Introduction:  Hepatic lipidosis is characterized by an excessive accumulation of fat (triglycerides) in the liver due to either increased deposition of fat or decreased secretion of lipoprotein (VLDL).  Currently feline hepatic lipidosis is the most commonly diagnosed hepatopathy of cats in the United States.  This condition can occur secondary to hypoxia (anemia, heart failure, pulmonary disease), drug toxicity (acetaminophen, griseofulvin, tetracycline), metabolic disorders (diabetes mellitus), or nutritional deficiencies (anorexia, essential amino acids), but is most frequently idiopathic in origin.

Pathogenesis:  The suggested mechanisms for hepatic lipidosis are complex and not well understood.  In cases of prolonged anorexia it is speculated that lipids are mobilized from peripheral fat stores at a rate faster than can be metabolized by the liver resulting in triglyceride accumulation within hepatocytes.  The rate-limiting steps in lipid dispersal from the liver include the oxidation of FFA in the hepatic mitochondria, and the secretion of lipoprotein (triglyceride + apoprotein).  Human studies have shown that decreased oxidation of FFA may be related to deficiencies in carnitine, the amino acid required for the transport of fatty acids into mitochondria.  Low levels of this may then lead to hepatic lipidosis.  Since most cat diets contain abundant carnitine, this may explain why hepatic lipidosis is seen less frequently in non-fasting cats.

Inadequate lipoprotein synthesis may also occur secondary to decreased apoprotein synthesis due to a deficiency of the essential amino acids arginine or taurine.  Research has shown that cats with idiopathic hepatic lipidosis have decreased serum levels of both arginine and taurine.  Arginine is an essential amino acid in cats that is necessary for normal urea cycle function and ammonium detoxification.

Without sufficient levels of apoprotein the triglycerides cannot be removed from the liver via the circulatory system, instead they accumulate in the hepatocytes resulting the a state of hepatic lipidosis.  Taurine is also required for hepatic conjugation of bile acids, thus deficiencies are linked with the development of intrahepatic cholestasis.

Gross pathology:  The livers from cats with hepatic lipidosis are typically diffusely enlarged with rounded edges, yellow, and greasy.  Samples will float when placed in solution.

Histopathology:  Well-executed biopsies or fine needle-aspirates of the liver will provide valuable information for the diagnosis for many hepatopathies.  When severe liver dysfunction is suspected, a coagulation profile should be submitted before attempting this procedure. 

    Either histopathology or cytology will reveal unstained vacuolated hepatocytes with increased size and displaced nuclei.  Cholestasis may also be noted on histopathology of the biopsy specimens.  
Click to view histopathology slide.

Presenting clinical signs:  Cats with hepatic lipidosis are frequently presented for complete to partial anorexia, sporadic vomiting, and lethargy. The owner may report a recent dietary change, stressful event, or recent illness.  Physical exam findings include weight loss exceeding 25% of body weight, and mild hepatomegaly. The magnitude of weight loss may be difficult to evaluate in cats as they may still present as obese.  Icterus is not usually evident in early disease, as this is a sign associated with severe hepatic dysfunction.  Ultrasound may show a diffusely hyperechoic liver consistent with decreased density secondary to lipid infiltration of the hepatocytes.  Abdominal radiographs may show evidence of peritoneal effusion or hepatomegaly.

Clinical pathology:   Biochemical profiles of cats affected with hepatic lipidosis are indicative of severe intrahepatic cholestasis.

• Marked increases in alkaline phosphatase (ALP).

• Mild to moderate increases in both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are the most commonly reported abnormalities.

• Serum gamma glutamyltransferase (GGT) is usually within normal limits.

• A hematological profile of affected cats often reveals a normocytic, normochromic, non-regenerative anemia, mature neutrophilia, and lymphopenia consistent with the chronic disease.

• In cases of significant hepatic dysfunction, hyperbilirubinemia, bilirubinuria, hypoalbuminemia, and increased serum bile acids may also be noted.

• Decreased production of coagulation factors may also result in coagulopathies.