33
Feline Hepatic Lipidosis
Feline hepatic lipidosis (FHL) is an acquired disorder
caused by the excessive accumulation of triglycerides in
the cells of the liver, which ultimately interferes with
the liver’s ability to function.1 It is one of the most com-
mon hepatobiliary disorders of cats and was historically
associated with a very high mortality rate.2,3 However,
the long-term prognosis of cats with hepatic lipidosis
has dramatically improved, due in large part to the use
of early and aggressive tube feeding, which success-
fully reverses the condition in many cats.4,5 Still, the
underlying cause of hepatic lipidosis is not completely
understood. Its onset is almost universally preceded
by a period of anorexia and most, but not all, cats that
develop FHL are overweight or obese.6 Less commonly,
hepatic lipidosis occurs secondarily to other pathologi-
cal conditions such as inflammatory bowel disease, renal
disease, or diabetes mellitus.
INCIDENCE AND CAUSE
In healthy animals, a dynamic relationship exists
among the fatty acids that are located in adipose tis-
sue, ­traveling in the blood, and stored in the liver.
Circulating fatty acids are taken up by the liver, where
they are either metabolized for energy or converted to
triglycerides and secreted back into the circulation. If
the supply of fatty acids to the liver exceeds the liver’s
capacity to oxidize or secrete them, lipidosis develops.7
Several studies support the theory that the origin of
excess hepatic triglycerides in cats with FHL is from
fatty acids mobilized from ­adipose tissue.8-10 Metabolic
changes that may ­contribute to hepatic lipidosis include
impaired mitochondrial or peroxisomal oxidation of
fatty acids in hepatocytes and reduced liver secretion of
the very–low-density lipoproteins (VLDLs) that carry
triglycerides in the bloodstream. Support for reduced
fatty acid oxidation is provided from a study of induced
FHL in adult female cats.11 Cats began to accumu-
late hepatic lipids during the weight gain phase of the
study, and this increase was associated with a reduc-
tion in mitochondrial numbers in liver cells. Liver lipid
accumulation continued ­during the weight loss stage
of the study, presumably as a result of impaired fatty
acid oxidation. Another study reported that overweight
cats experiencing rapid weight loss did not demonstrate
reduced VLDL transport from the liver, nor was there
a pronounced increase in triglyceride synthesis.12 Most
researchers agree that the pathogenesis of FHL is proba-
bly multifactorial, involving factors that affect fatty-acid
mobilization to the liver as well as the oxidation of fatty
acids or synthesis and, possibly, secretion of VLDLs.3,4
FHL is relatively common and is usually seen in
middle-aged cats with a history of obesity. Females are
reported to be twice as likely to be affected as males,
but this may reflect a higher incidence of obesity in the
females that were studied, rather than a true gender dif-
ference.6 There is also evidence that spayed females tend
to consume more food, which may predispose them to
overweight conditions.13 In the majority of cases, a cat
will have experienced a period of stress followed by par-
tial or complete anorexia. Although obesity in cats is
not consistently associated with hepatic accumulation
of lipids, the metabolic changes caused by prolonged
fasting can lead to rapid and severe hepatic fat accu-
mulation and the clinical signs associated with liver
disease. For example, when five healthy but obese cats
were fasted for a period of 4 to 6 weeks, three of the
cats remained healthy and two developed overt clinical
and laboratory signs of FHL.14 Subsequent studies by
the same group reported that voluntary fasting could
be induced by changing the diets of obese cats from a
highly palatable commercial diet to a less palatable puri-
fied diet.15 In this study, all of the cats refused to eat
the new diet and developed histological signs of hepatic
lipidosis over a period of 4 to 7 weeks.
Feline idiopathic hepatic lipidosis is fairly common
among middle-aged, obese cats. It most often occurs
after a period of partial or complete anorexia, usually
brought on by stress.
431
432  Canine and Feline Nutrition
Although prolonged fasting appears to be a consis-
tent finding in cats that develop FHL, the exact meta-
bolic changes responsible for the rapid accumulation
of lipid in the liver have not been completely eluci-
dated. Cats diagnosed with FHL typically show signs of
­protein malnutrition such as muscle wasting, ­anemia,
and hypoalbuminemia. It has been hypothesized that
deficiencies of arginine and methionine, secondary
to anorexia and protein malnutrition, are involved in
the onset of FHL. The cat requires a dietary source
of the amino acid arginine for the production of urea in
the liver. When the cat stops eating, prolonged anorexia
leads to a deficiency of arginine. Urea cycle activity is
depressed, and ammonia begins to accumulate in the
blood. Byproducts of this disruption in the urea cycle
can interfere with lipoprotein synthesis in the liver.16
Moreover, a deficiency of one or more essential amino
acids may limit the synthesis of the proteins needed
for production of lipoproteins by the liver, leading
to an accumulation of triglycerides.17 For example,
­methionine contributes to the development of hepatic
lipidosis in rats.18 In addition, taurine supplementation,
which is synthesized from methionine by most species,
has been shown to reduce liver lipid concentrations in
obese ­children.19 Because taurine is an essential nutri-
ent for cats, it has been speculated that low levels of
dietary taurine may contribute to FHL and providing
supplemental taurine to the diet may help to prevent
its development.11 Supportive research for the role of
protein and essential amino acids has shown that the
administration of small amounts of protein to obese
cats during fasting helps to prevent the accumulation
of hepatic lipids.20
Carnitine is a compound that is synthesized from
methionine and lysine, primarily in the liver. It is nec-
essary for the transport of long-chain fatty acids into
cellular mitochondria for oxidation. Human subjects
with carnitine deficiency show severe fat accumulation
in the liver and other organs and develop signs of liver
disease.21 Carnitine concentrations have been shown to
be increased in the muscle and liver of obese women
and also during periods of starvation in humans and
rats.22-24 Because of this association in other species
and because of evidence of reduced fatty acid oxidation
in the liver of obese cats, it had been theorized that a
deficiency of carnitine may be a contributing factor to
FHL. However, carnitine concentrations in the plasma,
liver, and skeletal muscle of cats with hepatic lipidosis
have been reported to be normal.25,26 Another study
reported increased plasma concentrations of carnitine
during a period of weight gain in cats fed a diet con-
taining normal carnitine levels, but liver carnitine did
not increase.27 The change in plasma concentration
was attributed to increased food consumption during
weight gain. Conversely, liver carnitine levels were not
higher in obese cats when compared with lean cats. It is
possible that increased liver carnitine is necessary dur-
ing the overweight condition to support normal fatty
acid oxidation in the liver and that insufficient levels
may contribute to the onset of FHL during periods of
anorexia and rapid weight loss (see p. 433).
CLINICAL SIGNS AND
DIAGNOSIS
Clinical signs of FHL include complete or partial
anorexia with a duration of 7 days or longer, depression,
jaundice, weight loss, and muscle wasting.28-30 Vomit-
ing and/or diarrhea are occasionally reported. ­Owners
usually report that the cat suddenly stopped eating
following a period of lifestyle change or stress. Com-
monly reported stresses include a move to a new house,
the arrival of new pets into the household, or a ­sudden
change in diet. Laboratory findings show increased
serum activities of liver-associated enzymes, increased
serum bilirubin and bile acid concentrations, and, in
some cases, increased blood urea nitrogen (BUN) and
plasma ammonia concentration.28 A nonregenerative
anemia characterized by irregularly shaped erythrocytes
is typically seen.4 The initial diagnosis of FHL is made
using medical history, clinical signs, and the results of
laboratory tests. The diagnosis is confirmed by a liver
biopsy or fine-needle aspirate showing excessive lipid
accumulation in the sampled hepatocytes.
TREATMENT
Regardless of the metabolic cause of FHL, it is
essential for the cat’s recovery that an early diagno-
sis is made and that supportive fluid and nutritional
therapy is started as soon as possible. Aggressive tube

f­ eeding is the treatment of choice because afflicted cats
will not eat voluntarily. Force-feeding is not recom-
mended because it can further stress the cat and does
not provide an accurate measure of the pet’s caloric
intake. For these reasons, tube feeding with a naso-
gastric tube or PEG (percutaneous endoscopic gas-
trostomy) tube is preferred by most veterinarians.31,32
The use of a gastrostomy tube involves direct surgical
entry into the cat’s stomach. This procedure allows
accurate and consistent delivery of nutrients and does
not interfere with the cat’s ability to swallow.29,31
Although surgical complications are a risk, most cats
tolerate gastrostomy and esophagostomy tubes better
than nasogastric tubes.
The composition of an ideal therapeutic diet for
cats recovering from FHL has not been determined.
A variety of diets have been recommended, includ-
ing blenderized high-protein cat diets, human enteral
products, and veterinary enteral products.32,33 Because
it is generally accepted that the provision of optimal
levels of dietary protein is essential, a high-protein,
high-fat product is needed. Veterinary foods that are
formulated for recovery are often appropriate because
they contain high levels of protein and are energy
dense. Cats that show clinical signs of hepatoencepha-
lopathy initially need to be fed a reduced-protein diet.
Protein content can be gradually increased as neuro-
logical signs resolve.
In addition to providing adequate protein, there is
evidence that supplementation with L-carnitine may
improve fatty acid oxidation in overweight cats that
are predisposed to FHL.11,27 Cats that were supple-
mented with L-carnitine (1000 milligram/kilogram
[mg/kg] diet) during a weight gain and fasting proto-
col designed to induce FHL had significantly increased
plasma, ­muscle, and liver carnitine concentrations
compared with unsupplemented cats during the weight
gain phase of the study.27 When cats were fasted,
­supplementation with carnitine ameliorated fasting
ketosis in cats that did not develop FHL, but did not
have this affect in cats that developed FHL. Conversely,
unsupplemented cats showed dramatic increases in
plasma free fatty acids and became ketotic during fast-
ing, whether or not FHL developed. Another study
showed that providing increased dietary L-carnitine
to obese cats that were fed for weight loss enhanced
Feline Hepatic Lipidosis  433
weight loss and improved fatty acid oxidation, but did
not affect hepatic ­lipidosis.11 These studies suggest that
L-carnitine may help to ­protect overweight cats
from fasting-induced FHL, but may be less effective
­therapeutically, once FHL has developed and aggressive
treatment is needed.
The initial tube feeding should provide ¼ to ½ of the
cat’s calculated metabolizable energy (ME) ­requirement.
This is gradually increased over a 1-week period to the
cat’s ME requirement. A minimum of four feedings
should be provided per day. Signs of hepatic dysfunction
begin to resolve as soon as the cat is receiving adequate
protein and energy intake. However, most cats require 3
to 6 weeks of intense dietary therapy before laboratory
values normalize, clinical improvement occurs, and the
cat’s appetite returns. Because it appears that acquired
food aversion is a component of the anorexia seen in
many cats with FHL, oral feeding should not be intro-
duced until tube feeding is well established and the cat
voluntarily shows a strong interest in food when it is
presented.
The cat’s owner must be willing to assist with the
nursing care of the pet because cats with hepatic lipi-
dosis may not eat well for several months. As the cat’s
appetite returns, the frequency of tube feedings should
be slowly decreased until the cat is consuming adequate
calories voluntarily. When vomiting can be controlled
and long-term adequate protein and ­calorie intake
is ensured, treatment is usually successful. However,
because many cats refuse to eat voluntarily for a period
of weeks to several months, management can be diffi-
cult for pet owners, and prognosis will be guarded until
the cat begins to eat voluntarily. Supportive treatment
involves minimizing any stress that the animal may
experience and, in some cases, administering appe-
tite stimulants. Although some investigators advocate
supplying supplemental carnitine during tube feed-
ing, recent evidence indicates that this is probably less
important than providing adequate carnitine to cats
that may be at high risk, such as overweight cats and
spayed females.11,13,27
Throughout the treatment period, frequent monitor­
ing of liver-associated enzymes in serum can be used as
an indicator of hepatic recovery. Because most cats with
FHL have a history of obesity, it is prudent to pre-
vent weight regain following recovery. If the cat is still
434  Canine and Feline Nutrition

o­ verweight, a weight loss protocol that allows a slow rate
of weight loss and includes a diet containing optimal
levels of protein should be followed (see Chapter 28,
pp.  328-335). Veterinary supervision is warranted
to ensure a slow rate of weight loss and prevent the
­recurrence of FHL. Most importantly, the cat’s lifestyle
and living conditions should be managed to minimize
or prevent stressful events that may lead to subsequent
­episodes of anorexia.
Early diagnosis is essential for successful treatment of
feline hepatic lipidosis (FHL). Tube feeding is the treatment
of choice, using either a nasogastric tube or ­gastrostomy.
The dietary solution should include high levels of protein
and energy. Most cats require 3 to 6 weeks of intense
dietary therapy before improvement is seen and the cat’s
appetite returns. Owner commitment and compliance
is important during treatment of FHL because affected
cats may not eat well for several months.

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