancreatitis, cholangiohepatitis, diabetes mellitus, hyperthyroidism, renal disease, and neoplasia.

Diagnosis

A presumptive diagnosis of hepatic lipidosis may be reached by history, physical examination, clinical laboratory testing, and relevant imaging studies. A liver fine-needle aspirate or, preferably, a surgical biopsy and histopathology along with the above supports the diagnosis. Biopsy alone is not sufficient for a definitive diagnosis. Other underlying conditions, such as metastatic neoplasia or bile duct carcinoma, can cause hepatic lipidosis. Anytime clinical HL is suspected, the veterinarian should also search for other underlying conditions that may be present.

Cats with idiopathic HL usually have a medical history of anorexia and weight loss. Many of these cats were also obese before the onset starvation. The medical history may also include vomiting, diarrhea, constipation, inappetance, and lethargy if there is an underlying condition. On physical examination, many cats with this disorder are depressed and jaundiced. Hepatomegaly may be found on palpation. Signs of bleeding disorders such as hematemesis and petechia are uncommon findings. Neurologic signs due to hepatoencephalopathy are uncommon. Ventroflexion of the neck due to muscle weakness may also be seen due to low concentrations of phosphorus, potassium, or thiamine.

Hematology test results are dependent on whether the condition is primary or secondary. The complete blood cell count (CBC) is usually normal in idiopathic hepatic lipidosis. With underlying disease, the packed cell volume can be normal or there can be a mild to moderate, normocytic, normochromic, nonregenerative anemia most likely due to the anemia of chronic / inflammatory disease. Poikilocytosis (abnormally shaped erythrocytes) is a common finding (Fig. 1) and may be due to abnormal lipid membrane metabolism within erythrocytes secondary to the hepatocellular disease. The leukocyte count is dependent on the underlying condition.

Fig. 1

The serum chemistry panel is characterized by hyperbilirubinemia and a greater than two-fold increase in aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) activities with a normal or mildly increased gamma-glutamyl transferase (GGT) activity. The degree of GGT activity helps to characterize this condition. In most acquired hepatobiliary diseases, GGT activity is substantially increased. In cases of hepatic lipidosis, GGT is only substantially increased when concurrent conditions such as pancreatitis or cholangiohepatitis are present. Hypokalemia is present in approximately 1/3 of hepatic lipidosis cases and is often a negative prognostic indicator. Hypophosphatemia is seen in less than 15% of cats with HL. Hypercholesterolemia is an uncommon finding, but it may occur with concurrent pancreatitis or bile duct obstruction. Low BUN concentration with a normal creatinine level occurs in about 50% of affected cats due to decreased urea formation by the liver. Serum albumin concentrations are low in about 20% of cats with HL. Serum bile acid concentrations may be increased, but once jaundice is apparent this test no longer provides additional information.

On urinalysis, most cats with hepatic lipidosis have a specific gravity of <1.020. Lipiduria is a common finding in these cats, but hematuria is uncommon. Bilirubinuria may also be present. Ammonium biurate crystals are a rare finding.

Although overt bleeding is uncommon, abnormal clotting profiles may be observed in up to 50% of cats with hepatic lipidosis. Prolongation of the prothrombin time due to vitamin K deficiency is the most common abnormality. Vitamin K deficiency can be due to anorexia or malabsorption resulting from cholestasis. The activated partial thromboplastin time (APTT) and activated clotting time (ACT) are also prolonged in some cats. Hypofibrinogenemia is also common with HL.

Cytologic features of hepatic lipidosis on biopsy include highly vacuolated hepatocytes with little evidence of an inflammatory response (Fig 2). Grossly, the appearance of hepatic lipidosis includes a markedly enlarged, usually yellow colored, friable liver, with rounded edges and a smooth surface (Fig 3). Histologically, most hepatocytes contain one large globule that alters the contour of the cell and may displace the nucleus (Fig. 4). Special stains (such as Oil Red O) may also be used to confirm the presence of lipid in the hepatocytes (Fig. 5).

Fig. 2	Fig. 3

Fig. 4	Fig. 5

Treatment

Nutritional therapy is the most effective treatment for idiopathic HL. Furthermore, almost all cats with HL require a feeding tube. Unless there are obvious signs of hepatic encephalopathy, the best diet is high in protein, which is in contrast to normal feeding guidelines for animals with liver disease. It should also contain appropriate nutrients and calories for the individual patient. Cats fed a high protein diet appear to better mobilize fat from hepatocytes.

Correction of dehydration and electrolyte imbalances is very important. During this period, a less invasive form of feeding tube such as a nasoesophageal tube should be used. An esophagostomy tube or gastrostomy tube should be placed once the cat is stabilized. Cats with HL should be fed approximately 60-80 kcal/kg/day. To initially treat dehydration, a balanced polyionic fluid such as lactated Ringer’s solution should be used. Electrolyte levels should be monitored closely. Potassium may need to be supplemented if the serum chemistry shows hypokalemia.

Several vitamin and dietary supplements have been advocated for the treatment of HL. Cats with hepatic lipidosis may have a deficiency of carnitine. Therefore carnitine (250-500 mg/cat/day) supplementation appears to improve the survival rate in affected cats by stimulating fatty acid oxidation. Subcutaneous administration of vitamin K₁ (0.5-1.5 mg/kg at 0, 12, and 24 hours) should be given if bleeding disorders are suspected. In cats with ventroflexion, thiamine (100mg PO or injection twice a day for 3 days) should be given. Oral vitamin E (100 IU/kg/day in food) and vitamin C (30 mg/kg/day in food) supplementation can also be given. Vitamins C and E may help combat oxidative stress commonly found in cats with HL. Oral taurine administration (250-500mg/cat/day in food) may be given because cats with hepatic lipidosis often have low taurine levels.

References

1. Center SA, Warner K: Feline hepatic lipidosis: Better defining the syndrome and its management. 16th Annual ACVIM Forum, pp. 56-58, 1998.

2. Griffin B: Feline hepatic lipidosis: Pathophysiology, clinical signs, and diagnosis. Compend Contin Educ Pract Vet 22:847-856, 2000.

3. Griffin B: Feline hepatic lipidosis: Treatment recommendations. Compend Contin Educ Pract Vet 22:910-921, 2000.

4. Center SA: Hepatic lipidosis in cats. Proceedings,Western Veterinary Conference, 2002.

5. Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal Medicine, Diseases of the Dog and Cat, 5th ed. Philadelphia, WB Saunders, 2000, pp.1329-1330.

6. Tams T: Handbook of Small Animal Gastroenterology, 2nd ed. St. Louis, WB Saunders, 2003, pp. 336-340.

7. Jubb KVF, Kennedy PC, Palmer N (eds): Pathology of Domestic Animals, 4th ed. San Diego, Academic Press, 1993, pp. 331-336.

Acknowledgment

"Sleeping Cat" © 2000 watercolor by Ruth A. Curry is from the Abate-Currry Gallery website.

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