2010 purina+pro fnl-12

SYMPOSIUM PROCEEDINGS
Critical Updates on
Canine and Feline Health
Sponsored by:
From 2010
NAVC and WVC
Conferences

Wait, Wait, Don’t Tell Me…
Controversial and Challenging
Feline Cases
Deborah S. Greco, DVM, PhD, DACVIM,
Senior Research Scientist, Nestlé Purina PetCare
Outline of diagnostic approaches that can help practitioners
solve three endocrine presentations in cats
Feline IBD: The Good (Diets), the Bad
(Bacteria), and the Ugly (Diagnosis)
Debra L. Zoran, DVM, PhD, DACVIM-SAIM,
College of Veterinary Medicine and Biomedical Sciences,
Texas A&M University, College Station, Texas
The role of intestinal bacteria and diet in the diagnosis
and management of IBD in cats
Treatment of Liver Disease:
Medical and Nutritional Aspects
David C. Twedt, DVM, DACVIM,
College of Veterinary Medicine & Biomedical Sciences,
Colorado State University, Fort Collins, Colorado
Understanding the major aspects involved in diagnosing
and treating canine and feline liver disease
From Problem to Success: A Weight
Loss Program That Works, Growing
Relationships, Not Girth in Cats
Margie Scherk, DVM, DABVP (Feline),
Vancouver, BC, Canada
Designing a weight loss program that can ensure success—
both for the cat and the client
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Symposium
Proceedings:
Critical
Updates on
Canine and
Feline Health
From 2010 NAVC and WVC Conferences

Disorders of the endocrine system are
routinely encountered in feline practice.
Certain endocrine disorders, such as hyperthyroidism
and diabetes mellitus, are relatively simple to diagnose
in cats, whereas others, such as hypoadrenocorticism,
are more challenging. This article outlines the diagnos-tic
approach for three common endocrine presentations
in cats—polydipsia/polyuria (PU/PD), weight gain, and
insulin resistance as reflected by clinical cases in the
field.
Evaluation of Polydipsia/Polyuria
One of the most common presenting complaints for endocrine
disorders is PU/PD. The major endocrine diseases that cause
PU/PD are, in order of frequency, diabetes mellitus, hyperthy-roidism,
hyperadrenocorticism, acromegaly or hypersomatotro-pism,
hypercalcemia resulting from hyperparathyroidism,
hypokalemia associated with hyperal-dosteronism,
diabetes insipidus, and
pheochromocytoma (Table 1).
The diagnostic approach to polydipsia
and polyuria is shown in Figure 1. In pa-tients
presenting with PU or PD, the cli-nician
must first document whether the
patient is indeed drinking or urinating
excessively. The most common condition
mistaken for PU is pollakiuria (Table 2)
resulting from urinary tract disease.
When the presence of PU/PD is suspect,
the clinician should ask several questions
to determine whether the cat is consum-ing
or eliminating excessive water. The
presence of large amounts of urine in the
litter box as opposed to small, more fre-quently
eliminated amounts of urine
points to PU and compensatory PD.
PD may be more difficult to identify
than PU. In general, because cats are
desert species, it is unusual to witness
cats drinking water frequently. In con-trast,
dogs are often presented for PD
when they are, in fact, just “sloppy”
drinkers. If the owner can quantitate
and measure the amount of water the
cat is drinking, any consumption of
water in excess of 60 to 70 ml/kg/day
would be considered PD.
Evaluation of Weight Gain
Endocrine causes of weight gain include,
in order of frequency, type 2 diabetes
mellitus, hyperadrenocorticism, hypothy-
Deborah S. Greco,
DVM, PhD, DACVIM,
Senior Research
Scientist,
Nestlé Purina
PetCare
Wait, Wait, Don’t Tell Me…
Controversial and Challenging
Feline Cases
Symposium
Proceedings:
Critical
Updates on
Canine and
Feline Health
Table 1. Causes of PU/PD
Nonendocrine Causes
Chronic renal failure
Hepatic disease (PSS)
Pyometra, pyelonephritis
Hypercalcemia of malignancy, vitamin D
toxicosis, granulomatous disease, chronic
renal failure, etc
Acute renal failure (nephrotoxicants)
Primary PU
Endocrine Causes
Diabetes mellitus
Hyperthyroidism
Hyperadrenocorticism
Hypercalcemia resulting from
hyperparathyroidism or hypoadrenocorticism
Hyperkalemia associated with
hyperaldosteronism
Diabetes insipidus (central, nephrogenic)
Hypersomatotropism (acromegaly)
Pheochromocytoma
PD = polydipsia; PSS = portosystemic shunt; PU = polyuria
2 Wait, Wait, Don’t Tell Me…Controversial and Challenging Feline Cases

Table 2. Distinguishing PU from Pollakiuria and Incontinence
Signs PU Pollakiuria Incontinence
Urination Active Active Passive
Frequency 2–3 times normal More than 3 times normal Nocturia
Urgency Uncommon Common None
Volume of urine Increased Small, multiple Variable
Mucus Rare Common Rare
Concentration of urine Dilute Concentrated Either
Weight loss Common Rare Rare
PU = polyuria
Test
Endocrine disorder
> 100 ml/kg/day H2O;
nocturia
fT4 (dialysis)
NORMAL
HIGH
hyperthyroidism
Bile acids, ultrasound
RULE OUT
PSS
DDAVP®
NO RESPONSE
Water deprivation test
NO RESPONSE
Nephrogenic DI
RESPONSE
Primary PD
RESPONSE
Central DI
ABNORMAL
MDB, CBC, U/A,
chemistry TT4,
blood pressure
INCREASED BUN/Cr;
low USG CRF
INCREASED BUN/Cr;
NORMAL/INCREASED USG
INCREASED Ca
ACTH stimulation
NORMAL
RULE OUT ARF
RULE OUT
Neoplasia (SCC, LSA)
INCREASED TT4
Hyperthyroidism
Hyperglycemia, glucosuria
Advanced DM
ABNORMAL
Addison’s disease
NO RESPONSE to insulin
DECREASED K
Measure aldosterone
RULE OUT
acromegaly (IGF)
RULE OUT
Cushing’s syndrome (LDDS)
Figure 1. Diagnostic Flowchart for PD and PU
ACTH = adrenocorticotropic hormone; ARF = acute renal failure; BUN = blood urea
nitrogen; Ca = calcium; CBC = complete blood count; Cr = creatinine; CRF = chronic
renal failure; DDAVP = brand name for desmopressin acetate; DI = diabetes insipidus;
DM = diabetes mellitus; fT4 = free thyroxine; IGF = insulin-like growth factor;
K = potassium; LDDS = low-dose dexamethasone suppression; LSA = lymphosarcoma;
MDB = minimum database; PD = polydipsia; PSS = portosystemic shunt; PU = polyuria;
SCC = squamous cell carcinoma; TT4 = total thyroxine; U/A = urinalysis;
USG = urine-specific gravity
Wait, Wait, Don’t Tell Me…Controversial and Challenging Feline Cases 3

(see Nestlé Purina Body Condition System).
Creating a diagnostic flowchart of common
rule outs can help eliminate endocrine disorders
as diagnostic differentials (Figure 2).
The dietary history is one of the most important
aspects of history taking for weight gain. The
examiner should ask what type of diet is being
fed—homemade, raw, or commercial. For com-mercial
diets, is the cat primarily fed dry food
or a mixture of dry and canned food? If the cat
is being fed a commercial food, also ask about
the specific brand, and if the diet is homemade,
ask for a complete list of ingredients.
Other important questions include:
■ How long has the diet been fed?
■ When was the diet changed last, and how
frequently is it changed?
■ How much is the cat eating, and how is the
food being measured (weighing vs cups)?
■ Is the cat fed ad libitum or restricted? How
many times per day is the cat fed?
roidism, acromegaly, and insulinoma (Table 3).
The primary differentials for nonendocrine
causes of weight gain, which are much more
common, feature overfeeding and the feeding of
treats. Patient records on the body condition
score (BCS) can help determine whether the
weight gain is a result of nonendocrine problems
Table 3. Causes of Weight Gain
Nonendocrine Causes
Overfeeding
Feeding treats
Feeding high caloric density food
Large abdominal tumors
Endocrine Causes
Hypothyroidism
Hypersomatotropism (acromegaly)
Insulinoma
Type 2 diabetes mellitus—early
Weight gain
Figure 2. Diagnostic Flowchart for Weight Gain
NORMAL
appetite
INCREASED
appetite
DECREASED
appetite
RULE OUT
overfeeding
Hyperglycemia,
increased
fructosamine
MDB MDB, TSH, TT4
NORMAL
MBD
LOW
BG
Low-carbohydrate diet,
insulin, oral hypoglycemics
Weight loss diet
OM
RULE OUT
insulinoma
RESPONSE NO RESPONSE
Early type 2 DM LDDS, IGF RESPONSE NO RESPONSE
Continue diet to
target weight
RULE OUT dietary
noncompliance
NORMAL
Repeat MDB,
TSH, TT4
HIGH IGF; acromegaly POSITIVE LDDS;
Cushing’s syndrome
NORMAL
Test
Endocrine disorder
LOW TT4 and
HIGH TSH
LOW TT4 and
LOW TSH
Hypothyroidism fT4 by dialysis
LOW fT4 NORMAL or HIGH fT4
Secondary
hypothyroidism
Euthyroid
sick syndrome
BG = blood glucose; DM = diabetes mellitus; fT4 = free thyroxine; IGF = insulin-like growth factor; LDDS = low-dose dexamethasone suppression;
MDB = minimum database; OM = Purina Veterinary Diets OM Overweight Management Feline Formula; TSH = thyroid-stimulating hormone; TT4 = total thyroxine

Ribs visible on shorthaired cats; no palpable fat;
severe abdominal tuck; lumbar vertebrae and wings
of ilia easily palpated.
TOO HEAVY IDEAL TOO THIN Call 1-800-222-VETS (8387), weekdays, 8:00 a.m. to 4:30 p.m. CT
Ribs easily visible on shorthaired cats; lumbar vertebrae
obvious with minimal muscle mass; pronounced abdominal
tuck; no palpable fat.
Ribs easily palpable with minimal fat covering; lumbar
vertebrae obvious; obvious waist behind ribs; minimal
abdominal fat.
Ribs palpable with minimal fat covering; noticeable
waist behind ribs; slight abdominal tuck; abdominal
fat pad absent.
Well-proportioned; observe waist behind ribs; ribs palpable
with slight fat covering; abdominal fat pad minimal.
Ribs palpable with slight excess fat covering; waist and
abdominal fat pad distinguishable but not obvious;
abdominal tuck absent.
Ribs not easily palpated with moderate fat covering;
waist poorly discernible; obvious rounding of abdomen;
moderate abdominal fat pad.
Ribs not palpable with excess fat covering; waist absent;
obvious rounding of abdomen with prominent abdominal
fat pad; fat deposits present over lumbar area.
Ribs not palpable under heavy fat cover; heavy fat
deposits over lumbar area, face and limbs; distention of
abdomen with no waist; extensive abdominal fat deposits.
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Wait, Wait, Don’t Tell Me…Controversial and Challenging Feline Cases 5

■ Who feeds the animal, and what
ages are the family members (eg,
children, grandparents)?
■ Are there other pets in the house-hold,
and what diets are they fed?
Table 4. Causes of Insulin Resistance
■ Does the cat have access to the
outdoors?
■ Does the cat receive supplements (eg, treats,
vitamins, yogurt)?
It is important to remember that many clients do
not perceive treats and additives (eg, table food) as
part of the cat’s diet and, therefore, may forget to
mention them.
Another tricky aspect is determining who
in the household is responsible for feeding the ani-mal.
Many times the primary caregiver is surprised
to find that another family member has been feed-ing
a specific food or treat without telling the pri-mary
caregiver. In addition, problems may arise
because owners have preconceived notions about
pet foods. Clients may indicate that they will not
feed certain flavors of foods or certain ingredients
because of “allergies.” Furthermore, it may be diffi-cult
to obtain an accurate dietary history because
clients may be embarrassed or unwilling to divulge
exactly what and how much is being fed. For these
Tips for Investigating Weight Gain
✔ In cats, always check the underside of the tarsus for evidence of diabetic
neuropathy.
✔ Ask the client to bring photographs of the patient from several years ago for
comparison of skull and facial changes.
✔ Check the patient’s teeth for increased interdental spaces (acromegaly).
✔ Assign a BCS and record each score in the patient’s medical record. Cats in
normal body condition (BCS 4–5 on the Nestlé Purina scale) will have ribs
easily palpable and normal abdominal tuck.
✔ If necessary, perform the knuckle test (quick BCS). Animals in normal body
condition have ribs that feel like the tops of the knuckles with the hand
extended. Overweight patients have ribs that palpate similar to the palm of
the extended hand.
BCS = body condition score
Nonendocrine Causes
Infection (eg, UTI, pulmonary,
skin disease)
Cancer
Immune disease
Drugs, pancreatitis, liver
disease, stress
Endocrine Causes
Hyperthyroidism
Hypothyroidism
Hypersomatotropism
(acromegaly)
UTI = urinary tract infection
reasons, having clients complete a written ques-tionnaire
is often the best and most expedient way
to obtain a dietary history.
Performing a thorough physical examination,
comparing the patient’s current weight with its
weight several years ago, and establishing the pa-tient’s
BCS are important for determining the rea-son
for weight gain (see Tips for Investigating
Weight Gain).
Evaluation of Insulin
Resistance
It is very rare to obtain a perfect glucose curve in
a patient. Generally, problems associated with
the blood glucose curve can be differentiated by
the characteristics of the curve and the insulin
dose (dosing interval).
If the patient is receiving less than 2.2 U/kg
per dose, the blood glucose curve is usually
indicative of one of the following:
■ Insufficient insulin dose—Corrective action,
increase dose
■ Short duration of action of insulin—
Corrective action, change to longer-acting
insulin or twice-daily dose regimen
■ Insulin-induced hypoglycemic hyper-glycemia
(Somogyi effect)—Corrective
action, reduce insulin dose by 25%
■ Insulin overlap or prolonged insulin
action—Corrective action, change to
shorter-duration insulin or insulin mixture
(ie, 30% regular, 70% NPH)
If the patient is receiving more than 2.2 U/kg
of insulin per dose, insulin resistance should be
investigated (Table 4). In cats, the top diagnos-tic
differentials for insulin resistance include
hyperthyroidism, hypersomatotropism
(acromegaly), and hyperadrenocorticism. ■

Feline inflammatory bowel disease (IBD)
applies to a number of poorly understood enteropathies
characterized by infiltration of inflammatory cells into
the gastrointestinal (GI) mucosa. The cellular infiltrate
is composed of variable populations of lymphocytes,
plasma cells, eosinophils, and neutrophils that can
be distributed throughout the GI tract.1-3 In severely
affected cats, this infiltrate may be accompanied by
changes in the mucosal architecture, including villus
atrophy, fusion, fibrosis, and lymphangiectasia.
Although IBD appears to be a common clinical problem
in cats, little is known about the etiopathogenesis or the
local and systemic consequences of the disease, including the
development of lymphoma and nutritional deficiencies.4 In
addition, the nature of inflammation associated with IBD is
just beginning to be characterized beyond the visible changes
in gross histopathology that have been described.5-11
This paper reviews what is known about feline IBD, with
particular focus on the role of commensal and pathogenic in-testinal
bacteria as well as diet in the diagnosis and manage-ment
of the disease.
Diagnostic Process
Feline IBD, a commonly diagnosed condition of adult cats,
is characterized by persistent clinical signs consistent with
GI disease (eg, vomiting, anorexia, weight loss, diarrhea)
that occur concurrently with histologic evidence of mucosal
inflammation.12 The median age of cats presenting with
IBD is around 7 years, and most cats present with a history
of these signs occurring intermittently for weeks to years.
Purebred cats, such as the Siamese and Abyssinian, may be
overrepresented, but definitive breed predilections have not
been reported. There is no reported predilection based on
sex.
Diagnosis by exclusion
Because clinical signs of IBD can be as-sociated
with various primary GI and
extra-GI diseases, it is important to
consider broad groupings of differen-tials
and obtain a minimum database
(ie, CBC, serum biochemical panel,
urinalysis) until sufficient data have
been collected to narrow the list of dif-ferentials.
A number of possible causes
of intestinal inflammation must be
considered, however, including infec-tious
disease, food sensitivity (allergy)
or food intolerance, endocrinopathies
(eg, hyperthyroidism), parasitic disease,
and neoplastic disease. These differentials
should be investigated thoroughly before
settling on a diagnosis of idiopathic IBD
and instituting a treatment plan.
Food allergy and intolerance can be
particularly difficult to distinguish from
IBD and other intestinal disorders, es-pecially
because of shared clinical signs
and identical histopathologic changes in
the bowel. Therefore, appropriate food
trials are an extremely important com-ponent
of both reaching a diagnosis and
implementing therapy in cats with GI
disease or suspected IBD. In addition to
food trials, the diagnostic plan for a cat
with chronic vomiting or diarrhea
should include multiple fecal examina-tions
or therapeutic deworming trials
with broad-spectrum agents, such as
fenbendazole, assessment of thyroid and
Debra L. Zoran,
DVM, PhD,
DACVIM-SAIM,
College of
Veterinary
Medicine and
Biomedical
Sciences,
Texas A&M
University, College
Station, Texas
Feline IBD: The Good (Diets),
the Bad (Bacteria), and the Ugly
(Diagnosis)
Symposium
Proceedings:
Critical
Updates on
Canine and
Feline Health
Feline IBD: The Good (Diets), the Bad (Bacteria), and the Ugly (Diagnosis) 7

FeLV/FIV status, and assessment of GI function,
including measuring cobalamin and folate and
conducting trypsin-like immunoreactivity (TLI)
and pancreatic lipase immunoreactivity (PLI)
tests.
Many cats with IBD have concurrent inflam-mation
of the liver and pancreas—a phenome-non
called triaditis.13 Because chronic pancreatitis
can cause few distinguishing signs and be diffi-cult
to diagnose by laboratory testing alone, a
degree of clinical suspicion is necessary to care-fully
assess cats.14,15 Serum cobalamin levels are
commonly decreased in cats with severe bowel
disease or pancreatitis. Furthermore, in cats with
hypocobalaminemia, diarrhea does not resolve
until replacement therapy has been instituted.
Cobalamin therapy in some cats may be life-long,
whereas in others, once the clinical disease
has been resolved, supplementation can be dis-continued.
Imaging and exploratory measures
In addition to laboratory evaluation, radiography
and ultrasonography are important aspects of
overall assessment of cats with possible IBD. Al-though
abdominal radiographs and ultrasound
findings cannot confirm IBD, they are essential
for ruling out other GI problems, including in-testinal
8 Feline IBD: The Good (Diets), the Bad (Bacteria), and the Ugly (Diagnosis)
foreign bodies, intussusception, masses,
and involvement of other organs, especially the
liver and pancreas. Many cats with intestinal in-flammation
have thickened loops of bowel,
changes in bowel layering, or evidence of mesen-teric
lymphadenopathy.16 These changes are not
indicative of a specific cause but are further con-firmation
of intestinal disease that requires addi-tional
assessment.
Abdominal ultrasonography can reveal impor-tant
information about the location and severity
of lesions, thereby suggesting whether endoscopy
or abdominal exploratory surgery might be the
appropriate next step. Because intestinal biopsy
specimens obtained either endoscopically or
during exploratory surgery are essential to con-firm
the presence of inflammatory infiltrates, ei-ther
diagnostic measure is an important part of
the process. However, a number of problems
have been associated with using histopathologic
changes or findings to diagnose IBD.17
First, problems correlating a pathologist’s
interpretation of inflammation found in the
GI biopsy specimen with the actual disease
have been well documented.5 The presence of
lymphocytes and plasma cells in the wall of the
gut does not mean the problem is idiopathic,
does not necessarily correlate with the cytokine
expression or degree of clinical disease, and
does not mean that IBD can be accurately dif-ferentiated
from lymphoma. As a result, stan-dards
for histopathologic interpretation of
biopsy specimens have been recommended by
pathologists to help improve the utility and
consistency of interpreting GI histopathologic
findings5,18 (see WSAVA Guidelines for GI
Histopathology).
Inflammatory response
The basis of the immunologic response in cats
with IBD is unknown, and it remains to be deter-mined
whether the inflammatory response results
from the presence of undefined pathogens or ex-emplifies
an inappropriate response to dietary
antigens or intraluminal commensal bacteria. De-termining
the cytokine and immune cell popula-tion
in cats with IBD is important from both a
WSAVA Guidelines for GI Histopathology
The WSAVA guidelines offer pertinent information about GI
histopathology.5 Small cell (ie, lymphocytic, low-grade)
lymphoma can be extremely difficult to distinguish from IBD.
Because the disease can be local (only in the jejunum or
ileum) or found only in the deeper layers of the intestinal wall
(submucosa or muscularis), if during endoscopy, biopsy
specimens are not obtained from the appropriate sites or are
inadequate in depth, lesions can be missed. If cats are not
responding to appropriate therapy or were responding to
therapy but are now losing weight or having recurrent
diarrhea despite therapy, the possibility of lymphoma should
be reconsidered. Several recent reviews on this subject
provide more details specific to GI lymphoma and its
management.18
WSAVA = World Small Animal Veterinary Association
Abdominal
radiographs and
ultrasound
findings cannot
confirm IBD but
are essential for
ruling out other
GI problems,
such as intes-tinal
foreign
bodies and
intussusception.

pathologic and therapeutic standpoint, as treat-ment
of IBD in cats is nonspecific and based on
dietary modification, administration of antibi-otics,
and suppression of the immune system.
The Role of Bacteria
In humans and experimental animals, recent
studies indicate a strong association between the
development of IBD and a breakdown of normal
tolerance mechanisms, host susceptibility, and
enteric microflora.19-22 It is likely that these same
factors are important in feline IBD9-11,23 (see Are
Bacteria a Key Component?). Modulation of the
enteric microenvironment in humans with IBD
has been shown to reduce proinflammatory cy-tokines
in the mucosa and, therefore, decrease
the inflammatory response.24 In humans, IBD
therapy has included antibiotics with immune-modulating
capacity, prebiotics, probiotics, and
immunosuppressants as well as other drugs that
modify cytokine release.22,25
Unfortunately, studies assessing modulation of
enteric flora (using probiotics, prebiotics, or other
specific therapy for cytokines) in cats with IBD
are only in the early stages. Nevertheless, few stud-ies
have shown that intestinal microbiota in cats
with IBD are clearly different from those in nor-mal
cats and often the difference is a decrease in
normal commensals (eg, bifidobacteria, lacto-bacilli)
and an increase in pathogenic species.6,9 At
this time, therapy for IBD in cats continues to in-clude
inflammatory suppression and antibiotic
therapy. The most effective IBD therapies include
steroids (ie, 1 to 2 mg/kg of prednisolone or
methylprednisolone PO Q 12 H) or other drugs
that interrupt the proinflammatory pathways ac-tive
in the gut. In cats that are intolerant of
steroids, budesonide therapy may be a reasonable
choice. Alternatively, in cats in which steroids are
no longer effective or are causing morbidity (eg,
diabetes), immunosuppressive therapy may be
necessary and is often effective. The two drugs
most commonly recommended and effective for
cats in this setting are cyclosporine and chloram-bucil.
Antibiotic therapy with 5 to 10 mg/kg of
metronidazole PO Q 12H has been effective for a
Are Bacteria a Key Component?
One group of investigators11 is seeking to determine the effect of
mucosal bacteria and their relationship to cytokine responses
and inflammation in the bowel of cats. Intestinal biopsies
were collected from 17 cats undergoing diagnostic
investigation of signs of GI disease and from 10 healthy
controls.11 Subjective duodenal histopathology ranged
from normal (10) to mild (6) to moderate (8) to severe (3)
IBD. The mucosal response was evaluated by objective
histopathology and cytokine mRNA levels in duodenal biopsies.
The number of mucosa-associated Enterobacteriaceae was higher
in cats with signs of GI disease than in healthy cats. These pathogens, including
Escherichia coli and Clostridium species, were associated with significant changes in
mucosal architecture, principally atrophy and fusion; up-regulation of cytokines,
particularly IL-8; and the number of clinical signs exhibited by affected cats.
The study findings indicate that an abnormal mucosa-associated flora is
associated with the presence and severity of duodenal inflammation and clinical
disease activity in cats. The observations provide a rational basis for future
investigations to address the potential causal involvement of mucosa-associated
bacteria. They are perhaps most consistent with a model proposed for the mucosal
response to gram-negative bacteria, whereby proinflammatory cytokines (eg, IL-1,
IL-8, IL-12) produced by epithelial cells in response to such stimuli as gram-negative
bacteria are modulated by macrophage production of IL-10. Support for this concept
in the canine GI tract is provided by studies of the small intestines of dogs in which
expression of IL-10 and IFN-β mRNA by lamina propria cells and the intestinal
epithelium was observed in the face of a luminal bacterial flora that was more
numerous than that of control dogs.23
Additional evidence that bacteria are a key component of IBD in cats has been
collaborated by Inness and coworkers,9 who characterized the gut microflora of both
healthy cats and cats with colonic IBD. Cats with IBD were found to have significantly
higher populations of Desulfovibrio (a genus of bacteria that produce toxic sulfides)
compared with normal cats, which had higher populations of bifidobacteria and
bacteroides (normal flora). These authors proposed that modulation of intestinal
flora with probiotics and dietary intervention to decrease the production of
pathogenic bacteria were likely important in treating cats with IBD.
Finally, another study10 found that the expression of cytokines in biopsy
specimens from the intestines of cats with IBD represented greater transcription
of genes encoding IL-6, IL-10, IL-12, TNF-α, and TGF-β than from those of cats
with normal intestines. These results also suggested that, in cats with IBD, both
proinflammatory and immune dysregulation features were present.
IBD = inflammatory bowel disease; IFN = interferon; IL = interleukin;
TGF = transforming growth factor; TNF = tumor necrosis factor
number of years and continues to be recommended
as initial therapy for IBD.12,26 There is also a widely
held belief that metronidazole is effective not only
because of its antibacterial properties but because of
concurrent immune-modulating properties. Some
data support these ideas, but the specific role of
metronidazole as treatment for IBD is still not
completely known. Because metronidazole may
be poorly tolerated and has potential for serious ad-verse
effects, it should not be given indefinitely.
Another antibiotic that may be useful in cats with
presumed IBD is tylosin at a dose of 10 to 20

Diets Designed to Promote GI Health
The highly digestible diets from different pet food
manufacturers have a variety of formulations—
different protein and carbohydrate sources, different
levels of fat, and various additives designed to
promote intestinal health (eg, fructooligosaccharide
[FOS], mannondigosaccharide [MOS], omega-3 fatty
acids, antioxidant vitamins, soluble fiber). If one type
of highly digestible diet has been fed for at least 2
weeks with minimal response, then it is entirely
reasonable to try another diet from a different
source or try an entirely different dietary strategy
(eg, high-protein/low-carbohydrate, novel antigen,
hydrolyzed diet). In addition, diarrhea may be
attributed to carbohydrate intolerance or bacterial
changes resulting from dietary changes. Thus, the
addition of probiotics or prebiotics to help influence
microflora is a reasonable therapeutic option, as is
the addition of either metronidazole or tylosin.
mg/kg PO Q 12 H; however, less is known about
the effects of tylosin on cats when used long-term.
27,28
Finally, data in humans with IBD are increas-ingly
showing that probiotics and antioxidant
prebiotic nutraceuticals may be important com-ponents
of therapy.25 At this time, it is difficult
to make specific recommendations concerning
the probiotic or nutraceutical therapy with the
greatest benefit because of the paucity of studies
in cats with IBD and the species-specific nature
of probiotics and their effects. However, probi-otics
that provide an immune-modulating effect
or that increase the number of beneficial species
while competing against pathogens might be ex-pected
to be helpful. In several studies in kit-tens,
probiotics containing Enterococcus faecium
(SF68) appeared to improve immune function
and had better responses to therapy when ex-posed
to enteric protozoa.29 Furthermore,
whereas probiotic therapy alone would not be
expected to produce clinical remission, cats un-dergoing
long-term therapy for IBD may bene-fit
from the addition of probiotics to their
treatment regimen.
The Role of Dietary Management
The use of diet to help manage GI disease is not
a new concept, but the type of diet to use has be-come
an increasingly complex issue. In many,
if not most, cats with mild IBD, especially those
without significant infiltrate of inflammatory
cells (mild to moderate infiltrate) or without sig-nificant
weight loss or other morbidity, the best
approach is to feed a highly digestible diet
or to change the diet to one with fewer additives,
flavorings, or other substances that may be associ-ated
with food intolerance. Many cats (nearly
two-thirds in one study) with chronic diarrhea
have complete resolution of clinical signs when
fed a highly digestible diet.30,31
Highly digestible diets are not defined in a reg-ulatory
sense but generally indicate a product
with protein digestibility of greater than 85%
(typical diets are 78% to 81%) and fat digestibility
of greater than 90% (typical diets are 77% to
85%). These diets are designed to provide food
that is easy to digest because it has moderate to low
fat, moderate to increased protein, and moderate
to decreased carbohydrates; may have additives to
improve intestinal health, such as soluble fibers,
omega-3 fatty acids, and increased antioxidant vi-tamins;
and contain no gluten, lactose, food color-ing,
preservatives, and similar additives. Many
different brands fall under the category of “highly
digestible,” but they are not all alike.
The protein digestibility of a diet is one of the
key factors that can determine its success in cats
with IBD. In general, meat-source proteins and
diets containing meat meals are more digestible
than plant-source proteins, and animal proteins
are more digestible than meat by-products. In
addition, to increase digestibility of foods in
cats, the number and amount of carbohydrates
in the food are decreased—a single-source car-bohydrate
food is better than foods with many
different sources, and highly digestible carbohy-drate
sources are better than complex plant-source
carbohydrates. Therefore, when one diet
from this category is not accepted or seems to
make the diarrhea worse, it cannot be assumed
that all diets in this category will be ineffective
and unaccepted. Diets from different manufac-
Treatment of IBD in
cats is nonspecific
and based on
dietary manage-ment,
antibiotic
treatment, and
immunosuppression.

Cobalamin Homeostasis
Cobalamin homeostasis is a complex, multistep process that
involves participation of the stomach, pancreas, intestines, and
liver. Following ingestion, cobalamin is released from food in
the stomach. It is then bound to a nonspecific cobalamin-binding
protein of salivary and gastric origin called
haptocorrin. IF, a cobalamin-binding protein that promotes
cobalamin absorption in the ileum, is produced by the
stomach and pancreas in dogs and the pancreas but not the
stomach in cats.35
The affinity of cobalamin for haptocorrin is higher at acid pH
than that for IF, so most is bound to haptocorrin in the stomach. After entering the
duodenum, haptocorrin is degraded by pancreatic proteases and cobalamin is
transferred from haptocorrin to IF.35
A portion of cobalamin taken up by hepatocytes is rapidly re-excreted in bile
bound to haptocorrin. This rapid turnover means that cats with cobalamin
malabsorption can totally deplete their body cobalamin stores within 1 to 2
months.35
Recent studies indicate that subnormal cobalamin concentrations are common in
cats with GI disease or exocrine pancreatic insufficiency.4 Investigation of the
relationship of subnormal serum cobalamin concentrations to cobalamin deficiency
and the effect of cobalamin deficiency on cats has revealed the clinical significance
of cobalamin deficiency in cats.4
Serum MMA concentrations (median; range) decreased after cobalamin
supplementation. Serum homocysteine concentrations were not significantly
altered, whereas cysteine concentrations increased significantly. Mean body weight
increased significantly after cobalamin therapy, and the average body weight gain
was 8.2%. Significant linear relationships were observed between alterations in
serum MMA and fTLI concentrations and the percentage of body weight change.
There is also emerging evidence that cobalamin supplementation may result in
clinical improvement of cats with IBD without recourse to immunosuppressive
therapy.15 In this respect, it is interesting to note that cobalamin deficiency is
associated with altered immunoglobulin production and cytokine levels in mice. The
impact of cobalamin deficiency on the immune environment of cats remains to be
established.
fTLI = feline trypsin-like immunoreactivity; IF = intrinsic factor; MMA = methylmalonic acid
turers have various formulations (see Diets De-signed
to Promote GI Health).
Novel Antigen or Elimination Diets
Allergy and intolerance are the most common ad-verse
reactions cats have to food. Food allergy or
hypersensitivity is an adverse reaction to a food or
food additive with a proven immunologic basis.
In contrast, food intolerance is a nonimmunologic
abnormal physiologic response to a food or food
additive. Food poisoning, food idiosyncrasy, and
pharmacologic reactions to foods also fall under
the category of food intolerance.
The specific food allergens that cause problems
in cats have been poorly documented, with only
10 studies describing the clinical lesions associated
with adverse reactions.30-33 In these reports, more
than 80% of cases were attributed to beef, dairy
products, or fish.
The incidence of food allergy in cats remains
unknown but is estimated to be only 15% to 20%
of all food-related causes of diarrhea.33 However,
food intolerance is believed to contribute to 60%
to 65% of feline diarrhea cases. In two separate
studies, a majority of cats responded to dietary
therapy with a highly digestible diet.31,34
The causes of dietary intolerance that need
to be carefully considered in feline diets are pri-marily
protein and carbohydrates—both sources
and amounts. The diagnosis of both food allergy
and intolerance is based on a dietary elimination
trial. The major difference between these two
types of adverse food reactions is the length of
time on the diet required to achieve a response
(cats with food allergy may require 6 to 12 weeks
on the elimination diet before an improvement
will be seen).
Various commercial and homemade elimination
diets, as well as diets formulated with hydrolyzed
proteins, may be used in cats with suspected food
allergy or intolerance. The key is to select a diet
that has a novel protein source based on a careful
dietary history and is balanced and nutritionally
adequate (commercial diets are best for this); how-ever,
a homemade elimination diet may be nec-essary
to find an appropriate test diet. If a
homemade diet must be used for long-term
therapy, a complete and balanced diet containing
the necessary protein sources should be formulated
by a nutritionist. For most cats with food allergy,
avoiding the offending food is most effective and
can result in complete resolution of signs. How-ever,
short-term steroid therapy can decrease the
concurrent intestinal inflammation until the ap-propriate
food sources can be identified.
GI disease may decrease the availability of a
number of micronutrients, such as vitamins and
minerals, thereby having important consequences
on the pathogenesis, diagnosis, and treatment of
the disease. The diagnostic utility of measuring
the serum concentrations of cobalamin and folate
in cats with suspected intestinal disease has re-cently
been established. Although the impact of
deficiencies in cobalamin and folate are not com-

B12) in cats with gastrointestinal disease. Simpson KW,
Fyfe J, Cornetta A, et al. J Vet Intern Med 15:26-32, 2001.
5. Histopathological standards for the diagnosis of gastrointesti-nal
inflammation in endoscopic biopsy samples of the dog and
cat: A report from the World Small Animal Veterinary Associa-tion
Gastrointestinal Standardization Group. Day MJ, Bilzer
T, Mansell J, et al. J Comp Pathol 138:1-43, 2008.
6. Molecular characterization of intestinal bacteria in healthy
cats and cats with IBD. Ritchie L. MS dissertation. Texas
A&M University, 2008.
7. Quantitative evaluation of inflammatory and immune re-sponses
in cats with inflammatory bowel disease. Goldstein
RE, Greiter-Wilke A, McDonough SP, Simpson KW. Am
Coll Vet Intern Med Proc, 2003.
8. Immune cell populations in the duodenal mucosa of cats
with inflammatory bowel disease. Waly NE, Stokes CR,
Gruffydd-Jones TJ, et al. J Vet Intern Med 18:113-122, 2004.
9. Molecular characterisation of the gut microflora of healthy
and inflammatory bowel disease cats using fluorescence in
situ hybridisation with special reference to Desulfovibrio spp.
Inness VL, McCartney AL, Khoo C, et al. J Anim Phys
Anim Nutr 91:48-53, 2006.
10. Measurement of cytokine mRNA expression in intestinal
biopsies of cats with inflammatory enteropathy using quan-titative
real-time RT-PCR. Van Nguyen N, Tagliner K,
Helps CR, et al. Vet Immunol Immunopathol 113:404-414,
2006.
11. The relationship of mucosal bacteria to duodenal histopathol-ogy,
cytokine mRNA, and clinical disease activity in cats with
inflammatory bowel disease. Janeczko S, Atwater D, Bogel E,
et al. Vet Microbiol 128:178-193, 2008.
12. Inflammatory bowel disease. Current perspectives. Jergens
AE. Vet Clin North Am Small Anim Pract 29:501-521, 1999.
13. Relationship between inflammatory hepatic disease and inflam-matory
bowel disease, pancreatitis and nephritis in cats. Weiss
DJ, Gagne JM, Armstrong PJ. JAVMA 209:114-116, 1996.
14. Pancreatitis in cats: Diagnosis and management of a chal-lenging
disease. Zoran DL. JAAHA 42:1-9, 2006.
15. Diagnosis of pancreatitis. Steiner JM. Vet Clin North Am
Small Anim Pract 33:1181-1195, 2003.
16. Radiographic, ultrasonographic and endoscopic findings in
cats with inflammatory bowel disease of the stomach and
small intestine. 33 cases (1990-1997). Baez JL, Hendrick MJ,
Walker LM, Washabau RJ. JAVMA 215:349-354, 1999.
17. Interobserver variation among histopathologic evaluation of
intestinal tissues from dogs and cats. Willard MD, Jergens
AE, Duncan RB, et al. JAVMA 220:1177-1181, 2002.
18. Feline alimentary lymphoma: Demystifying the enigma. Wil-son
HM. Top Companion Anim Med 23(4):177-184, 2008.
19. Chemokine expression in IBD: Mucosal chemokine expres-sion
is unselectively increased in both ulcerative colitis and
Crohn’s disease. Banks C, Bateman A, Payne R, et al. J
Pathol 199:28-35, 2003.
20. Bacterial interactions with cells of the intestinal mucosa: Toll-like
receptors and NOD2. Cario E. Gut 54:1182-1193, 2005.
21. Experimental models of inflammatory bowel disease reveal
innate, adaptive, and regulatory mechanisms of host dia-logue
with the microbiota. Elson CO, Cong Y, McCracken
VJ, et al. Immunol Rev 206:260-276, 2005.
22. Inflammatory bowel disease: Epidemiology, pathogenesis,
and therapeutic opportunities. Hanauer SB. Inflam Bowel
Dis 12(Suppl 1):S3-S9, 2006.
23. Intestinal cytokine mRNA expression in canine inflamma-tory
bowel disease: A meta-analysis with critical appraisal.
Jergens AE, Sonea IM, Kauffman LK, et al. Comp Med
59:153-162, 2009.
pletely known, the role of cobalamin in normal
function of the GI tract and in many other aspects
of metabolism is well documented4,15,35 (see
Cobalamin Homeostasis). Furthermore, because
cats are obligate carnivores that consume much
higher amounts of protein in their diet, the im-portance
of cobalamin and other B vitamins in
maintaining protein metabolism cannot be over-stated.
Therefore, evaluation of all cats with GI
disease, not just cats with IBD, is an important
part of not only the diagnostic process but also the
management of these diseases.
Although other vitamin or mineral deficiencies
may occur with longstanding or severe IBD, they
are less likely (because of storage of fat-soluble vi-tamins
and some minerals) and supplementation
without documentation of a deficiency can be
dangerous. Thus, supplementation of fat-soluble
vitamins is not generally recommended unless
signs of deficiency, such as bleeding from vitamin
K deficiency, are occurring or tissue or blood levels
of the vitamin are determined.
Closing Remarks
In conclusion, much remains to be learned
about the complex interplay between GI mi-croflora,
dietary antigens, the epithelium, im-mune
effector cells, and soluble mediators in the
feline GI tract in health and disease. The devel-opment
of feline-specific reagents together with
the growing realization of the nutritional conse-quences
of IBD have precipitated a shift beyond
reliance on qualitative histology, holding prom-ise
for improved understanding, therapy, and
prevention in the future. ■
References
1. Lymphocytic plasmacytic gastroenteritis in cats: 14 cases
(1985-1990). Dennis JS, Kruger JM, Mullaney TP. JAVMA
200:1712-1718, 1992.
2. Lymphocytic plasmacytic enterocolitis in cats: 60 cases
(1988-1990). Hart JR, Shaker E, Patnaik AK, et al. JAAHA
30:505-514, 1994.
3. Idiopathic inflammatory bowel disease in dogs and cats: 84
cases (1987-1990). Jergens AE, Moore FM, Hayness JS, et
al. JAVMA 200:1603-1608, 1992.
4. Subnormal concentrations of serum cobalamin (vitamin
Allergy and
intolerance are
the most common
adverse reactions
cats have to food.
The incidence of
food allergy in
cats is unknown,
but food intole-rance
probably
accounts for 60%
to 65% of feline
diarrhea cases.

24. Differential effect of immune cells on non-pathogenic gram-negative
bacteria-induced nuclear factor-kappaB activation
and pro-inflammatory gene expression in intestinal epithe-lial
cells. Haller D, Holt L, Parlesak A, et al. Immunology
112:310–320, 2004.
25. Probiotics in gastrointestinal diseases. Guarner F. In Versa-lovic
J, Wilson M (eds): Therapeutic Microbiology: Probiotics
and Related Strategies —Washington, DC: ASM Press, 2008,
pp 255-271.
26. Idiopathic inflammatory bowel disease in cats: Rational
treatment selection. Trepanier L. J Feline Med Surg 11:32-
38, 2009.
27. Inflammatory bowel disease. German AJ. In Bonagura J,
Twedt D (eds): Kirk’s Current Veterinary Therapy XIV—St.
Louis, MO: Saunders/Elsevier, 2008, pp 501-506.
28. Tylosin responsive diarrhea. Westermarch E. In Bonagura J,
Twedt D (eds): Kirk’s Current Veterinary Therapy XIV—St.
Louis, MO: Saunders/Elsevier, 2008, pp 507-509.
29. Effect of supplementation with Enterococcus faecium (SF68)
on immune functions in cats. Veir JK, Knorr R, Cavadini
C, et al. Vet Ther 8:229-238, 2007.
30. Food sensitivity in cats with chronic idiopathic gastrointestinal
problems. Guilford WG, Strombeck DR, Rogers Q, et al. J
Vet Intern Med 15:7-13, 2001.
31. Dietary therapy of feline diarrhea. Guilford WG, Center
SA, Strombeck DR, et al. NZ Vet 51:262-265, 2003.
32. Adverse reactions to foods: Allergies versus intolerance. Roude-bush
P. In Ettinger SJ, Feldman EC (eds): Textbook of Veterinary
Internal Medicine, ed 6—St. Louis, MO: Elsevier, 2005, p 153.
33. Food allergy in dogs and cats: A review. Verlinden A, Hesta
M, Millet S, et al. Crit Rev Food Sci Nutr 46:259-273, 2006.
34. Evaluation of two diets in the nutritional management of
cats with naturally occurring chronic diarrhea. Laflamme
DP, Martineau B, Jones W, et al. Vet Ther 5:43-51, 2004.
35. Early biochemical and clinical responses to cobalamin sup-plementation
in cats with signs of gastrointestinal disease
and severe hypocobalaminemia. Ruaux CG, Steiner JM,
Williams DA. J Vet Intern Med 19(2):155-160, 2005.

Few controlled studies are investigating
treatments for liver disease in dogs and
cats. When recommending specific therapeutic ap-proaches,
however, most authors point out the im-portance
of linking adequate nutritional support with
specific therapies and general hepatic support. Man-agement
of liver-related complications should also
be addressed if and when they occur. This article cov-ers
the major aspects associated with managing liver
disease in small animals and outlines some basic
treatment goals (see box).
Nutritional Management
The liver is paramount in metabolism and plays a key role in
regulating protein, carbohydrates, fat, vitamins, and minerals.
Metabolic derangements that occur in dogs and cats with liver
disease can lead to malnutrition, impaired hepatic regeneration,
and the clinical consequences of hepatic insufficiency (eg, he-patic
encephalopathy [HE], ascites, gastrointestinal [GI] ulcera-tion,
coagulopathy, immunosuppression). The liver also has the
unique ability to regenerate following injury, a process that oc-curs
through appropriate nutrition.
The overall goal of nutritional management
of liver disease is predominately supportive
and requires a fine balance between promoting
hepatocellular regeneration and providing nu-trients
to maintain homeostasis without ex-ceeding
the metabolic capacity that leads to
accumulation of toxic metabolites.
Basic nutritional concepts
One of the most important aspects of liver dis-ease
therapy is ensuring that the patient has
appropriate energy intake to prevent anorexia
and weight loss, thereby minimizing catabo-lism.
Adjustments to the diet are required
when malnutrition is present. To this
end, practitioners must first calculate
the patient’s caloric needs.
Calculation of the basal energy re-quirement
(BER) is based on the
weight of lean body mass; the weight
of fat or ascites is not included (see
box). The BER is then multiplied by
an illness factor estimated to be 1.0
to 1.4 to achieve daily caloric needs.1
Although no comprehensive studies
have looked at illness factors in dogs
or cats with liver disease, studies have
shown that humans with cirrhosis have
an energy intake comparable with that of
normal controls.2 Energy requirements
should be individually adjusted to main-tain
optimal body weight.
It is important to ensure that poor
diet palatability is not the reason a pa-tient
refuses to eat. Patients can be of-fered
an ideal diet for a particular
condition, but I would rather have
David C. Twedt,
DVM, DACVIM,
College of
Veterinary
Medicine &
Biomedical
Sciences,
Colorado State
University, Fort
Collins, Colorado
Treatment of Liver Disease:
Medical and Nutritional Aspects
Symposium
Proceedings:
Critical
Updates on
Canine and
Feline Health
How to Calculate BER
• For animals weighing < 2 kg:
70 x [kg*] 0.75 = kcal/day
• For animals weighing > 2 kg:
30 x [kg*] + 70 = kcal/day
• Nutritional requirements for most cats
can also be expressed as 50–55 kcal/kg
body weight.
*Of lean body mass
BER = basal energy requirement
Treatment Goals
✔ Remove or correct inciting
cause if identified.
✔ Provide adequate nutrition and
prevent malnutrition.
✔ Provide specific treatment for
hepatic disease and/or related
complications.
✔ Provide an environment for
optimal hepatic function and
regeneration.
14 Treatment of Liver Disease: Medical and Nutritional Aspects

Treatment of Liver Disease: Medical and Nutritional Aspects 15
patients eat almost any diet than nothing at all.
When nutritional requirements are not being met
by voluntary intake, enteral supplementation
should be considered.
Fat
A misconception about dietary fat content and
liver disease is prevalent, especially in the nutri-tional
management of feline hepatic lipidosis. In
general, dogs and cats with liver disease have a
good tolerance for dietary fat. Fat not only im-proves
palatability but provides important energy
density to the diet. Therefore, lipid restriction
typically is not necessary for dogs or cats with
liver disease; this also holds true for cats with id-iopathic
hepatic lipidosis. However, dietary con-trol
is probably the most important aspect of
managing a case of hepatic lipidosis.
Carbohydrates
Carbohydrates should make up no more than
35% of the diet’s total calories for cats and 45%
for dogs.3 Adequate carbohydrate intake is impor-tant
to maintain glucose concentrations, especially
in dogs with advanced liver disease or when hypo-glycemia
is a concern in patients with portosys-temic
shunts (PSS). Feeding frequent small meals
throughout the day may help patients maintain
glucose concentrations.
I have observed hypoglycemia in some dogs
with cirrhosis and PSS and hyperglycemia in
some cats with hepatic lipidosis or cats receiving
steroids. In conjunction with liver disease (and
sometimes concurrent steroid therapy), cats with
glucose intolerance or a tendency to develop hy-perglycemia
after a meal will require a lower-car-bohydrate
diet. The best way to prevent hyper- or
hypoglycemia is to feed frequent small meals. In
general, I prefer to feed an energy-dense, low-fiber
diet to patients with liver disease. However, man-aging
dietary fiber plays a role in how it relates to
the treatment of hepatic encephalopathy.
Protein
A misconception about protein content and liver
disease also exists. It was previously thought that
patients with liver disease should be placed on a
As a general
recommendation,
dietary protein
should represent
15% to 20% of
the digestible
kilocalories in
the diet.
Dietary Protein Intake
The goals of dietary protein intake are to:
✔ Adjust quantities and types of nutrients to
meet the patient’s nutrient requirements.
✔ Avoid production of excess nitrogen by-products
that cause hepatic encephalopathy.
✔ Provide a high-quality, highly digestible
protein source.5 Poor-quality proteins may
aggravate hepatic encephalopathy and fail to
promote hepatic regeneration.
Protein requirements for patients with liver
disease may be greater than those for normal
dogs and cats. Most quality commercial and
prescription diets are suitable for this purpose.
protein-restricted diet to reduce the liver’s work-load
and the production of detrimental nitroge-nous
waste products. This approach is not well
substantiated, however. Many veterinary nutri-tionists
and gastroenterologists now believe that
restricting protein could be detrimental, especially
if patients have a negative nitrogen balance.4
As a general recommendation, dietary protein
should represent 15% to 20% of the digestible
kilocalories (kcal) in the diet.3Most highly di-gestible
diets (eg, GI diets) are adequate for pa-tients
with most liver conditions5 (see Dietary
Protein Intake). Protein restriction should only be
instituted in patients with evidence of protein in-tolerance—
most often patients with PSS or signs
of HE.6 In these situations, lower protein content
and diets with a milk- or plant-based protein
source rather than a meat source are recommended
to prevent HE and colonic production of excess
nitrogen by-products. Because cats have such a
high protein requirement, I rarely—if ever—limit
protein intake in cats with liver disease, such as
lipidosis, and find HE an uncommon consequence
in cats.
Basic Therapeutic Options
Antiinflammatory therapy
Decreasing inflammation should be specifically
addressed in dogs with chronic hepatitis and
possibly in cats with some types of cholangitis.
At Colorado State University, our clinical im-pression
suggests that antiinflammatory therapy
is beneficial in some if not all cases of chronic

hepatitis, but this approach remains controver-sial
because no good controlled studies have
been conducted in dogs.
One retrospective study found that some dogs
with chronic hepatitis tend to have a prolonged
survival when treated with corticosteroids,7 al-though
dogs of many different breeds and a di-versity
of histology and concurrent therapies
were included. Nevertheless, the use of steroids
versus the use of no steroids offered benefits in
some cases (around 25%), and these responders
may in fact represent dogs with immune-medi-ated
liver disease. An initial dose of 1 to 2
mg/kg/day of prednisone or prednisolone is sug-gested.
When clinical improvement is suspected
or after several weeks of therapy, the dose can be
gradually tapered to 0.5 mg/kg/day or Q 48 H.
The only accurate way to evaluate response to
therapy is to evaluate biopsy specimens in approx-imately
6 to 8 months. It is impossible to deter-mine
any improvement based on liver enzymes
because of concurrent steroid hepatopathy. Al-ternatively,
practitioners could stop steroid ad-ministration
and recheck the enzymes in 1 to 2
months after the steroid effects on the liver have
resolved. Persistent elevations would suggest that
hepatitis is continuing.
Some reports also show improvement of im-mune
hepatitis in humans treated with budes-onide.
8 These patients had fewer side effects from
systemic steroids because of the rapid first-pass he-patic
metabolism of budesonide. This drug may
be an option in some dogs or cats with inflamma-tory
liver disease because it may somewhat lessen
the side effects associated with steroids.
Because of the side effects of corticosteroids
and the failure to successfully monitor liver en-zymes
while receiving steroids, other immuno-suppressive
therapy, including azathioprine9 and
cyclosporine, may represent a more rational ap-proach
(see Getting the Most Out of Antiin-flammatory
Therapy in Dogs).
Hepatic copper metabolism
Copper is an essential trace metal required for
many metabolic functions. The liver is quintes-sential
in regulating the concentration and ex-cretion
of excess copper through bile. Hepatic
copper concentrations can increase in dogs because
of either a primary genetic defect or diminished
copper excretion secondary to cholestatic liver dis-ease.
Copper accumulation caused by cholestatic
disease does not occur as frequently, and copper
concentrations are lower than in breed-associated
copper hepatotoxicity. With either mechanism of
copper accumulation, subcellular damage to hepa-tocytes
can result. Damage from copper apparently
results in lipid peroxidation and mitochondrial
damage.10
If the liver biopsy of a dog with chronic hepati-tis
indicates significant abnormal hepatic copper
accumulation, then dietary copper chelators or
zinc therapy should be instituted. Hepatic copper
levels of greater than 1,000 mcg/g of dry weight
liver (normal < 400 mcg/g liver) require therapy
to reduce copper concentrations.
It is first important to feed diets with a lower
copper content and to avoid nutritional supple-ments
with additional copper. A restricted copper
intake of about 1.25 mg/1,000 kcal of metaboliz-
Getting the Most Out of
Antiinflammatory Therapy in Dogs
Azathioprine is an effective immunosuppressant shown to
increase survival in humans treated for chronic hepatitis
when administered in conjunction with corticosteroids.9
The therapy may also be beneficial in dogs (do not use
azathioprine in cats because of toxicity) by increasing the
immunosuppressive response and enabling reduction of
both the steroid dose and side effects. Initially, a dose of 2.2
mg/kg/day is suggested, followed by Q 48 H after several
weeks. The level of glucocorticoids can frequently be reduced
when using azathioprine. Of importance, azathioprine has infrequently been
associated with drug-induced hepatic necrosis or acute pancreatitis. If the
dog worsens clinically or the alanine aminotransferase (ALT) value increases
dramatically, I would stop the medication.
At Colorado State University, we have realized good clinical response when
using cyclosporine in some dogs with chronic hepatitis. Our experience using
5 mg/kg Q 12 H or Q 24 H (without steroids) has been encouraging in dogs believed
to have immune-mediated chronic hepatitis. The veterinary formulation Atopica
(www.atopica.com) is a microemulsified preparation with the same properties and
bioavailability as the human product Neoral (www.pharma.us.novartis.com) and
its generic counterpart. Generally after several days or longer, I will obtain a
blood level at the trough (before the next pill). The ideal range of blood levels is
400–600 ng/mL.
Many dogs develop gingival hyperplasia when higher concentrations of
cyclosporine are administered. Azithromycin at 10 mg/kg/day for 4–6 weeks will
often decrease gingival hyperplasia. With evidence of clinical response at a dose of
5 mg/kg Q 12 H, I often decrease the frequency to Q 24 H and eventually to alternate-day
therapy. Using cyclosporine alone, practitioners can follow the level of liver en-zymes
and direct therapy based on response without the need for liver biopsy.

able energy (ME) has been suggested.3 The cop-per
content is listed on the label of most diets; if
not, the manufacturer should be able to provide
this information. If a homemade diet is used,
liver, shellfish, organ meats, and cereals are all
high in copper content and should be excluded.
Copper-specific chelators (eg, penicillamine,
trientine) are the standard therapies used to re-move
excess hepatic copper in cases of breed-asso-ciated
copper hepatotoxicity. Chelators bind with
copper either in the blood or the tissues and then
promote copper removal through the kidneys.11-13
Zinc therapy has a number of potential benefits
in dogs with chronic hepatitis. Zinc has antifi-brotic
and hepatoprotective properties11,14 (see
The Role of Oral Zinc Therapy). When zinc is
administered as the acetate, sulfate, gluconate, or
other salt, it has proven effective in preventing he-patic
copper reaccumulation in humans who have
Wilson’s disease and have been decoppered with
chelators.4 When these patients received oral zinc,
hepatic copper concentrations did not increase.
Choleretic drug therapy
Decreasing cholestasis has been shown to be ben-eficial
in humans and animals with cholestatic he-patobiliary
disease. As serum bile concentrations
increase (predominately cytotoxic bile acids), cell
membrane permeability changes and fibrogenesis
can occur. Ursodeoxycholic acid (300-mg cap-sules)
is a choleretic agent developed to dissolve
gallstones but later found to have positive effects
in patients with chronic hepatitis. This synthetic
hydrophilic bile acid essentially changes the bile
acid pool from more toxic hydrophobic bile acids
to less toxic hydrophilic bile acids. Ursodeoxy-cholic
acid has been shown to increase bile acid–
dependent flow and minimize hepatocellular
inflammatory changes, fibrosis, and some im-munomodulating
effects.15,16
The hepatoprotective characteristics of ur-sodeoxycholic
acid, much like those of antibi-otics,
make it good adjunct therapy at a dose of 15
mg/kg/day. No toxicity has been observed in dogs
or cats at this dose.15,16 However, some practition-ers
are concerned about using it if there is a possi-bility
of bile duct obstruction (for fear of biliary
rupture). Although with bile obstruction surgical
correction is indicated, ursodeoxycholic acid is not
a prokinetic and will not worsen the disease. This
drug has been shown in controlled studies to be
beneficial in humans with primary biliary cirrho-sis.
17 I routinely supplement ursodeoxycholic acid
in dogs with hepatitis and cats with cholangitis.
Antifibrotic drug therapy
Corticosteroids, zinc, and penicillamine all have
some antifibrotic effects but are used predomi-nately
for their other effects. Colchicine, which has
been used in treating humans with chronic hepati-tis
and other types of liver fibrosis, reportedly in-terferes
with the deposition of hepatic collagen and
stimulates collagenase activity to break down de-posited
fibrous tissue in the liver. It also is shown
to have some antiinflammatory properties. How-ever,
convincing data on the benefits of colchicines
are lacking for humans and dogs with liver disease.
A critical appraisal of colchicine use in humans
with chronic hepatitis now questions its effective-ness;
in fact, a large, placebo-controlled study of
chronic hepatitis in humans found no benefits,
and the study authors did not recommended its
use.18
If liver biopsy
indicates
significant
abnormal copper
accumulation,
then dietary
copper chelators
or zinc therapy
should be
instituted.
The Role of Oral Zinc Therapy
Oral zinc therapy works by causing an induction
of the intestinal copper-binding protein metalloth-ionein.
Dietary copper binds to the metallothionein
with a high affinity that prevents transfer from the
intestine into the blood. When the intestinal cell
dies and is sloughed, the metallothionein-bound
copper becomes excreted through the stool.11
An initial induction dose of 15 mg/kg Q 12 H
(or 50–100 mg Q 12 H) of elemental zinc is sug-gested.
14 After 1–3 months of induction, the dose
can be reduced by approximately half. The goal is
to have serum zinc concentrations greater than
200 mcg/dL but less than 500.
Zinc must be administered on an empty stomach
and has the frequent side effect of vomiting. Re-placement
zinc therapy administered at a dose of
2–3 mg/kg/day is given for its antioxidant effects
and replacement value in animals with zinc deple-tion
in their liver.

Three case reports of colchicine use in dogs have
indicated questionable results.19-21 However, based
on these reports, a dose of 0.03 mg/kg/day has
been suggested. The generic form is inexpensive,
with generally only minimal GI side effects noted
at high doses.
Recently losartan, an angiotensin-II receptor
antagonist used for treating high blood pressure,
has shown some effects in preventing hepatic fi-brosis
by preventing up-regulation of the stel-late,
or collagen-producing, cells in the liver.
Clinical response to losartan has been noted in
human studies of hepatitis.22
Antibiotic therapy
Antibiotics are indicated in some patients with
primary hepatic infections, such as bacterial hepa-titis,
cholangitis, or leptospirosis. The selection of
appropriate antibiotics is based on culture and
sensitivity testing. There is, however, evidence that
secondary bacterial colonization may take place in
a diseased liver.23 Kupffer cells, which are fixed he-patic
macrophages, function in filtering the portal
blood of bacteria and other toxic products. Kupf-fer
cell dysfunction in patients with liver disease
could account for a secondary bacterial infection.
This is supported by studies that have identified
bacteria in many hepatic cultures.24 Therefore, it
may be prudent to initiate antibiotic therapy for
at least a trial of several weeks in patients with sig-nificant
hepatic disease (ie, chronic hepatitis).
Amoxicillin, amoxicillin–clavulanic acid, ceph-alosporin,
or metronidazole therapy is suggested.
Metronidazole may have some immunosuppres-sive
properties as well as anaerobic antibacterial
mechanisms. Because of hepatic metabolism of
metronidazole, I recommend a dose of 7.5 to 10
mg/kg Q 12 H, which is much lower than that
used for other bacterial infections.
Vitamins and Nutraceuticals
for Liver Support
Although vitamin and nutraceutical adjunct ther-apies
have gained interest in managing certain
types of liver disease, few published reports have
shown their benefit in clinical disease; much of
the information gathered has been generated from
in vitro studies. Some current information as well
as suggested uses of pertinent vitamins and nu-traceuticals
are presented here.
Vitamins
Because vitamin metabolism, specifically vitamin
storage and the conversion of provitamins to a
metabolically active state, takes place in hepato-cytes
of the liver, the vitamin status of patients
with liver disease needs to be considered.
Fat-soluble vitamins (ie, A, D, E, K) are prone
to be deficient because they require bile salts to
form intestinal micelles for absorption. In pa-tients
with cholestatic liver disease, bile acids ab-normally
excrete into the intestine, affecting the
uptake of fat-soluble vitamins.25Water-soluble
vitamins (ie, B, C) are generally found in high
concentrations in the liver, where many are
stored as coenzymes. In patients with liver dis-ease,
increased demand for these vitamins, al-tered
conversion to the vitamin’s active form, or
decreased hepatic storage may occur.
Vitamin E. Vitamin E (α-tocopherol) func-tions
as a cellular membrane-bound antioxidant.
Evidence now shows that oxidative damage
from free radical generation occurs in patients
with liver disease.26 Because cellular damage is
likely multifactorial in these patients, free radi-cals
may play an important role in initiating or
perpetuating this damage.27,28
Vitamin E is inexpensive and safe when sup-plemented
at a dose of 10 IU/kg/day: d-α-
tocopherol , the natural form of vitamin E, is
recommended because of greater uptake, disper-sion,
and bioactivity compared with the more
common synthetic dl-α-tocopherol. d-α-Tocoph-erol
is also retained in tissues by a 2:1 ratio over
the synthetic formulation.25 In patients with sig-nificant
cholestatic liver disease, I suggest a
water-soluble formulation.
Vitamin C. Vitamin C (ascorbic acid) is an im-portant
soluble intracellular antioxidant that
helps convert oxidized tocopherol radicals back to
active α-tocopherol. Vitamin C is also necessary
Fat-soluble
vitamins A, D, E,
and K are prone
to be deficient
because they
require bile salts
for absorption.
Water-soluble
vitamins B and C
are generally
found in high
concentrations
in the liver.

for the synthesis of carnitine, which is important
for transporting fat into mitochondria. Humans
with liver disease often have low hepatic vitamin
C concentrations, partially because they cannot
synthesize vitamin C; however, dogs and cats can
synthesize this vitamin.
Although vitamin C supplementation may be
beneficial in treating liver disease, supplementa-tion
of excessive amounts of vitamin C may be
deleterious in patients with increased hepatic
copper or iron concentrations because ascorbate
is believed to promote oxidative damage caused
by these transition metals.26
Vitamin K. Vitamin K stores in the liver can
become depleted in patients with advanced liver
disease and can result in serious coagulopathy.
Deficiency can occur from reduced intestinal
absorption from cholestatic liver disease or as
the result of advanced liver dysfunction with a
failure of hepatic conversion to the vitamin K-dependent
coagulation factors (ie, factors II,
VII, IX, X). This can result in prolongation of
coagulation as measured by prothrombin time
or activated partial thromboplastin time and can
cause significant bleeding.
Vitamin K supplementation is warranted in
patients with liver disease to maintain hepatic
stores. With severe cholestasis or overt coagula-tion
abnormalities, 0.5 to 2.0 mg/kg of par-enteral
vitamin K1 (phytonadione) SC Q 12 H
for two or three doses (or until normalization of
prothrombin time) is recommended for dogs
and cats with hepatic disease. Vitamin K1 sup-plementation
is recommended for 24 to 36
hours before invasive procedures, such as he-patic
biopsy or feeding tube placement.6
Vitamin B. B vitamins are important in many
metabolic functions and may become deficient
in both dogs and cats with liver disease. How-ever,
deficiencies are difficult to diagnose or ana-lytically
document. Because B vitamins are
water-soluble, they are relatively nontoxic and
supplementation using a B-complex formulation
is recommended in patients with liver disease.
Cats are particularly prone to vitamin B12
(cobalamin) deficiency. Subnormal concentrations
of vitamin B12 have been reported in cats with
liver disease, particularly idiopathic hepatic lipido-sis.
29 Cats with cholangiohepatitis frequently have
concurrent inflammatory bowel disease or chronic
pancreatitis and subsequent cobalamin deficiency.
The recommended dose of cobalamin for cats is
250 mcg SC weekly until normal cobalamin con-centrations
have been maintained. There is not
enough vitamin B12 in B-complex formulations
to correct its deficiency in cats.
Nutraceuticals
The North American Veterinary Nutraceutical
Council defines a nutraceutical as “a non-drug sub-stance
that is produced in a purified or extracted
form and administered orally to patients to provide
agents required for normal body structure and
function and administered with the intent of im-proving
the health and well being of animals.”30
Many nutraceuticals used in animals are listed as
nutritional supplements. Typical categories include:
■ Antioxidants
■ Omega fatty acids
■ Amino acids
■ Chondroprotective agents
■ Herbals
■ Probiotics
Although some nutraceuticals have shown po-tential
for improving veterinary care, little infor-mation
is known about their purity, dosage, safety,
side effects, and effectiveness.With a few excep-tions,
little has been done to address these issues.
Included here are nutraceutical compounds
that have shown some scientific evidence for
both effectiveness and relative safety in the man-agement
of liver disease.
S-Adenosylmethionine. S-Adenosylmethio-nine
(SAMe), a naturally occurring molecule
synthesized in all living cells, is essential in inter-mediary
metabolism and has both hepatoprotec-tive
and antioxidant properties.
The liver normally produces abundant SAMe,
but evidence also suggests conversion from me-thionine
to SAMe is hindered in patients with
liver disease and, therefore, results in the depletion
of glutathione concentrations.31 Orally adminis-tered
SAMe (but not oral glutathione) has been
shown to increase intracellular glutathione levels
Although some
nutraceuticals
have shown
potential for
improving
veterinary care,
information
about their
purity, dosage,
safety, side
effects, and
effectiveness
remains limited.

in hepatocytes and prevent gluta thione depletion
when exposed to toxic substances.32 Therefore,
SAMe in part acts as an anti oxidant, replenishing
the gluta thione stores. Preliminary veterinary
studies suggest that SAMe supplementation in-creases
hepatic glutathione concentrations in nor-mal
cats and prevents glutathione depletion in
dogs with steroid-induced hepatopathy .32 SAMe
treatment following acetaminophen administra-tion
prevented hepatic glutathione depletion.33
Because SAMe is easily oxidized, it is important
to use products that have been tested for their sta-bility.
In addition, product purity can vary from
formulation to formulation, so it is advisable to
use products from reputable companies.
N-Acetylcysteine. N-Acetylcysteine, the
acetylated variant of the amino acid L-cysteine,
is an excellent source of the sulfhydryl groups.
It is converted in the body into metabolites that
stimulate glutathione synthesis, thereby promot-ing
detoxification and acting directly as free rad-ical
scavengers.
N-Acetylcysteine has historically been used
as a mucolytic agent for various respiratory ill-nesses
but apparently also has beneficial effects
in conditions characterized by oxidative stress or
decreased glutathione concentrations. N-Acetyl-cysteine
is currently the mainstay of treatment
for acetaminophen-induced hepatotoxicity.33 It
also appears to have some clinical usefulness as a
chelating agent in treating acute metal poison-ing,
both as an agent protecting the liver and
kidney from damage and as intervention to en-hance
elimination of metals.
N-Acetylcysteine is available in a drug formu-lation
and as a nutritional supplement. The oral
dose recommended for acetaminophen toxicity
is 70 mg/kg Q 8 H. The IV loading dose of
140 mg/kg is followed by a dose of 70 mg/kg.
N-Acetylcysteine reportedly has extremely low
toxicity with few side effects. I use N-acetylcys-teine
IV when the patient is vomiting or too
sick to take oral SAMe, which is my preference
as maintenance therapy.
Phosphatidylcholine. Phosphatidylcholine is a
phospholipid used as a nutritional supplement for
its hepatoprotective effects. A building block for
cell membranes, phosphatidylcholine is required
for normal bile acid transport. It is thought to be
hepatoprotective by improving membrane in-tegrity
and function.
In vitro studies have shown that phosphatid-ylcholine
increases hepatic collagenase activity
and may help prevent fibrosis.34 Clinical trials
have indicated that phosphatidylcholine protects
the liver against damage from alcohol, viral hep-atitis,
and other toxic factors that operate by
damaging cell membranes.34
Several phosphatidylcholine supplements are
available. No major side effects have been reported
other than occasional nausea or diarrhea. Phos-phatidylcholine
is rapidly absorbed, enhances ab-sorption
of other compounds, and is included as a
carrier in one silybin product.
Given the apparent safety of phosphatidyl-choline,
animal studies would be worthwhile.
L-Carnitine. L-Carnitine is a vitamin -like sub-stance
found in most cells. Because it is predom-inately
synthesized in the liver, liver disease can
precipitate deficiency. Clinically, carnitine defi-ciency
has been associated with increased am-monia
concentrations, hypoglycemia, and fatty
livers.35
In one study, carnitine given to obese cats un-dergoing
rapid weight loss from caloric restric-tion
was found to protect against hepatic
triglyceride accumulation.35 Some studies sug-gest
that L-carnitine deficiency may play a role
in the pathogenesis of idiopathic feline hepatic
lipidosis; however, carnitine concentrations were
higher in the plasma, liver, and muscle of study
cats than in control cats.36
A deficiency of carnitine may lead to impaired
mitochondrial function, but studies failed to
show carnitine deficiency in cats with hepatic
lipidosis.37 Supplementation with 250 mg/day
of carnitine in cats with lipidosis is reportedly
associated with better survival rates, but this has
not been documented.
Silymarin. Silymarin, an active extract of milk
thistle, grows wild throughout Europe and has
In preliminary
studies, SAMe
supplementation
increased hepatic
glutathione
concentrations in
normal cats and
prevented
glutathione
depletion in dogs
with steroid-induced
hepatopathy.

been used there for more than 2,000 years as a
medical remedy for liver disease. In the United
States, silymarin is classified as a nutraceutical.
Mounting evidence suggests that milk thistle
has medicinal benefits for various types of liver
disease as well as a protective effect against hepa-totoxins.
A recent poll of liver patients at one
U.S. hepatology clinic found that 31% were
using alternative agents for their disease and that
milk thistle was the most common nontradi-tional
therapy.38 Several human trials have as-sessed
the efficacy of silymarin in the treatment
of liver disease. The data are somewhat difficult
to interpret because of the limited number of
patients, poor study design, variable etiologies,
and lack of standardization of preparations with
different dosing protocols. However, compelling
evidence suggests that silymarin has a therapeutic
effect in humans with acute viral hepatitis, alco-holic
liver disease, cirrhosis, and toxin- or drug-induced
hepatitis.39
To date, limited clinical studies have evaluated
the efficacy of silymarin in dogs and cats with
liver disease. In one placebo-controlled experi-mental
study of dogs poisoned with the
Amanita phalloides mushroom, silybin had a sig-nificant
positive effect on liver damage and sur-vival
outcome.40
The purity and potency of commercial milk
thistle products vary by manufacturer, and the
therapeutic dose for dogs and cats is unknown,
although suggested doses range from 50 to 250
mg/day. Milk thistle reportedly has extremely
low toxicity. When the active isomer silybin is
complexed with phosphatidylcholine, oral uptake
and bioavailability are greater.41
I recently conducted a pharmacokinetic study
of silybin, specifically evaluating Marin
(www.nutramaxlabs.com) in normal cats. There
was evidence of some oxidative protection in red
blood cells but no outward signs of toxicity at a
dose of 5 mg/kg. A new compound Denamarin
(www.denamarin.com) contains SAMe and sily-bin–
phosphatidylcholine and is available in a
chewable formulation. The combination of
compounds apparently has good absorption and
is very stable.
Hepatic Complications
Secondary complications can develop as liver
disease becomes advanced. HE, GI ulceration,
and ascites are common in patients with advanced
hepatitis or cirrhosis.
Hepatic encephalopathy
HE results from either portosystemic shunting of
blood (congenital or acquired) or hepatocyte de-pletion
from acute or chronic liver disease. Many
factors can cause HE, most of which are derived
from nitrogenous products produced in the GI
tract. Ammonia is only one of many substances
that cause HE but is commonly used as its marker.
Plasma amino acid concentrations may become al-tered
in patients with liver disease. Increased levels
of aromatic amino acids are hypothesized to form
false neurotransmitters, leading to HE, whereas
higher concentrations of branched-chain amino
acids had a more protective effect5 (see HE and
Dietary Protein3,5,42).
There are three basic therapeutic goals for man-aging
HE (see box on page 22). The first step is
using enemas to clean the colon of both bacteria
and protein substrates for ammonia production.
Slightly acidic enemas can lower the pH of the
colon, thereby ionizing ammonia and reducing its
absorption. Povidone-iodine can safely be given by
Mounting
evidence suggests
that milk thistle
has medicinal
benefits for
various types of
liver disease as
well as protective
effects against
hepatotoxins.
HE and Dietary Protein
The importance of the dietary protein source has been studied in humans with HE
and several experimental studies in dogs with PSS.42 Vegetable and dairy protein
sources with lower concentrations of aromatic amino acids have produced the
best results in maintaining a positive nitrogen balance with minimal encephalo-pathic
signs.5 Foods using soybean meal averted encephalopathic signs in dogs
with experimentally created shunts,42 and Purina Veterinary Diet HA Hypoaller-genic
formula could be an option in these cases. In addition, dairy products (espe-cially
cottage cheese) have been frequently recommended for use in homemade
foods for dogs and cats with PSS and chronic hepatic insufficiency.3 However, the
amino acid composition of these protein sources is not significantly different from
that of meat sources, suggesting that other food factors (eg, digestibility, levels of
soluble carbohydrate, fermentable fiber) are important.
Fermentable carbohydrates in crease microbial nitrogen fixation, reduce intra-luminal
ammonia production in the gut, and promote colonic evacuation. Fer-mentable
fiber added to the diet has been shown to decrease ammonia
production. Commercial and homemade foods can be supplemented with various
sources of soluble fiber, such as psyllium husk fiber.
HE = hepatic encephalopathy; PSS = portosystemic shunt

enema as a 10% solution (weak-tea color) that will
both acidify the colon and have antiseptic action,
thereby reducing bacterial numbers.
Intestinal antibiotics can be used to alter bowel
flora and suppress urease-producing organisms
important in forming factors that cause HE. An-tibiotic
suggestions include oral ampicillin, amino-glycosides
(eg, neomycin, kanamycin, gentamicin),
or metronidazole. Metronidazole at a dose of 7 to
10 mg/kg PO Q 12 H has been useful in control-ling
anaerobic urease-producing
bacteria. Practitioners should
monitor patients carefully be-cause
metronidazole is partially
metabolized in the liver; the
lower dose range is suggested.
A nondigestible disaccharide
lactulose given orally can acidify
the colon, convert ammonia to
ammonium that is poorly ab-sorbable,
and thus trap ammonia
in the colon. The fermentation
products of lactulose can also act
Basic Therapeutic Goals for HE
1. Recognize and correct precipitating
2. Reduce intestinal production and
absorption of neurotoxins, with
special emphasis on ammonia.
3. Achieve the fine balance between
providing too much and too little
protein.
HE = hepatic encephalopathy
as an osmotic laxative and reduce colonic bacteria
and protein substrates. Lactulose is not absorbed
systemically and is considered safe. A dose of 1 to
10 ml PO Q 8 H is generally effective, but the
dose should be adjusted to cause three or four soft
stools a day. Lactulose can also be given by enema
when treating severe cases of HE.
Gastrointestinal ulceration
Ulceration in the GI tract, a common occurrence
in both advanced acute and chronic liver disease,
can cause GI signs, such as vomiting and anorexia.
In addition, blood loss into the intestinal tract
promotes HE because blood is an excellent pro-tein
source of ammonia production. Gastric ulcers
should be treated with a histamine-2 (H2) blocker,
such as 2 to 5 mg/kg of ranitidine Q 8 H to Q 12
H and a 1 mg tab/25 kg of oral sucralfate Q 8 H
given 1 hour before ranitidine.
Cimetidine should be avoided in patients with
liver disease because it is metabolized by the liver
causes of HE.
and is an enzyme suppressor that can alter the he-patic
metabolism of other drugs. If blood loss is se-vere
and there is need for transfusion, only fresh
blood should be administered because ammonia
concentrations can increase in stored blood.
Ascites
In patients with liver disease, ascites occurs
when portal hypertension, hypoalbuminemia,
and renal sodium and water retention work in
concert to cause fluid exudation. The presence
of ascites is a poor prognostic indicator.
Diuretics are the major means of managing as-cites
in small animals. Too rapid removal of ascitic
fluid can cause metabolic complications and pre-cipitate
HE. The goal of diuretic therapy should
be gentle water diuresis.
The two diuretics most commonly used are
furosemide and spironolactone. The general
consensus at CSU is that spironolactone is more
effective with liver disease. The loop diuretic
furosemide can, however, cause marked dehy-dration
and loss of potassium, which can precip-itate
HE. In patients with liver disease, sodium
reabsorption at the distal tubule may be great
and may counter the effects of furosemide at-tributable
to elevated aldosterone concentrations
(reported to occur in some dogs with liver dis-ease).
43 Spironolactone at a dose of 1 to 2
mg/kg/day is consequently the first-line diuretic.
Furosemide can be added later if necessary. If an
animal has tense ascites, paracentesis should be
performed to decrease intraabdominal pressure,
relieve compression of the venous circulation,
and improve patient comfort.
Summary
It is critical to recognize the complexity of the
medical and nutritional needs of patients with
liver disease. Practitioners should formulate an
individualized therapeutic and dietary plan ac-cordingly.
Because there are few good controlled
studies evaluating liver disease therapy, it is im-portant
to carefully monitor each patient and
adjust the treatment, based on clinical response
of the patient, laboratory changes, or histologic
findings. ■
Cimetidine
should be
avoided in
patients with
liver disease
because it is
metabolized by
the liver and is
an enzyme
suppressor that
can alter hepatic
metabolism of
other drugs.

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concentrations in cats with idiopathic hepatic lipidosis and in
healthy cats. Jacobs G, Cornelius L, Keene B, et al. Am J Vet
Res 51:1349-1351, 1990.
38. Milk thistle and chronic liver disease. Hoofnagel JH. Hepatol-ogy
42:4, 2005.
39. Milk thistle (Silybum marianum) for the therapy of liver dis-ease.
Flora K, Hahn M, Rosen H, et al. Am J Gastroenterol
93:139-143, 1998.
40. Complementary and alternative medicine in chronic liver dis-ease.
Seef LB, Lindsay KL, Bacon BR, et al. Hepatology
34:595, 2001.
41. Bioavailability of a silybin-phosphatidylcholine complex
in dogs. Filburn CR, Kettenacker R, Griffin DW. J Vet Phar-macol
Ther 30:132-138, 2007.
42. Apparent dietary protein requirement of dogs with portosys-temic
shunt. Laflamme DP, Allen SW, Huber TL, et al. Am J
Vet Res 54:719-723, 1993.
43. Sodium retention and ascites formation in dogs with experi-mental
portal cirrhosis. Levy M. Am J Physiol 233(6):F572-
F585, 1977.

Obesity is the number one nutritional
disorder in pets in the western world. Twenty-five per-cent
of cats seen by veterinarians in the United States
and Canada are overweight or obese.1 In optimal condi-tion,
cats should carry 15% to 20% body fat.
In 1998, Donoghue and Scarlett2 studied diet and obesity in
cats. Using multivariate statistical analysis controlled for age,
they showed that obesity is a risk factor for:
■ Diabetes mellitus
■ Skin problems
■ Hepatic lipidosis
■ Lameness
Other researchers have found that a chronic overweight state,
in cats as well as in other species, is associated with an in-creased
risk for:3-5
■ Hyperlipidemia
■ Insulin resistance
■ Glucose intolerance
■ Feline lower urinary tract disease
■ Anesthetic complications
■ Dyspnea and Pickwickian syndrome
■ Exercise intolerance
■ Heat intolerance
■ Impaired immune function
■ Exacerbation of degenerative joint disorders
■ Dermatologic conditions
Interestingly, mixed-breed cats were found to be at higher
risk for becoming overweight than purebred cats were. While
this might be genetic, husbandry and awareness of the cat
probably play a role. By keeping cats indoors, we eliminate
their need to work for food and defend themselves. We leave
them without stimulation for much of
the day and feed them excessive quanti-ties
of palatable, calorie-dense diets.
Neutering has been shown to reduce
the energy requirements (resting meta-bolic
rate) of cats by 20% to 25%.6,7 A
link has been shown between serum lep-tin
levels and weight and fat gains follow-ing
gonadectomy.8 Increased leptin levels
may contribute to the decreased insulin
sensitivity seen in overweight cats.9
These tendencies make it important
that we counsel our clients to measure
the amounts of food being fed and to
watch carefully for weight gain and adjust
calorie intake accordingly. Ingesting 10
extra pieces of an average maintenance
kibble each day above a cat’s energy needs
can result in a weight gain of 1 pound of
body fat in 1 year. Russell and cowork-ers10
showed that the frequency of feed-ing,
along with the quantity fed, makes a
significant difference. Feeding small
meals more often and limiting the num-ber
of treats offered together provide the
most appropriate feeding strategy, given
innate feline physiology,11,12 and thus as-sist
with weight loss.
Assessing Body Composition
and Condition: Tools
Cats reach their adult weight at about 12
Margie Scherk,
DVM, DABVP
(Feline),
Vancouver, BC,
Canada
From Problem to Success:
A Weight Loss Program That
Works, Growing Relationships,
Not Girth in Cats
Symposium
Proceedings:
Critical
Updates on
Canine and
Feline Health
24 A Weight Loss Program That Works, Growing Relationships, Not Girth in Cats

A Weight Loss Program That Works, Growing Relationships, Not Girth in Cats 25
to 15 months of age. This can be used as a guide to
determine an individual’s ideal size, assuming opti-mal
body condition score (BCS) at that time.
It is easier to prevent weight gain than to lose
weight. The prevalence of obesity increases after
2 years of age, plateaus until about 12 years, and
then declines thereafter.13 Thus, an approved
strategy is to:
1. Record a body weight at every veterinary visit.
2. Calculate the percent weight change to iden-tify
trends. This is a valuable tool for detecting
weight change patterns and, in my experience,
helpful in identifying cats with early chronic
illness, including pancreatitis, cholangitis, and
bowel malabsorptive conditions (eg, inflam-matory
bowel disease, intestinal lymphoma,
adenocarcinoma). Likewise, a percentage
weight change that is increasing gradually
helps to identify cats at risk for obesity.
% Weight change = (Current weight – Previous weight)
Previous weight
3. Assess the BCS at every visit, categorizing the
individual’s shape as emaciated, thin, ideal,
heavy, or grossly obese on a scale of 1 to 9 (see
page 5) or 1 to 5. For a cat in ideal condition,
the bony prominences of the body (ie, pelvis,
ribs) can be readily palpated but not seen or
felt above the skin surfaces. There should be
insufficient intraabdominal fat to obscure or
interfere with abdominal palpation.
4. Assess muscle condition using a muscle score
to help define whether weight is adequately
proportioned to lean versus fat.
5. In questionable cases, use radiography and ultra-sonography
to assess falciform fat deposits, par-alumbar
fat, and perirenal fat. In research
settings, dual energy x-ray absorptiometry
(DEXA) evaluation is used for the most accurate
bone density, muscle mass, and fat calculations.
What to Feed
It is not enough to simply feed less of a normal
diet. Not only will the patient be unhappy and
feel hungry, but all nutrient quantities will be de-creased,
not just the calories. A diet should be bal-anced
according to energy content. When cats eat
enough of the diet to meet energy requirements,
then their protein, vitamin, and mineral needs will
be met as well.
In cats, exceeding protein needs beyond mainte-nance
requirements helps to induce satiety. When
they were fed a diet with 45% of calories from pro-tein,
cats lost more fat and less lean mass compared
with cats fed a diet with 35% of calories from pro-tein,
despite similar total weight loss and rate of
weight loss.14
There are a number of approaches to feline
weight loss:
1. High protein protects (minimizes loss of ) lean
mass, stimulates cellular energy metabolism and
protein turnover, and may enhance satiety.
2. High moisture can reduce caloric density,
which promotes short-term weight loss: It
takes a few weeks to a few months for cats to
adapt to the lower-caloric density (as fed) in
canned foods versus dry foods; however, this
only works for some cats.
3. High fiber can reduce caloric density and induce
satiety. Some cats will self-restrict calorie intake
when fed a dry, high-fiber, low-calorie diet.
4. Low fat will reduce caloric density. High-fat
diets are a risk factor for inducing obesity and
are generally not considered optimum for a
weight loss diet. That said, some cats will lose
weight on a high-protein, high-fat, low-car-bohydrate
diet.
Ultimately, it is the calories ingested versus ex-pended
that is required for loss of weight. Given
the benefits of achieving lean body mass using
the first approach, a goal of at least 40% protein,
dry basis, in a low-fat diet (6% to 10% fat) or
more protein in a higher-fat diet (12% to 16%
fat) is a healthy approach to take.
The energy requirement for an individual is
made up of several components: daily energy re-quirement
(DER*), resting energy requirement
(RER), exercise energy requirement (EER), thermic
effect of food (TEF), and adaptive thermogenesis
(AT): DER = RER + EER + TEF + AT. Because
the RER varies among individuals, a manufacturer’s
recommendations may be too high for a given cat.
A goal of at least
40% protein, dry
basis, in a low-fat
diet (6% to 10%
fat) or more
protein in a
higher-fat diet
(12% to 16% fat)
is a healthy
approach to take.
*Unlike metabolizable energy requirement (MER), DER includes
energy required for activity, such as work, gestation, and growth, as
well as energy needed for maintaining normal body temperature.

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