Page 609 - Small Animal Internal Medicine, 6th Edition

CHAPTER 35 Hepatobiliary Diseases in the Cat 581

the Veterinary Poisons Information Service (https:// Diagnosis
vpisglobal.com/our-research/). In general, drug- or toxin- Clinical evidence that suggests drug- or toxin-induced
VetBooks.ir induced hepatic injury in cats is extremely uncommon, and (e.g., known exposure); normal liver size to mild generalized
hepatic damage includes the following: supportive history
most reactions are acute, occurring within 5 days of expo-
tender hepatomegaly; laboratory test results consistent with
sure. The character and severity of the toxic reaction depend
on the characteristics of the substance, dose, and duration of acute liver injury (e.g., high serum ALT and/or AST levels,
exposure. hyperbilirubinemia); and, if the exposure was nonlethal,
Three therapeutic agents have been reported to be hepa- recovery with discontinuation of the agent and specific or
totoxic in some cats—tetracycline, diazepam, and stanozo- supportive care. There are no pathognomonic histologic
lol. Veterinarians have used these agents for years without changes in the liver, although necrosis with minimal inflam-
known deleterious effects. For each drug, clinical and clini- mation and lipid accumulation are considered typical find-
copathologic signs of hepatotoxicosis developed within 2 ings. In many cases, all clinical and clinicopathologic markers
weeks of daily oral administration at recommended dosages. of a toxic liver insult are present, but the inciting chemical
The adverse hepatic reaction to tetracycline was serious cannot be identified. In the case of hepatotoxicity from ther-
but nonlethal, and the cat recovered completely after drug apeutic agents, idiosyncratic reactions can occur that are not
discontinuation and 6 weeks of supportive care (Kaufman dose-related, although drug overdose is usually the reason
et al., 1993). Histologic findings in the liver included cen- for liver injury.
trilobular fibrosis, mild cholangiohepatitis, and mild lipid
deposition in hepatocytes. In the cats that experienced Treatment
diazepam-associated hepatic failure, the outcome was death In cats with suspected acute hepatotoxicity, the basic prin-
in 16 of 17 despite intensive treatment. The oral dosages ciples for treatment of toxicoses are applied:
of diazepam that cats received, primarily for inappropriate
urination, ranged from 1 mg every 24 hours to 2.5 mg every • Preventing further exposure and absorption
12 hours. The histologic lesions in the liver were similar • Managing life-threatening cardiopulmonary and renal
to those observed in the cat with tetracycline-associated complications
hepatic injury but more severe: massive, predominantly • Hastening elimination of the substance
centrilobular necrosis; suppurative cholangitis; and mild • Implementing specific therapy if possible
lipid vacuolation in some cats. Because of the severity • Providing supportive care
of the lesions reported in cats apparently susceptible to
diazepam-associated hepatic necrosis, serum liver enzyme Because few hepatotoxins have specific antidotes, the
levels should be evaluated during the window of days 3 to success of recovery often relies on time and aggressive sup-
5 of administration in cats given diazepam by mouth. Until portive care. More guidance on supportive treatment of
there is more information to improve the understanding of acute toxic hepatopathy is provided in Box 36.4.
this lethal and unpredictable hepatic reaction, use of other Acetaminophen is one of the few toxins with a specific
agents for control of behavior and elimination problems in antidote. Acetaminophen is particularly toxic to cats, in
cats is recommended. Cats that experienced an adverse reac- which the usual hepatic detoxification pathways of sulfation
tion to stanozolol were healthy or had chronic renal failure and glucuronidation are particularly limited. Acetamino-
(14 of 18 cats) or gingivitis or stomatitis (2 of 3 cats; Harkin phen is oxidized to a toxic metabolite that causes methe-
et al., 2000). Serum ALT levels were markedly increased moglobinuria within hours of ingestion and Heinz body
in most cats given 1 mg PO every 24 hours for several anemia, hemolysis, and liver failure within 2 to 7 days of
months or 4 mg PO every 24 hours (and 25 mg IM once) ingestion. N-acetylcysteine is a specific antidote that binds
for 3 weeks; all but one survived after the drug was dis- the toxic metabolite and increases the glucuronidation
continued, and intensive supportive care was instituted. The process. It should be administered at a dose of 140 mg/kg
histologic lesions were moderate to marked diffuse centri- IV or PO as a loading dose and then continued at 70 mg/
lobular lipidosis and evidence of intrahepatic cholestasis— kg q6h for a total of seven treatments, or for up to 5 days.
accumulation of bile and lipofuscin in hepatocytes and There is also evidence that additional S-adenosylmethionine
Kupffer cells. (20 mg/kg, or 200-400 mg total daily) is beneficial in cats
The discriminatory eating habits of cats may account for with acetaminophen toxicity because it replenishes gluta-
the relatively uncommon occurrence of hepatotoxicity from thione, which inactivates the toxic metabolite (Webb et al.,
ingested environmental toxins such as pesticides, household 2003). In addition, a recent study suggested that silymarin
products, and other chemicals. It is certainly possible that was beneficial for treating experimental acetaminophen tox-
many adverse hepatic reactions to drugs or toxic chemicals icity in cats. A single dose of 30 mg/kg PO given to cats at
go unnoticed in cats because the first clinical signs of illness the same time as acetaminophen or 4 hours later was as effec-
are vomiting and diarrhea, after which the medication is tive at preventing elevation in liver enzymes, bilirubin, and
stopped. If the signs resolve, there usually is no further evalu- methemoglobin levels as a single dose of N-acetylcysteine
ation, and the medication is not readministered to prove that (Avizeh et al., 2010). It is unclear how to extrapolate these
the substance caused the reaction. findings to the clinical setting, but the use of N-acetylcysteine,