Drugs such as mebendazole occasionally can produce acute diffuse hepatic necrosis, and oxybendazole-diethylcarbamazine has been associated with nonspecific hepatitis especially in Doberman Pinschers, Samoyeds and Akitas. Increased APTT and PT with changes in liver biochemical profile occur in the acute or end-stage form of toxicity. In dogs, sustained topical or parenteral glucocorticoid use produces a characteristic steroid hepatopathy with hepatomegaly and accumulation of glycogen within hepatocytes. Clinically, signs are those of hyperadrenocorticism with laboratory findings of markedly increased SAP, increased ALT and GGT. Liver biopsy shows typical lesions of vacuolar hepatopathy and swelling of hepatocytes. Naturally occurring as opposed to iatrogenic hyperadrenocorticism produces a similar clinical and laboratory picture. While steroid hepatopathy is the most common cause of increased SAP in dogs, it seldom occurs in cats.

Anticonvulsants such as primidone, phenytoin and phenobarbital produce chronic hepatic disease after long-term use, which may progress to cirrhosis and hepatic failure after 2-3 years. Phenobarbital generally has a less toxic effect although these drugs cause increases in serum ALT and SAP.

Thiacetarsamide is used to treat dogs for heartworm disease and can produce acute hepatic injury and liver failure. Increases in ALT and SAP are seen in about 20% of dogs treated with this drug. More recently, ivermectin or milbemycin has replaced arsenicals for treating heartworm disease.

In cats, acetaminophen toxicosis produces severe oxidative stress to hepatocytes as cats lack the ability to conjugate glucuronides for detoxification of the drug.

End-stage liver disease from a variety of causes produces cirrhosis (widespread hepatic fibrosis with abnormal hepatic architecture from nodular regeneration). In addition to the laboratory biochemical changes typical of liver dysfunction, excessive bleeding may be seen clinically from decreased platelet numbers and/or increased coagulation times.

Various neoplasms can involve the liver. Primary neoplasms are usually hepatocellular (hepatoma, hepatic carcinoma), bile duct carcinoma, or multicentric lymphosarcoma. Metastic liver neoplasia usually arises from mammary gland adenocarcinoma, splenic hemangiosarcoma or pancreatic carcinoma.

Because the liver is the primary site of coagulation factor synthesis, significant hepatic disease produces prolongation of coagulation tests and may cause an overt bleeding tendency. Other factors contribute to the hemostatic abnormalities seen with liver disease including production of structurally abnormal clotting factors, increased consumption leading to local or disseminated intravascular coagulation (DIC), impaired hepatic clearance with sequestration of platelets and clotting factors in the hepatic microcirculation, and fibrinolytic abnormalities. Up to 85% of humans and 66% of dogs with liver disease are reported to have an elevated PT and APTT, although 93% of dogs, and 82% of cats studied recently, had at least 1 coagulation abnormality. In cats with hepatic lipidosis, 45% had an abnormal coagulation profile.

In the recent study of 22 cats, the PT was most commonly prolonged (16/22) and factor VII activity was low in 15 of them. This finding reflects the very short half-life of factor VII which has been used in humans and animals as a marker for hepatic dysfunction and for response to therapy (reversal of deficiency state). The underlying pathogenesis in this group of cats included vitamin K deficiency (11/22), reduced hepatic synthesis (13/22), indeterminate cause (3/22), and DIC (1/22). Importantly, cats with marked increases in SAP were those most likely to show coagulation abnormalities.

In acute generalized or chronic end-stage liver failure, the patient may exhibit DIC. Classical laboratory changes are moderate to severe thrombocytopenia, prolonged PT, APTT, and thrombin time, low antithrombin III and fibrinogen, presence of fragmented red blood cells (schizocytes), and elevated fibrin degration products or D-dimer.

References: Cornelius and Bjorling, In Morgan (ed.), Handbook Sm Anim Pract, 2nd ed, Churchill Livingstone, 1992, pp 437-458; Bateman et al, Vet Emerg Crit Care 1998; 8:29-45; Lisciandro et al, J Vet Int Med 1998; 12:71-75.