Feline hepatic lipidosis (HL), a syndrome characterized by hepatocellular accumulation of lipid, intrahepatic cholestasis
and hepatic dysfunction, is one of the most common liver disorders of the domestic cat accounting for approximately 50% of
biopsy diagnoses. It may be a primary (idiopathic) condition or secondary to another disease process. Despite widespread interest
and the numerous studies performed since HL was first described in the veterinary literature in 1977, the causes and pathogenic
mechanisms of the disease are still largely unknown. However, even with our relatively limited understanding of HL significant
progress has been made in the therapy of this condition, reducing mortality from a value of close to 90% in the original descriptions
to approximately 10% in more recent studies utilizing aggressive nutritional support.
This talk is intended to provide some background information about our current understanding of HL. In addition to discussing
some of the potential predisposing factors, causes, and mechanisms of the disorder, information and ideas about nutritional
support and therapeutic options for HL patients will be discussed in detail.
What causes hepatic lipidosis in cats?
The primary histologic changes in HL are severe lipid accumulation within hepatocytes and canalicular bile stasis. There are
numerous specific potential causes and mechanisms for these types of changes, however, it is very likely that the pathogenesis
of HL is multifactorial. A better understanding of the unique pathways of hepatic metabolism in felines is needed to provide
insight into how derangements and interactions of these pathways can lead to development of clinical disease. Proposed mechanisms
for HL development include roles for metabolic changes associated with starvation and/or obesity, protein deficiency, relative
carnitine deficiency, essential fatty acid deficiency, dysregulation of hormone-sensitive lipase, and insulin resistance among
Lipid buildup is obviously a key part of the pathogenesis of HL and leads to storage of excess lipid within vacuoles in the
hepatocytes. When accumulation of these vacuoles becomes excessive, changes in liver function are observed. This is not necessarily
true of many other species in which lipid accumulation is less dramatic, but also often relatively innocuous.
An observed increase in the concentration of lipids within the liver may be due to several factors. The concentration will
increase after high-fat meals, when fat stores are mobilized (e.g. fasting), during periods of increased hepatic synthesis,
or when metabolism, processing, and secretion of lipids within the liver are decreased. Accumulation of lipids occurs when
there is an imbalance between delivery of fatty acids to the liver and the ability of the liver to oxidize them for energy
or release them in the form of very-low-density lipoproteins (VLDLs).
Increased delivery can occur during mobilization of fat stores for energy during periods of fasting/starvation or deficiency
of specific nutrients. In most cats that develop HL there is a period of partial to complete anorexia that precedes the development
of clinical signs related to HL by days to weeks. During this period there is protein restriction (which may be a key component
of the disease) and release of stored fatty acids from adipose tissue. These fatty acids should be oxidized by the liver for
energy, but in cats that develop HL there may be a decreased capacity for hepatic lipid metabolism and/or processing. Electron
microscopy of these cats has demonstrated decreased quantities of several of the components of the cellular machinery needed
to oxidize lipids. In addition restriction of protein intake (e.g. anorexia) may lead to down regulation of the synthesis
of proteins that are required for formation VLDLs. In one study, histologic evidence of HL was apparent in 15/15 fasted obese
cats by 2 weeks. Clinical signs of HL were present in 12/15 of these cats by weeks 5-7 and seemed to be associated with a
body weight decrease of about 30-35%.
Impaired fatty acid oxidation also appears to be significant in cats with HL. Carnitine, taurine and essential fatty acids
have received a lot of attention for their roles in maintaining membrane integrity and functions necessary for utilization
of lipids for energy. Carnitine is required for fatty acid transport through hepatic mitochondrial membranes where they can
be oxidized. One theory suggests that in HL the demand for carnitine is greater than stores or synthesis can provide for.
In one study, cats fed 25% of their caloric requirements had minimal lipid accumulation when carnitine supplementation was
provided compared to control cats. However, this benefit was significantly reduced in another study when there was inadequate
There is also some evidence of decreased glucose tolerance and decreased insulin responses to glucose infusions in fasted
cats that subsequently developed HL. In addition, the high levels of non-esterified fatty acids found in some studies suggest
that there may be inappropriate regulation of hormone sensitive lipase.
It is established that obesity and fasting (although not necessary) appear to be risk factors for HL in cats. Further studies
are required to gain a better understanding of the other risk factors and pathophysiologic mechanisms of disease however.