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Proceedings of the
International Congress of the Italian
Association of Companion Animal
Veterinarians
June 8-10, 2012 - Rimini, Italy

Next SCIVAC Congress:

Mar. 8-10, 2013 Pisa, Italy
SCIVAC International Congress
Canine Leishmaniasis and other Vector-Borne diseases.
Current State of Knowledge

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Congress Organizers
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RIMINI, 8-10 GIUGNO 2012
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Canine hepatic disease: from diagnosis to therapy

Robert J. Washabau
VMD, PhD, Dipl ACVIM, Minnesota, USA

TOXIC HEPATOPATHY
Pathogenesis and Etiology Toxic hepatopathy in the dog
is a direct injury to hepatocytes or other cells in the liver
attributable to medical therapies or environmental toxins. A
partial list of toxins follows:
Mechanisms of Hepatotoxicity - The liver is an important
site of drug toxicity and oxidative stress because of its proximity and relationship to the gastrointestinal tract. Seventyfive to 80% of hepatic blood flow comes directly from the
gastrointestinal tract and spleen via the main portal vein.
Portal blood flow transports nutrients, bacteria and bacterial antigens, drugs, and xenobiotic agents absorbed from the
gut to the liver in more concentrated form. Drug-metabolizing enzymes detoxify many xenobiotics but activate the
toxicity of others. Hepatic parenchymal and non-parenchymal cells may all contribute to the pathogenesis of hepatic
toxicity. The major mechanisms of hepatotoxicity are outlined in the accompanying handout (Feline Hepatobiliary
Disease), and include: Bile Acid-Induced Hepatocyte Apoptosis, Cytochrome P4502E1-Dependent Toxicity, Peroxynitrite-induced Hepatocyte Toxicity, Adhesion Molecules and
Oxidant Stress in Inflammatory Liver Injury, Microvesicular Steatosis, and Nonalcoholic Steatosis.
Diagnosis of Hepatotoxicity Clinical evidence includes
supportive history, mild generalized hepatomegaly, elevated
serum liver enzyme activities (predominantly ALT and
AST), hypoalbuminemia and hypocholesterolemia, and
recovery or death depending upon severity and magnitude of
exposure. There are no pathognomonic histologic changes in
the liver, although necrosis with minimal inflammation are
considered classic findings.
Treatment of Hepatotoxicity Few hepatotoxins have
specific antidotes, and recovery relies almost exclusively on
symptomatic and supportive therapy.

INFECTIOUS HEPATITIS
Acute canine infectious hepatitis has been associated with
canine hepatitis virus (canine adenovirus type-1; CAV-1)

infection, acidophil cell hepatitis virus infection, leptospirosis, Helicobacter canis infection, Tyzzers disease, Hepatzoon canis infection, and Rocky Mountain spotted fever.
CAV-1 was a common cause of infectious hepatitis in the
dog in the 1970s and 1980s, but appears to be of lesser clinical significance during the past decade. Canine acidophil
cell hepatitis has only been reported in Great Britain to date.
Canine leptospirosis is a significant cause of liver injury in
domestic dogs.
It is associated with acute cholestatic hepatic disease and
renal failure in infected animals. Liver injury has been
reported mostly in association with the canicola, icterohemorrhagiae, and grippotyphoas serovars, but any serovar has
the potential to induce liver injury. Leptospirosis is readily
treated if recognized early enough in the course of the disease. Chronic hepatitis and cirrhosis may result if the animal
survives the infection.

INFLAMMATION (CHRONIC HEPATITIS)

AND CIRRHOSIS
Chronic hepatitis is a heterogeneous group of mixed
inflammatory-necrotizing disorders of the liver. Some
chronic hepatitis lesions have a known underlying etiology
and pathogenesis, but the vast majority of these cases are
poorly understood. The chronic hepatitis liver is typically
characterized by lymphocyte and plasma cell infiltrates with
varying degrees of biliary hyperplasia and fibrosis. Some of
the known causes of chronic hepatitis are:
Chronic hepatitis in dogs has previously been referred to
as chronic active hepatitis, akin to an immune disorder in
human beings. That terminology has since been abandoned.
Chronic hepatitis can progress to cirrhosis and end-stage liver disease. Cirrhosis is characterized by fibrosis and regenerative nodules that result in disorganization of the hepatic
lobular architecture. Despite advances in modern molecular
biology, cirrhosis is still considered to be an irreversible
pathologic state of the liver.
The extracellular matrix (ECM) of the liver provides cells
with positional information and a mechanical scaffold for
adhesion and migration. The ECM consists of collagens,
glycoproteins, proteoglycans, glycosaminoglycans and molecules that are bound specifically by the ECM, such as cer-

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tain growth factors, cytokines, matrix metalloproteinases,

and processing enzymes such as tissue transglutaminase and
procollagen propeptidases. Hepatic stellate cells are the
major source of the collagens that comprise fibrosis and cirrhosis, as well as of the tissue inhibitors of metalloproteinases (TIMPS) which inhibit collagen degradation. If
clinical signs of liver failure are already present, the longterm prognosis is poor. Cirrhosis is usually accompanied by
portal hypertension, ascites, multiple acquired portasystemic
shunts, and encephalopathy.

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Diagnosis Affected dogs and cats may have only subtle

laboratory abnormalities (mild increases in ALT & AST;
mild hypoalbuminemia, hypoglycemia, and hypocholesterolemia; low blood urea nitrogen; and microcytosis). Diagnosis is best achieved by coupling a liver function test (bile
salts and/or NH3 quantitations) to a liver imaging technique,
e.g., ultrasonography, scintigraphy, or contrast portal venography. Liver biopsy typically reveals hypoplasia of the portal tracts.

HEPATIC ABSCESS
GRANULOMATOUS HEPATITIS
Atypical granulomatous hepatitis has been reported in
dogs in association with fungal disease (e.g., histoplasmosis), generalized lymphosarcoma (e.g., lymphomatoid
granulomatosis), intestinal lymphangitis and lymphangiectasia, and infection with Bartonella henselae. In western
Europe and throughout the middle east, granulomatous
hepatitis is almost always associated with visceral leishmaniasis.
Sporadic cases of leshmaniasis are reported throughout
the United States. Recent reports have impugned Bartonella species in the development of granulomatous hepatitis
and peliosis hepatis lesions in dogs. The importance of
Bartonella spp. in the pathogenesis of either lesion remains
to be determined.

Hepatic abscesses are rare in dogs, but the clinical signs

and clinicopathologic findings are similar to other inflammatory hepatic diseases. Most hepatic abscesses are a result
of ascending infection from the biliary tract; hematogenous
spread of organisms via the portal vein, hepatic artery, or
umbilical vessels; or trauma. Concurrent factors or conditions that may predispose to the development of hepatic
abscess include biliary tract disease, diabetes mellitus, pancreatitis, neoplasia, and long-term glucocorticoid administration. Ultrasonography is necessary to document hepatic
abscessation, and it may be useful to monitor response to
therapy. Both medical and surgical treatments may be used
successfully to treat hepatic abscesses in dogs.

HEPATIC AMYLOIDOSIS
PORTASYSTEMIC SHUNTS
Pathogenesis and Etiology Diversion of portal blood
flow to the central circulation depletes the liver of nutrients,
hormones, and growth factors. Portosystemic shunts in dogs
are both intra-hepatic and extra-hepatic, although most
shunts arise outside the liver from the left gastrosplenic vein.
Clinical signs of hepatoencephalopathy dominate the clinical syndrome because of inadequate hepatic clearance of
enterically-derived toxins such as ammonia, mercaptans,
short-chain fatty acids, gamma-aminobutyric acid, and
endogenous benzodiazepines. Decreased hepatic blood flow
and lack of hepatotrophic factors such as insulin, glucagons,
and nutrients result in hepatic atrophy.
Clinical Features Affected dogs appear stunted, fail to
grow, and have clinical signs consistent with hepatoencephalopathy, e.g., anorexia, depression, and lethargy. Clinical signs of hepatoencephalopathy (HE) tend to wax and
wane and are often interspersed with normal periods. Signs
of HE may be exacerbated by a protein-rich meal, gastrointestinal hemorrhage, or by supplementation with methionine-containing urinary acidifiers. Gastrointestinal signs of
intermittent anorexia, vomiting, and diarrhea are common
nonspecific features of hepatic dysfunction. PU/PD is another common clinical sign in dogs with portasystemic shunting. Onset of clinical signs with feeding and delayed recovery from anesthetic events are reported more frequently with
canine portosystemic shunts.

In dogs and cats, amyloid deposition is usually secondary

to sustained systemic inflammatory response, e.g., chronic
infection, chronic inflammation, immune disorders, and
malignancy. Amyloidosis is a familial disorder in the Chinese Shar Pei dog, and in Abyssinian, Oriental, and Siamese
cats. Hepatic amyloidosis has also been reported secondary
to vitamin A toxicity in cats. Deposition of amyloid fibrils
within and between hepatic sinusoids results in progressive
organ dysfunction. Concurrent amyloid deposition in the
kidneys, liver, spleen, and adrenal glands can occur, but
clinical manifestations of renal failure are most common.
Laboratory data and imaging findings are consistent with
liver disease, but they are otherwise non-specific. Definitive diagnosis requires tissue biopsy and Congo red staining. Precautionary note Livers infiltrated by amyloidosis
tend to bleed following biopsy. There are no effective treatments for this syndrome. Colchicine has been recommended because it may block formation of amyloid in the early
stages of the disease. Dimethyl sulfoxide ahs been recommended because it may promote resorption of amyloid.
With progressive amyloidosis lesions, the prognosis for
long term survival is poor.

Address for correspondence:

Robert J. Washabau Professor of Medicine and Department Chair
College of Veterinary Medicine, University of Minnesota
1352 Boyd Avenue, St. Paul, Minnesota 55108
(612) 625-5273 Office/E-Mail:washabau@umn.edu

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