Liver disease can be frustrating to diagnose and often difficult to treat. The clinical signs of liver disease in the cat are usually non-specific and include anorexia, depression, weight loss and vomiting. Jaundice, when present, may assist the clinician localise the disease process to the hepatobiliary system (provided that haemolytic anaemia is not the cause). However, jaundice is not always present in animals with liver disease and a variety of different aetiologies can cause hepatobiliary disease and jaundice. Other clinical signs include fever, abdominal effusion, and CNS signs.
Liver disease can be caused by pathology within the liver parenchyma or by disorders of the biliary tree. It can be difficult to differentiate the location of liver pathology (hepatic vs. post-hepatic) using clinical pathology alone yet such differentiation can be important in deciding what is the most appropriate diagnostic or therapeutic step to take next. Surgical correction of post-hepatic obstruction may be feasible whereas surgery is indicated in primary hepatocellular disease to obtain biopsies. Hepatic biopsies may be obtainable by other means (such as ultrasound guided percutaneous biopsy).
The surgical expertise required to correct post-hepatic obstructions can be considerable and it is important to recognise that a specialist surgeon may be needed if your own surgical skills do not extend to procedures such as cholecystojejunostomy.
Clinical signs of hepatic disease
Cats with hepatic disease may present with some or all of the following clinical signs:
Vomiting +/- diarrhoea.
Bleeding tendencies (coagulopathy).
GIT haemorrhage not necessarily due to coagulopathy.
None of these clinical signs is unique to liver disease and may occur in a vast array of different disease processes.
Clinical pathology—specific feline challenges
Alkaline phosphatase (ALP). ALP is bound to membranes of bile canaliculi and bile ducts. Values are increased by any condition causing cholestasis, either intra- or extra-hepatic. Cholestasis results in increased synthesis and regurgitation of the enzyme from the biliary system into the serum.
The half-life of ALP varies between dogs and cats. In the dog, the half-life is 72 hours, in the cat only six hours. As well, feline bile canaliculi do not excrete as much ALP in cholestasis as dogs. Therefore, any elevation in cats is very significant and cholestasis and jaundice will occur often without an elevation in ALP. In contrast to the dog, systemic conditions, other than hyperthyroidism and bone growth do not cause induction of ALP synthesis in cats without concurrent cholestatic disease.
Gamma glutamyl transpeptidase (GGT). ALP is slightly more sensitive than GGT for detection of cholestatic disease in dogs but GGT is slightly more sensitive than ALP in cats. GGT increases may be greater than ALP in feline extrahepatic bile duct obstructions, cholangio-hepatitis and cirrhosis. Disproportionately low GGT with high ALP can be a useful pointer to hepatic lipidosis.
Bilirubinaemia and bilirubinuria. Dogs (males more than females) have a low resorptive threshold for bilirubin. They also have renal enzyme systems that produce and conjugate bilirubin to a limited extent. Therefore, mild bilirubinuria (up to 2+) can occur in normal dog urine of greater than 1.025 specific gravity. In contrast, cat kidneys cannot conjugate bilirubin and their renal threshold is nine times higher, therefore bilirubinuria in a cat is always pathological.
Cholesterol. Increased serum cholesterol in a jaundiced patient usually indicates major bile duct occlusion particularly in cats.
Causes of liver disease in cats
The types of pathological processes that result in liver disease in cats are relatively limited. Suppurative cholangitis is not a common histological diagnosis but it may occur more commonly than appreciated by pathologists, probably because routine symptomatic treatment instituted by most practitioners for any sick cat (intravenous fluids and antibiotics) is often effective in resolving the disorder. Pancreatitis and duodenitis are often concurrent.
In North America, hepatic lipidosis is the most common hepatic disease in cats. However, in other countries such as Australia, cases of hepatic lipidosis are very uncommon.
Non-suppurative or lymphocytic cholangitis commonly causes jaundice and may be associated with abdominal effusion. Hyperglobulinaemia is a common feature of lymphocytic cholangitis.
Primary neoplasia is very uncommon in cats and includes hepatocellular carcinoma and bile duct carcinoma. Secondary neoplasia is more common and includes lymphosarcoma, mast cell tumours and haemangiosarcoma.
Feline infectious peritonitis, and rarely, toxoplasmosis, may affect the liver.
Acute toxic hepatopathy can occur in cats particularly as they have a reduced capacity to metabolise many drugs, particularly phenolic compounds, compared to dogs. However, presumably because of their discriminatory eating habits, many potential toxins are not clinically relevant.
Congenital portacaval shunts have been reported in cats. Single extrahepatic shunts are the predominant shunt type although intrahepatic shunts have been reported. Clinical signs that occur more frequently in cats compared to dogs include: hypersalivation, aggression and seizures. Poor growth and GI signs are reported less frequently in cats compared to dogs. There are some differences in clinical pathology tests in cats compared to dogs. Increased liver enzymes and hypoalbuminaemia appear to occur less consistently in cats with hepatic encephalopathy compared to dogs; fasting and/or postprandial serum bile acids are invariably increased in dogs but may be normal in cats; and the incidence of ammonium biurate crystalluria appears to be less in cats than dogs.
Single or multiple hepatic cysts are very occasionally identified in cats but are rarely of clinical significance. Clinical signs may be observed in polycystic disease if accompanied by dilation of the common bile duct.
Treatment of hepatic disease
Treatment of specific conditions
The options for treatment of feline liver disease are not very extensive. Suppurative cholangitis is treated by antibiotics. When choosing an appropriate antibiotic the following characteristics should be considered if results of culture and sensitivity testing are not available: good liver and bile penetration, effective for suspected organisms (gram negative enteric bacteria and anaerobes) and non-toxicity. There is usually a good response to treatment although relapses are relatively common.
Lymphocytic cholangitis usually responds well to glucocorticoid treatment at a dose of 2 mg/kg q24h tapering over six to eight weeks to 1 mg/kg q48h. Antibiotics are also commonly used concurrently because abnormalities in the biliary tree can predispose to ascending infection. For cats whose clinical and pathologic signs do not permit a clear differentiation of suppurative vs. non-suppurative cholangitis, antibiotic treatment should be initiated first. If clinical improvement is not noted after one week, then glucocorticoid treatment can be instituted. There is no specific treatment for FIP. Clindamycin is the drug of choice for treating toxoplasmosis.
Treatment with ursodeoxycholic acid may be considered in cats with lymphocytic plasmacytic cholangitis. It is believed to be most beneficial in disorders where bile toxicity plays an important role in the ongoing pathology. The efficacy of ursodeoxycholic acid in veterinary patients has not been definitely established although anecdotal reports suggest it may have some benefit in patients with chronic inflammatory hepatobiliary disease. Some authors recommend ursodeoxycholic acid treatment for all cats with cholangiohepatitis where extrahepatic biliary obstruction has been eliminated. The dose is 10–15 mg/kg q24h or divided and given q12h. It is recommended that ursodeoxycholic acid be administered for three to four months after which the patient should be reassessed for improvement in biochemical markers of hepatocellular pathology. If there has been improvement, treatment is continued, but if there has been no improvement or progression, either treatment should be terminated or additional therapies such as glucocorticoids or colchicine added.
Infection. The immuncompetency of animals with hepatic disease has not been studied but extrapolating from humans, patients with serious acute or chronic liver disease have a high frequency of bacteraemia. Sepsis is a common cause of death in human patients with fulminant hepatic failure. It is therefore reasonable to prophylactically treat patients with liver disease with appropriate antibiotics, especially if there is evidence of pyrexia, leukocytosis or clinical deterioration.
Bleeding tendencies. In severe acute or chronic hepatic failure, synthesis and activation of coagulation proteins may be impaired resulting in a multi-factor coagulopathy. Subclinical coagulopathy does not require treatment but if there is obvious bleeding, a fresh blood transfusion is required to temporarily provide clotting factors. Vitamin K levels may be depleted in patients with biliary obstruction due to reduced absorption of fat-soluble vitamins. In these patients, treatment with vitamin K1 is useful prior to surgery and biopsy. In patients with coagulation defects secondary to primary hepatocellular disease, vitamin K treatment is usually not effective.
Dietary management. The aim of dietary management in patients with liver disease is to provide sufficient nutrients and energy to support hepatic tissue repair, reduce the metabolic load on the liver, such as amino acid deamination, glyconeogenesis, lipid metabolism and bile secretion, and minimise the potential for encephalopathy to develop. Diets should contain high quality protein in moderate amounts and rely on non-protein sources for most of the kilojoules. Feline L/D (Hills) or home-prepared diets based on cottage cheese, eggs, rice and liver are useful.
Patients with liver disease can have difficulties metabolising or utilising vitamins, especially B complex vitamins, or absorbing fat-soluble vitamins if they have bile duct obstruction. It is therefore usually worthwhile to supplement the diet with a multivitamin formulation or to administer vitamins by injection as needed.
Fluid therapy. Intravenous fluid therapy is required for many patients with liver disease, particularly if they are refusing all food and liquids and/or are vomiting. Hypokalaemia may occur, particularly if there is concurrent chronic renal failure and a balanced electrolyte solution should be supplemented with 20–30 mmol KCl/litre. In chronic hepatic failure, inappropriate sodium retention is common therefore, once the patient is rehydrated, the fluid should be changed to one with lower sodium concentration such as 0.45% NaCl/5% dextrose.