Diagnosis

The liver plays a central role in a wide range of metabolic processes and this is reflected in the multitude of pathophysiological derangements that can occur in liver disease. The liver has however a great reserve capacity to perform these functions, and clinical signs occur only when this reserve capacity is exhausted by extensive and progressive disease.

The exocrine pancreas is also essential for the optimal digestion and absorption of nutrients. Conversely to hepatic diseases, disorders of the exocrine pancreas were once believed to be rare in cats, but pancreatitis and exocrine pancreatic insufficiency cases are now recognized with increasing frequency which is likely due to improvements in diagnostic accuracy for this disease. Nutritional support is the keystone in management of cats with liver and pancreatic diseases.

H. Carolien RUTGERS
DVM, MS, Dipl. ACVIM, Dipl. ECVIM-CA, DSAM, MRCVS

Carolien graduated from Utrecht State University and completed an internship at the University of Pennsylvania and a residency and Masters degree at the Ohio State University. In between she worked in referral small animal practice. She joined the University of Liverpool in 1985 as a Lecturer in Small Animal Medicine and moved in 1990 to the Royal Veterinary College, where she later became a Senior Lecturer. She is now an independent consultant. Carolien has published more than 100 scientific papers and book chapters, and has lectured widely in the UK and abroad. Her major research interests are in gastroenterology and liver disease. She is a Diplomate of the American College of Veterinary Internal Medicine (ACVIM), a Foundation Diplomate of the European College of Veterinary Internal Medicine - Companion Animals (ECVIM-CA), and a RCVS Diplomate in Small Animal Medicine. Carolien has been a foundation Board member of the ECVIMCA and a member of the RCVS Small Animal Medicine and Surgery Board, and a Diploma examiner for both.

Vincent BIOURGE
DVM, PhD, Dipl. ACVN, Dipl. ECVCN

Vincent Biourge graduated from the Faculty of Veterinary Medicine of the University of Liège (Belgium) in 1985. He stayed as an assistant in the nutrition department for 2 more years before moving to the Veterinary Hospital of the University of Pennsylvania (Philadelphia, USA) and to the Veterinary Medical Teaching Hospital of the University of California (Davis, USA) as a PhD/resident in clinical nutrition. In 1993, he was awarded his PhD in Nutrition from the University of California and became a Diplomate of the American College of Veterinary Nutrition (ACVN). In 1994, he joined the Research Center of Royal Canin in Aimargues (France) as head of scientific communication and then as manager of the nutritional research program. Vincent is now Scientific Director of Health Nutrition at the Research Center of Royal Canin. He has published more than 30 papers, and regularly presents scientific papers as well as guest lectures at International Veterinary Medicine and Nutrition meetings. He is also a Diplomate of the European College of Veterinary Comparative Nutrition (ECVN).

1. Hepatobiliary Disease

Introduction

The liver is essential for the digestion, absorption, metabolism and storage of most nutrients (Table 1). Liver disease often results in malnutrition, which aggravates the disease process and affects outcome (Center, 1996; LaFlamme, 1999); it is therefore imperative to maintain nutritional status. Early nutritional intervention can reduce morbidity and mortality. Nutritional support is especially important in anorexic cats, since cats are uniquely predisposed to the development of idiopathic hepatic lipidosis when anorexic.

In acute liver disease, treatment is mainly aimed at supporting the patient during the process of hepatic regeneration, and cats may fully recover provided there has been only a single sublethal insult to the liver. In chronic liver disease, which is the most common form of liver disease in cats, the emphasis is on supporting the limited remaining metabolic capabilities of the liver and to minimize complications.

Clinical Signs

Clinical signs of liver disease in the cat are generally vague and non-specific, and more specific signs such as icterus occur only when the disease is advanced.

Diagnosis

Clinical Signs

Cats with liver disease usually do not show any clinical signs until the disease is advanced, and symptoms are vague and variable. Partial or complete anorexia and vomiting are the most common and sometimes the only clinical signs. Other clinical signs include weight loss, depression, vomiting, and occasionally diarrhea (Table 2). Jaundice and abnormal liver size are the physical findings most suggestive of liver disease, but these may also be seen in other diseases not related to the liver. Cats with liver disease tend to have hepatomegaly, but small liver size can be seen in cats with portosystemic shunts or cirrhosis. The only sign specific for liver disease is acholic (grey) feces, found in complete extrahepatic bile duct obstruction, but this is rarely found.

Differential Diagnosis

Jaundice

Jaundice is generally a late sign of liver disease, but tends to occur earlier in the course of feline liver disease than in dogs. It generally signifies severe cholestatic disease, either due to hepatocellular disease or posthepatic causes (extrahepatic bile duct obstruction, biliary rupture) (Figure 1). Hemolytic anemia, which can also cause jaundice, is rare in cats.

Figure 1. Jaundice in a Rex cat. (© C. Rutgers).

Altered Liver Size

Hepatomegaly (Figure 2) is a common finding in cats with both acute and chronic liver diseases, and results from hepatic infiltration with inflammatory cells, fat, neoplastic cells or amyloid. Reduced liver size can however be seen in cats with congenital portosystemic shunts, and in rare end-stage lymphocytic cholangiohepatitis with cirrhosis (Webster, 2005).

Figure 2. Hepatomegaly in a cat. Enlarged, yellow and friable liver from a cat that died from hepatic lipidosis. (© Sharon Center (reprinted from Waltham Focus 14.2, 2004)).

Ascites

Cats with liver disease generally do not develop portal hypertension as dogs do, and ascites is therefore an infrequent finding. It may however occur when progressive lymphocytic cholangitis has resulted in cirrhosis, and it then tends to be a modified transudate. The effusion has to be distinguished from that due to protein-losing diseases (transudate), congestive heart failure and neoplasia (modified transudate), and peritonitis, hemorrhage, and ruptured gall bladder (exudates).

Laboratory Testing

Since many of the clinical signs associated with liver disease are non-specific, laboratory assessment is essential to identify and monitor hepatic disease. However, laboratory tests will not recognize specific diseases and may furthermore be influenced by non-hepatic disease (e.g., hyperthyroidism). Baseline tests (hematology, serum biochemistries and urinalysis) are useful in initial screening to look for evidence of hepatic disease as well as other abnormalities.

- Hematological testing may reveal anemia or alterations in erythrocyte size and shape, such as microcytosis (e.g., portosystemic shunts), acanthocytes and poikilocytosis. Anemia is usually nonregenerative and most likely associated with chronic disease; a regenerative anemia is uncommon and may reflect infection with blood parasites (Haemobartonella, Babesia), and rarely auto-immune hemolysis. Leukogram changes are inconsistent and depend upon the underlying cause of the disease (Webster, 2005).

- Serum biochemistries are usually characterized by increased liver enzyme activities; hyperbilirubinemia is variable. In cats, the half-life of both serum alkaline phosphatase (ALP) and alanine aminotransferase (ALT) is much shorter than in dogs, and liver enzyme induction (e.g., corticosteroids) is uncommon. However, high liver enzymes are frequently seen in hyperthyroid cats. Gamma-glutamyl transpeptidase (γGT) is a similar enzyme to ALP that increases with cholestasis and is more sensitive for feline inflammatory biliary tract disease than ALP. This may be in part because γGT arises from predominately bile duct epithelium. Cats affected with idiopathic hepatic lipidosis usually have marked increases in ALP while γGT concentrations show only mild increases, in contrast to cats with biliary tract disease where there are usually proportionally higher γGT concentrations than ALP concentrations (Center, 1996).

- Urinalysis may show bilirubinuria, which is always abnormal in cats since they have a high renal threshold for bilirubin. Cats with portosystemic shunts may have low urine specific gravity and ammonium biurate crystalluria.

Measurement of fasting and 2-hour post-prandial total serum bile acid concentrations is a sensitive and specific indicator of hepatic function, useful for the diagnosis of subclinical liver diseases and portosystemic shunts. Determination of urine sulfated and nonsulfated bile acids has also been suggested as an alternative diagnostic test for liver disease in cats (Trainor et al., 2003), but this needs further evaluation.

The presence of fasting hyperammonemia can document hepatic encephalopathy (HE), particularly in cats with portosystemic shunts, although not all animals with HE will have abnormal fasting blood ammonia levels. Difficulties in sample handling limit the diagnostic usefulness of this test. Coagulation tests are furthermore indicated in animals with a bleeding tendency and prior to liver aspiration or biopsy (Lisciandro et al., 1998; Center et al., 2000).

Diagnostic Imaging

Survey abdominal radiography can be used to assess liver size and shape, and occasionally radiopaque choleliths (Figure 3), but ultrasonography gives more specific information about alterations in the liver parenchyma, biliary system, and portal vasculature (Leveille et al., 1996; Newell et al., 1998) (Figure 4). Ultrasonography performed by an experienced operator has a high accuracy in detecting intrahepatic portosystemic shunts (Holt et al., 1995). Color flow and pulse wave Doppler ultrasonography gives the additional advantage of visualization of blood flow direction and measurement of portal blood flow velocity (d’Anjou et al., 2004). Ultrasonography can furthermore be used for cholecystocentesis and culture in cats with suspected suppurative cholangiohepatitis, and for precision ultrasound-guided hepatic biopsy. Mesenteric portography can be used before or during surgery to confirm the diagnosis and establish the morphology of the shunting vessel. Suspected portovascular anomalies can also be evaluated by contrast nuclear scintigraphy; this is however limited to research institutions due to the need for radioactivity.

Figure 3. Lateral abdominal radiograph of a cat with cholelithiasis. Cholelithiasis is visible as multiple radiopaque densities. (Courtesy of CR Lamb, Royal © C. Rutgers Veterinary College).  

Figure 4. Ultrasound of a cat with cholestatic jaundice. The ultrasound shows a dilated common bile duct (BD), portal vein (PV), and a hypoechoic hepatic mass. (© C. Rutgers).  

Biopsy and Surgery

The ultimate diagnosis of feline liver disease other than that caused by a congenital portosystemic shunt is usually made by histological examination of a liver biopsy (Figure 5), which is essential to clarify the cause of abnormal liver tests and/or size and to develop an appropriate treatment plan (Figure 6). Samples can be obtained by fine needle aspiration, percutaneous ultrasound-guided biopsy or surgically. Fine needle aspiration can give useful information in cats with diffuse diseases such as hepatic lymphoma or idiopathic hepatic lipidosis, and may indicate the presence of inflammatory liver disease, but in most cases a biopsy is preferred for assessment of cellular changes and structure of the hepatic parenchyma (Wang et al., 2004). Coagulation status must be assessed prior to the procedure, since hemorrhage is the most common complication. Cats with cholestatic disease rapidly develop fat-soluble vitamin deficiencies, and coagulopathies responsive to vitamin K1 administration can be seen in feline hepatic lipidosis or severe cholangiohepatitis (Center et al., 2000).

Figure 5. Liver biopsy. Biopsy is essential to clarify the cause of abnormal liver tests and/or size. (© V. Biourge).  

Figure 6. Diagnosis of liver disease.