Feline Hepatic Disease: Dennis Zawie, D.V.M., and Michaels. Garvey

Symposium on Advances in Feline Medicine II
Feline Hepatic Disease
Dennis A. Zawie, D.V.M.,* and MichaelS. Garvey, D.V.M.t
The liver has long been an enigma, frustrating the physician as well as
the veterinarian. Diagnosis and treatment ofliver diseases are made difficult
by the complexity of hepatic function and the lack of early demonstrative
signs of hepatic dysfunction. The liver has a tremendous reserve capacity
that often compensates for hepatic tissue destruction until extensive damage
has occurred. At the time of presentation, then, the patient is often seriously
ill.
Feline hepatic disease has historically been a particularly difficult area
of internal medicine, owing to a lack of knowledge of the inner workings of
the feline liver. Fortunately, this is changing. Certain key differences
between the canine and feline liver have been identified, and recent clinical
and histopathologic studies have added significantly to our understanding
of feline hepatic disease.
HEPATIC ANATOMY
Feline hepatic anatomy differs only slightly from the dog. The major
pancreatic duct in the cat joins the common bile duct prior to its entry into
the duodenum. 29 • 38 • 49 • 55 Because of this anatomic relationship between the
pancreatic duct and common bile duct, pathology in the liver and biliary
tree is sometimes associated with pathology in the pancreas. 37
As in the dog, the hepatic blood supply comes from both the portal
vein and hepatic artery. Branches of these vessels appear at the periphery
of hepatic lobules, and together with a bile ductule form a portal triad.
Blood entering the hepatic sinusoids flows along the luminal boundary of
the hepatocytes toward the central veins, which, in turn, collect blood for
return to the heart. Two thirds of the hepatic blood supply is from the
From the Animal Medical Center, New York, New York
*Diplomate, American College of Veterinary Internal Medicine; Staff Internist and Head,
Gastroenterology Service
7 Diplomate, American College of Veterinary Internal Medicine; Staff Internist and Chairman,
Departments of Medicine and Surgery
\'eterinary Clinics of North America: Small Animal Practice-Val. 14, No. 6, November 1984 1201
1202 DENNIS A. ZAWIE AND MICHAELS. GARVEY
partially deoxygenated blood of the portal vein and one third from the
oxygenated blood of the hepatic artery. Hepatocytes near central veins are
particularly susceptible to hypoxia because they are farthest away from the
nourishment of the portal triad blood supply. Anemia and congestive heart
failure are two common causes of hypoxia that damage hepatocytes near
central veins, ultimately causing centrilobular necrosis.
Hepatocytes secrete bile into small intercellular channels called bile
canaliculi. Bile flows in the opposite direction of hepatic blood through
these canaliculi and bile ductules to the gallbladder. In response to
cholecystokinin, the gallbladder contracts, forcing stored bile through the
common bile duct into the small intestine.
METABOLIC FUNCTIONS OF THE LIVER
The metabolic functions of the liver are the most diverse and complex
of any organ in the body. The clinical signs and biochemical alterations
seen in hepatic disease reflect a loss of these functions.
The liver plays an integral role in protein, fat, carbohydrate, vitamin,
and mineral metabolism. It manufactures and excretes bile necessary for
proper fat absorption, synthesizes plasma proteins necessary for normal
blood coagulation, and detoxifies and excretes many endogenous and
exogenous substances.
It has been documented that feline liver metabolism differs from that
of other species in two ways: (1) there is a relative deficiency of glucuronyl
transferase, which affects this species' ability to metabolize many drugs 4
(refer. to the article "Idiosyncracies of Drug Metabolism in Cats" for a full
discussion of this subject) and (2) there is an inability to synthesize the
amino acid arginine, an integral part of the Krebs ornithine (urea) cycle,
which converts ammonia to urea. 9 · 43 • 46 These two differences may play an
important role in the pathogenesis of certain feline liver diseases.
BILIRUBIN METABOLISM
Bilirubin is derived primarily from the metabolism of hemoglobin.

Normal bilirubin metabolism depends on (I) delivery to the liver, (2) uptake
by the hepatocyte, (3) storage in the hepatocyte, (4) conjugation with
glucuronic acid, and (5) excretion in bile.
Unconjugated bilirubin (indirect bilirubin), which is fat soluble, is
bound to plasma albumin and transported to hepatocytes. At the hepatocyte
cell membrane, albumin is detached, and unconjugated bilirubin is trans-
ported to the smooth endoplasmic reticulum by Y (ligandin) and Z binding
proteins. 69 Here, conjugation with glucuronic acid occurs, forming water-
soluble bilirubin glucuronide (direct bilirubin), which is then excreted into
the biliary tree. It should be emphasized that excretion is the slowest and,
therefore, the rate-limiting step in bilirubin metabolism. Once in the small
intestine, bilirubin is transformed into urobilinogen. The majority of uro-
bilinogen is oxidized to urobilin (stercobilin), which gives feces its charac-
FELINE HEPATIC DISEASE 1203
teristic color. The remainder is reabsorbed, circulated, and again excreted
in bile. A small amount of reabsorbed urobilinogen is excreted in urine as
urinary urobilinogen.
JAUNDICE
Jaundice is classified as prehepatic, hepatic, and posthepatic. 26 Prehe-

patic jaundice occurs in hemolytic anemia when an increased bilirubin load
overwhelms the hepatic uptake capability. Hepatic jaundice results from
hepatocellular dysfunction or intrahepatic cholestasis. Posthepatic jaundice
is produced by obstruction of the biliary tract after it leaves the liver.
Conjugated bilirubin is not bound to albumin; thus, it can readily
enter tissues. It has a particular affinity for tissues high in elastic fibers,
such as skin and sclera. Observable tissue staining occurs with lower levels
of conjugated, rather than unconjugated, bilirubin. 26
CLINICAL SIGNS
The clinical signs of feline liver disease vary depending on the specific
disease and extent of liver pathology. The most common clinical sign is
partial or complete anorexia. Occasionally, anorexia will be the only clinical
or historical abnormality noted. Vomiting, diarrhea, polyuria, polydipsia,
fever, weight loss, depression, and seizures may occur. These signs are
nonspecific and may be seen in a variety of feline diseases. Occasionally,
an astute owner will observe jaundice.
PHYSICAL EXAMINATION
Cachexia, dehydration, jaundice, and other signs of metabolic illness

are often found in cats with liver disease. Mild jaundice is most easily
observed in the sclera, soft palate, or under the tongue. Careful abdominal
palpation may reveal a mass or ballotable fluid. Hepatomegaly is a charac-
teristic finding; in fact, small livers are rarely seen in feline hepatic disease,
in contrast with other species. Liver size has little diagnostic or prognostic
importance in the cat. Anterior uveitis and chorioretinitis may be associated
\\ith jaundice and liver pathology in systemic infections (FeLV, FIP,
toxoplasmosis).
LABORATORY EVALUATION OF FELINE LIVER DISEASE
Biochemical testing is essential for proper evaluation of feline liver

disease. It is important to realize that no single biochemical test will
determine the functional state of the liver.
Table 1. Distribution of 100 Cats with Abnormal Serum LDH Levels

Renal disease 21
Cardiac disease 16
Liver disease (including diabetic hepatic lipidosis) 14
Pulmonary disease 11
Trauma 10
Gastrointestinal disease 10
Anemia 5
Others 13
From case records of The Animal Medical Center compiled during an 18-month period,
1976-1977. (From Twedt, D. C., and Gilbertson, S. R.: Data presented during feline medicine
seminar. In Proceedings of the American Animal Hospital Association, Boston, 1977.)
Liver Enzymes
Alanine Aminotransferase (ALT). ALT (formerly SGPT) is liver-specific
in cats. It is considered a leakage enzyme because hepatocyte plasma
membrane permeability must be altered for ALT to rise in the serum.
Factors increasing membrane permeability include necrosis, hepatotoxins,
hypoxia, inflammation, and fatty infiltration. 15 The half-life of ALT is short
(approximately 2 hours in the dog). 26 Continued elevation of ALT activity
represents continued leakage from damaged hepatocytes but is not an
accurate measurement of the potential reversibility of the hepatic injury.
Aspartate Aminotransferase (AST). AST. (formerly SGOT) is also a
leakage enzyme. The enzyme is present primarily in liver and muscle.
Although AST activity may increase in liver disease, its presence in tissues
other than liver makes its elevation less specific for hepatocellular disease
than ALT elevation.
Lactate Dehydrogenase (LDH). Because of the presence of this enzyme
in many body tissues, it is not a specific indicator of liver disease (Table
1). 15 Isoenzymes of LDH can be measured, but this is costly, time
consuming, and offers no more information regarding liver disease than
already obtained by ALT determination.
Serum Alkaline Phosphatase (SAP). SAP is produced in bone, liver,
kidney, uterus, and intestine.' Although this enzyme may be elevated in a
variety of feline diseases (Table 2), higher elevations are more consistent
with liver disease. Hepatic SAP is a microsomal enzyme produced by bile
ductular epithelium when stasis occurs within the biliary tree. Any disease
process decreasing bile flow (cholestasis), either intrahepatic or extrahepatic,
will induce elevations of hepatic SAP.
The half-life of SAP is considerably shorter in the cat (6 hours) than
the dog (72 hours). 30• 31 In addition, feline hepatic tissue contains only one
third the concentration of SAP per gram when compared to canine hepatic
tissue. 26 As a result, elevations of SAP in cats will be more moderate and
occur later in liver disease than in the dog, given the same degree of
cholestasis. Mild elevations of SAP (two to three times normal) should be
considered very significant when evaluating feline liver disease.
Gamma Glutamyl Transpeptidase (GGT). GGT is found in the renal
cortex, intestinal mucosa, pancreas, and liver. 66 This enzyme has been
shown to increase in experimentally induced liver disease in cats and
Table 2. Distribution of 50 Cats with Abnormal Serum

Alkaline Phosphatase (SAP) Levels
Liver disease 20
Hepatic lipidosis (idiopathic and diabetic) (7)
Cholangiohepatitis (4)
Hepatic neoplasia (1)
Other hepatobiliary disease (8)
Renal disease 11
Feline infectious peritonitis 3
Lymphosarcoma 3
Trauma 3
Hemolytic anemia 2
Other 4
appears to be a reliable indicator of cholestasis. The sensitivity of GGT is

similar to that of SAP in cats. 66 At the present time, there does not appear
to be any advantage in using GGT over SAP in the evaluation of cholestatic
liver disease.
ALT and SAP are useful indicators offeline liver disease. Even though
ALT activity increases from disruption of hepatocyte membrane integrity
and SAP elevates from cholestasis, it is rare to have one enzyme elevated
without the other. Although patterns in enzyme elevation can be suggestive
of certain types of liver disease, a specific diagnosis can never be made
from enzymatic determinations alone. It is important to establish trends in
these enzymes to monitor progress. High elevations that quickly return to
normal are less significant than moderate elevations that persist for a longer
period.
Bile Pigments
Serum Bilirubin. Biochemical testing is often necessary to establish
elevations of total serum bilirubin when the concentration is less than 3 mg
per dl.33 • 69 We refer to 'these elevations as biochemical jaundice. Although
cats with liver disease may have biochemical jaundice, this abnormality is
not specific for primary liver disease and may occur in many feline diseases
(Table 3). This probably represents mild hepatic involvement associated
with the underlying disease process due to anorexia, toxins, or infection.
U nconjugated hyperbilirubinemia may occur during fasting. 69 Although
it has not been documented in the cat, fasting hyperbilirubinemia may be
a cause of biochemical jaundice associated with any disease causing anorexia.
An adequate caloric intake is necessary for normal glucuronyl transferase
activity and for normal concentrations of Y and Z binding proteins so that
bilirubin metabolism may proceed normally. Theoretically, because of low
levels of glucuronyl transferase and severe protein catabolism secondary to
anorexia, cats would appear to be particularly susceptible to fasting hyper-
bilirubinemia.
When total serum bilirubin is greater than 3 mg per dl, jaundice can
Table 3. Distribution of 67 Cats with Serum Total Bilirubin Levels

between 1.0 and 3.0 mg per dl
BIOCHEMICAL JAUNDICE
Renal disease 14
Infectious panleukopenia 9
Liver disease (including diabetic hepatic lipidosis) 7
Lymphosarcoma 7
Trauma 7
Feline infectious peritonitis 5
Pyometra 5
Others 5
be detected clinically. 33 There is a high correlation between clinical jaundice

and primary feline hepatic disease (Table 4).
The Vandenbergh test is designed to help differentiate between
hemolytic, hepatocellular, and obstructive jaundice. The test measures the
concentrations of conjugated and total bilirubin. The difference between
the two is the unconjugated bilirubin. The test has limited application for
several reasons: (1) it is rarely necessary to use the test to confirm
hemolysis; 69 (2) at low concentrations the test is inaccurate; 15• 69 and (3) most
liver diseases are not purely obstructive or hepatocellular, but rather a
combination of the two. As a result, interpretation of the test may be
difficult ..
Urine Bilirubin. Conjugated bilirubin may appear in the urine of
normal dogs. Its presence in the urine becomes less important as the
specific gravity increases. The cat has a renal threshold for bilirubin that is
nine times higher than that of the dog. 25 Because of this, any bilirubin in
Table 4. Distribution of 76 Cats with Serum Total Bilirubin Levels

Greater than 3.0 mg per dl
CLINICAL JAUNDICE
Liver disease 52
Hepatic lipidosis (idiopathic and diabetic) 18
Cholangiohepatitis 14
Toxic hepatopathy lO
Biliary obstruction 4
Hepatic neoplasia 4
Other hepatopathy 2
Feline infectious peritonitis ll
Hemolytic anemia 5
Lymphosarcoma 3
Infectious panleukopenia 2
Trauma 2
Pancreatitis 1
the urine of cats should be considered abnormal regardless of the specific
gravity.
Urine Urobilinogen. Urine urobilinogen may increase in hemolytic and
hepatocellular disease. The presence of urobilinogen in the urine suggests
some patency of the bile duct. The absence of urobilinogen in the urine
suggests complete biliary obstruction. Unfortunately, urine urobilinogen
determination is subject to many factors. False negative results may occur
with antibiotic therapy because a reduction in intestinal flora results in
decreased urobilinogen production, and the rapid intestinal transit seen in
diarrhea may interfere with intestinal reabsorption of urobilinogen. 59 Neg-
ative results can also occur if the urine is dilute or exposed to sunlight. 69
Plasuna Proteins
Albumin. Albumin is synthesized only in the liver. This function is
maintained until there is severe, diffuse liver daunage. In our experience,
hypoalbumineunia is uncounmon in cats with liver disease, but when it is
present, it indicates end-stage liver disease and a poor prognosis.
Globulin. Elevated serum globulin is often seen with chronic liver
disease. A failure in hepatic phagocytosis occurs, allowing antigens normally
cleared by the hepatic reticuloendothelial system to reach the systemic
circulation. 69 When this occurs, increased amounts of immunoglobulins are
produced, resulting in a polyclonal gamunopathy (both beta and gamma) on
serum protein electrophoresis. 69
Blood Glucose
Hypoglycemia. The liver plays an essential role in carbohydrate metab-
olisun. Hepatic glycogen storage and gluconeogenesis are important for the
maintenance of normal blood glucose. Hypoglycemia may result from
extensive liver disease, particularly if the patient is anorexic; however, in
our experience this is an uncomunon finding in cats.
Hyperglycemia. Cats with hyperglycemia due to diabetes mellitus may
present with clinical or biochemical jaundice secondary to hepatic lipidosis.
It must be remembered that cats in general are prone to stress hypergly-
cemia; cats with primary liver diseases are no exception. Repeated blood
glucose determination may be necessary to differentiate stress hypergly-
cemia from diabetes mellitus. Stress hyperglycemia rarely exceeds 300 mg
per dF 2 and usually resolves in 6 to 24 hours. 61
Heunatology
In many cases, the white blood cell count of cats with liver disease is
normal. Leukocytosis may result from stress or may be secondary to
suppuration or necrosis. 12
Normocytic, norunochromic nonregenerative anemia is a common find-
ing. 12 Decreased protein metabolism, decreased red blood cell survival,
and reduced erythropoiesis may all contribute to the anemia. Regenerative
anemia secondary to blood loss froun coagulation abnormalities 69 or gastroin-
testinal hemorrhage may be seen. 10
Coagulation Profile
The liver synthesizes the majority of plasma clotting factor proteins,
including factors I, II, V, VII, IX, and X. Factors II, VII, IX, and X are
vitamin K dependent. Because factors II and X are common to both the
intrinsic and extrinsic clotting mechanisms, both the prothrombin time (PT)
and partial thromboplastin time (PTT) may be prolonged in liver disease.
Factor VII has the shortest half-life, so the PT usually becomes prolonged
prior to the PTT.
Vitamin K is fat-soluble and requires the presence of bile in the small
intestine for proper absorption. In complete biliary obstruction, vitamin K
will not be absorbed. In this instance, the PT and PTT will return to
normal with the parenteral administration of Vitamin K. In severe hepato-
cellular disease, the PT and PTT will not be corrected by parenteral vitamin
administration, because the liver is incapable of synthesizing clotting
proteins.
Disseminated intravascular coagulation (DIC) may result from exten-
sive liver injury due to the release of large amounts of tissue thromboplas-
tin. 69 The prognosis is obviously poor if DIC is present with hepatic disease.
Sulfobromophthalein and Indocyanine Green
Sulfobromophthalein (BSP) and indocyanine green (ICC) retention are
true tests of hepatic function. Each dye must be transported to the liver,
removed from the blood by hepatocytes, conjugated in hepatocytes, and
excreted in bile. BSP retention is determined by collecting a blood sample
30 minutes after intravenous injection of 5 mg BSP per kg of body weight.
Current information suggests that BSP is cleared rapidly in the cat. 11 Most
clinically normal cats retain less than or equal to 2 per cent BSP after 30
minutes. 11 Consequently, as opposed to the dog, we consider BSP retention
greater than 2 per cent to be suggestive of abnormal liver function or
reduced hepatic blood flow. ICC retention is determined by collecting a
blood sample 30 minutes after intravenous injection of 1.5 mg ICC per kg
of body weight. Because of the slightly longer half-life, slower disappearance
rate, and higher 30-minute retention, the ICC retention test may become
the preferred diagnostic test in the cat. 11
BSP and ICC clearance from the blood depends on normal hepatic
blood flow. Therefore, diseases interfering with normal circulation, such as
heart failure and shock, will falsely elevate retention. Also, these tests will
always be abnormal in jaundiced patients. 69
Bile Acids
Elevated bile acid values are a sensitive indicator of hepatic disease in
man. Although bile acid determination is not routinely used in cats,
investigators currently studying bile acid values suggest that this test may
become an important diagnostic aid in evaluating feline cholestatic liver
disease. 10
Blood Ammonia
Resting blood ammonia levels may be elevated in severe, acquired
liver diseases, such as biliary cirrhosis and hepatic lipidosis, or in congenital
portacaval anomalies.
Anorexia, which results in arginine deficiency, may reduce the func-

tional rate of the Krebs ornithine (urea) cycle. 46 This, in combination with
progressive hepatic dysfunction may result in hyperammonemia. It has
been demonstrated experimentally that arginine deficiency in cats can lead
to hepatic encephalopathy. 46 It should be noted that resting blood ammonia
levels do not always correlate with clinical signs of hepatic encephalopathy,
because muscle tissue can take up almost 50 per cent of the circulating
ammonia. 77
The ammonia tolerance test can be a useful indicator of liver function,
especially with end-stage liver disease and congenital portacaval anoma-
lies. 40 • 69 • 75 Blood ammonia levels are determined prior to the oral admin-
istration of 100 mg per kg NH 4Cl and 30 minutes thereafter. 15 The normal
liver has a tremendous capacity to handle ammonia and little elevation is
expected after 30 minutes. This test should not be performed if the animal
is extremely ill or if resting hyperammonemia is already present, because
hepatic coma or death can result.
LIVER BIOPSY
The importance of a liver biopsy cannot be overemphasized. It is the

single most informative test that can be performed for evaluation of feline
liver disease. A biopsy often allows a specific diagnosis to be made, provides
information on the current state of the liver, helps establish a prognosis,
and may suggest a course of therapy. There are three commonly used
biopsy techniques: (I) percutaneous needle biopsy, (2) laparoscopy and (3)
surgical laparotomy.
Percutaneous needle biopsy techniques using Tru-Cut or Menghini
needles have recently been reviewed. 27 This technique requires only .mild
sedation and has the added advantages of being quick and inexpensive.
The procedure is technically simple when there is hepatomegaly, and
representative tissue samples are obtained with diffuse lesions, both of
which are characteristic of many feline liver diseases. Because this is a
blind biopsy technique, foca1 hepatic lesions may be missed, postbiopsy
bleeding cannot be evaluated, and other organs may be perforated or
biopsied. The complications of this technique are directly related to the
inexperience of the person performing the biopsy. 27
In our hospital, laparoscopy is routinely used. This technique allows
direct visualization of the liver, so specific areas can be biopsied. Addition-
ally, diagnostic tissue samples are readily obtained, and accurate observa-
tions and interpretation of gross changes in the liver can be made. However,
this procedure is more time-consuming, usually requires general anesthesia,
and utilizes expensive equipment.
Surgical laparotomy is the most consistently accurate means of evalu-
ating the feline liver and biliary tract. Furthermore, it gives the most
consistently diagnostic tissue samples. Laparotomy is the only method
whereby extrahepatic obstructive lesions can be evaluated and corrected.
Because this procedure is the most invasive and requires prolonged
anesthesia, it may pose considerable risk to debilitated cats.
Despite the fact that a diagnosis can be obtained from a liver biopsy,
the decision to biopsy should always be weighed against the potential risk
to the patient. Selection of the biopsy technique is based on previous
medical work-up (radiographs, trends in biochemical alterations), clinical
evaluation, and economic considerations.
A coagulation profile should be performed prior to a liver biopsy. If
general anesthesia is necessary to obtain a liver biopsy in cats, 10 to 30 mg
of ketamine given intravenously, followed by intubation and halothane
anesthesia, is a relatively safe anesthetic regimen.
CLINICAL FELINE HEPATIC DISEASE
The feline liver is secondarily affected by a number of infectious and

metabolic diseases. Hepatic involvement is common in feline infectious
peritonitis (FIP), multicentric lymphosarcoma, myeloproliferative diseases,
and hemolytic disorders. Even though they are often associated with
jaundice (see Tables 3 and 4), these conditions will not be discussed in this
article, because they more appropriately fall within the scope of other
articles in this symposium. We will concentrate on primary hepatic diseases
of the cat.
HEPATIC LIPIDOSIS
Hepatic lipidosis (fatty liver) is a common cause of feline liver

diseas.e 10• 12· 33• 71 and is the most frequently diagnosed hepatopathy in our
feline patients. Diabetes mellitus is a well-documented cause of hepatic
lipidosis in the cat, as well as in other species. 2 • 8 • 18 • 26 • 35-3 7, 61 • 62 • 65 • 71 A large
number of cats with hepatic lipidosis, however, do not have the hypergly-
cemia, glycosuria, and ketoacidosis usually associated with diabetes melli-
tus. 6 • 9 • 12• 33 • 72 • 73 The fatty liver in these cats is often called idiopathic hepatic
lipidosis.
Diabetes mellitus most frequently occurs in middle-aged and old cats
(range of 2 to 15 years), with no reported breed or sex predilection. 52 Cats
with diabetic hepatic lipidosis have signs consistent with the primary
disorder. In the early stages of diabetes mellitus, these signs include
polydipsia, polyuria, polyphagia, weight loss, hepatomegaly, and possibly
jaundice. 45· 61 · 62 A rapid progression to anorexia, vomiting, dehydration, and
mental depression, varying from lethargy to coma, is seen when severe
ketoacidosis or hyperosmolarity occurs. 61 • 62 This disease is usually easy to
diagnose with routine laboratory testing.
Several reports in the literature describe idiopathic hepatic lipidosis in
a total of 28 cats. 6 · 9 • 72 • 73 There is disagreement among the authors regarding
the typical signalment of these cats. Hepatic lipidosis is said to occur
primarily in young cats in one reporf3 and in old cats in another. 9 The
mean age of all 28 cats is 6.3 years (range of 9 weeks to 13 years), which is
younger than the mean age reported in cats with diabetes mellitus. 62 The
authors of one paper reported a higher incidence of this disease in females
Table 5. Pathogenesis of Hepatic Lipidosis

METABOLIC DEFECT ETIOLOGY
t FF A delivery Diabetes mellitus Glucagon

Starvation Catecholamines
Overnutrition Somatotropin
Obesity Glucocorticoids
Ketosis* Thyroxine
t Fatty acid oxidation Alcohol Bacterial toxins
~ Phospholipid synthesis Choline deficiencyt Methionine deficiencyt
t Triglyceride synthesis Alcohol
~ Apoprotein synthesis Protein deficiency Tetracycline
Diabetes mellitus Bacterial toxins
Carbon tetrachloride Jejunal bypass (bacterial toxins)
Phosphorus Hypoxia
t Apoprotein coupling Orotic acidt
t Lipoprotein release Orotic acidt Alcohol(?)
Unknown Pregnancy:j: Reye' s sydrome§
Data compiled from references 2, 14, 18, 26, 32, 36, 37, 54, 58, and 60.
*Ruminants
tExperimental
:j:Human, bovine, ovine
§Human
and a disproportionate occurrence in Siamese cats, 9 but these findings were

not supported elsewhere. 73 It has also been stated that all cats are obese
prior to the development of idiopathic hepatic lipidosis, 9 but this has been
disputed in other reports. 6 • 72
A possible explanation for the controversy concerning signalment is
that feline idiopathic hepatic lipidosis may not be one specific syndrome,
but a morphologic and functional change in the liver that can result from
multiple etiologies. Con'Sequently, there probably is no characteristic sig-
nalment, history or nutritional state. A number of toxic, metabolic, nutri-
tional, and endocrine disorders result in hepatic lipidosis in man and other
species (Table 5), and fatty liver has been produced experimentally in
laboratory animals with drugs, toxins, and dietary modifications. 18 It is
unlikely, therefore, that hepatic lipidosis has the same etiology in all
affected cats.
Prolonged anorexia, often of several weeks duration, is the most
common sign associated with feline idiopathic hepatic lipidosis. 6 · 9 • 73 It
appears that anorexia is the inciting cause of hepatic lipidosis in many cats,
but it may be a result of this liver disease in others. Other signs reported
in cats with fatty livers include severe weight loss, hepatomegaly, dehydra-
tion, jaundice, salivation, and severe depression of the central nervous
system, which may terminate in coma and death. 6 • 9 · 72 • 73
Nonregenerative, normocytic, normochromic anemia is commonly seen
in cats with hepatic lipidosis 6 • 9 • 12• 73 and stress leukocytosis can occur. 6 ALT
and SAP are frequently elevated, and, although there are exceptions, SAP
elevations are usually greater in this disease than in other feline liver
1212 DENNIS A. ZA WIE AND MICHAEL S. GARVEY
diseases. 9· 12 Total serum bilirubin is often elevated in cats with diabetic or

idiopathic hepatic lipidosis, but hyperbilirubinemia occurs more frequently
and is usually more severe with the idiopathic type. 12· 45 Liver biopsy is
necessary to differentiate idiopathic hepatic lipidosis from other feline liver
diseases, because biochemical testing alone is not diagnostic.
Histopathology of Hepatic Lipidosis
Hepatic lipidosis affects the entire liver, causing it to be yellow, greasy,
friable, and enlarged, often with rounded borders. Although the actual fat
is lost during tissue processing, 36 histopathologic examination reveals evi-
dence of a varying degree of lipid accumulation in hepatocytes, with little
or no inflammation present. All hepatocytes in a lobule are diffusely affected
in some specimens, whereas in others, hepatocyte involvement is primarily
periportal or centrilobular. 6 • 72 · 73 Mild to marked centrilobular necrosis can
be observed, 73 but, in our experience, is not a common finding.
Two distinct morphologic patterns of hepatocyte lipid accumulation
may be seen histopathologically. In one, individual hepatocytes contain one
large lipid vacuole that displaces the nucleus from the center of the
cell. 36· 37•71 In the other, the nucleus is not displaced and the intracellular
lipid is contained in many small vacuoles, giving the hepatocyte a foamy
appearance. 37• 71 Both the macrovacuolar type 6 and the microvacuolar
type 72 • 73 have been described in clinical reports of cats with hepatic lipidosis.
Although the significance of these different morphologic patterns has not
been determined and awaits further study in the cat, the same two patterns
are seen in human hepatic lipidosis and have diagnostic and prognostic
importance. Three disorders are associated with microvacuolar hepatic
lipidosis'in man: acute fatty liver of pregnancy, tetracycline-induced hepa-
topathy, and Reye's syndrome. In contrast to conditions causing macrova-
cuolar hepatic lipidosis (alcoholism, starvation, and malnutrition), thes~
three disorders are acute and fulminant, with a high incidence of hepatic
encephalopathy and a high mortality rate (greater than 70 per cent). 2• 32• 58• 67
Hepatic Encephalopathy
Many cats with hepatic lipidosis present with historical signs of
neurologic dysfunction and/or severe depression of the central nervous
system. 9 · 72 • 73 It is possible that these central nervous system signs represent
hepatic encephalopathy due to severe hepatic dysfunction secondary to
hepatic lipidosis. Elevated serum ammonia levels and abnormal ammonia
tolerance tests have been seen in these cats, 9 supporting a diagnosis of
hepatic encephalopathy.
The amino acid arginine is an important component of the hepatic urea
cycle (Krebs ornithine cycle), which transforms ammonia into urea for
excretion. Experimentally induced arginine deficiency produces hepatic
encephalopathy in cats, 9 • 46 presumably owing to decreased hepatic urea
cycle function. 13 Cats cannot synthesize arginine; 46 thus, they are dependent
on a dietary source. Because cats with severe hepatic lipidosis are anorexic,
arginine deficiency theoretically may occur. Arginine deficiency combined
with the hepatic dysfunction is a possible pathogenesis for the hepatic
encephalopathy seen in feline hepatic lipidosis.
Other possible factors contributing to hepatic encephalopathy in cats

with hepatic lipidosis are elevated fatty acid levels and thiamine deficiency.
Fatty acids have been incriminated in the pathogenesis of fatty liver
associated hepatic encephalopathy in man, particularly in Reye' s syn-
drome.13· 77 Due to enhanced peripheral lipolysis, many cats with hepatic
lipidosis would be expected to have elevated fatty acid levels. Thiamine
deficiency is a predisposing factor to hepatic coma in man/ 3 we have
observed clinically apparent thiamine deficiency in many sick, anorexic
cats.
Hepatic Lipid Metabolism
Understanding the pathogenesis of hepatic lipidosis requires some
knowledge of basic lipid physiology8 • 24· 65 and the central role that the liver
plays in fat metabolism. 2• 18 · 26· 36· 58· 71 Free fatty acids (FF A) are derived
from two major sources, diet and peripheral fat lipolysis, and are transported
to the liver in the serum. After uptake to hepatocytes, FF A are oxidized
for energy, utilized to form phospholipids or cholesterol, degraded to
ketone bodies, and esterified to triglycerides, which are stored in the
hepatocytes. Intracellular triglycerides are coupled with specific "lipid
acceptor" apoprotein molecules to form lipoproteins, which are then re-
leased from hepatocytes into the blood. Lipoproteins are transported to
adipose tissue where, under the influence of lipoprotein lipase, triglycerides
are detached from apoproteins and deposited in peripheral fat stores. The
level of lipoprotein lipase is dependent on insulin; 65 thus, in the absence of
insulin, triglycerides are not hydrolyzed and circulate back to the liver. 8
Lipolysis of peripheral fat stores is also regulated primarily by insulin.
Insulin levels have an inverse relationship to the level of the catalyzing
enzyme, hormone-sensitive lipase. 8 Consequently, in the presence of
insulin, hormone-sensitive lipase decreases and lipolysis is inhibited. When
insulin levels are low, as in diabetes mellitus or starvation, hormone-
sensitive lipase increases, lipolysis is favored, and FF A are transported to
the liver. 2· 62· 64· 65· 69 Other hormones, including glucagon, catecholamines,
somatotropin (growth hormone), glucocorticoids, and thyroxine, elevate the
level of hormone-sensitive npase. 8
Hepatic lipidosis is the result of defective lipid metabolism. In the
normal state, there is a balance between hepatic triglyceride formation and
release. When the balance is upset, triglyceride accumulates in hepatocytes,
producing a fatty liver. Because there are a number of steps in the normal
metabolism of fat, hepatic lipidosis may occur as the result of several
metabolic defects (see Table 5).
Possible Causes of Feline Hepatic Lipidosis
Except for diabetes mellitus, there is no proven etiology of feline
hepatic lipidosis. Based on what is known about fatty liver in man and
other species and what is understood about feline metabolism, there are
several reasonable, but theoretical, causes of idiopathic hepatic lipidosis in
the cat. It is unlikely that any one cause is responsible for the disease in
all affected cats.
Chronic Anorexia. During periods of decreased nutritional intake,
plasma insulin levels fall to maintain a normal blood glucose. Low insulin
levels promote lipolysis of peripheral fat stores, resulting in an increase in
FFA transport to the liver and hepatic triglyceride synthesis. Although
many animal species (bear and emperor penguin, for example) can exclu-
sively utilize peripheral fat stores for extended periods of time, the cat
must catabolize protein for some of its energy requirement. 43 Therefore,
chronic anorexia in cats results in rapid and severe muscle wasting. It is
possible that apoprotein synthesis in the liver decreases at some point,
impairing release of triglyceride from hepatocytes. It is also possible that
chronic anorexia in cats leads to the production of orotic acid, which causes
triglyceride accumulation in hepatocytes 9 (see Table 5).
It has been postulated that feline idiopathic hepatic lipidosis is a
specific syndrome that begins with chronic anorexia in an obese cat
secondary to stress. 9 Although this may explain the disease in some cats, it
does not apply to all. Not all affected cats are obese, and not all chronically
anorexic, obese cats develop clinically evident hepatic lipidosis.
Bacterial Toxins. Bacterial toxins produced in the intestinal tract may
cause hepatic lipidosis. 26• 69 In man, jejunal bypass surgery for obesity has
been documented as a cause of fatty liver. 32 It was thought that the fatty
liver developed secondary to malnutrition and rapid weight loss in an obese
person. It has been recently shown, however, that the hepatic lipidosis
results from toxins produced by an overgrowth of anaerobic bacteria in the
bypassed intestinal loop. 14 The fatty liver can be reversed or prevented by
controlling the bacteria with metronidazole. Although difficult to prove, it
is possible that some cats develop hepatic lipidosis secondary to an abnormal
production of bacterial toxins in the intestinal tract.
Other Toxins. For a long time, fatty liver secondary to chronic alcohol
ingestion in man was thought to be due to malnutrition. 60 It was subse-
quently determined that the hepatic abnormality was due to the toxic effect
of alcohol on hepatocytes. 54• 60 Numerous drugs, chemicals, and plant toxilis
cause hepatic lipidosis, 37 particularly if there is chronic exposure to small
amounts of toxin. With larger doses of toxin, hepatic necrosis is commonly
seen. 37• 39• 69 Significant hepatic necrosis was present in some cats with
hepatic lipidosis reported in the literature, 73 but a toxic etiology was not
proven.
Protein-Calorie Malnutrition. Consumption of a disproportionately low
amount of protein in relation to caloric need can lead to fatty liver in man. 2
This appears to be related to hepatocyte apoprotein levels. Because cats
have a high dietary protein requirement, they may be particularly suscep-
tible to protein-calorie malnutrition. One cat with hepatic lipidosis was fed
a diet of dry dog food, 6 which contains far less protein than the cat' s
maintenance requirement. It is possible that this diet contributed to the
development of hepatic lipidosis.
Endocrine Disorders. Because diabetes mellitus is a known cause of
hepatic lipidosis and insulin is essential for proper lipid metabolism, it is
difficult to ignore insulin deficiency as a potential cause of hepatic lipidosis,
even in those cats without profound hyperglycemia. We commonly see
prolonged, mild fasting hyperglycemia and abnormal glucose tolerance in
cats with hepatic lipidosis. These findings have also been reported by other
authors. 9 Because the hyperglycemia is prolonged, it is unlikely to be
stress-related. 61 An absolute or relative insulin deficiency is a possible cause
for the fasting hyperglycemia and abnormal glucose tolerance and could
also lead to hepatic lipidosis secondary to increased peripheral lipolysis.
Peripheral insulin resistance, which produces a relative deficiency of
this hormone, is common in humans with excessive adipose tissue 8 • 64 and
possibly occurs in obese cats. This hypothesis is supported by one study in
which normal to elevated serum insulin levels were noted in obese cats
with hepatic lipidosis. 9 These cats also had mild fasting hyperglycemia and
abnormal tolerance to an exogenous glucose load, presumably due to
peripheral insulin resistance.
We have performed intravenous glucose tolerance tests on several cats
!obese and nonobese) with hepatic lipidosis. Typically, they develop pro-
found hyperglycemia, which does not resolve for several hours. Simulta-
neous serum insulin determinations in a few cats revealed no change from
the baseline level in response to the induced hyperglycemia. This suggests
absolute insulin deficiency, rather than insulin resistance, as the cause of
the glucose intolerance.
If an absolute insulin deficiency is a cause of feline hepatic lipidosis,
serum glucagon would also be lower than normal or the cats would have
typical diabetes mellitus. It is known that profound hyperglycemia and
ketoacidosis, which are normally associated with diabetes mellitus, are
dependent on both glucagon excess and insulin deficiency. 56• 57• 62 • 64 · 65 In
contrast, experimental suppression of both insulin and glucagon in man and
in dogs causes only mild hyperglycemia and no hyperketonemia, even
when insulin levels are very low. 5 6 • s7 Abnormal tolerance to exogenous
glucose loading continues even though both hormones are suppressed,
because the test depends entirely on insulin. 57 It is probable that increased
FFA transport to the liver will also be present, because peripheral lipolysis
is more dependent on decreased insulin than on increased glucagon. 56
Possibly, then, hepatic lipidosis could occur as a result of an absolute
deficiency of both insulin and glucagon. This would explain the mild fasting
hyperglycemia, abnormal glucose tol~rance without a simultaneous rise in
serum insulin, and increased peripheral lipolysis. Interestingly, a very
similar disease syndrome in man is produced by tumors secreting somato-
statin, a hormone that suppresses both insulin and glucagon. s7 Although
somatostatin is known to exist in cats, 57 any suggestion that it is involved
in the pathogenesis of feline hepatic lipidosis is speculative.
Treatment of Feline Hepatic Lipidosis
Hepatic lipidosis occurring in nondiabetic cats has a guarded to poor
prognosis. Because the etiology is usually unknown, treatment is generally
supportive. We are successful in treating between 10 and 20 per cent of
cats with this disease. It is our experience, however, that when therapy is
successful, hepatic lipidosis does not recur.
Initial therapy is directed toward rehydration of the cat with intrave-
nous fluids. Once the cat is hydrated, multiple B vitamins and glucose (2.5
to 5.0 per cent) are added to the fluids. Supportive care is continued during
hospitalization for medical work-up and liver biopsy. After the diagnosis
1216 DENNIS A. ZAWIE AND MICHAEL 5. GARVEY
has been established, frequent force-feeding is instituted with canned cat

food or baby food. A pharyngostomy or gastrostomy tube may be used if
the cat is unable to be force-fed.
Occasionally, a cat with hepatic lipidosis will begin eating on its own
after several days of supportive therapy. Most often, however, anorexia
persists to the time of release from the hospital, requiring continued force-
feeding by the owner at home. A cooperative, dedicated cat owner is a
prerequisite to successful treatment of this disease, because home nursing
care may be required for several weeks. Anabolic steroids and a multiple
vitamin supplement are often prescribed during this period. A persistent
owner will sometimes be rewarded by a return of the cat' s appetite, usually
heralding resolution of the problem. Many owners, however, become
discouraged and elect euthanasia.
We have treated several cats that had abnormal glucose tolerance and
documented insulin deficiency with low doses of insulin (V4 to 1 unit, NPH
insulin daily). If a cat is anorexic, we use an intravenous glucose drip (5.0
to 10.0 per cent) to avoid hypoglycemia. Some cats have responded well to
this treatment, evidenced by a rapid return of appetite and resolution of
hepatic lipidosis after several weeks to several months of therapy. Repeat
glucose tolerance tests on a few cats were normal after insulin treatment,
and serum insulin levels rose normally compared to the baseline sample.
We have received similar anecdotal reports from other veterinarians, but
it is clear that many cats with hepatic lipidosis do not respond to insulin
therapy.
Lipotrophic compounds containing methionine and choline are not
recommended for use in this disease. They are only effective in resolving
hepatic lipidosis caused by a dietary deficiency of these substances, which
has only been produced experimentally. In addition, excess methionine
favors the development of hepatic encephalopathy. 12• 26• 67 • 77
If hepatic encephalopathy is evident at the time of hospitalization,
warm saline enemas can be used to remove colonic ammonia and other
toxins and to reduce the number of ammonia-producing colonic bacteria.
Lactulose, * a nonabsorbable disaccharide fermented by bacteria, can be
used to minimize further ammonia absorption from the colon. During
bacterial fermentation, acid is released, thereby lowering the colon pH and
reducing ammonia absorption. 3 • 13 • 23 • 67 Initially, lactulose may be adminis-
tered rectally (5 to 10 ml); thereafter it may be administered orally (1 ml
per 10 pounds, three times a day).
A low protein diet is usually recommended for individuals with hepatic
encephalopathy. However, an ample supply of dietary protein for apopro-
tein synthesis and arginine for urea cycle function may be more important
than protein restriction in resolving hepatic encephalopathy in cats with
hepatic lipidosis.
CHOLANGIOHEPATITIS COMPLEX
The second most common liver disease affecting cats in our hospital is
cholangiohepatitis complex. Included in this complex are a number of
*Cephulac. Merrell-Dow, Cincinnati, Ohio.

related inflammatory disorders of the hepatobiliary system, or possibly a

number of stages in the progression of a single disease. There are several
reports in the literature describing inflammatory hepatobiliary disease in
cats. 16· 29 • 38• 47 • 49• 55• 69 · 72 and documenting its frequent occurrence. 12• 33 De-
spite this, there is very little known about the etiology or natural progression
of feline cholangiohepatitis.
Cats with cholangiohepatitis present with a variety of nonspecific signs:
anorexia, depression, fever, weight loss, vomiting, dehydration, hepato-
megaly, and jaundice. Elevations of serum total bilirubin, ALT, and SAP
are typically seen, particularly in the later stages of disease. Generally, the
total serum bilirubin and ALT are higher in cats with cholangiohepatitis
than in cats with other liver diseases, 12 although this cannot be relied on in
any individual case. Only liver biopsy can distinguish this disease from
hepatic lipidosis and other feline hepatopathies.
Ascending bacterial infection of the biliary tree, with eventual hepatic
parenchymal involvement, has been postulated as the initiating cause of
cholangiohepatitis. 12• 29 • 37 Bacteria, usually E. coli, 12• 29 have been cultured
from the bile of affected cats, but it is possible that bacterial invasion of
the biliary system occurs secondary to cholestasis. A frequent coincidence
of cholangiohepatitis and pancreatic disease has been noted, 29 • 37 · 38• 49 • 55 • 69
possibly due to the anatomic association of the common bile duct and
pancreatic duct. We see a high incidence of cholecystitis and duodenitis,
as well as pancreatitis, in cats with cholangiohepatitis. It is unknown
whether the disease begins in the biliary tree, the pancreas, or a common
source such as the small intestine. What effect, if any, reflux of pancreatic
secretions into the bile duct or bile into the pancreatic duct has on the
disease process is also unknown.
We commonly see biopsy specimens of cats with inflammatory hepa-
tobiliary disease, including many that are similar to those reported in the
literature. Although different terminology is used in individual reports to
classifY and describe the diseases, 16• 29 • 55• 72 it is obvious that they share
many common features. Based on our observation, we feel that these
different histopathologic diagno~es represent stages in the progression of
one disease, which we refer to as cholangiohepatitis. It appears that acute
suppurative inflammation begins in the biliary system, extends into hepatic
lobules, becomes chronic and progressive, and culminates in end-stage
liver disease.
Cholangiohepatitis may be separated clinically into three progressive
stages based on liver biopsy histopathology: (1) suppurative cholangi-
tis/cholangiohepatitis, (2) chronic, nonsuppurative cholangiohepatitis, and
(3) biliary cirrhosis. Although these divisions are convenient from a clinical
and therapeutic standpoint, it must be emphasized that they are largely
arbitrary from a histopathologic point of view. Therefore, the clinician must
communicate with his or her pathologist. The terminology is not important
as long as information is gained regarding the extent of hepatic parenchymal
involvement, the presence or absence of suppuration, and the potential for
reversibility of the lesions.
Suppurative Cholangitis/Cholangiohepatitis
A diagnosis of suppurative cholangitis describes suppurative inflam-
mation confined to the biliary tree without hepatic lobular invasion. The
most prominent histopathologic feature of this stage is the presence of
many polymorphonuclear (PMN) cells in portal triads, mainly around bile
ductules. Even though we believe suppurative cholangitis to be the
beginning of the cholangiohepatitis complex, we rarely see liver biopsy
specimens of cats at this stage. Prior to hepatocyte involvement, most cats
are asymptomatic, precluding hepatic biopsy. When suppurative cholangitis
is identified, however, the same treatment used for suppurative cholan-
giohepatitis is recommended.
Cats with suppurative cholangiohepatitis are usually clinically ill. Early
signs may include fever, anorexia, depression, and vomiting, but there may
be no obvious indication of liver involvement. Leukocytosis is usually the
only hematologic abnormality, 12 • 29 and jaundice may not be present early
in the disease. Some cats probably recover from the acute signs without
treatment; others are treated for nonspecific illness, with or without
antibiotics, and may recover. If recovery from the acute illness does not
occur, the cat will eventually develop anorexia, dehydration, and jaundice.
The time period between the initial illness and the development of more
serious signs is quite variable. Cholangiohepatitis may exist in cats as a
subclinical illness for an extended period of time. 33
We commonly see liver biopsy specimens from cats at the stage of
suppurative cholangiohepatitis. Histopathology reveals a mixed inflamma-
tory cell infiltrate (predominantly PMN cells) around bile ductules and
variable invasion of hepatic lobular parenchyma with accompanying degen-
eration arid necrosis. Occasionally, "casts" of white blood cells in a matrix
of bile are observed in bile ductules. Early mild fibrosis and bile ductule
hyperplasia are also occasionally seen.
Intravenous fluid therapy with glucose (2.5 to 5.0 per cent) is recom-
mended for cats with suppurative cholangiohepatitis, because they are
usually anorexic and dehydrated. Often, multiple B vitamins are added to
the fluids to compensate for decrl:)ased intake and increased loss of these
water-soluble vitamins. Clinically apparent thiamine deficiency is not unu-
sual in our hospital among sick, anorexic cats receiving fluid therapy without
the added B vitamins. Hypokalemia may also occur in these cats/2 serum
potassium levels should be monitored, and potassium supplemented when
needed.
Parenteral vitamin K1 (5 mg intramuscularly, once to twice a day) may
be a necessary addition to supportive therapy if a coagulation profile is
abnormal. Cholestasis and decreased gallbladder contraction are inevitably
associated with this disease, and vitamin K absorption from the intestinal
tract is impaired in the presence of decreased duodenal bile flow. 10
Antibiotics are a crucial part of therapy, and the choice of antibiotics
is both important and controversial. The ideal antibiotic would be excreted
in bile in an active form and be active against intestinal coliforms. Commonly
used antibiotics, such as aminoglycosides, penicillins, trimethoprim/sulfa,
and first generation cephalosporins, are not excreted in bile in an active
form. This makes their use in cholangiohepatitis highly questionable.

Sufficient biliary excretion of active drug occurs with chloramphenicol,
tetracycline, and erythromycin, but these drugs also have disadvantages.
Erythromycin is ineffective against most gram-negative bacteria, and tet-
racycline can be hepatotoxic. Chloramphenicol may produce anorexia in
cats, which is an unwanted complication in cats with hepatic disease.
We feel that chloramphenicol is the best choice because it is very
effective against intestinal coliforms and most anaerobic bacteria, and it
undergoes an enterohepatic circulation, which assures a high concentration
in bile. The chloramphenicol-induced anorexia that occurs in cats is probably
dose related and may be avoided by using a lower dosage. We recommend
a dosage of 50 mg orally, twice daily, for cats with cholangiohepatitis.
Chloramphenicol base is preferred, because the injectable succinate form
is not active until hepatic transformation occurs, and the oral palmitate
form has reduced bioavailability. If a particular cat cannot tolerate chlor-
amphenicol even at the reduced dose, then tetracycline would be the best
alternative. Antibiotic treatment should be continued for 2 to 4 weeks. A
repeat liver biopsy after a course of therapy would be extremely helpful in
planning further treatment. Unfortunately, however, most of our clients
refuse repeat biopsy.
Metronidazole is being commonly used for anaerobic bacterial infec-
tions in man, 7• 14• 22· 48 • 59• 76 often in combination with an aminoglycoside
antibiotic. This drug may be useful for infectious hepatobiliary disease in
the dog and cat for several reasons. Anaerobic bacteria may play a role in
the pathogenesis of cholangiohepatitis, and metronidazole is effective against
most anaerobes. Also, this drug is active without hepatic transformation, is
bacteriocidal, and is excreted in bile. 21 • 59 Additionally, metronidazole has
been shown to have some activity against E. coli. 59
Chronic Nonsuppurative Cholangiohepatitis
Cats surviving suppurative cholangiohepatitis may progress to chronic
nonsuppurative cholangiohepatitis, a stage characterized by chronic hepa-
tobiliary inflammation, which. persists after suppuration has diminished.
Chronic, often subclinical, inflammation may be the end result of hepatic
injury from a variety of causes, including viral and bacterial infections,
exposure to drugs and chemicals, bacterial and dietary toxins, and immune-
mediated diseases. 5 9 Cats at this stage often present with clinical jaundice,
mild anemia, and severe weight loss, which are evidence of a chronic
disease process.
It has been demonstrated experimentally that the immune system can
perpetuate chronic hepatic inflammation. 69 Involvement of the immune
system in chronic inflammatory liver disease does not, however, indicate a
state of true autoimmunity. Damaged hepatocytes release antigens that
cause the activation of immunocompetent cells. These cells, in turn, damage
additional hepatocytes, and the process continues. 69 It has not yet been
determined if immune mechanisms contribute to the progression of cholan-
giohepatitis in the cat. 55
Accumulation of abnormal amounts of copper in the liver is known
to cause chronic active hepatic inflammation in man and in the
dog. 10• 26 • 34• 55• 68 • 69 Because copper is normally excreted in bile, cholestatic
diseases are usually associated with an increase in hepatic copper
levels. Chronic nonsuppurative cholangiohepatitis in cats has been com-
pared to primary biliary cirrhosis of man, 55 a disease in which copper
accumulation contributes to the development of cirrhosis. 10• 68 Feline hepatic
copper concentrations elevate significantly with experimentally induced
biliary obstruction, 10 but one cat with chronic nonsuppurative cholangio-
hepatitis had normal liver copper levels. 55 Additional study is needed to
determine if copper plays a significant role in the progression of feline
cholangiohepatitis.
Liver biopsy of cats at the chronic, nonsuppurative stage reveals a
periportal infiltration of predominantly lymphocytes and plasma cells, with
lesser numbers of macrophages and neutrophils. Hyperplasia of bile duc-
tules is always observed, and lymphoid cell aggregates are occasionally
seen. 16• 38 • 55 The presence of fibrous connective tissue, particularly in
periductal areas, is a prominent histopathologic feature, documenting a
chronic inflammatory process. The extrahepatic biliary system and the
pancreas are similarly affected. 37• 55
A recent report in the literature described three cats with chronic
lymphocytic cholangitis. 55 The histopathologic description is similar to other
cases of chronic nonsuppurative cholangiohepatitis except for characteristic
and abundant lymphoid cell aggregates. In addition, a long disease course
characterized by intermittent illness, prolonged remissions, and excellent
response to treatment was observed. The authors feel that these cats
represent a specific syndrome that was compared to primary biliary cirrhosis
of man. Another recent report describes one cat with inflammatory hepa-
tobiliary disease which was compared to primary sclerosing cholangitis of
man. 16 We also recognize cases of chronic nonsuppurative cholangiohepatitis
with numerous lymphoid cell aggregates and/or profound sclerosis, but are·
uncertain, at this point, whether or not these cases warrant separate
classification.
Treatment with corticosteroids has been recommended for cats with
chronic nonsuppurative cholangiohepatitis. Significant improvement has
been seen in some cases with prednisolone (2.2 mg per kg per day initially
and tapered to l.l mg per kg per day every other day). 55 · 69 We have used
the same protocol with results varying from acceptable improvement to no
improvement. Cortiosteroid therapy does not appear to cure the disease,
but it may slow down its progression. This effect may be due to suppression
of inflammation, modulation of the immune system, or both. Antibiotics
may still be necessary early in this stage if there is any histopathologic
evidence of continued infection.
Biliary Cirrhosis
The final stage in the progression of cholangiohepatitis is biliary
cirrhosis. 55•72 Cats in this stage usually present with clinical jaundice, severe
cachexia, hepatomegaly, and possibly ascites. Besides elevations of liver
enzymes previously mentioned, additional biochemical alterations indicat-
ing severe loss of hepatic function may appear at this stage. These include
hypoalbuminemia, hyperglobulinemia, and coagulopathy unresponsive to
vitamin K1 therapy, all of which indicate a poor prognosis.
Cirrhosis is often associated with a small liver in the dog, but cats with
biliary cirrhosis usually have hepatomegaly. Liver biopsy reveals severe
portal fibrosis, often traversing hepatic lobules. 55 • 72 Marked bile duct
hyperplasia, nodular hyperplasia, and a variable degree of chronic inflam-
mation are also observed. In severe cases, there is very little normal liver
tissue remaining. Extensive fibrosis and chronic inflammation are also
present in the pancreas, gallbladder, and bile duct. In our experience, only
a small percentage of cats with cholangiohepatitis survive long enough to
develop biliary cirrhosis.
Little can be done therapeutically at this stage except to provide
supportive therapy. Dietary modification is the best treatment for canine
hepatic cirrhosis, 69 but altering the diet of a cat can be unrewarding,
especially in one with a poor appetite. In general, frequent small feedings
of a diet composed mostly of carbohydrates and lesser amounts of good
quality protein would be appropriate. However, cats have a high dietary
protein requirement to decrease the utilization of body proteins for energy. 43
Because of this, protein restriction will not be as satisfactory in the cat as
it is in the dog. Also, ample dietary arginine is particularly important in
cats, as discussed in the previous section.
Ascites is rare in cats with liver disease, but it may occur with biliary
cirrhosis. A combination of increased pressure in the portal system and
hypoalbuminemia will make ascites more likely than will portal hypertension
alone. This is further reason to provide these cats with as much dietary
protein as they can tolerate. Control of ascites can be achieved by a
combination of a loop diuretic (furosemide, 2.5 to 5.0 mg, once a day or
every other day) and abdominocentesis. Caution must be advised regarding
the use of loop diuretics in cats with biliary cirrhosis. 69 They are very
potent and may easily cause dehydration and azotemia in cats. Hypokalemia
may also occur with loop diuretics, particularly at high doses or in cats with
decreased nutritional intake. Both azotemia and hypokalemia are predis-
posing factors to the development of hepatic encephalopathy. 13 Potassium-
sparing diuretics and a gre'ater reliance on abdominocentesis may be used
if problems develop.
Even though many cats with biliary cirrhosis still have biopsy evidence
of chronic hepatic inflammation, the continued use of corticosteroids at this
stage may produce undesirable side effects. Corticosteroid-induced sodium
retention may hasten the onset of ascites. Also, by increasing gluconeogen-
esis, these drugs cause catabolism and deamination of body proteins; the
released amine groups are ammonia precursors, which favor the develop-
ment of hyperammonemia and hepatic encephalopathy.
Complications of Cholangiohepatitis
Bile Sludging. We have observed that sludging of bile in the gallblad-
der, common bile duct, and intrahepatic bile channels is a frequent and
serious complication of cholangiohepatitis in cats. The consistency of bile
appears to be altered in the presence of chronic cholestasis and bacterial
infection. Bile becomes viscous and cannot flow through intrahepatic and
extrahepatic bile channels, causing an obstructive pattern biochemically. 33

Once sludging of bile occurs, the prognosis for eventual recovery becomes
very poor, regardless of the histopathologic staging of the disease.
We have attempted surgical intervention to correct the obstruction
caused by the sludged bile and find that these cats have large, unexpressable
gallbladders. Sludged bile can be removed from the gallbladder and
common bile duct, but if there is a similar problem in intrahepatic bile
channels, this procedure will accompiish little. Cholecystojejunostomy has
been performed without success, 16 most likely because of the same reason.
We have had some limited success with this procedure in a few cats.
Because the prognosis depends greatly on the degree of bile sludging,
early diagnosis and treatment appears to be very important in the manage-
ment of feline cholangiohepatitis. We are also attempting to prevent bile
sludging with an orally administered synthetic bile acid, dehydrocholic
acid* (62.5 mg [¥4 tablet], orally, three times a day). Theoretically, this
drug stimulates the flow of bile and increases its fluidity. Although it is
considered useless in man except as a laxative, 3· 23 we have seen a response
in some cats that supports its usage early in the disease process. Admini-
stration of dehydrocholic acid is contraindicated in the presence of complete
biliary obstruction. 3
"White Bile" Syndrome. Occasionally at surgery or necropsy we have
observed clear, viscous fluid without bile pigments in the gallbladder of a
cat with cholangiohepatitis. One case report in the literature also mentions
this finding, 16 which appears to be a phenomenon associated only with this
disease. This "white bile" is actually fluid and mucus secreted by the
gallbladder epithelium. The lack of bile pigment in the gallbladder is
thought to result from obstruction of bile flow. 36 This appears to be
associated with severe intrahepatic bile sludging and, as such, dictates an
unfavorable prognosis.
Cholelithiasis. Choleliths are also occasionally found in the gallbladder
and common bile duct of cats with cholangiohepatitis. 29 • 47 These choleliths
are radiolucent and are composed mostly of bile pigment. They are dark
green to almost black, and friable. We feel that these pigment stones
develop for the same reason that bile sludging occurs-as a result of chronic
cholestasis and bacterial infection in the biliary tree and gallbladder. It has
been postulated by others that the choleliths lead to the infection. 29 If
encountered at surgery, pigment stones should be removed. There appears
to be no reason to perform a cholecystectomy under these circumstances.
Hepatic Encephalopathy. Hepatic encephalopathy may occur in cats
with cholangiohepatitis, particularly in cats whose livers are approaching
end stage. We do not feel that this is a common occurrence, because the
majority of these cats probably die before end-stage liver disease occurs.
Pathophysiology and treatment of hepatic encephalopathy are discussed
earlier in this article.
TOXIC HEPATOPATHY
Toxic hepatopathy is the third most common cause of clinical liver

disease in our feline patient population. The presenting signs are variable
*Decholin. Dome Laboratories, West Haven, Connecticut.

and may include anorexia, depression, vomiting, diarrhea, dehydration,
and jaundice. Elevations in serum total bilirubin and ALT are usually the
most prominent biochemical abnormalities. 26 · 66 • 69 Because the presenting
signs and laboratory data are nonspecific, histopathology is necessary to
diagnose the problem. Liver biopsy reveals a characteristic pattern of zonal
hepatocyte necrosis, usually without a corresponding degree of inflamma-
tion. 39• 69 Such a pattern suggests a toxic etiology, but the actual toxin is
usually undetermined.
There are many potential causes of hepatotoxicity, including heavy
metals, insecticides, many organic compounds, bacterial and fungal toxins,
environmental chemicals, various plant toxins, pharmaceutical agents, en-
dogenously formed toxins, and toxins released by diseased organs elsewhere
in the body. 69 The toxic potential of any substance depends upon its own
characteristics, including its chemical formulation, dose, and duration of
exposure, and characteristics of the patient, including individual host
susceptibility, species differences, and the individual's diet and condi-
tion. 26, 39
The liver is particularly susceptible to toxic injury for several reasons.
The liver plays a major role in the metabolism and excretion of drugs and
other potential toxins. During this process, hepatotoxic intermediates of
metabolism may be produced. 32 • 44 The portal vein is the major source of
hepatic blood supply. Thus, many hepatocytes are marginally oxygenated,
which increases the toxic potential of many agents. 32• 39 Also, because the
portal circulation receives blood from the intestinal tract, the liver is the
first organ exposed to a variety of ingested toxic substances, bacterial toxins,
and toxins formed in the colon by bacterial degradation. 32 • 44
A-diagnosis of toxic hepatopathy includes a wide spectrum of clinical
possibilities ranging from fulminant hepatic necrosis and acute death to
chronic subclinical disease. 7°Cats that do not die from an acute toxic insult
may respond to supportive therapy. Intravenous fluids, usually with glucose
(2.5 to 5 per cent) and vitamin B complex added, are necessary in anorexic
and vomiting cats. If the offending agent is present in the intestinal tract
at the time of presentation, attempts should be made to bind or evacuate
it to reduce further absorption. Once the cat begins to eat, a diet rich in
high biologic value protein and low in colonic toxin precursors would be
ideaL 69 In practice, however, drastic changes in diet are not well accepted
by many cats. We find that chicken or beef baby food, fed in small amounts
frequently, is an acceptable alternative initially. Specific antidotal therapy
for toxic hepatopathy is usually impossible, because the inciting agent is
rarely identified.
Drug-induced Toxic Hepatopathy
Many useful therapeutic agents have a hepatotoxic potential. In man
it has been estimated that drug-induced hepatotoxicity is responsible for
up to 5 per cent of jaundice diagnoses, and 25 per cent of cases of acute
hepatic failure. 26 · 78 • 79 Drugs and other toxic substances are metabolized by
the liver in a two-stage process. 4 • 58 First, biotransformation (usually oxida-
tion) occurs by means of the cytochrome P450 enzyme system in the smooth
endoplasmic reticulum of the hepatocyte. This step creates intermediate
metabolites, many of which are more toxic than the parent compound.
Second, the metabolites are conjugated with glucuronic acid, sulfate, or
other endogenous substances to render the metabolites water soluble and
capable of excretion.
Cats have a relative deficiency of glucuronyl transferase, 4 which is an
enzyme necessary for conjugation with glucuronic acid. Because of this,
glucuronidation takes place slowly in this species, allowing toxic metabolites
created by biotransformation to build up in the liver. 4• 23 Therefore, a large
number of drugs that are safe for use in most species are toxic to cats.
Acetaminophen is an example of such a drug. Ingestion of a small amount
causes a syndrome characterized by methemoglobinemia, hemolytic ane-
mia, and hepatic necrosis. 20 • 26 Acetaminophen can be excreted directly by
glucuronidation or sulfation. 4 Because glucuronidation occurs slowly in the
cat and because the sulfate pool is limited, much of the drug is oxidized to
toxic metabolites, which are normally conjugated with glutathione for
excretion. 23 • 44 • 67 The cat' s hepatic glutathione stores are rapidly depleted
and toxicity develops. Treatment with N-acetylcysteine* (140 mg per kg,
orally, every 4 hours for four to six doses) replenishes glutathione and is an
effective therapy. 23 • 44 • 67
FELINE HEPATIC NEOPLASIA
Primary hepatic neoplasia is uncommon. Hepatocellular carcinoma,

bile duct carcinoma, hemangiosarcoma, and carcinoids have been re-
ported. 1• 19• 51 · 69 The clinical signs are nonspecific, but progressive anorexia,
weight· loss, and jaundice are usually observed. Physical examination may
reveal a palpable abdominal mass, and routine abdominal radiographs may
help differentiate neoplasia from other causes of hepatomegaly.
Total serum bilirubin elevations are usually mild. 12 Serum ALT and
SAP activity are variable but usually do not reach the magnitude of hepatic
lipidosis or cholangiohepatitis. 12 An exception would be bile duct adenocar-
cinoma causing bile duct obstruction. In this instance, higher levels of total
bilirubin, SAP, and ALT would be expected. 10
Hemangiosarcoma typically occurs in liver and spleen. 51 Clinical pres-
entation, including acute onset of anemia, hypovolemic shock, and hemo-
peritoneum, is similar to that seen in the dog.
In all cases, therapy is directed toward removal of the tumor, but
metastasis or extensive hepatic involvement is often present, precluding
surgical correction.
Systemic mastocytosis is an interesting syndrome that occurs in cats. 41
Neoplastic mast cells invade hematopoietic organs, resulting in severe
splenomegaly, milder hepatomegaly, bone marrow infiltration, and occa-
sionally mastocytemia. Histamine release from mast cells causes excessive
gastric hydrochloric acid production resulting in duodenal inflammation or
ulceration. 80 Because of this, vomiting is the predominant clinical sign.
Although the prognosis is guarded, prolonged remission can be achieved
*Mucomyst. Mead Johnson Laboratories, Evansville, Indiana.

following splenectomy with concomitant cimetidine* administration (20 to

40 mg per kg divided three or four times a day). 41
In our hospital, only seven cases of primary hepatic lymphosarcoma
(LSA) have been seen in the last 7 years; however, the liver is typically
involved in multicentric LSA along with lymph nodes, spleen, and kid-
neys.28 Special care must be taken using combination chemotherapy when
extensive liver infiltration and impaired liver function are present. Metho-
trexate and L-asparaginase are hepatotoxic, and cyclophosphamide requires
adequate liver function for conversion to its active chemotherapeutic
metabolites. 42 If extensive LSA infiltration is present in the liver, massive
liver necrosis can ensue following chemotherapy, precipitating acute hepatic
failure and DIC.
EXTRAHEPATIC BILE DUCT OBSTRUCTION
Cats with extrahepatic biliary obstruction usually have nonspecific

clinical histories including anorexia, fever, intermittent vomiting, and
weight loss. Biochemical abnormalities include hyperbilirubinemia, hyper-
cholesterolemia, and elevated AST and SAP activity. 10 The magnitude of
these elevations depends upon the chronicity of the disease and degree of
obstruction. In experimentally induced total biliary obstruction, serum
bilirubin levels gradually increased, reaching a maximum level after several
weeks, and then slowly decreased. 10 Other indications of complete biliary
obstruction are normalization of PT and PTT with parenteral vitamin K
administration, acholic stools (secondary to the absence of fecal bile pig-
ments), and the absence of urine urobilinogen.
Short of laparotomy, there are no easily performed diagnostic tests or
techniques to differentiate intrahepatic from extrahepatic diseases in the
cat. Cholangiography is rarely performed. Needle biopsy or laparo-
scopic biopsy may be performed. The liver parenchyma can be examined
histologically and then the need for surgical laparotomy can be ascertained.
Pancreatitis, pancreatic neoplasia, pancreatic fibrosis, stricture of the
common bile duct, bile duct· adenocarcinoma, bile pigment stones, and
sludged bile are common causes of extrahepatic obstruction. All of these
problems except pancreatitis require surgical intervention and correction.
Acute pancreatitis is an elusive diagnosis in the cat and rarely documented.
In our experience, serum amylase and lipase are not reliable indicators of
the disease. At best, the diagnosis of feline pancreatitis can only he
suspected based on clinical experience. As previously discussed, chronic
pancreatitis is frequently associated with the cholangiohepatitis complex.
CONGENITAL PORTACAVAL ANOMALIES
Congenital portacaval anomalies are a well-recognized clinical entity

in dogs hut are recognized infrequently in cats. 40 · 75 Elevated liver enzymes,
*Tagamet. Smith Kline and French, Philadelphia, Pennsylvania.

BSP retention, elevated blood ammonia levels, and an abnormal ammonia

tolerance test support the diagnosis. Ultimately, diagnosis is based on
intraoperative angiography of the portal venous system. 63
Cats with portacaval anomalies range in age from 3 months to 3 years.
Common clinical signs are anorexia, ptyalism, depression, blindness, be-
havioral changes, and grand mal seizures. As in the dog and man, portacaval
anomalies in cats have clinical signs of hepatic encephalopathy.
Hepatic encephalopathy has a complex, multifactorial etiology. Syner-
gistic action between ammonia, methyl mercaptans, short chain fatty acids,
and false neurotransmitters and their effects on neuronal metabolism are
thought to produce the encephalopathic signs. 77 Metabolic abnormalities
such as hypoglycemia, hypokalemia, and alkalosis may exacerabate hepatic
encephalopathy. 77
Medical therapy for hepatic encephalopathy in the cat has been
previously discussed. Surgical correction by partial ligation of the portacaval
shunt vessel has been successfully performed in cats. 40
FELINE HYPERTHYROIDISM
Hyperthyroidism was first reported in 1979; 52 since then, it has become

a frequently diagnosed endocrine disorder of cats. Some of the clinical signs
of hyperthyroidism, such as polyuria, polydipsia, diarrhea, vomiting, and
weight loss, can mimic those seen in primary feline liver disease. More
importantly, elevated liver enzyme activities are the most common bio-
chemical alterations seen in feline hyperthyroidism. In a recent report, 75
per cent of hyperthyroid cats had elevated SAP activity, 66 per cent had
elevated AST activity, and 54 per cent had elevated ALT activity. 53
Biochemical jaundice is occasionally observed. 53 Hyperbilirubinemia in man
associated with hyperthyroidism is rare but can occur if a complication such
as infection is present or if thyrotoxicosis aggravates pre-existing liver
disease. 35 Histologic changes reported in the liver of human beings with
hyperthyroidism include fatty infiltration and focal centrilobular necrosis.
These histologic changes are nonspecific and probably reflect damage from
cardiac failure and severe weight loss. 35 These changes have been reported
in feline livers. 53
Diagnosis of feline hyperthyroidism is based on palpation of thyroid
nodules, elevated serum thyroxine (T4) and triiodothyronine (T3 ), and, when
available, positive thyroid scans. Appropriate medical or surgical therapy
for hyperthyroidism results in return of elevated SAP, AST, and ALT
activity to normal. 53
OTHER CAUSES OF FELINE LIVER DISEASE
Infections with trematodes (Platynosomum spp.) have been reported

in cats in the southern United States, Bahamas, and other tropical areas. 5
Occasionally, we have seen liver flukes at our hospital, but historically all
cats have lived in endemic areas. Even if special fecal examination tech-
niques are used, ova are identified in only one third of the cases. 50 Liver
biopsy may be necessary to document the presence of flukes in the bile
ducts. Therapy for liver flukes has been evaluated. 5 · 17 Praziquantel (20 mg
per kg)* or nitroscanate (100 mg per kg) given in a single dose has been
effective. 5
Large cysts originating in the biliary tree may be seen but are
infrequent. In our experience, these hepatic cysts can be solitary or multiple
and obtain a large size. They occur in cats over 10 years of age and are
incidental findings on physical examination. Clinical signs are usually
absent, but if present, result from the size of the mass rather than primary
liver disease. Care must be taken not to confuse benign cysts with a
neoplastic process. Surgical correction is curative.
Abscess, diaphragmatic hernia, and direct trauma can result in hepatic
damage in cats. Parasitic diseases (hepatozoonosis, cytauxzoonosis, toxo-
plasmosis) and systemic fungal infections may be important causes of feline
liver disease in endemic areas.
SUMMARY
Species differences in anatomy, physiology, and biochemistry lead to
many dissimilarities between the canine and feline liver. Major differences
exist in the interpretation of liver function tests, the significance of bio-
chemical jaundice, the consequences of anorexia, and the efficiency of
hepatic metabolic systems. Biochemical alterations in total bilirubin, ALT,
and SAP may indicate the presence of disease in the feline liver. It is,
however, impossible to make accurate diagnoses without liver biopsy. A
liver biopsy can provide a diagnosis and prognosis and can guide the
therapeutic plan. The feline hepatic diseases most frequently seen in our
hospital are hepatic lipidosis, cholangiohepatitis complex, toxic hepatopathy,
and hepatic neoplasia. Less common diseases of the feline liver include
extrahepatic biliary obstruction, portacaval vascular anomalies, hepatic
parasites, hepatic cysts, and diaphragmatic hernia. Systemic diseases that
can effect the liver of cats are feline infectious peritonitis, multicentric
lymphosarcoma, myeloprolifertive diseases, hemolytic anemia, infectious
panleukopenia, and systemic fungal infections.
ACKNOWLEDGMENT
The authors wish to thank Dr. Steven R. Gilbertson for providing data, knowledge, and
invaluable assistance in the preparation of this manuscript.
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Symposium on Advances in Feline Medicine II

Feline Hepatic Disease

Dennis A. Zawie, D.V.M.,* and MichaelS. Garvey, D.V.M.t

From the Animal Medical Center, New York, New York

METABOLIC FUNCTIONS OF THE LIVER

Bilirubin is derived primarily from the metabolism of hemoglobin.

Jaundice is classified as prehepatic, hepatic, and posthepatic. 26 Prehe-

Cachexia, dehydration, jaundice, and other signs of metabolic illness

LABORATORY EVALUATION OF FELINE LIVER DISEASE

Biochemical testing is essential for proper evaluation of feline liver

Table 1. Distribution of 100 Cats with Abnormal Serum LDH Levels

Table 2. Distribution of 50 Cats with Abnormal Serum

appears to be a reliable indicator of cholestasis. The sensitivity of GGT is

Table 3. Distribution of 67 Cats with Serum Total Bilirubin Levels

be detected clinically. 33 There is a high correlation between clinical jaundice

Table 4. Distribution of 76 Cats with Serum Total Bilirubin Levels

Anorexia, which results in arginine deficiency, may reduce the func-

The importance of a liver biopsy cannot be overemphasized. It is the

CLINICAL FELINE HEPATIC DISEASE

The feline liver is secondarily affected by a number of infectious and

Hepatic lipidosis (fatty liver) is a common cause of feline liver

Table 5. Pathogenesis of Hepatic Lipidosis

t FF A delivery Diabetes mellitus Glucagon

and a disproportionate occurrence in Siamese cats, 9 but these findings were

diseases. 9· 12 Total serum bilirubin is often elevated in cats with diabetic or

Other possible factors contributing to hepatic encephalopathy in cats

has been established, frequent force-feeding is instituted with canned cat

*Cephulac. Merrell-Dow, Cincinnati, Ohio.

related inflammatory disorders of the hepatobiliary system, or possibly a

form. This makes their use in cholangiohepatitis highly questionable.

extrahepatic bile channels, causing an obstructive pattern biochemically. 33

Toxic hepatopathy is the third most common cause of clinical liver

*Decholin. Dome Laboratories, West Haven, Connecticut.

FELINE HEPATIC NEOPLASIA

Primary hepatic neoplasia is uncommon. Hepatocellular carcinoma,

*Mucomyst. Mead Johnson Laboratories, Evansville, Indiana.

following splenectomy with concomitant cimetidine* administration (20 to

EXTRAHEPATIC BILE DUCT OBSTRUCTION

Cats with extrahepatic biliary obstruction usually have nonspecific

CONGENITAL PORTACAVAL ANOMALIES

Congenital portacaval anomalies are a well-recognized clinical entity

*Tagamet. Smith Kline and French, Philadelphia, Pennsylvania.

BSP retention, elevated blood ammonia levels, and an abnormal ammonia

Hyperthyroidism was first reported in 1979; 52 since then, it has become

OTHER CAUSES OF FELINE LIVER DISEASE

Infections with trematodes (Platynosomum spp.) have been reported

*Droncit, Haver-Lockhart Laboratories, Shawnee Mission, Kansas.

The Animal Medical Center

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