Feline hepatic lipidosis

Hepatic lipidosis in the cat is a common and life-threatening condition, but a considered approach can often result in a positive outcome. 

Introduction

First described in 1977, hepatic lipidosis (HL) has since emerged as the most commonly diagnosed hepatobiliary disease in cats (1,2). Accumulation of triglycerides within hepatocytes engenders hepatocyte swelling and intrahepatic cholestasis, oxidative damage, secondary inflammation, and ultimately hepatic dysfunction (1,2). Metabolic complications and systemic ramifications of HL are diverse, and include electrolyte imbalances, insulin resistance, pancreatitis, hyperammonemia, hepatic encephalopathy and coagulopathies. Therefore, feline hepatic lipidosis (FHL) is associated with significant morbidity and often requires hospitalization for initial stabilization, with the possibility of several weeks of intensive treatment for complete recovery, and it carries a guarded-tofavorable prognosis overall.

Pathophysiology

Feline HL is defined by abnormal accumulation of lipid-filled vacuoles within hepatocytes. In severe cases, fat accounts for over 30% of the total liver weight, in striking contrast to normal cats where hepatic fat content rarely exceeds 1-5% (3,4). The predominant fat type in FHL is adipose tissuederived triglycerides, from enhanced lipolysis during catabolic states of starvation, rather than de novo synthesis of triglycerides in the liver (2,3). Furthermore, impaired oxidation and utilization of fat within hepatocytes, diminished redistribution of fat from the liver to peripheral tissues, and altered lipoprotein metabolism all contribute to the development of FHL (4,5). Whether an individual propensity to develop FHL exists is debatable; a female predisposition is infrequently reported (1,6,7), but there is no obvious gender or breed predilection. The most salient risk factor for FHL is probably obesity, owing to pre-existing abnormalities in lipid and carbohydrate metabolism and higher fat reserves (2). Nonetheless, HL has been shown to develop irrespective of the body condition score (8), and FHL should always be suspected when compatible history, clinical findings and laboratory abnormalities exist.

Experimentally, HL develops after several weeks of restricted caloric intake, but in the clinical setting periods of anorexia as short as two days have been reported to precede the diagnosis 1,6,7,9. These reports, however, are subjective, relying on owner perception of food intake by their cat, and must therefore be cautiously interpreted. Maintenance energy requirements should be reduced by more than 50% for HL to develop, but the composition of the diet, rather than its caloric density alone, is also important 2. A diet deficient in essential amino acids (AA) might predispose to hepatic lipid accumulation, while L-carnitine supplementation can protect against FHL even in the face of severe caloric restriction 2,10.

Cats are obligate carnivores, whose capacity to endogenously synthetize many essential fatty acids and AA has been greatly diminished or lost over time. Furthermore, feline carbohydrate metabolism is different from omnivorous species, with cats having a lower overall requirement for carbohydrates, a propensity to utilize fats and proteins over carbohydrates for energy, and a tendency to favor AA-dependent pathways of gluconeogenesis to maintain normoglycemia 1,2. These peculiarities are reflected in their diet, which is primarily protein and fat-based, and might also account for their proclivity to accumulate fat in the liver in states of food deprivation. For example, compared to dogs and humans, endogenous production of several long-chain polyunsaturated fatty acids is reduced in cats. These fatty acids protect against HL by promoting triglyceride oxidation and glycogen synthesis rather than lipogenesis, but these protective properties are lost when dietary intake is reduced, which may contribute to the development of FHL 1. Cats also have limited capacity to synthesize enough arginine, methionine, cysteine and taurine. Depletion of these essential AA interferes with beta-oxidation of non-esterified fatty acids (NEFA), diminishes the production of very low density lipoprotein particles which transport triglycerides from the liver to the rest of the body, and reduces endogenous L-carnitine production, thereby preventing transportation of NEFA to mitochondria 1,2. Lastly, impaired insulin secretion and responsiveness in peripheral tissues are common in obese cats and in cats with FHL 4, and this promotes lipolysis and mobilization of NEFA from peripheral tissues. Collectively, these dietary deficiencies, metabolic derangements and hormonal changes culminate in the development of FHL. 

History and clinical findings

Protracted periods of hyporexia/anorexia always precede the development of FHL 6,7,9, which in turn may result from inadvertent food deprivation, decreased palatability of new diets, or stressful environmental situations (e.g., boarding, change of ownership, moving to a new house). Secondary FHL implies the presence of an identifiable underlying disease and occurs in 50-95% of cats 1,6,7,9. Therefore, a thorough questioning and diagnostic work-up is warranted to identify and address any possible underlying cause (Table 1). 

Table 1. Classification of feline hepatic lipidosis (FHL) and selected etiologies.

* FIP: Feline infectious peritonitis
** FeLV: Feline leukemia virus

Weight loss is invariably present, as the result of decreased caloric intake. Even in cats with an ostensibly normal bodyweight, a more careful physical examination often reveals a decreased body condition score and sarcopenia, especially in the hindlimbs and epaxial muscles. Lethargy, weakness, clinical signs referable to the gastrointestinal tract (e.g., vomiting, diarrhea, constipation), dehydration and hepatomegaly are frequent complaints and findings. Jaundice is common, and is best appreciated in the sclera or pinnae, in addition to mucosal surfaces 6,7,9 (Figure 1). Ptyalism, albeit a non-specific sign, might be the only clinical manifestation of hepatic encephalopathy (HE) in FHL, and occurs in a minority of cases. Furthermore, ptyalism at presentation has been associated with a worse outcome 9. Other etiologies of ptyalism include oral diseases, nausea, and idiosyncratic reactions to orally administered medications. 

Additional, less frequent clinical signs can arise secondary to FHL-associated complications (e.g., bleeding diathesis; HE; skin fragility syndrome) or the underlying etiology (e.g., fever with infections or inflammatory diseases such as pancreatitis; polyuria and polydipsia in cats with kidney disease or diabetes, etc.).

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