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with jaundice (Figure 1) but rarely develop asmall cirrhotic liver hence; with the exception ofportosystemic shunts, the finding of a small liveris unusual in the feline patient. It should also beremembered that the liver may be affected bysystemic diseases such as feline infectious periton-itis (FIP). This article reviews the complexgroup of disorders that is feline inflammatoryliver disease. Outwith the scope of this article, butmentioned where appropriate when consideringdifferential diagnosis, are the non-inflammatoryconditions, the most important of which is hepaticlipidosis (HL). Other non-inflammatory causesinclude liver neoplasia, portosystemic shunts,amyloidosis, and polycystic liver disease.

Inflammatory liver diseaseGiven that feline inflammatory liver disease moretypically affects the biliary system it should morecorrectly be called cholangitis, and in the UKcholangitis is the most commonly identified felineliver disorder. Different forms of cholangitis may beidentified by histopathology of liver biopsies.Unfortunately, numerous different terminologieshave been used over the years in the veterinaryliterature, hence the WSAVA have produced guidelinesin an attempt to standardize the diagnosis (1).

IntroductionIn the broadest terms, conditions affecting thefeline liver may be divided into inflammatory andnon-inflammatory diseases. Unlike dogs, whereinflammatory conditions tend to affect the hepaticparenchyma, in cats the biliary system is morecommonly affected, with extension into the hepaticparenchyma only in more severe cases. As a result,cats with hepatic disease will frequently present

Feline inflammatory liver disease - an overview

KEY POINTS

Conditions affecting the feline liver may be dividedinto inflammatory and non-inflammatory diseases.Causes of liver disease in cats are frequentlydifferent from those identified in dogs.

Patients with liver disease may vary in theirpresentation from mild, vague clinical signs toseverely ill patients with multiple metaboliccomplications.

Differential diagnosis of the most common clinicalsigns (jaundice, ascites and hepatomegaly) areconsidered. Specific diagnosis of the underlyingdisease usually requires biopsy.

Naso-esophagal, esophogal or gastrotomy tubefeeding are necessary in anorexic cats.

Danille Gunn-Moore, BSc, BVM&S, PhD, FHEA,MACVSc, MRCVS Faculty of Veterinary Medicine,University of Edinburgh, UKDr. Gunn-Moore graduated withdistinction from the University ofEdinburgh in 1991. After a year in

small animal practice she joined the Feline Centre at theUniversity of Bristol, initially as the Feline Advisory BureauScholar, then the Duphar Feline Fellow, and completed aPhD study in feline infectious peritonitis in 1997. After ashort period as lecturer in veterinary pathology at BristolVeterinary School, she returned to Edinburgh to establishthe Feline Clinic. She is now Professor of Feline Medicineand Head of Companion Animal Sciences.

Nicki Reed, BVM&S,Cert VR, DSAM (Feline)Dipl. ECVIM-CA, MRCVSFaculty of Veterinary Medicine,University of Edinburgh, UK

Dr. Reed qualified from the Universityof Edinburgh in 1988 and worked

in mixed practice before returning to the University in1999, where she initially ran the Facultys first opinionsmall animal clinic; she subsequently accepted thepost of Feline Advisory Bureau Senior Clinical Scholarin Feline Medicine in 2004. Dr. Reed is currently a Lecturerin Companion Animal Medicine at the University ofEdinburgh, with particular interests in critical care andfeline medicine.

Published in IVIS with the permission of the editor Close window to return to IVIS

Vol 20 No 3 / 2010 / Veterinary Focus / 3

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The cholangitis complex comprises lymphocyticcholangitis (LC), neutrophilic cholangitis (NC),and chronic cholangitis associated with liver fluke(1). Mild lymphocytic portal hepatitis should notbe over-interpreted as it is believed to be a non-specific reactive change possibly reflecting extra-hepatic disease or resolving hepatitis: >80% ofcats over 10 years of age were reported to havethese mild changes in one study (2).

Lymphocytic cholangitisPreviously termed non-suppurative or lymphocytic-plasmacytic cholangitis/cholangiohepatitis, theetiology of this condition is not known but animmune-mediated mechanism may play a role.

PresentationCats of any age may be affected, but disease isseen most typically in young to middle aged cats;Persian cats may have an increased risk (3).Clinical signs are usually chronic and insidiousin nature, but may be acute. Affected cats aretypically jaundiced, but appear to be clinically well,and are often polyphagic. Weight loss may beseen, despite a good appetite. Anorexia can also beseen, as can vomiting and/or diarrhea. Cats mayhave a palpably enlarged liver, and enlargedmesenteric lymph nodes; mild generalized lympha-denopathy may also be present. The disease mayprogress to causing chronic biliary cirrhosis withascites, hepatic encephalopathy, and bleedingtendencies. Ascites may be present in acute casesdue to a hepatic exudate (which can make thiscondition difficult to differentiate from wet FIP),and in chronic cases from portal hypertensionresulting from periportal fibrosis and cirrhosis.

DiagnosisSerum biochemistry often reveals mild/moderately(occasionally severely) increased liver enzymes,increased bile acids, hyperbilirubinemia, hyper-globulinemia, and hypoalbuminemia. Hematologymay reveal mild anemia, lymphopenia or lympho-cytosis, monocytosis, and/or thrombocytopenia.Blood clotting times are frequently prolonged.Ascitic fluid, if present, is typically high in protein.Ultrasound examination may show heterogeneoushepatic parenchyma, which is often hyperechoic.Histopathology typically shows periportal lympho-cytic infiltration. Portal fibrosis and proliferationof biliary ductules may also be seen.

Figure 1. Cats with liver disease exhibiting jaundice.

Differential diagnoses Differential diagnoses in a cat presenting withsome or all of the above signs are numerous andare summarized in Tables 1-3. The primarypossibilities to consider would be FIP (especiallyif ascites is present), NC, hepatic lipidosis (HL),lymphoma, and if weight loss with a good appetiteis present, hyperthyroidism or exocrine pancreaticinsufficiency.

TreatmentTreatment is largely empirical, as it is important toremember that there are NO specific treatmentsfor liver disease. Supportive therapies for hepaticdisease may be beneficial (see Table 4).

Prednisolone (1-2 mg/kg q 12h per os). Due to thesuspected immune-mediated etiology, immuno-suppression is considered appropriate. Onceremission of clinical signs is achieved, the doseshould be tapered over 6-12 weeks to 1 mg/kg q48h) and maintained on every other day ifneeded.

Other immunosuppressive agents may beconsidered e.g. methotrexate (0.13 mg/cat peros q 8-12h for 3 doses; given every 7-10 days),chlorambucil (2-5 mg/m2 per os up to onceevery 48h or 2-4 mg per os every 1-3 weeks),or cyclosporin A (measure serum levels, startat 2 mg/kg per os q 12h). Note that these drugsare all potentially hepatotoxic. Do not giveazathioprine; it is toxic to cats.

FELINE INFLAMMATORY LIVER DISEASE - AN OVERVIEW



PrognosisLimited studies are available on the outcome ofcats with LC, but the authors clinical experience isthat cats with this condition generally respondwell to treatment. Cats with ascites carry a poorerprognosis than those presenting with jaundicealone, as ascites may represent more markedfibrosis due to more advanced disease. Althoughclinical signs may resolve, owners should bewarned of the potential for relapse, and some catsmay require chronic therapy with prednisoloneto prevent relapses when medication is stopped.

Neutrophilic cholangitisPreviously termed suppurative or exudativecholangitis/cholangiohepatitis, both acute (ANC)and chronic (CNC) forms are described. Neutro-philic cholangitis is attributed to ascendingbacterial infection from the gastrointestinal tract.Infection may also ascend up the pancreatic bileduct, hence the frequent association with NC andpancreatitis. Inflammatory bowel disease (IBD) isalso frequently associated with these conditions,resulting in the term triaditis. Recently Helico-bacter infection has been suggested to play a rolein development of NC (4).

PresentationCats of any age may be affected, but middle-agedto older cats are reported to be affected moretypically. With ANC clinical signs are typicallysevere, and include fever, anorexia, vomiting andlethargy. Vomiting is frequent in all types of biliarydisease, possibly because inflammation of the bileducts stimulates their rich autonomic nerve supplyand triggers the emetic center of the brain. Catswith ANC may be jaundiced and/or demonstrateabdominal pain. Acute disease may progressto chronic disease. CNC typically has a waxingand waning time course of months to years, withperiods of anorexia, vomiting and weight loss.Cats with CNC may be jaundiced and showhepatomegaly; ascites is rare. Systemic signs may be associated with secondaryinfections, typically of the liver and/or pancreasand triaditis is common: in one study 83%of cases had concurrent IBD whilst 50% hadpancreatitis (5).

DiagnosisInitially with ANC, when the inflammation islimited to the larger bile ducts and gallbladder,there may be little or no changes in the total

Table 1.

Differential diagnoses of jaundice.

Pre-hepatic

Infection- M. hemofelis- M. hemominutum- M. turicensis- B. felis- FeLV

Immune-mediated- Primary IMHA- Drugs - methimazole- Toxin- Paracetamol/

acetaminophen- Propofol- Onions- Methylene blue

Metabolic- Hypophosphatemia- Diabetic ketoacidosis

Anomalous- Pyruvate kinase deficiency

(Abyssinian, Somali cats)- Porphyria- Erythrocyte fragility

(Abyssinian, Somali cats)

Post-hepatic

- Cholelithiasis- Rupture of bile duct or

gallbladder- Neoplasia- Pancreatitis- Pancreatic mass lesions- Obstruction of common bile

duct by duodenal disease

Hepatic

Cholangitis- Lymphocytic- Acute neutrophilic- Chronic neutrophilic- Hepatic lipidosis

Toxin- Drugs- Heavy metals

Neoplasia- Hepatocellular

carcinoma- Hepatoma- Biliary carcinoma

Infection- FIP- Toxoplasmosis

Amyloidosis (Siamese cats)

Cystic disease

Sepsis

- Salmonella- E. coli- Streptococcus spp.- Staphylococcus spp.



bilirubin and even the liver enzymes. Moretypically, there are mild to moderate increases inALT, ALP, GGT, bile acids and bilirubin. Most CNCcases have raised liver enzymes (with GGTtypically being proportionately higher than ALP).Hematology may reveal a mild to moderateleukocytosis, typically due to neutrophilia. Chronicor severe disease may result in mild anemia,lymphopenia or lymphocytosis, monocytosis,and/or thrombocytopenia. Prolonged clottingtimes may also be identified. Radiographs areoften unhelpful, with ultrasound examinationbeing the imaging modality of choice. The livertypically appears heterogeneous with increasedechogenicity. The bile ducts are typically distended(> 5 mm) and often tortuous in appearance. Thegallbladder may appear distended, with a thick-ened wall (> 1 mm) which suggests cholecystitis.Cholelithiasis (gallstones) may occasionally develop.Associated findings may include enlarged mesen-teric lymph nodes, pancreatic irregularity, and/orthickening of the duodenal walls. Ultrasoundguidance may also be used to obtain an aspirate ofbile from the gallbladder (taken through the rightmedial liver lobe where the gallbladder is attachedto the liver to reduce the risk of intra-peritonealleakage of bile). This procedure carries the riskof bile peritonitis, particularly if cholecystitis ispresent or a large bore needle is required forcentesis due to the inspissated nature of the bile.Aspirates from both the liver and bile shouldideally be sent for cytological assessment andbacterial culture (preferably aerobic and anae-robic culture). Liver biopsies are more reliable forassessment of hepatic architecture.


Differential diagnosisPrimary differential diagnoses to consider foracute disease include pancreatitis, sepsis, systemicinfections (e.g. Salmonella, FIP, toxoplasmosis),HL, hepatotoxicity or biliary tract obstruction.

TreatmentDue to the association with infection, anti-bacterials are administered, along with supportivetherapies (Table 4). Antibacterials may need to

LymphomaHepatocellular carcinomaHepatomaBiliary carcinomaMastocytoma

Cholangitis (lymphocytic,neutrophilic)

Hepatic lipidosisDiabetes mellitusHyperadrenocorticismAcromegaly

Lysosomal storage diseasesPolycystic liver/kidney disease AmyloidosisTelangectasis/peliosis

Cardiac disease

FIPToxoplasmosis (especially kittens)

Table 3.

Differential diagnosis of hepatomegaly.

Neoplasia

Inflammatory

Metabolic/endocrine

Anomalous

Congestion

Infectious

Table 2. Differential diagnoses of ascites.

Transudate

Decreased oncotic pressure- Protein-losing nephropathy- Protein-losing enteropathy- Decreased synthesis (liver

disease)- Malnutrition- Severe burns

Increased hydrostatic pressure- Cardiac failure- Portal hypertension- Cirrhosis- Portal vein thrombosis- Portal vein hypoplasia

Exudate

Septic peritonitis FIP Bile peritonitis Toxoplasmosis

Modified Transudate

Neoplasia- Abdominal carcinomatosis- Lymphangiosarcoma

Inflammation- Pancreatitis- Cholangitis

Other

Hemoabdomen Uroabdomen



Medication

s-adenosyl methionine(SAMe)

Ursodeoxycholic acid(UDCA)

Milk thistle (common name forSilybum marianum)

Cobalamin (vitamin B12)

Vitamin K1

Vitamin E

Maropitant

Metoclopramide

Ranitidine

Comments

Nucleotide essential for major hepatic biochemicalpathways with antioxidant and hepatoprotectiveproperties. A higher dose is required if enteric coatedtablets are crushed for administration via feeding tube.

Synthetic hydrophilic bile acids that aid bile flow. Ithas anti-inflammatory, immuno-modulatory, and anti-fibrotic activities, and is cytoprotective to hepatocytes.

Contains silybinin (silybin/silymarin); may be usefulfor treatment of chronic and acute liver disease,including exposure to hepatotoxins (e.g. Amanitaphalloides: Death Cap mushrooms) and cirrhosis.

Liver cobalamin stores may be depleted in the face ofnormal serum cobalamin; may help stimulate appetite.

Use 25G needle if given by injection to reduce risk ofhematoma formation.Vitamin K required for variousclotting factors.

Antioxidant often depleted with anorexia or mal-absorption.

Anti-emetic.

Central anti-emetic effect in cats questionable due to lackof dopaminergic receptors, but peripheral prokineticeffects.

Preferred to cimetidine due to intestinal prokineticeffect.

Dose

20-40 mg/kg PO q 24h

10-15 mg/kg PO q 24h

Optimal dosage unknown, rangefrom 20-50 mg/kg PO q 24h

0.125-0.25 mg/cat SC q 7-14 days

0.5-1.0 mg/kg PO or SC q 12hfor 3 doses

10 IU/kg PO q 24h

0.5-1.0 mg/kg SC q 24h

1 mg/kg q 24h IV as constant rateinfusion

2 mg/kg PO or SC or IV q 8-12h

be given for 1-3 months. E. coli is the most frequent-ly isolated organism, but mixed infections arenot uncommon. Ideally, antibacterials should beadministered as directed by culture and sensitiv-ity of bile and/or liver samples, but empiricchoices are as follows:

Amoxicillin/clavulanate (11-22 mg/kg per os q8-12h) or

Cephalexin (10-35 mg/kg per os q 8-12h) plus afluoroquinolone (well concentrated in bile). Theauthors prefer marbofloxacin (2 mg/kg per os q24h) over enrofloxacin because of the risk ofirreversible blindness in cats plus

Metronidazole for its effect against anaerobesand its immune-modulating effects (7.5-10 mg/kgper os q 12h). Do not use higher doses, as these

can be hepatotoxic, neurotoxic and potentiallyteratogenic.

Clindamycin (5.5 mg/kg per os q 12h) hasefficacy against anaerobes and gram positiveorganisms, but not gram negative organisms.It is concentrated in the bile, but care shouldbe taken with hepatic impairment, as this isthe main route of metabolism.

In very severe cases give according to 4quadrant cover IV (i.e. to cover gram positiveand negative, anaerobes and aerobes e.g.amoxicillin/clavulanate + fluoroquinolone +clindamycin or metronidazole).

Supportive therapies may be required formanagement of pancreatitis (e.g. intravenousfluid therapy, analgesia, antibiotics) and if IBD is

Table 4. Supportive therapies for feline hepatic disease.



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present, concurrent therapy with prednisolonemay also be required.

PrognosisPrognosis may depend in part on the severity ofthe disease at presentation and any concurrentproblems. The majority of cats are reported tosurvive in excess of 1 year, with 1 study reporting amedian survival time of 29 months (6).

Mixed cholangitisSome cases of disease are difficult to categorize,due to the mixed nature of the inflammatorydisease. This is especially true in more chroniccases. Unless infection can be ruled out bynegative culture of bile and hepatic tissue, it iswise to initiate antibacterial therapy in thesecases, accepting that prednisolone may also berequired if the response to antibacterials alone isnot adequate.

Chronic cholangitis associated withliver flukesThis condition is reported in association with anumber of species of the Opisthorchiidae familywhich require both snails and fish as intermediatehosts. Endemic areas for fluke species includethe Americas, India, China, Japan and NorthernEurope. Cats acquire the infection by eating rawfish, with the immature flukes migrating from theintestine to the liver via the bile ducts. Low gradeinfections may be asymptomatic, but heavyburdens may cause anorexia, vomiting, weightloss, abdominal pain, lethargy and icterus. Aperipheral eosinophilia may be present, butelevations in liver enzymes may be transient.Diagnosis requires demonstration of the adultflukes or operculated eggs on liver biopsy samplesor aspirated bile. Treatment comprises prazi-quantel (30 mg/kg per os q 24h for 5-10 days),but surgical cannulation and drainage of bilemay be required for more severe cases.

Other causes of inflammatoryliver diseaseFIP may be associated with elevated liver enzymesand bilirubin due to pyogranuloma formation andhepatic necrosis. Usually other clinical signs willbe present to suggest a systemic disease process,but differentiation of LC with ascites may requirebiopsy. Toxoplasmosis may be associated with

elevated liver enzymes, and less commonly, icterus.Diagnosis is usually based on elevated IgMantibody titers.

Drug reactions may induce hepatic damageeither through toxicity or idiosyncratic reactions.The most commonly recognized drugs causingtoxicity include diazepam, methimazole andcarbimazole, potentiated sulphonamides,tetracyclines, phenobarbitone, griseofulvin(especially FIV+ve cats) and paracetamol(acetaminophen).

Nutrition in cholangitis casesWhilst some cats with cholangitis may continue toeat well, or if inappetant may respond to tempting,hand feeding or syringe feeding, many cats mayrequire placement of feeding tubes. In the firstinstance, naso-esophageal tubes are preferred,as they are easy to place and do not require

Figure 3. Placement of an esophagostomy feeding tube in a cat.

Figure 2. A naso-esophageal feeding tube providing nutrition to a cat.



1. WSAVA Liver Standardization Group. WSAVA Standards for Clinical andHistological Diagnosis of Canine and Feline Liver Diseases. Philadelphia:Saunders Elsevier, 2006; 68-71.

2. Weiss DJ, Gagne JM, Armstrong PJ. Characterization of portal lymphocyticinfiltrates in feline liver. Vet Clin Pathol 1995; 24: 91-95.

3. Lucke VM, Davies JD. Progressive lymphocytic cholangitis in the cat. J SmallAnim Pract 1984; 25: 249-260.

4. Greiter-Wilke A, Scanziani E, Soldati S, et al. Association of Helicobacterwith cholangiohepatitis in cats. J Vet Intern Med 2006; 204: 822-827.

5. Weiss DJ, Gagne JM, Armstrong PJ. Relationship between inflammatoryhepatic disease and inflammatory bowel disease, pancreatitis, and nephritisin cats. J Am Vet Med Assoc 1996; 209: 1114-1116.

6. Gagne JM, Armstrong PJ, Weiss DJ, et al. Clinical features of inflammatoryliver disease in cats: 41 cases (1983-1993). J Am Vet Med Assoc 1999; 214:513-516.


REFERENCES

Step 1 - Calculate calorie requirements based onresting energy requirements (RER).

RER (kcal) = 70 x [bodyweight (kg)]0.75

Step 2 - Identify the calorie content of the diet(kcal/mL).

Daily volume of food (mL) =

Step 3 - Calculate maximal volume to feed at onemeal (10 mL/kg). Allow for fluid used toflush the feeding tube. Calculate the numberof meals required per day.

Patients that have been anorexic for anumber of days may develop metaboliccomplications (re-feeding syndrome) as aresult of changing from a catabolic state.To try to prevent this, feeding should begradually re-introduced, for example on dayone give 1/3 of calculated RER, day two 2/3of RER and day three total RER.

Table 5.

Calculation of nutritional requirements.

anesthesia (Figure 2). In addition, the risk ofhemorrhage is minimal. However, the narrowdiameter of the feeding tube limits the type of dietthat can be administered via the tube, andirritation of the nasal passages may develop withprolonged use. Assuming the cat can toleratea general anesthetic, an esophagostomy tube(Figure 3) is easy to place and allows for moreprolonged feeding, potentially in the homeenvironment. If the underlying disease merits it,a gastrostomy tube may be placed, although thisis a more complicated technique requiring amore prolonged anesthetic. The cats individualcaloric requirement should be calculated so anappropriate feeding plan can be generated(see Table 5).

ConclusionInflammatory feline liver disease is a relativelycommon problem in general practice. Accuratediagnosis requires examination of biopsy materialobtained from the liver, ideally by histopathology.With appropriate supportive treatment, theprognosis for these conditions is generallyfavorable, although recurrence is possible andan owner should always be informed of this.

RER (kcal)Diet kcal/mL


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