Page 716 - Clinical Small Animal Internal Medicine

684 Section 7 Diseases of the Liver, Gallbladder, and Bile Ducts

restricted to sulfonamides causing severe intrahepatic bile required. Carprofen may also cause simultaneous renal
VetBooks.ir duct necrosis and irreparable cholestasis. Anecdotally, toxicity. Carprofen toxicity causes marked elevation of
all liver enzymes, bile acids, and bilirubin. It is not known
although not well documented, liver toxicity has also been
reported for azathioprine, ketoconazole, fen/oxibendazole,
phenobarbital, halothane, methoxyflurane, cephalexin, if other NSAIDs can cause similar hepatotoxicity.
amoxicillin, oxacillin, nafcillin, erythromycin, clindamycin, Sulfonamide Toxicity in Dogs and Cats
and several other drugs. The hepatic lesions may include Repeated or prolonged treatment with sulfonamides
canalicular cholestasis and/or liver cell vacuolization and (including trimethoprim/sulfa) may occasionally lead to
in severe cases liver cell necrosis. There are no large an idiosyncratic toxicity of the liver in both dogs and cats.
studies to document the true risk and toxicity of these The intrahepatic bile ducts appear to be targeted, espe-
drugs. Relatively well‐documented toxicity is reported for cially the collecting bile ducts receiving bile from the
diazepam (cats), acetaminophen (paracetamol) in dogs smaller liver lobules. In most cases, these intrahepatic
and cats, and carprofen in dogs. components of the biliary tree undergo complete necrosis,
leading to very severe intrahepatic cholestasis. The degree
Specific Toxins of cholestasis is comparable to that of complete extrahe-
Diazepam Toxicity in Cats patic bile duct obstruction. Clinical signs include a sudden
This toxicity has all the features of an idiosyncratic reac- onset of anorexia, depression, vomiting, polyuria, and
tion, and has only been reported in cats receiving several occasionally acholic stool, in combination with marked
doses of diazepam. Toxicity results in severe necrosis of icterus. Sometimes the liver is moderately enlarged. The
the entire liver lobule, leading to fulminant liver failure resulting clinical signs are those of severe cholestasis with
and severe signs including inappetence, vomiting, severe preservation of liver function. At ultrasonography, the
lethargy, hepatic encephalopathy, coagulopathy, and gallbladder may be entirely empty. The diagnosis requires
jaundice. Liver enzymes, including the transaminases careful histologic examination of the liver, since the lesions
ALT/AST, and also ALP and bile acids are significantly have a specific pattern. Management includes immediate
elevated. Only symptomatic treatment is possible and withdrawal of the drug, and therapy with the choleretic
the prognosis is poor in most cases. drug ursodeoxycholic acid. Complete recovery has never
been documented and surviving cases need to be treated
Acetaminophen (Paracetamol) Toxicity in Dogs and Cats lifelong with ursodeoxycholic acid.
Too high a dose of acetaminophen may cause severe oxi-
dative hepatic damage. The result is hepatocellular Biologic Toxins
necrosis which, depending on the dose, may involve the Amanita mushrooms and blue algae are the two impor-
entire liver lobule and cause complete liver failure. tant producers of biologic toxins, which may cause very
Acetaminophen has been used as an experimental drug severe liver damage. Both toxic mushrooms and blue algae
to induce reproducible acute liver failure in dog models, cause severe necrosis of hepatocytes, and this is dose
and it is one of the most used suicide drugs in humans. dependent. In most cases, the damage is very severe and
If acetaminophen toxicity is suspected, antioxidative associated with complete liver necrosis (fulminant hepati-
drugs such as SAM‐e and N‐acetylcysteine are advised. tis). This leads to massive increases of all liver parameters
However, the proven effect of these drugs was tested in (enzymes, bile acids, ammonia, etc.). Clinical signs are
experimental situations in which the drug was given comparable to those of the drug toxicities, and may include
together or before the toxic drug. Treatment after the hepatic encephalopathy, jaundice, spontaneous bleeding,
occurrence of the toxicity, as occurs naturally, may be and severe lethargy. Therapy is supportive, with antiemet-
less successful. The most important treatment is imme- ics and intravenous fluid administration, and normaliza-
diate gastric lavage. Supportive care with intravenous tion of blood pH and electrolytes. Forced diuresis may
fluids and enteral feeding may also be required. If hepatic help to relieve the signs of hepatic encephalopathy.
encephalopathy with severe hyperammonemia is pre-
sent, the prognosis is often very poor.
Neoplasia
Carprofen Toxicity in Dogs
This nonsteroidal antiin flammatory drug (NSAID) may Primary Tumors
cause idiosyncratic hepatic toxicity. The toxicity usually
occurs after prolonged or repeated treatments, and may Hepatocellular Carcinoma
cause very severe liver damage. Immediate drug with- Etiology/Pathophysiology
drawal and supportive care, with intravenous fluids and Among epithelial tumors, hepato cellular carcinoma
intensive therapy, result in a favorable outcome for (HCC) occurs more frequently than hepatocellular ade-
most cases, although several weeks of treatment may be noma. Both tumors are usually solitary and can become