Feline Hepatic Lipidosis 

Hepatic lipidosis, also called fatty liver syndrome, is the most common life-threatening liver disorder in obese cats. Obesity is the most predisposing factor. It is characterised by accumulation of triglycerides or neutral lipid within more than 50% of hepatocytes (liver cells), which results in severe cholestasis (bile obstruction) and liver dysfunction. It is triggered commonly by prolonged anorexia (stress, boarding, concurrent illness, etc). It may be a primary idiopathic disease or secondary to other diseases that cause anorexia. The most commonly reported primary diseases are cholangiohepatitis, biliary obstruction and inflammation, intrahepatic or extrahepatic neoplasia, inflammatory bowel disease, pancreatitis and diabetes mellitus.

 Hepatic lipidosis occurs for any reason that forces a cat to begin to metabolise its own body fat rather than energy from food. As far as I know, this disorder probably does not occur as a primary problem. It is usually secondary to something else which causes the cat not to eat. It is more common in obese cats because they tend to metabolise fat more readily than thinner cats. Cats do not metabolise fat well. So the fat globules build up in a "backlog" in the cell, eventually making it unable to perform its normal functions at all, resulting in jaundice (yellowing of membranes (see Fig. 2).

Figure 2. Icterus (Jaundice) in hepatic lipidosis

There are many many things which will cause a cat not to eat for a several days. In many cases, the original cause of anorexia is gone when hepatic lipidosis becomes a problem. In other cases, it is necessary to find and correct the original problem in order to succeed in treating hepatic lipidosis.

Diagnosis 

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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, diarrhoea, constipation, inappetence, 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.

Haematology 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, non-regenerative anaemia most likely due to the anaemia 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 coloured, 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 1 & 2

Fig 3 & 4

Treatment

The goal of nutritional support is to provide 60-80 kcal/kg body weight per day and 3-4g protein/kg body weight per day. It is essential not to restrict protein as it is needed to form lipoproteins necessary for transporting triglycerides out of the liver.

Cats with hepatic lipidosis do not usually feel like eating. Therefore, it is usually necessary to force feed them in some way. The most consistently successful approach is to implant an esophagostomy tube (stomach tube through their body wall) and feed them through the stomach tube. It make take several months to reach the point a cat will eat on its own again. Many people are reluctant to implant stomach tubes and try to force feed orally or use appetite stimulants. Sometimes this works. Usually when it doesn't work, the cat is much worse off and it may be too late to take the other approach.

Recommended supplements for 6-8 weeks: L-Carnitine (250mg/day), taurine (250-500mg/day), thiamine (50-100mg/day), vitamin E (100-400 IU/day), potassium gluconate (2-4 mEq/day), s-Adenosylmethionine (Denosyl®) and zinc (7-8 mg/day).

Appetite stimulants such as benzodiazepines are contraindicated due to requiring hepatic biotransformation.

Prognosis

The commonly reported survival rate is 50-60%. Almost all deaths occur in the first few weeks of the disease. Survival improves if stress can be minimised during this time, if an orogastric or esophagostomy tube placed and if the required nutritional support is given.

Prevention

Prevention of hepatic lipidosis is best ensured by maintaining the recovered cat on a suitable diet that is low in fat and has a low glucose index, such as Hills M/D diet.

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.