Feline-hepatic Lipidosis -pathophysiology,clinical Signs And Diagnosis

Vol. 22, No. 9 September 2000

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Refereed Peer Review

FOCAL POINT ★ Cats with hepatic lipidosis (HL)— a common, reversible cause of icterus in cats—should be systematically evaluated for concurrent underlying diseases that could alter prognosis, treatment, and recovery.

Feline Hepatic Lipidosis: Pathophysiology, Clinical Signs, and Diagnosis Auburn University

KEY FACTS ■ Experimentally, dietary energy must be restricted 50% to 75% for at least 2 weeks to induce HL in cats. ■ HL frequently occurs secondary to other underlying diseases, most commonly cholangiohepatitis, inflammatory bowel disease, or chronic pancreatitis. ■ Serum biochemical profiles of cats with HL reveal marked elevations in bilirubin and alanine aminotransferase, dramatic increases in alkaline phosphatase, and normal to mild increases in γ-glutamyltransferase. ■ Nearly half of all cats with HL have at least one coagulation abnormality, most commonly vitamin K deficiency. ■ Coagulation abnormalities are positively correlated with the magnitude of increase in serum alkaline phosphatase.

Brenda Griffin, DVM, MS ABSTRACT: Feline hepatic lipidosis is a common form of hepatobiliary disease in domesticated cats. Typical clinical findings include anorexia, weight loss, muscle wasting, icterus, hepatomegaly, and increased serum liver enzyme activities. Although the cause of the disorder remains undetermined, its pathogenesis likely involves the unique pathways of protein and lipid metabolism in cats. Diagnosis is based on history, physical examination, clinical pathology, radiography, abdominal ultrasound, cytology of fine-needle liver aspirates, and liver biopsy. When hepatic lipidosis is suspected, a clinical investigation into predisposing conditions should be made.

F

eline hepatic lipidosis (HL) is a syndrome characterized by severe hepatocellular lipid accumulation, intrahepatic cholestasis, and impaired liver function. First described in 1977 by Barsanti and colleagues,1 HL is one of the most common liver diseases in cats, representing 49% of 175 feline liver biopsies in one recent study.2 It occurs primarily in middle-aged to older cats. The cause of HL is unknown. Its pathogenesis likely involves the unique pathways of protein and lipid metabolism in cats. Feline HL may occur either as a primary event (idiopathic feline HL) or secondary to another disease process. This article discusses the pathophysiology, clinical signs, and diagnosis of feline HL. A companion article will discuss the treatment of this important feline disease.

PATHOPHYSIOLOGY The lipid concentration in the liver increases after ingestion of a high-fat meal, as a result of mobilization of fat stores during fasting, or because of hepatic synthesis of lipids from carbohydrates.5,7 Lipid is typically oxidized within mitochondria or secreted as part of a very-low-density lipoprotein. If lipid buildup occurs, lipid is stored in vacuoles within hepatocytes. HL occurs when lipid accumulation becomes severe. In most species, lipid accumulation is innocuous; in

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cats, however, metabolic deweight. Histologic examinarangements and liver dysfunction of weekly liver biopsy tion appear to occur in respecimens revealed that obesisponse to hepatocellular lipid ty was not associated with liver accumulation. parenchymal lipid accumulaThe mechanisms of hepatic tion but that fasting resulted fat accumulation include inin HL in all 15 cats beginning creased delivery of fatty acids at 2 weeks. Histologic examito the liver, decreased release nation of successive liver biopof very-low-density lipoprosies revealed progressive hepateins, and decreased oxidation tocyte lipid accumulation of fatty acids within mitoin all 15 cats. These findings chondria. 5,7 Increased fattysuggest that clinical HL should acid mobilization to the liver not develop in otherwise occurs during starvation. Cats healthy obese cats after only a with HL usually have a perifew days of fasting. od of anorexia that leads to Laboratory models have severe protein restriction and been developed to define the adipose tissue mobilization to degree of food restriction rethe liver, resulting in excessive quired to induce HL in cats. hepatic triglycerides. In addiOne author found that lipid tion, starvation may reduce Figure 1—Although hepatic lipidosis most commonly af- did not accumulate in the livthe synthesis of the proteins fects obese housecats, obesity is not the only factor in- ers of six cats fed 60% of their required for very-low-density volved in its pathogenesis. calculated maintenance enerlipoprotein formation, which gy requirements for 14 weeks in turn makes the liver unable but did accumulate in the livto remove excess triglycerides. ers of six other cats fed only 25% of their calculated Transmission electron microscopy reveals that the hepmaintenance energy requirements for the same amount atocytes of cats with HL have reduced quantities of perof time.10 In another study, weight loss was induced in six obese oxisomes, endoplasmic reticulum, Golgi complexes, lysoand six non-obese cats by feeding them 50% of their somes, and mitochondria.8 These organelles all perform metabolic functions necessary for hepatic lipid metabcalculated maintenance energy requirements for 29 olism and fatty-acid oxidation. Electron microscopy days; none of the cats developed apparent changes in studies also demonstrate that lipid-distended bile canaliphysical, hematologic, or serum biochemical values inculi collapse, resulting in intrahepatic cholestasis. As a sedicative of HL.11 Based on this study, the degree of energy restriction needed to induce HL was defined to be quela, both serum and tissue concentrations of bile acids between 50% and 75%. No differences between obese increase and hepatotoxic bile acids accumulate, further and non-obese cats in terms of their responses to food damaging the liver parenchyma. restriction were observed in either of these models. Although the precise pathologic mechanism(s) of feThus it appears that near-total anorexia, restriction of line HL remains a mystery, most researchers believe that an essential nutrient, significant weight loss, or factors multiple factors associated with cats’ unique metabolism other than obesity are required for the development of of proteins and lipids are involved. Proposed pathophysiHL (Figure 1). ologic mechanisms include metabolic changes associated Another proposed pathophysiologic mechanism of with starvation and obesity, protein and nutrient defifeline HL involves carnitine, an amine synthesized from ciencies, relative carnitine deficiency, and insulin resistmethionine and lysine. Carnitine is required for transance. port of fatty acids through hepatic mitochondrial memOne study confirmed that long-term fasting may inbranes for oxidation and removal. Plasma, liver, and duce clinical HL in obese cats.9 Voluntary fasting occurred when obese cats were offered a purified, nutriskeletal muscle carnitine concentrations are higher in tionally complete but unpalatable diet. Clinical signs and cats with HL than in control cats,12 suggesting that increased carnitine synthesis may be a metabolic response laboratory results consistent with HL were observed in to HL to facilitate fatty-acid oxidation.7 If the demand 12 of 15 cats after 5 to 7 weeks of fasting and were assofor carnitine exceeds its synthesis, a relative deficiency ciated with a 30% to 35% reduction in initial body ANOREXIA ■ OBESITY ■ DIETARY ENERGY RESTRICTION ■ CARNITINE

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of carnitine would exist despite the increased concentrations.7 This theory of relative carnitine deficiency is supported by a study that assessed the effects of increased dietary carnitine in an HL model in cats.13 In cats fed 25% of their required energy needs, hepatic lipid accumulation was minimal in cats given supplemental carnitine compared with control cats. This finding implies that carnitine requirements are much higher for cats with increased mobilization of fat to the liver than for normal cats. Carnitine supplementation may thus be a rational and beneficial treatment for cats with HL. Insulin resistance is another theory to explain the cause of HL. Breakdown of stored body fat (lipolysis) normally occurs when insulin function is inadequate. Both glucose tolerance and insulin response to glucose infusion were decreased in healthy cats undergoing severe restriction of calorie intake and weight loss, and the cats subsequently developed HL.14 When cats were returned to a positive nutritional plane, glucose tolerance and insulin response normalized and HL resolved. This phenomenon suggests that once energy restriction occurs, poor insulin function may set up a cycle for continued lipolysis and ultimately the development of HL.

CLINICAL SIGNS Feline HL is a disease of middle-aged to older cats of either sex; no known breed predilections exist. One retrospective study of 77 cats with severe HL showed that female cats were affected nearly twice as often as males.15 A second retrospective study of 96 cats by some of the same authors, however, revealed approximately equal numbers of affected male and female cats.3 Most cats that develop HL are obese housecats.5 Illness is usually preceded by anorexia of a few weeks’ duration.1 Some cats become anorectic after a stressful event (e.g., a move to a new home, separation from an owner) or a change to a less-palatable (e.g., weight-reduction) diet. Owners often note a progressive onset of anorexia and depression accompanied by intermittent vomiting over several weeks. Median duration of illness before diagnosis was 4 weeks in one study.15 As liver function worsens, cats may develop icterus, severe loss of muscle mass, and such signs of hepatoencephalopathy as severe depression and ptyalism. Icterus can be detected on the soft palate first, followed by yellow tinting of the sclera, mucous membranes, and skin. Neurobehavioral signs indicative of hepatoencephalopathy other than ptyalism and depression are rare.15 Physical examination findings usually include obvious hepatomegaly, jaundice, dehydration, and a loss of at least 25% of body weight. Retrospective studies indicate that 49% to 76% of

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cats have secondary HL.3,15 According to the authors of these studies, this range may reflect increased motivation to identify underlying or initiating diseases. Disorders associated with secondary HL include liver diseases (cholangiohepatitis, extrahepatic bile duct obstruction, portosystemic vascular anomalies), neoplasia (urinary bladder transitional cell carcinoma, intestinal adenocarcinoma, intestinal lymphosarcoma, metastatic carcinoma), renal diseases (pyelonephritis, chronic interstitial nephritis), hyperthyroidism, gastrointestinal diseases (eosinophilic enteritis, lymphocytic–plasmacytic enteritis), diabetes mellitus, and pancreatitis.15 Retrospective studies have demonstrated an increased incidence of inflammatory bowel disease and chronic pancreatitis in cats with cholangiohepatitis.16 In fact, cholangiohepatitis, inflammatory bowel disease, and chronic pancreatitis are the most common diseases associated with secondary HL.3 One recent study characterized the incidence of acute pancreatitis in cats with HL.17 Five (38%) of 13 cats histologically diagnosed with HL also had acute pancreatitis. Cats with HL alone were indistinguishable from those with concurrent acute pancreatitis in terms of signalment, history, physical examination, and clinicopathologic features, except that cats with acute pancreatitis were more likely to be cachectic and have peritoneal effusion and coagulation abnormalities. The recovery rate was 20% for cats with concurrent acute pancreatitis compared with 50% for cats with HL alone. Because of the rate of disease coincidence, the difficulty in identifying cats with concurrent acute pancreatitis, the opposing therapies of the two diseases, and the significant prognostic differences, cats with HL should be rigorously evaluated for concurrent acute pancreatitis (see Pancreatitis in Cats17,18). Feeding a cat with HL may exacerbate acute pancreatitis, whereas fasting a cat with acute pancreatitis may worsen HL.

DIAGNOSIS Diagnosis of feline HL should be based on history, physical examination, clinical pathology, radiography, abdominal ultrasonography, and cytology of fine-needle aspirates of the liver. Definitive diagnosis is based on liver biopsy; HL is present when more than 50% of hepatocytes in an acinus have vacuolar lipid accumulation.15 When HL is suspected, a clinical investigation into predisposing conditions for secondary HL should be made. Serum total thyroxine concentrations, feline leukemia virus and feline immunodeficiency virus testing, and chest radiography should be used to rule out primary diseases and screen for metastasis (neoplastic disease may be an underlying condition). Additional

INSULIN RESISTANCE ■ PTYALISM ■ CONCURRENT ACUTE PANCREATITIS

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diagnostic tests (e.g., toxoplasmosis titers, heartworm tests) may be indicated based on results of other tests or geographic location.

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assess liver function is obtained by collecting paired fasting and postprandial samples of serum Feline acute pancreatitis is an infrequently bile acids. 19 Elevations in recognized disease; it is characterized by acute serum bile acids indicate the inflammation of the pancreas, and clinicopathologic presence of cholestasis and are Clinicopathologic more sensitive than is bilirubin findings are consistent with extrahepatic 17 Features for the detection of cholestasis. cholestasis. Peripancreatic fat necrosis and acinar Clinicopathologic features cell necrosis and inflammation are common Bilirubinuria, which preare characterized by hyperbilicedes the development of bilirubinemia and at least a two- findings. Lethargy and anorexia are the most rubinemia, is another useful fold increase in the activities common clinical signs of pancreatitis in cats; marker of cholestasis (or other of serum alanine aminotrans- vomiting and abdominal pain are reported only cause of hyperbilirubinemia) in ferase, aspartate aminotrans- occasionally.18 Causes of acute pancreatitis in cats cats. Although dogs may norferase, and alkaline phospha- have not been definitively established. Antemortem mally have small quantities of tase (ALP), with only a small, diagnosis is difficult. Prognosis is poor, and cats bilirubin in concentrated urine if any, increase in γ-glutamylsamples, bilirubinuria in cats is transferase activity.15 The most with acute pancreatitis have a worse prognosis always abnormal and is a predramatic increases usually in- compared with cats with chronic pancreatitis. lude to hyperbilirubinemia. Chronic pancreatitis is often an incidental volve ALP concentrations, with Other results of serum bioover half of the cats in one large finding at necropsy in cats and is characterized by chemical profiles in cats with study having fivefold or greater interstitial fibrosis, acinar atrophy, and lymphocytic HL include normal concentraincreases.15 The near-normal infiltrates.17 The cause of chronic pancreatitis is tions of total protein, normal values of serum γ-glutamylor mildly subnormal albumin transferase activity contrast also unknown. concentrations, normal to subwith the substantial increases in normal blood urea nitrogen asγ-glutamyltransferase activity that develop in other forms sociated with a normal creatinine concentration, normal of acquired feline hepatobiliary disorders (e.g., cholangioor mildly increased total cholesterol concentration, and hepatitis).15 euglycemia to hyperglycemia.15 Electrolyte concentraEvaluation of serum globulin concentrations can tions vary, with hypokalemia being the most frequent also be helpful in distinguishing HL from other serious and significant abnormality15; signs of severe hypokal15 emia include profound weakness and ventroflexion of cholestatic disorders. Most diffuse hepatobiliary diseases are associated with an acute-phase inflammatory the neck. response and hyperglobulinemia. Serum biochemical Decreased blood urea nitrogen concentration associprofiles of cats with primary HL are typically characterated with HL may be caused by chronic anorexia or inized by normal globulin concentrations. sufficient urea-cycle function.15 Hypercholesterolemia is usually seen in cats with extrahepatic cholestasis caused Evaluation of serum total bilirubin concentration by bile-duct obstruction. The mechanism for hyperand serum ALP activity may be useful in differentiating cholesterolemia in feline HL is unknown. Hyperglybetween primary (idiopathic) and secondary HL. In cemia may be associated with stress (catecholamine reone large retrospective study of feline HL, the median sponse) or changes in glucose tolerance and/or insulin total bilirubin concentration of cats with primary HL response. Other laboratory changes may reflect dehydrawas 4.8 mg/dl compared with 1.9 mg/dl in cats with tion, electrolyte abnormalities, and chronic illness. secondary HL.15 Serum ALP concentrations reflected a median 6.9-fold increase above maximum normal referBaseline hematologic test results of cats with HL are ence range values in cats with primary HL versus a 3.8characterized by a normal packed cell volume or mild to fold increase in cats with secondary HL. moderate nonregenerative anemia, the presence of poikAlthough the majority of cats with HL are icteric, the ilocytes, and a normal leukocyte count.15 The cause of poikilocytosis in cats with HL and liver disease is absence of hyperbilirubinemia does not exclude a diagunknown. It has been suggested that alterations in cellnosis of HL. Elevations in serum liver enzymes develop wall lipid may induce conformational changes in erybefore hyperbilirubinemia, and histologic evidence of throcytes or that altered liver function may compromise severe HL precedes development of cholestasis.15 Hepatic function should be evaluated in any nonicteric cat erythrocyte metabolism, leading to loss of membrane with suspected HL. The best diagnostic information to integrity.

Pancreatitis in Cats17,18

BIOCHEMICAL PROFILES ■ BILIRUBINURIA ■ HYPOKALEMIA ■ POIKILOCYTOSIS

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Coagulopathies Coagulopathies are common in cats with a variety of liver diseases, including HL. One study found the prevalence of coagulation abnormalities in 22 cats with naturally occurring liver disease to be 82%.20 Approximately 45% of cats with HL have one or more coagulation abnormalities.3,15 Clinical bleeding tendencies, as evidenced by bruising, overt bleeding, or excessive bleeding from venipuncture sites, were noted in 20% of cats in the largest retrospective study of felines with HL.3 Clinical bleeding tendencies were noted in 50% of cats with one or more coagulogram abnormalities. This finding suggests that lack of clinical bleeding tendencies does not exclude the presence of a coagulopathy. All cats with HL should be evaluated for coagulopathies by performing a platelet count and coagulation profile (activated partial thromboplastin time, prothrombin time, fibrinogen, and fibrin degradation products). Abnormal coagulation test results may reflect vitamin K deficiency, decreased production of clotting factors by the liver, or consumptive coagulopathies. The most common abnormality is prolongation of the prothrombin time consistent with vitamin K deficiency.3,15 Cats with HL may develop vitamin K depletion secondary to anorexia and malabsorption of vitamin K as a result of severe cholestasis; this is because vitamin K is a fatsoluble vitamin and thus requires bile excretion into the intestines for fat absorption. Hypofibrinogenemia is another common coagulogram abnormality in cats with HL.3,15 It may correspond to hepatic synthetic failure and absence of an acute phase response. Increased serum ALP activity showed significant statistical correlation with coagulation abnormalities in a study of 22 cats with naturally occurring liver disease.20 Vitamin K deficiency, which occurred in 50% of these cats, was the most common coagulation abnormality. These findings suggest that hepatic diseases resulting in marked cholestasis and marked increases in serum ALP activity (such as HL) are likely to be associated with derangements of vitamin K absorption and may increase the risk for coagulopathies and bleeding. Diagnostic Imaging Radiography and abdominal ultrasonography can be helpful in diagnosing feline HL. These imaging techniques often reveal hepatomegaly and assist in excluding other disease processes potentially associated with secondary HL. Abdominal ultrasonography is particularly useful because it can help rule out biliary obstruction, focal masses, and acute pancreatitis. In addition, it can be used to guide biopsies of the liver and/or other structures as indicated based on findings. VITAMIN K DEFICIENCY ■ HYPOFIBRINOGENEMIA

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Ultrasonography is perhaps the best noninvasive tool for evaluating the pancreas. As mentioned, cats with HL should be rigorously evaluated for concurrent acute pancreatitis. However, diagnosing pancreatitis in cats is extremely challenging because clinical signs and clinicopathologic features are vague and nonspecific. In addition, serum amylase, lipase, and trypsinlike immunoreactivity concentrations are frequently normal.21,22 Such radiographic changes as decreased contrast in the cranial abdomen, dilated and gas-filled small intestine, and transposition of the duodenum are sometimes present but may be subtle. Experienced ultrasonographers, however, can usually locate and visualize the pancreas where it lies dorsomedial to the duodenum. An acutely inflamed pancreas frequently appears as a hypoechoic mass.21,23 Variable amounts of free abdominal fluid may be present as well23; if so, abdominocentesis to obtain fluid for cytologic evaluation is indicated and may yield valuable diagnostic information. Ultrasonography reveals the lipidic liver to be diffusely hyperechoic. Ultrasonographic diagnosis has classically been based on evaluation of the relative echogenicity of the liver compared with that of falciform fat (i.e., the liver appears hyperechoic compared with falciform fat in cats with HL).24 Although this criterion was initially believed to be a highly sensitive and specific diagnostic indicator of HL, a recent prospective study revealed that the liver is diffusely hyperechoic compared with falciform fat in clinically normal obese cats.25 Additionally, both lymphosarcoma and cirrhosis have been described as diffusely hyperechoic diseases of the liver.26 The presence of a hyperechoic liver, therefore, is neither a specific finding nor a sensitive indicator of HL in cats. Hepatobiliary scintigraphy is a noninvasive diagnostic imaging technique that has been recently evaluated for diagnosis of feline hepatobiliary diseases. Although this technique can be useful in assessing the severity of hepatic dysfunction and determining whether extrahepatic biliary obstruction is present, it cannot differentiate specific disease entities.27

Fine-Needle Aspiration Although laboratory testing and diagnostic imaging can identify a high likelihood of HL, evaluation of hepatocellular morphology is required to make a definitive diagnosis. Fine-needle aspiration of the liver may reveal vacuolar changes typical of HL (Figure 2) but should be interpreted with caution because it cannot rule out such concurrent liver diseases as cholangiohepatitis with certainty and may miss focal lesions. Fine-needle aspirates can usually be collected with no or only minimal sedation, and complications are extremely rare (see Fine-Needle Aspiration of the Feline

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Figure 2—Cytology of a fine-needle aspirate from the liver of a cat with hepatic lipidosis. The severe cytoplasmic vacuolization of the hepatocytes represents fatty infiltration.

Liver). Hepatic cytologic samples are most useful in diagnosing diffuse diseases that readily exfoliate cells, such as HL or lymphosarcoma.

Liver Biopsy Definitive diagnosis of feline HL requires histopathologic evaluation of a liver biopsy specimen. Liver biopsies offer the advantage of evaluating both hepatocellular morphology and liver lobule architecture. Cats should be evaluated for coagulopathies before undergoing liver biopsy. Pretreatment with subcutaneous vitamin K1 (1 mg/kg 12 hours before biopsy) is advised.3,4 Techniques for obtaining liver tissue include exploratory celiotomy and percutaneous needle biopsy (blind, ultrasound-guided, or laparoscopic methods). The technique selected largely depends on the condition of the cat and the skill and experience of the surgeon. Because of metabolic derangements and impaired liver function, cats with severe HL are often poor surgical candidates,3,4,7 and major surgery should be avoided before the initial stabilization phase of their therapy.3,4 Advantages of exploratory surgery include the ability to visually inspect the liver, select biopsy sites, control bleeding, and obtain biopsies from other organs. Both impression smears of biopsy specimens and histopathologic evaluation are recommended. In a retrospective study of 56 hepatic cytology specimens, cytologic evaluation of impression smears concurred with histopathologic diagnosis in 83% of specimens.28 Results of cytology may be obtained rapidly and may aid practitioners in making treatment decisions while they await results of histopathology. In cats with HL, histopathology reveals the presence of swollen vacuolated hepatocytes and canalicular bile stasis. Vacuoles stain with oil red-o, confirming the presence of lipid. Little

ABDOMINAL ULTRASONOGRAPHY ■ ABDOMINOCENTESIS ■ CYTOLOGY ■ HISTOPATHOLOGY

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Fine-Needle Aspiration of the Feline Liver ■ Place the cat in dorsal recumbency with the body tilted so that the thorax is slightly higher than the abdomen. In this position, the liver moves caudally, usually allowing palpation of an enlarged liver. ■ Use a 10-ml syringe and a 1-inch, 22- or 23-gauge needle to perform fine-needle aspiration. A 1.5-inch needle may be needed in obese cats (selection of needle length can be aided by reviewing abdominal radiographs to identify the thickness of the falciform fat pad through which the needle is to be inserted to reach the liver). ■ Shave and sterilely prepare the cranioventral abdomen between the costal arches. ■ If the liver cannot be palpated, perform blind aspiration by inserting the needle midway between the midline and the left costal arch at a level 1 cm caudal to the end of the xiphoid process (see figure). (Care should be taken to avoid entering the right side of the liver to prevent accidental aspiration of the gall bladder.) ■ Aiming cranially, insert the needle at an 80˚ to 90˚ angle. (Care should be taken to avoid the use of longer needles or narrower insertion angles to prevent penetration of the diaphragm.) ■ Advance the needle approximately 1 inch. Briskly aspirate two or three times, applying 3 to 6 ml of suction each time. A brisk linear advancement of the needle followed by a return to its original position while suction is maintained may aid in sample retrieval. (Care should be taken to avoid excessive motion of the needle during

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aspiration to prevent trauma to the liver and contamination of the sample with peripheral blood.) Release all pressure and withdraw the needle. If blood appears in the hub of the needle at any time during aspiration, discontinue aspiration, select an adjacent site, and reaspirate. Immediately eject aspirated material onto slides: Remove the needle, fill the syringe with air, and expel the air through the needle. Grossly, liver aspirates appear reddish brown. Place a second glass slide on top of the sample and gently slide it off the lower slide (i.e., make a “squash prep smear”). Air-dry slides as rapidly as possible to preserve cellular morphology. Examine one slide to determine whether the sample is adequate. Multiple aspirations often improve diagnostic yield.

to no inflammation is present. On gross examination, the liver appears yellow and mottled. Its cut surface is often greasy, and sections float in water or formalin.

line HL. Current therapeutic recommendations will be discussed in a future article.

SUMMARY Feline HL is a common hepatobiliary disease in domesticated cats and results in severe impairment of liver function. All cats with HL need thorough systematic evaluation to rule out primary underlying diseases. Persistent anorexia should be avoided, particularly in obese cats. Cats that are anorectic for less than 1 week, however, are unlikely to develop HL.9 The pathogenesis of feline HL is multifactorial, and studies are needed to focus on the unique pathways of hepatic metabolism leading to lipid accumulation and clinical disease. Results of such studies should be useful in the development of methods to prevent and treat fe-

The author thanks Drs. D. S. Spano, DVM, PhD, Diplomate American College of Veterinary Practitioners, and D. K. Macintire, DVM, MS, Diplomate American College of Veterinary Internal Medicine and American College of Veterinary Emergency and Critical Care, College of Veterinary Medicine, Auburn University, Alabama, for their encouragement in writing this article.

ACKNOWLEDGMENTS

REFERENCES 1. Barsanti JA, Jones BD, Spano JS, et al: Prolonged anorexia associated with hepatic lipidosis in three cats. Feline Pract 7:52–57, 1977. 2. Gagne J, Weiss DJ, Armstrong PJl: Histopathologic evalua-

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3. 4. 5. 6. 7. 8. 9. 10. 11. 12.

13. 14.

15. 16. 17.

tion of feline inflammatory liver disease. Vet Pathol 33:521– 526, 1996. Center SA, Warner K: Feline hepatic lipidosis: Better defining the syndrome and its management. Proc 16th Annu ACVIM Forum:56–58, 1998. Norsworthy G: Improving survival in cats with hepatic lipidosis. Proc TNAVC:285, 1998. Dimski DS, Taboada J: Feline idiopathic hepatic lipidosis. Vet Clin North Am Small Anim Pract 25:357–373, 1995. Jacobs G, Cornelius L, Allen S, Greene C: Treatment of idiopathic hepatic lipidosis in cats: 11 cases (1986–1987). JAVMA 195:635–638, 1989. Dimski DS: Feline hepatic lipidosis. Semin Vet Med Surg (Small Anim) 12:28–33, 1997. Center SA, Guida L, Zanelli MJ, et al: Ultrastructural hepatocellular features associated with severe hepatic lipidosis in cats. Am J Vet Res 54:724–731, 1993. Biourge VC, Groff JM, Munn RJ, et al: Experimental induction of hepatic lipidosis in cats. Am J Vet Res 55:1291– 1302, 1994. Armstrong PJ: Feline hepatic lipidosis. Proc 7th Annu ACVIM Forum:335–337, 1989. Dimski DS, Buffington CA, Johnson SE, et al: Serum lipoprotein concentrations and hepatic lesions in obese cats undergoing weight loss. Am J Vet Res 53:1259–1262, 1992. Jacobs G, Cornelius L, Keene B, et al: Comparison of plasma, liver, and skeletal muscle carnitine concentrations in cats with idiopathic hepatic lipidosis and in healthy cats. Am J Vet Res 51:1349–1351, 1990. Armstrong PJ, Hardy EM, Cullen JM, et al: L-carnitine reduces hepatic fat accumulation during rapid weight reduction in cats. Proc 10th Annu ACVIM Forum:810, 1992. Biourge V, Nelson RW, Feldman EC, et al: Effect of weight gain and subsequent weight loss on glucose tolerance and insulin response in healthy cats. J Vet Intern Med 11:86–91, 1997. Center SA, Crawford MA, Guida L, et al: A retrospective study of 77 cats with severe hepatic lipidosis: 1975–1990. J Vet Intern Med 7:349–359, 1993. Weiss DJ, Armstrong PJ, Gagne J: Inflammatory liver disease. Semin Vet Med Surg (Small Anim) 12:22–27, 1997. Akol KG, Washabau RJ, Saunders HM, Hendrick MJ: Acute pancreatitis in cats with hepatic lipidosis. J Vet Intern

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Med 7:205–209, 1993. 18. Hill RC, Van Winkle JJ: Acute necrotizing pancreatitis and acute suppurative pancreatitis in the cat: A retrospective study of 40 cases (1976–1989). J Vet Intern Med 7:25–33, 1993. 19. Center SA, Erb HN, Joseph SA: Measurement of serum bile acid concentrations for diagnosis of hepatobiliary disease in cats. JAVMA 207:1048–1054, 1995. 20. Lisciandro SC, Hohenhaus AE, Brooks M: Coagulation abnormalities in 22 cats with naturally occurring liver disease. J Vet Intern Med 12:71–75, 1998. 21. Williams DA: Feline pancreatic disease. Proc 15th Annu ACVIM Forum:407–408, 1997. 22. Swift NC, Marks SL, MacLachlan NJ, et al: Serum-like immunoreactivity in the diagnosis of feline pancreatitis [abstract]. Proc 17th Annu ACVIM Forum:699, 1999. 23. Nyland TG, Mattoon JS, Wisner ER: Ultrasonography of the pancreas, in Nyland TG, Mattoon JS (eds): Veterinary Diagnostic Ultrasound. Philadelphia, WB Saunders Co, 1995, pp 85–94. 24. Yeager AE, Mohammed H: Accuracy of ultrasonography in the detection of severe hepatic lipidosis in cats. Am J Vet Res 53:597–599, 1992. 25. Nicoll RG, O’Brien RT, Jackson MW: Qualitative ultrasonography of the liver of obese cats. Proc 1996 Annu Sci Meet Am Coll Vet Res:7–10, 1996. 26. Newell SM, Selcer BA, Cornelius LM: Imaging techniques for evaluating feline hepatobiliary disease. Vet Med 9:859– 868, 1994. 27. Newell SM, Selcer BA, Roberts RE, et al: Hepatobiliary scintigraphy in the evaluation of feline liver disease. J Vet Intern Med 10:308–315, 1996. 28. Kristensen AT, Klausner JS, Weiss DJ, Hardy RM: Liver cytology in cases of canine and feline hepatic disease. Compend Contin Educ Pract Vet 12(6):797–809, 1990.

About the Author Dr. Griffin is affiliated with the Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, Alabama. She is a Diplomate of the American College of Veterinary Internal Medicine.