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Diagnosing Liver DiseaseA roundtable discussion

Diagnosing Liver DiseaseA roundtable discussion

Sponsored by an educational grant from IDEXX Laboratories

Dr. Dennis DeNicola: As every practi-tioner knows, liver disease can be frus-trating to diagnose.Today’s roundtableincludes internationally recognizedexperts who share a common goal: toprovide practical information that willhelp readers diagnose hepatic disease indogs and cats. Let’s begin by addressingthe various types of liver disease.

Types of liver disease Dr. David Williams: First, we must differ-entiate between dogs and cats becauseliver disease is so different in each spe-cies.Also, I categorize liver disease asjuvenile-onset and hereditary (differenttypes but with some overlap) vs. adult-onset and acquired.And then acute vs. chronic.

Dr. David Twedt: I classify liver disease bybasic histologic findings, such as inflam-matory or noninflammatory changes. Forexample, cholangitis is more common incats and chronic hepatitis is more com-

mon in dogs. In some dog breeds, abnor-mal copper accumulation is one cause ofhepatitis. I also see a range of acute toxicliver diseases associated with variousdrugs or other compounds, as well asneoplastic liver disease.

Next, I classify conditions that may beassociated with extrahepatic biliary ob-structive disease, such as those caused bycholelithiasis or pancreatitis, followed bythe vascular diseases, including the con-genital portosystemic shunts usuallyidentified in young dogs.

Finally, another common classificationis various histologic changes that occursecondary to other systemic and meta-bolic diseases. Some refer to these liverchanges—where the liver is not the pri-mary problem—as reactive hepatopa-thies. Every day, practitioners must try todetermine if the patient has secondarychanges or primary liver disease. Forexample, does the dog have Cushing’ssyndrome? Does the cat have hyperthy-roidism and secondary changes? Or do

they both have primary liver disease? I think the secondary changes are themost common cause of abnormal liverenzyme activities.

Dr. Robert Hawthorne: Practitionerslook at an animal’s history and physi-cal examination findings and worktoward a histologic diagnosis. Manyliver cases are presented to us as ictericdogs or cats. But I think we’re gettingbetter at catching these liver diseasesearlier with biochemical testing. So I classify liver diseases similarly—byspecies, age, and whether a patient’shistory reveals a toxic insult or injury.Then I proceed with diagnostic testingto differentiate problems such as vac-uolar hepatopathy, cholangiohepatitis,and extrahepatic diseases.

Dr. Sharon Center: I would add anothercategory: cats with hepatic lipidosis anddogs with vacuolar hepatopathies.We seea large number of dogs with a vacuolar

Moderator:Dennis DeNicola,DVM, PhD, DACVP

IDEXX LaboratoriesWestbrook, Maine

Participants:Sharon Center, DVM, DACVIM

Dept. of Clinical SciencesCollege of VeterinaryMedicineCornell UniversityIthaca, New York

Robert Hawthorne, DVM

White Rock AnimalHospitalDallas,Texas

Brian Poteet,MS, DVM, DACVR, DABSNM

Gulf Coast VeterinarySpecialistsHouston,Texas

Jörg M. Steiner,MED.VET, DR.MED.VET, PhD,DACVIM, DECVIM-CA

Dept. of Veterinary SmallAnimal Clinical SciencesCollege of VeterinaryMedicine & BiomedicalSciencesTexas A&M UniversityCollege Station,Texas

David Twedt, DVM, DACVIM

Dept. of Clinical SciencesCollege of Veterinary Medi-cine & Biomedical SciencesColorado State UniversityFort Collins, Colorado

David A.Williams,MA, VETMB, PhD, MRCVS, DACVIM,DECVIM-CA

Dept. of Veterinary SmallAnimal Clinical SciencesCollege of VeterinaryMedicine & BiomedicalSciencesTexas A&M UniversityCollege Station,Texas

DIAGNOSING LIVER DISEASEA ROUNDTABLE DISCUSSION

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hepatopathy that represents a uniquehistologic response associated withsteroid hormone abnormalities orresponse to a systemic disease.

PrevalenceDeNicola: What is the prevalence ofliver disease in dogs and cats?

Center: Practitioners see a lot of animalswith increased liver enzyme activities.These animals may or may not have liverdisease because increased enzyme activi-ty may merely reflect the sentinel organstatus of the liver and its secondary re-sponse to systemic and metabolic condi-tions. So doctors must perform thoroughdiagnostic testing to determine whichanimals truly have liver disease.

Williams: So the question becomes,“What percentage of animals with ab-normal liver enzyme activities truly haveliver disease?” I suspect it’s less than 10%.

Hawthorne: I agree; the prevalence ofprimary liver disease is 10% or less.

Causes of liver disease DeNicola: So let’s first address the mostcommon causes of primary liver disease,starting with infection-based hepatitis.How often do you see that?

Center: In our referral institution, weculture everything, and we find positivecultures (multiple colonies) on our liverbiopsies up to 30% of the time. Experi-mental data1,2 indicate that transmuralpassage of bacteria from the alimentarycanal can be an important factor invok-ing liver injury.

While we do see dogs with hepatichistopathologic lesions similar to lesionsclassified as viral hepatitis in people, wehaven’t identified causal viral infectionsin veterinary medicine (other than ade-novirus, for which we vaccinate).3

DeNicola: Obviously, there are manyways of classifying liver disease. Table 1on page 4 includes some of the morecommon disease entities using a histo-logic classification scheme.As discussed,the overall impression about the inci-dence of primary liver disease in animalswith suggestive liver enzyme abnormali-ties is 10% or less.

Clinical signsDeNicola: Besides icterus, what are othercommon signs of liver disease?

Hawthorne: Certainly we see the “ain’tdoing right” animals with lethargy.Wemay see elevated enzyme activities,weight loss, or possibly ascites.

Twedt: The signs in dogs with liver fail-ure are quite straightforward: gastroin-testinal signs, such as vomiting and diar-rhea, and, as the disease progresses,

ascites, icterus, and possibly neurologicsigns attributed to hepatic encephalopa-thy. But earlier in the disease process, thesigns can be quite vague. I think a lot ofdogs have liver disease with no clinicalsigns. If a blood chemistry profile identi-fies abnormal liver enzyme activities,then veterinarians can identify liver dis-ease with a proper workup.The liver hasa great reserve capacity. So if you seepatients with clinical evidence of liverdisease, such as ascites or icterus, theylikely have advanced disease.

Dr. Jörg Steiner: I categorize clinicalsigns into groups—subclinical, mild,moderate, and severe.

DeNicola: It is essential, then, thatpatients with possible liver disease

receive complete physical examinationsand diagnostic workups. Something assimple as dental disease may be causingthe increased liver enzyme activities.And aside from end-stage liver patientswith obvious clinical signs, it’s impor-tant to look for cyclic problems andgeneral signs that are not specific to the liver but could be associatedwith the gastrointestinal tract, kidneys,or the pancreas.

Major enzyme categoriesDeNicola: In veterinary schools, liverenzymes are usually categorized as indi-cators of 1) cholestatic disease and 2)hepatocellular injury or leakage. Is this a reasonable approach?

Center: We should use the phrase“cholestatic-induction enzymes” whenreferring to alkaline phosphatase (ALKP)based on a collection of investigativestudies.The activity of ALKP reflects aninduction phenomenon associated withenhanced protein transcription.This phe-nomenon has been widely studied as aresponse to corticosteroids (endogenousand exogenous).

DeNicola: I agree. It would help prac-titioners recognize that 1) inductionof the classically identified cholestaticenzymes, such as ALKP and gamma glutamyl transferase (GGT), is not just due to cholestasis and 2) otherenzymes, including alanine amino-transferase (ALT), can be induced to a much lesser degree with the samestimuli. Are there additional classifica-tion suggestions beyond cholestatic-induction enzymes?

Steiner: Why classify them at all?There are only three or four enzymes,so I just think about how they can be elevated.

Center: For practitioners, it makes adifference because seeing an animalwith increased transaminases oneweek and then observing increasedcholestatic enzyme activity a weeklater suggests that the patient had ahepatic insult during the first week.The enzyme activities collectively cantell a story about the associatedpathologic process.

“Practitioners see a lot of animals with increasedenzyme activities. To determine which animals truly have liver disease,doctors must perform thorough diagnostic testing.”

—Sharon Center, DVM, DACVIM

DIAGNOSING LIVER DISEASE

Alanine aminotransferaseDeNicola: Now let’s discuss each enzymeand address elevation, liver specificity, andhalf-life. I’d like to start with ALT.Whatdoes an elevation of ALT indicate?

Steiner: Hepatocellular damage. IncreasedALT activity is primarily an indication ofhepatocellular injury—at least in dogsand cats.

DeNicola: So what about mild increases inALT? What is clinically relevant?

Twedt: I sometimes see dogs with slightALT increases and, histologically, they’recompletely normal.This is often frustrat-ing. Perhaps a specific lesion was missed,or the histology did not reflect changes inhepatocyte membrane permeability withALT leakage. I think animals with ALTincreases and no clinical signs should befollowed serially. If the enzymes are twoor three times the normal range or per-sistent and unexplainable, those are thepatients I want to investigate further.

DeNicola: What does a marked increase inALT mean vs. a minor increase?

Twedt: ALT is a sensitive indicator ofliver disease but not necessarily specificfor a primary disease that we have totreat.We have to keep that in mind. Inaddition to assessing the enzyme values,we need to evaluate the entire patientfor systemic disease and always deter-mine the animal’s drug history.Variousmedications can cause liver changes andincreased enzyme activity.We must al-ways perform a physical examination toidentify whether the animal has otherobvious problems, such as neoplasia.Theenzyme values alone don’t specify theliver as the problem.

Steiner: I use a twofold and fivefold rule.With a twofold to fivefold ALT elevationin an otherwise normal animal presentedfor an elective procedure, I watch thatpatient and recheck it. I may postpone theprocedure, but if it’s medically indicated—for example, a dental cleaning in a patientthat eats poorly because of its dental dis-ease—I do not postpone.With a persistenttwofold elevation that is reproducible overtwo or three months, I get more aggres-sive diagnostically. If the ALT is initially

higher than a fivefold elevation, I pursueadditional diagnostics immediately.

Center: When we find threefold increasesin serum ALT activity, we go back with afresh mindset and review the patient’s his-tory, asking specific questions about drugs,herbal or alternative therapies, foodchanges, and topical treatments.We’re particularly alert to changes that caninvoke a vacuolar hepatopathy in dogs.This is a major cause of increased liverenzyme activity secondary to a variety ofnonhepatic primary health problems.

Increased ALT activity is also commonin hyperthyroid cats and cats with subclin-ical hepatic lipidosis, low-grade cholangio-hepatitis, or inflammatory bowel disease.

If ALT activity is increased threefoldand the history and physical examinationfindings suggest a problem, we recom-mend a liver function test.We do this inour hospital by evaluating paired serumbile acid concentrations (a fasting or ran-dom sample followed by a two-hour post-prandial sample).

If function tests are abnormal, we rec-ommend abdominal ultrasonography anddiscuss the possibility of a liver biopsy.The ultrasonogram helps establish liversize; allows us to collect a preliminaryhepatic aspiration sample for cytologicinspection; and helps us evaluate the bil-iary tree, pancreas, and alimentary canal.The ultrasound findings may increase theindex of suspicion for certain disorders(e.g., a small liver with irregular marginsin chronic hepatitis [dogs]).

If liver function tests are normal, werecheck liver enzymes in two to threeweeks. If liver function remains normalbut liver enzymes remain abnormal, werecommend an abdominal ultrasound.Ultimately, with chronicity, we may rec-ommend a liver biopsy.

Williams: So the more abnormal theenzyme activity is, the more certain youare that something’s going on.

Hawthorne: Many practitioners still regardmeasurement of ALT and ALKP activitiesand total bilirubin concentration as liverfunction tests.They’re not.

DeNicola: Right. Practitioners need to domore than a general blood chemistry pro-file to accurately assess liver function.

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Types of HepaticDisease

Hepatocellular injuryReversible injuryIrreversible injury (necrosis)

Hepatitis InfectiousNoninfectiousToxic

ObstructiveIntrahepatic Extrahepatic

HepatopathyVacuolar (dog and cat)Copper storage (dog)Hepatic lipidosis (cat)

VasculopathyPortosystemic shuntMicrovascular anomaly

NeoplasiaPrimary hepaticSecondary (metastatic)

Hepatic insufficiencyHepatic cirrhosis

Table 1

A ROUNDTABLE DISCUSSION

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Steiner: Out of 100 dogs with a two-fold or threefold ALT elevation, only afew develop liver disease requiring treat-ment. I’m not saying we shouldn’t testfor these abnormalities, but I think weneed to be cautious about being overag-gressive with follow-up diagnostics.

Hawthorne: That’s a good point.Afterpracticing for more than 20 years, I findmyself getting caught in a trap. Mynew-graduate colleagues focus on theseenzyme elevations and say,“We’ve gotto check them.” But the animal is clini-cally normal.The client then wants tosee the older doctor because the olderdoctor won’t run all the tests again. Onthe other hand, if we don’t recheck theenzyme activities six months later, wemay have an animal in crisis.

Center: And the records prove that youdidn’t pursue it.

DeNicola: Let’s say a practitioner has ayoung animal that needs a dental clean-ing or lipoma removal.The physicalexamination findings are normal, butpresurgical blood tests reveal a twofoldto threefold elevation in ALT activity.What should happen next?

Center: Too often the veterinarian ig-nores the results, anesthetizes the dog,and performs the elective procedure.The dog does fine and returns muchlater for its annual visit, at which timethe liver enzymes are still abnormal andeven a little higher than before.Again,the abnormal results aren’t investigatedwith additional diagnostics.This goes onand on. Ultimately, the dog is referred tous and we identify advanced copperstorage disease upon liver biopsy.We seethe liver enzyme abnormalities docu-mented in the record but no indicationthat additional diagnostics were offered.

I would have anesthetized the dogand performed the procedure, but I’dhave had the animal return sooner torecheck the liver enzyme activities. Ifthe enzyme activities remained high, Iwould have 1) performed liver functiontests (or at least offered the option), 2)explained what information I expectedto obtain, and 3) offered imaging stud-ies. If the liver function tests and imag-ing results were normal but the ALT

activity remained chronically high, Iwould have recommended a liver biop-sy. Sometimes this process takes monthsbefore an owner is motivated to achievea definitive diagnosis.

Hawthorne: Let’s say I have a middle-aged dog with moderate dental diseasethat is receiving a nonsteroidal anti-inflammatory drug (NSAID) because hehas trouble traversing stairs. Last year thedog’s ALT activity was at the low end ofthe reference range. But the preanes-thetic blood test results now show thatthe dog’s ALT activity has increasedtwofold or threefold above the referencerange.The increase could be related tothe dog’s dental disease or the drug.

The owner doesn’t want to stop theNSAID because the dog has been actinglike a puppy again.What would you do?

Twedt: I would take the dog off thedrug, clean the teeth, and follow up. Ifthe enzyme abnormalities resolve, thenI’d pursue other options, such as chon-droprotective agents or specialty diets.And if the enzymes remain abnormal,I’d pursue the liver.

Steiner: I agree, but I’d also makesure the owner is 100% comfortable

with doing the procedure now ratherthan waiting.

Center: I would stop the drug, initiateantibiotic therapy for 10 days, recheckthe enzymes, and clean the teeth.Youdon’t want to pursue liver disease beforeyou’ve cleaned the teeth.

DeNicola: So when should practitionersautomatically pursue liver function test-ing when ALT is increased? What aboutanimals with no previous test results, noobvious dental disease or other clinicalfindings? Should those animals immedi-ately undergo additional diagnostics?

Hawthorne: In animals with twofold tothreefold ALT increases, I’d recheckthem in three to four weeks. If the en-zyme activities are persistently high—that red flag has gone up two or threetimes—practitioners need to pursueadditional diagnostics, even in clinicallynormal animals.

Twedt: After practitioners have investi-gated drugs, alternative therapies, andother diseases, and if they’re performingan ovariohysterectomy or other abdom-inal surgery on a patient with increasedenzyme activity, they should always takea liver biopsy while they’re in there.

Steiner: I perform additional diagnosticsimmediately in patients with a fivefoldto sevenfold increase in ALT activity,even if they don’t have clinical signs. Butin cases with up to fivefold ALT eleva-tions, I monitor them and add othertests as needed.

DeNicola: What is the half-life of ALTand how does it affect test interpretation?

Hawthorne: ALT activity seems to spiketwo to three days after a hepatic insult.

DeNicola: How long will ALT activityremain elevated? Or how often shouldwe test to evaluate hepatocellular injury?

Center: An acute hepatic insult hasramifications beyond a single day.Hepatocytes adjacent to those under-going cytolytic necrosis will also bedamaged. Enzymes are liberatedbecause of primary and secondary

“ALT is a very sensitive indicator of liver disease but not necessarily specificfor a primary disease that we have to treat.”

—David Twedt, DVM, DACVIM


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PUTTING THE PIECESTOGETHER:• ALT elevations in dogs

and cats primarily indicate hepatocellulardamage.

• ALT activity seems tospike two to three daysafter a hepatic insult.

• ALT’s half-life is veryshort, but you have to consider all the other things occurringin the liver, plus systemic disease and drug therapy.

• Two sources of ALKP are liver and bones.

phenomena. But if it’s a one-time insult,the enzyme activities will decrease. Forexample, in dogs receiving NSAIDs, youmay see ALT activities increase abruptlyand then decline over a three-week periodafter drug withdrawal.The enzyme activitydoesn’t normalize as soon as the drug iswithdrawn, which you would expect witha simple induction phenomenon.

While the rate of liver enzyme declinecan be important over a relatively shorttime period, a decline in enzyme activityover a long time period can be misinter-preted.A substantial decline in functionalhepatic mass may develop such that on-going inflammation may not increase theenzyme activities as high as previouslydemonstrated.This scenario can be ob-served in dogs with cirrhosis where labo-ratory parameters may appear quiescentover six months or so. However, one daythe dog may present for advancing ascitessecondary to portal hypertension andhepatic fibrosis.

Twedt: ALT’s half-life is very short, butyou have to consider all the other thingsoccurring in the liver, plus systemic diseaseand drug therapy. In asymptomatic clinicalcases with increased enzyme activities, Imonitor the patient for several weeks. Ifenzymes do not return to normal in twoto three weeks, I consider an ongoinginsult, and that is a key to further investi-gating the patient.

Center: An abstract presented at anACVIM conference details the half-life of injected transaminases.They were re-ported as 77 hours for ALT and 22 hoursfor aspartate aminotransferase (AST).4

Williams: So two to three days.We retestin intervals of weeks rather than days.

DeNicola: If we use the short half-lifeinformation regarding ALT, retestingbefore the three- to four-day period won’tprovide much information unless thepatient has significant progressive disease.

Steiner: I wouldn’t say that. If a dogcomes in acutely sick with an ALT of 800U/L, I want to know whether it’s 300 or3,000 U/L the next day.

Center: But checking them too frequent-ly can also lead to mistakes. For exam-

ple, we see animals when they’re desper-ately ill.They may be dehydrated, andwe run the first blood sample collected.Then an intern loads the patient withfluids.The next morning, we collect asecond blood sample, and the liverenzyme activities are decreased, butthey’re not in the normal range.Theymay be half what they were on the firsttest, but part of that is a dilution effect.So practitioners need to watch thetrends but be aware of a dilutional phe-nomenon when rehydrating severelyhemoconcentrated patients.

DeNicola: So generally speaking, muchdepends on the clinical presentation.Theanimals with active disease, primary or sec-ondary, may need more frequent testing,while asymptomatic animals with increasedliver enzyme activities may not need to beretested for several weeks to a month.

Alkaline phosphataseDeNicola: Let’s discuss the enzyme that’sprobably the most confusing to practition-ers and clinical pathologists:ALKP.Whatsources of this enzyme should practitionersconsider to be important?

Steiner: Two sources of ALKP are liver and bones. But in dogs, two isoenzymesoriginate from the liver: a liver-specificisoenzyme and a corticosteroid-inducedisoenzyme.

Center: Studies show that the corticosteroid-induced isoenzyme in hepatocytes derives from the bilecanaliculi (a specialized portion of the membrane between the hepatocytes)and the intestines.5-7 The important fact clinically is that this enzyme isinduced before it increases in serum.This is why it reflects both cholestasisand induction.

DeNicola: What is the value of isoenzymecharacterization?

Hawthorne: We look at increases in ALKPactivity as a cholestatic problem. Ormaybe it’s induction.We’ve seen ALKPincreases in some patients with inflamma-tory bowel disease, and we wonder whyALKP is elevated. It’s probably comingfrom the gut, but we still look at that as acholestatic mechanism.


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DeNicola: It’s a complicated issue because even with induction, such ascorticosteroid induction, there’s hepa-topathy present as well, which results incholestatic isozyme increases.At thatpoint, the ALKP isoenzyme patternbecomes relatively insignificant to us.

At what point above the referencerange do we need to categorize ALKPas cholestatic or induced?

Center: We’ve seen ALKP activities tentimes higher (or more) than normal asan apparent result of induction.

DeNicola: But let’s discuss lower increas-es.At what point can we eliminate boneand intestinal ALKP isoenzymes andconsider cholestatic disease?

Center: I would be very surprised ifbone produced more than a twofoldincrease.

Twedt: Two times. Maybe three, max.

DeNicola: That’s what the literature says,so twofold to threefold is our cutoffpoint. But how specific is ALKP (indogs) as a cholestatic disease indicatorwhen ALKP activity is above thattwofold to threefold increase?

Steiner: Of my canine patients withgreater than fourfold ALKP elevations,about 80% have Cushing’s disease,long-term corticosteroid administra-tion, or some other condition—notcholestatic disease. So I would say 20%of dogs with fourfold ALKP elevationshave cholestatic disease, but that’s pure-ly an estimate.

DeNicola: If we compare a dog with agreater than threefold ALKP increaseto a dog with a greater than threefoldincrease in ALKP plus an ALT eleva-tion, does that change your impressionof what the ALKP increase means?

Steiner: If a dog has a threefold ALKPelevation and a 1.5-fold ALT elevation,the ALKP is the driving force behindmy workup. But if both enzyme activi-ties are increased threefold, then ALTbecomes the driving force of my work-up, and I search more intently for Cush-ing’s disease than cholestatic disease.

Twedt: With increases in ALKP activityalone, I always think of corticosteroids,including topical medications, such asotic or ophthalmic preparations.

Center: Or homeopathic agents thatcontain adrenocorticotropic hormones(ACTHs).

Twedt: My differential diagnoses fordogs with increased ALKP activities areCushing’s disease, hepatocellular adeno-mas, vacuolar hepatopathies, and possiblymetastatic bone tumors. I often do imag-ing studies because I’m concerned aboutneoplasia in older dogs with elevatedALKP activity.

DeNicola: What about dogs with high ALKP but no obvious signs ofCushing’s disease—they’re just drink-ing a little more.What’s the next diag-nostic step?

Center: We perform ultrasound-guided, fine-needle liver aspirates tosee whether a vacuolar change is pres-ent. If we detect a vacuolar cytologicpattern, we sit down with the ownerand discuss evaluating corticosteroidhormones, including a sex hormoneprofile. For us, it is more affordable to

discuss this option at the outset of test-ing so we can either 1) survey thesample for cortisol abnormalities, 2)store a portion of the sample for futuresex hormone profiling (pre- and post-ACTH administration), or 3) pursuedirect testing of cortisol and sex hor-mone values.

Steiner: I do the hormone profile, too.But I do an ACTH stimulation test firstand obtain enough serum for the sexhormone profile as well. I measure cor-tisol concentrations first because it’s aninexpensive test and I can do it in-house. If the ACTH stimulation test isnormal, I send the samples for sex hor-mone testing.

Twedt: If I see a dog with a highALKP and signs that may be compati-ble with Cushing’s disease, I’ll do anACTH stimulation test. If the patienthas a high ALKP and no signs thatindicate Cushing’s disease, I will doimaging studies to make sure I’m notdealing with morphologic liverchanges. I have identified patients withliver neoplasia or other problems. Imay do a fine-needle aspirate, and ifthe owner agrees, I’ll measure the sexhormone concentrations. I find manyof these vacuolar hepatopathies haveincreased 17-hydroxyprogesteroneconcentrations.

Hawthorne: Advanced diagnostic imag-ing is not a routine test for practition-ers.The crux of diagnosing these liverdiseases is and will be, for the foresee-able future, blood work—repeatableblood work and referrals. In my opin-ion, we don’t do as many biopsies aswe should.Twenty-five years ago whenI started practicing, exploratory laparo-tomies were done all the time.We gotlots of good answers, and now we’reafraid to do them.

DeNicola: What do you do if a felinepatient has increased ALKP activity?

Williams: I do additional workups to look for significant liver disease.

Twedt: I think it’s unusual to see highALKPs in cats, except for cats with hepatic lipidosis.

“Practitioners need to domore than a general bloodchemistry profile to accu-rately assess liver function.”—Dennis DeNicola, DVM, PhD, DACVP


Center: Except we see high ALKPs insome cats with chronic cholangiohepatitis.

DeNicola: So increased ALKP is quite spe-cific for cholestatic disease in cats. Muchof this is based on the well-documentedextremely short half-life of ALKP in catsfrom noncholestatic sources, such as bone and the gastrointestinal tract.Thisshort half-life for ALKP in the cat is a double-edged sword because the half-lifefor cholestatic-source ALKP is also short.This makes ALKP extremely specific forcholestasis; however, because of the shorthalf-life of the cholestatic source of ALKP,we see many cases of cholestasis in the catwithout an increased ALKP.The sensitivityof ALKP for cholestasis in the cat is relatively low.

Gamma glutamyl transferaseDeNicola: Let’s discuss GGT. In what tis-sues is it found, and which diseases causeGGT activity increases?

Twedt: GGT is found in the intestine,pancreas, liver, and kidneys. It indicatesinduction and cholestasis. I evaluate GGTmore commonly in cats.When I’m tryingto decide if a cat has biliary tract disease orhepatic lipidosis, I look at GGT in rela-tionship to ALKP;ALKP may be higherthan GGT activities in hepatic lipidosis.I’ve also had cases where GGT has beenthe major enzyme abnormality in dogshaving significant cholestatic liver disease.So I don’t discount GGT in dogs.

DeNicola: In the normal liver,ALKP isassociated with the bile canalicular surfaceof the hepatocyte, but GGT is associatedmore with the biliary epithelial cells. Inthat regard, I look at the enzymes as a pro-file. GGT may not be associated with anactive cholestatic process, but it may indi-cate biliary epithelial hyperplasia. How dothe rest of our panel members use GGT?

Center: We evaluate GGT, which is cellmembrane-affiliated, in dogs and cats.Anearly study we did showed that cats thatdid not have cholangiohepatitis or pancre-atitis as primary disorders causing inappe-tence and hepatic lipidosis didn’t developGGT elevations.8 Consequently, GGT canbe used as a flag to indicate inflammatorydisease involving cell membranes in the

pancreas or liver. In some of our cats withhepatitis, GGT activity is higher than thecoordinate ALKP activity when you lookat the achieved fold increases, respectively.

DeNicola: I agree. If practitioners evaluateGGT, they must make sure they have anaccurate reference range for the speciesthey’re dealing with.

Center: I would suggest that practitionerslook at GGT activity in dogs with ahepatic mass. If GGT is increased, it mayindicate a hepatocellular carcinoma, amalignancy that they’d want to investigateby obtaining thoracic radiographs andlooking for metastatic disease.

Hawthorne: I agree. In that situation, thecost-benefit ratio of measuring the GGTis very good.

DeNicola: What about GGT half-life?

Center: I think the induction phenome-non underlying the enzyme increasemakes it a moot point. Usually, the induc-tion phenomenon abates slowly so that theserum enzyme activity diminishes slowly.

ASTDeNicola: I would like to briefly discussAST.AST is relatively widely distributedin tissues not specific to the liver, makingincreases in enzyme activity difficult tointerpret. Do any of you use it specificallyfor the liver?

Twedt: I associate increased AST activitywith muscle and liver problems. First I lookat creatine kinase (CK) activity. If this ishigh, I assume that the AST elevation indi-cates muscle damage. But I keep in mindthat major muscle damage can cause ALT,AST, and muscle creatine kinase (CK3 )activity increases. However, if AST increasesoccur in conjunction with marked ALTincreases, that supports hepatocellular dam-age.AST is found in mitochondria, and itis free in the cytosol. Marked increases ofALT and AST and normal CK suggest sig-nificant hepatocellular damage.

DeNicola: If you can eliminate muscleand erythrocyte origins (hemolysis),what does the AST and ALT profile tellyou regarding their return to normal values?

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PUTTING THE PIECESTOGETHER:• Increased ALKP is quite

specific for cholestaticdisease in cats.

• If AST increases occur in conjunction withmarked ALT increases,that further confirmshepatocellular damage.

• Terrier breeds, including(but not limited to)Yorkshire terriers,bichons, Shih Tzus,Tibetan spaniels, andHavanese, may haveabnormally increasedserum bile acid concen-trations because ofmicrovascular dysplasia.


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Twedt: AST has a shorter half-life, so if you’re following a case and see theAST returning to the normal range,that may be a better indicator of prog-nosis, especially in animals with acuteliver toxicoses.

Center: I evaluate AST activity in dogs and cats. In animals with acutefulminant hepatic failure, the ASTactivities are often profoundly in-creased, possibly reflecting mitochon-drial and more severe hepatocellularinjury. No one has yet demonstratedthe utility of the AST:ALT ratio asapplied in human medicine where itimplicates the severity of hepatocellu-lar necrosis (i.e., AST > ALT signifiesmitochondrial injury).

DeNicola: Other liver enzymes, such asSDH and LDH, provide minimal valuefor the small animal practitioner.Practitioners won’t get SDH valuesfrom in-clinic chemistry analyzers.Some doctors will get them from aca-demic hospitals or reference labs. SDHactually proves to be relatively specificfor hepatocellular injury and is helpfulin ruminants and horses where ALT haslittle or no value.

LDH is available with some in-clinic chemistry analyzers and from ref-erence laboratories.Veterinarians mustkeep in mind the wide distribution ofLDH and be cautious in interpretingincreased enzyme activity.

Liver function testingDeNicola: Liver enzyme activities don’t relay information about liverfunction. Elevations in these enzymesindicate only hepatocellular injury(ALT), induction or cholestasis(ALKP), and cholestasis (GGT). Inaddition, enzymes don’t say anythingabout the reversibility or irreversibilityof the damage.With that said, how doyou define a function test?

Williams: A liver function test evaluatesthe overall functional capacity of oneaspect of liver metabolic activity.Andinadequate perfusion will also impairhepatic function.

Twedt: That’s an important pointbecause the liver has many different

functions, and there isn’t one functiontest that evaluates all of them.

Hawthorne: The liver has more than1,500 documented functions.

DeNicola: Traditionally, we sort func-tion tests into five categories: hepaticsynthesis, peripheral blood uptake,conjugation, secretion, and portalblood clearance. Is this reasonable forpractitioners trying to decipher theseverity of liver disease? Some of the function tests are included in ourroutine chemistry profiles, such asalbumin, glucose, and cholesterol forsynthesis and bilirubin profiles forperipheral blood uptake, conjugation,and secretion.

Center: But there are extenuating circumstances associated with all theparameters on a chemistry profilerelating to liver function, which makesdata interpretation a complex process.Glucose is a good example. Does the animal have sepsis? What’s theinsulin concentration? Is it a dog or acat? How old is it? Does the patienthave a high white blood cell count?Has the animal been receiving intra-venous dextrose?

DeNicola: So even if you’re addressingliver-specific parameters, you still have

to consider other variables and look atthe whole animal.

Sensitivity of liver function testsDeNicola: What is the sensitivity of thecommonly used function tests for he-patic synthesis (albumin, glucose, andcholesterol) vs. hepatic uptake, conjuga-tion, and secretion (bilirubin and bileacid profile)?

Steiner: By definition, they can’t besensitive because the liver has an overca-pacity for almost anything it synthesizes.I don’t think there’s a single test thatwould show a change with less than50% damage.

Twedt: But the sensitivity increases asyou go down that list.

DeNicola: You’re saying that tests like thebile acid profile are more sensitive thanalbumin, glucose, or cholesterol concen-trations or bilirubin profiling.

Serum bile acid assaysDeNicola: Bile acid assays are sensitiveindicators of hepatobiliary disease.Whenshould bile acid assays be done?

Williams: If you measure bile acidsonly in animals with suspected liverdisease, you can interpret the testresults with confidence. If you measurebile acids routinely as part of a meta-bolic panel and not just in patientswith suspected liver disease, a numberof animals will have abnormal testresults that are difficult to interpretbecause their clinical pictures do not fitwith primary liver disease.

DeNicola: So do you choose to performa bile acid assay based on clinical pres-entation or your enzyme panel results?

Williams: It depends on the wholeclinical picture: the animal’s clinicalsigns, the abnormalities that the chem-istry panel does or doesn’t reveal, andwhether the patient is a young dog or cat.

Twedt: I measure bile acids if the liverenzyme activities are abnormal and Iwant to investigate the liver’s function

“If I have a feline patient withincreased ALKP activity, I doadditional workups to look forsignificant liver disease.”

—David A. Williams, MA, VETMB, PhD,MRCVS, DACVIM, DECVIM-CA


10

Repeat liver functiontest and liver

enzymes in 3 to 4weeks.

Monitor biannually.

ALT elevated ALT normal

Perform liver function test.**Monitor. Re-evaluatein 3 to 4 weeks.

Other diseasespresent

Primary liver diseaseis not confirmed;

investigate nonhepat-ic disease, discontinue

drug therapy, etc.

Other diseases not presentOther diseasespresent

Collect history and performphysical examination.

Perform blood chemistry,CBC, and urinalysis.

The Steps in Investigating Liver Disease

Abnormal liverenzymesNo abnormal clinical signs

Review drug and travel history. Investigatenonliver disease, such as hypothyroidism

or adrenal disease where appropriate.

Abnormal clinical signs

Signs and test results sug-gestive of liver disease*

Vague, nonhepaticclinical signs present

Review drug and travelhistory. Investigate

nonliver diseases, such ashypothyroidism, adrenal,or autoimmune disease

where appropriate.ALT is >3 times referencerange (show repeatability

within days to weeks).

ALT is <2 to 3times refer-ence range.

Other diseasesnot present

Primary liver diseaseis not confirmed;

investigate nonhepat-ic disease, discontinue

drug therapy, etc.

Normal results Abnormal results

Normal results

Perform liver function test.**

Perform diagnosticimaging

(radiography and ultrasonography).***

Consider liver aspirateand/or biopsy.****

Normal results Abnormal results

Recheck liverenzymes and consid-er liver function test.

* Overt hepatic signs: Ascites, palpable liver mass, icterus withouthemolytic disease, hepatic encephalopathy, hypoglycemia,hypoalbuminemia, hypocholesterolemia, bilirubinemia.

** Care should be taken during sample collection to avoid hemolysis.*** Accuracy of results are equipment and operator dependent.

**** Coagulation panel (PT, PTT, BMBT, platelet evaluation) shouldbe completed before sample collection.

Recheck liverenzymes in 3 to 4 weeks.

Abnormal results


11

or if I suspect a vascular anomaly, suchas a congenital portosystemic shunt. IfI see an animal with obvious liver dis-ease or a large, palpable liver mass, Iwouldn’t do a bile acid assay. I use bileacids to tell me if I should furtherinvestigate the liver.

DeNicola: So focusing on the group ofanimals with abnormal liver enzymeactivities (vs. general screening) is proba-bly most valuable.

Hawthorne: In our practice, we measurebile acids after obtaining a blood chem-istry panel showing elevated liver en-zyme activities but before performingimaging studies.

Twedt: Bile acid assays are relativelyinexpensive, and they provide a lot ofgood information.

Center: There’s just one problem, and ithappens in terrier breeds, including (butnot limited to) Yorkshire terriers, ShihTzus, Maltese, bichons,Tibetan spaniels,and Havenese. Many of these breedsmay have abnormally increased serumbile acid concentrations because ofmicrovascular dysplasia.

Williams: And there could be otherthings going on as well, especially in Yorkshire terriers.They can have protein-losing enteropathy but not havemajor liver disease, and, in many cases,those small intestinal diseases are detect-ed by observing panhypoproteinemia onblood chemistry panels.

DeNicola: How should practitionersperform total bile acid assays?

Williams: Practitioners need to conductboth fasting and post-feeding tests onevery patient at the same visit.The tim-ing for the post-feeding is two hours.

Hawthorne: Does the type of diet—low- or high-protein, low- or high-fat—affect the results?

Center: We compared different dietsduring development of the clinicalserum bile acid test. Our findingsserved as the basis for recommending amaintenance canned-food product in

an attempt to standardize the testingprocedure.The point is to feed a mealthat will consistently stimulate entericand gallbladder motility and producean adequate challenge of the entero-hepatic bile acid circulation.9 Table 2on page 12 provides guidelines for bileacid testing.

DeNicola: What values should practi-tioners consider as important increasesabove the reference ranges?

Center: We set a range of up to 25µmol/L for dogs and up to 20 µmol/L

for cats.9 These values are based on abroad spectrum of samples from ill ani-mals that were definitively shown not tohave liver disease.

DeNicola: So the fasting and the post-prandial samples should fall below that20 to 25 µmol/L range.

We’ve already said that bile acid assaysare sensitive indicators of hepatobiliarydisease, whether it’s hepatocellular dys-function, a vascular perfusion problem, orcholestatic disease. Is it possible to useserial bile acids to follow defined liverdisease progression or regression?

Twedt: I use serial bile acid assays indogs that have had shunt surgery todetermine if the procedure was success-ful.With hepatocellular disease, it iscommon for bile acids to fluctuate fromsample to sample with continued dis-ease, but they will return to normalwhen the disease resolves.

Center: Bile acid results can widely vac-illate with changes in intestinal motilityand gastric emptying. Numerous physio-logic variables influence this test.

Williams: We’ve done repeatabilitystudies on unconjugated bile acids,and they are all highly variable whenthey are abnormally high.The concen-trations are all abnormal, but the rangefrom day to day or even hour to houris huge. Post-feeding changes are alsoenormous.Total bile acids can alsovary markedly, and it is not uncom-mon for fasting serum bile acids to begreater than the postprandial levels,probably reflecting contraction of thegallbladder in the fasting state.

DeNicola: Is there a situation wheredoctors shouldn’t perform total bileacid assays?

Twedt: I wouldn’t measure them if Iknow an animal has overt liver disease.

DeNicola: In that case, you would dothe next logical diagnostic procedure,which is a biopsy.

Williams: The bottom line is that if prac-titioners obtain abnormal serum bileacid concentrations in patients that prob-ably don’t have liver disease (based onthe entire clinical picture), they shouldconsider malabsorption diseases, such assmall intestinal disease and pancreaticinsufficiency, which are often associatedwith changes in the intestinal microflora.It may or may not be appropriate topursue possible liver disease further eventhough serum bile acids are increased. Iwasn’t aware of that three years ago, butI’m absolutely convinced of it now.

Plasma ammonia concentrationDeNicola: What about ammonia testing?The liver obviously plays a critical role

“The liver has an overcapacityfor almost anything it synthesizes. I don’t thinkthere’s a single test thatwould show a change withless than 50% damage.”—Jörg M. Steiner, MED.VET, DR.MED.VET,

PhD, DACVIM, DECVIM-CA


12

in metabolizing ammonia originating fromprotein metabolism; ammonia is processedto urea, which is then excreted throughthe kidneys. Should we be measuring rest-ing (fasting) and postchallenge plasmaammonia levels to evaluate liver function?

Hawthorne: We do it as a screening testwhen we suspect hepatoencephalopathy.

Steiner: I use basal ammonia concentra-tions as an early monitoring tool in dogswith severe liver disease. If the ammoniaconcentration is elevated, I assume the doghas subclinical hepatic encephalopathyeven if the dog doesn’t show any neuro-logic signs. I’ll treat for hepatic encepha-lopathy, and if the dog responds with bet-ter behavior or a better appetite, then Ikeep treating for it.

Center: I look for urine biurates (ammo-nium biurate crystalluria) in dogs with sus-pected portosystemic vascular anomalies.Ammonium biurate crystals are easy torecognize and indicate the presence ofhyperammonemia. Detecting hyperam-monemia does have value as nothing elsewe can measure correlates with hepaticencephalopathy better than ammonia.However, not all patients with portosys-temic vascular anomalies are hyperam-monemic. Nevertheless, many of them willdemonstrate ammonium biurate crystal-luria when several urine samples from dif-ferent days are examined.

Twedt: We rarely perform ammonia test-ing; I don’t use it as a diagnostic or screen-ing test. But I measure baseline ammoniaconcentrations in cases where I suspecthepatic encephalopathy or observe signs ofdementia or depression.

DeNicola: Is ammonia testing worthwhilein icteric dogs that have cholestasis?

Center: If they’re symptomatic, I think youcan get the same information by evaluat-ing the urine carefully. In my opinion,veterinarians must be able to identifyammonium biurates because I think thatsome technicians reading urinalyses aren’tsufficiently trained to detect these crystals.

DeNicola: I think we can summarize thatplasma ammonia measurement is valuablefor characterizing patients with hepatic

encephalopathy. Identifying ammoniumbiurate crystalluria, which is commonlyseen with persistent hyperammonemia,may provide the same information.

BilirubinDeNicola: Total bilirubin concentration iswidely accepted as being a valuable test,but what about conjugated and unconju-gated bilirubin profiles?

Steiner: Research has shown that theyaren’t useful.10,11

Center: We evaluate both profiles becausewe have the reagents, and the results arereported on our profiles. But the van denBergh fractionation of total bilirubin intodirect (conjugated) and indirect (unconju-gated) moieties is not useful for achieving a definitive diagnosis.

Twedt: We don’t include them.

DeNicola: What’s your basic argumentwith them—the fact that it’s 50-50 un-conjugated and conjugated or that theydon’t help you determine if cholestasis is present?

Center: The conjugated bilirubin gets protein-bound.

“Digital radiography is tremendous because,unlike traditional radiographyusing film, you can make a technique error and still obtaina quality image, thanks to computer post-processing.”—Brian Poteet, MS, DVM, DACVR, DABSNM

Guidelines for BileAcid Testing

1. Don’t collect a blood sam-ple and force it through asmall needle into a Vacu-tainer.This will result inhemolysis and confuse resultinterpretation. Hemoglobinshares an absorption spec-trum with the test endpointdye, which obfuscates inter-pretation of the serum bileacid concentration.

2. Remove the needle fromthe collection syringe, andgently place the blood sam-ple into a heparinizedVacutainer tube.

3. Don’t submit samples inseparator tubes; leakage of alipemic sample will result inhemolysis that will contami-nate the separated serum. Itis better to centrifuge thesample, separate the serumor plasma, and specify ultra-centrifugation for removal of potentially interferinglipemia. Lipemia substantiallyinterferes with spectrophoto-metric endpoint detection.If these steps are taken, therewill be less of a probleminterpreting serum bile acidtest results.

Table 2


13

RadiographyDeNicola: When should diagnosticimaging be used in evaluating liver dis-ease or liver function in dogs and cats?

Dr. Brian Poteet: Anytime an animal hasclinical signs that can be attributed tothe liver or the biliary system and if theinitial blood work shows elevated liverenzyme activities. Practitioners shouldstart with radiographs of the abdomenbecause they provide information thatcan’t always be obtained using ultra-sonography. In our practice, we rarelyperform ultrasonography withoutobtaining plain films first.

DeNicola: So what should practitionersbe looking for primarily?

Poteet: They should first look for an en-larged or small liver, then for a liver withan irregular shape (Figures 1 and 2).Also,any decrease in abdominal serosal detailcan indicate a modified transudate orblood leaking from the liver.

DeNicola: What about patient positioning?

Poteet: A lot of veterinarians, especiallywith dogs that weigh more than 40 or50 lbs, will shoot one lateral and oneventrodorsal view and miss the cranialand caudal aspects of the abdomen.Theyneed to radiograph the entire abdomenon both views. If they’re looking at theliver and stomach, they need to see theentire liver.

Twedt: It’s also important to investigatefor other abdominal problems that could

cause abnormal liver enzyme activities. Icheck for evidence of prostatic or renaldisease and pyometra.

DeNicola: What about new technologyin basic radiology?

Poteet: Digital radiography is tremen-dous because, unlike traditional radiog-raphy using film, you can make a tech-nique error and still obtain a qualityimage, thanks to computer post-processing.You still need a cooperativeanimal that is positioned correctly, butdigital radiography reduces the numberof retakes and eliminates the need forprocessors and chemicals.The problemright now is cost. Digital radiography is

relatively expensive for many practition-ers. But that should change over time asmore doctors make the switch.

UltrasonographyDeNicola: What protocol should practi-tioners follow when they perform liverultrasonography?

Poteet: Perform a systematic and thor-ough abdominal evaluation every time,especially with deep-chested dogs.Whenevaluating the liver specifically, I usuallystart on the left side of the liver andadvance to the right side with the dog in dorsal recumbency. I make sure that Isee the entire liver and that I don’t gothrough it so fast that I miss subtle nod-ules. In deep-chested dogs, you may notsee everything underneath the dia-phragm, so you may need to place thetransducer in the intercostal spaces andclip a little more hair to evaluate thatpart of the liver.Also, I make sure I usethe abdominal settings on the machine,not the cardiac settings.

DeNicola: How long does a completeultrasonographic liver evaluation take?

Poteet: For general practitioners, Iwould say from five to eight minutes.

DeNicola: What information can practi-tioners gather from ultrasonographicliver evaluations?

Poteet: When I show practitioners howto perform liver ultrasonography, Ibegin by evaluating the intrahepaticvessels, the extrahepatic vessels, and the

“We measure bile acids afterobtaining a blood chemistrypanel showing elevated liverenzyme activities before performing imaging studies.”

—Robert Hawthorne, DVM

Figure 1. A radiograph showing a small liver. The overallliver volume is decreased, and the stomach axis is deviat-ed cranially.

Figure 2. A radiograph showing a mildly enlarged liver.The liver extends beyond the costal arch, and the stom-ach axis is deviated caudodorsally.The caudal ventralaspect of the liver tapers normally.


porta hepatis, looking for evidence of anyabnormal vascular structures and evaluat-ing the normal structures for laminarblood flow (Figure 3).Then I evaluate thegallbladder and bile ducts for dilatation.Finally, I look at the liver itself and try torule out common problems (Table 3).

DeNicola: Is ultrasonography helpful incases of steroid- or sex-hormone-inducedvacuolar hepatopathy?

Poteet: Most of the animals with vacuolarhepatopathy have diffusely hyperechoiclivers. Ultrasonography is a sensitive test,but it also lacks specificity.The only wayto confirm a diagnosis is through a fine-needle aspirate or a biopsy, but I thinkultrasonography can help.

Center: What landmarks do you usewhen you’re performing a vascular liver evaluation?

Poteet: First, I look at the caudal venacava where it passes underneath the liverdorsally.Then I look for the portal veinand the porta hepatis as it enters the liverand try to follow the branches into theliver periphery.

Inside the liver, I look for the hypere-choic walls that are usually associated withthe portal veins in the periphery of theliver; the hepatic veins don’t have those.Unless there’s a lot of free fluid in theabdomen, ultrasonography doesn’t differ-entiate liver lobes very well.

Center: What size comparisons do youmake to determine whether the vascula-ture within the liver at the porta hepatis is normal?

Poteet: There are no standards for hepat-ic vein diameter as it enters the liver. Ithink that determination is based onexperience.The portal vein and the cau-dal vena cava should be similar in size,but there’s a lot of variation.The caudalvena cava itself varies in size with theanimal’s respiration.

Center: I don’t think most practitionerscan do the vascular evaluations that youcan do. I have many referrals where practi-tioners have tried, but they end up withincorrect diagnoses for the vascular groupof diseases.

Poteet: That’s probably true.We don’tuse ultrasonography to find exactlywhere single-vessel, extrahepatic shuntsare because it takes me 30 to 45 minutesto do it. But in rare cases, you can findmultivessel, extrahepatic shunts in dogsfairly quickly.

Advanced diagnosticsDeNicola: When should practitioners refera case for advanced diagnostics, such ascomputed tomography (CT) or magneticresonance imaging (MRI)?

Poteet: CT should be performed on alllarge-breed dogs suspected of having an

14

Possible Findings with Liver

Ultrasonography

• fatty liver disease in cats

• nodular regeneration

• end-stage liver disease

• passive liver congestion

• liver abscesses

• benign cysts in the liver

• hepatocutaneous syndrome

• different types of neoplasms(hemangiosarcoma, adeno-carcinoma, lymphosarcoma,mast cell disease)

Table 3

Figure 3. Static ultrasound image showing turbulent blood flow in a dilated and tortuous intrahepatic shunt.

intrahepatic shunt. It’s wonderful be-cause you can use contrast to deter-mine specifically where the shunt islocated.When we suspect a portosys-temic shunt based on clinical signs andelevated pre- and postprandial bileacids, we perform scintigraphy (portalscans). Scintigraphy can also help dif-ferentiate a macroscopic shunt frommicrovascular dysplasia.

We rarely perform MRIs for liverdisease.At this point, I think that liverMRIs are unexplored in veterinarymedicine.Abdominal CTs are reallyquick compared with MRIs.

Monitoring patients with liver diseaseDeNicola: Dr. Poteet, do you use imag-ing to monitor liver disease in patients?

Poteet: Probably not as much as Ishould.We use imaging to monitor thenumbers of nodules in oncology pa-tients. Part of the decision comes downto pet owner finances. If imaging isn’tgoing to change the animal’s treatment,then it may not be worth it financially.

DeNicola: We’ve already discussed thefrequency of measuring liver enzymeactivities. In general, practitioners don’tneed to monitor liver enzymes dailyexcept in progressive cases.With stablediseases, several days to a week betweentesting will help predict the generalcourse of the disease. Is there anythingelse practitioners should do?

Center: I recommend a laparoscopicliver biopsy and another biopsy sixmonths to a year later to evaluate thedisease progression. Either way, a changein medication may be warranted.

Another important step that practi-tioners should remember is recordingbody condition scores. Record a quan-titative score because it reflects the pet’s health.

Twedt: Proper monitoring depends onthe disease you’re dealing with. If you’retalking about chronic biliary tract dis-eases in cats or chronic hepatitis in dogswith copper storage disease, you need torebiopsy to determine the patient’sresponse to therapy. I often reevaluatechronic hepatitis cases with liver biop-sies at six-month to one-year intervals.With acute disease, monitor the liverenzyme activities, make sure they returnto normal, and make sure the animalsare doing well clinically.

As far as monitoring response totherapy, you can’t use laboratory teststo determine if dogs receiving cortico-steroids for inflammatory liver diseaseare getting better or not. In these cases,a liver biopsy is often required.

DeNicola: I want to thank the partici-pants in this roundtable discussion.Theirexpertise in the area of liver and gas-trointestinal disease is invaluable, andhopefully the information that has sur-faced today will aid veterinarians intheir day-to-day evaluation of patientswith liver disease.

It’s clear that we must utilize our vari-ous diagnostic modalities, including clin-ical chemistry testing and diagnosticimaging, in conjunction with importantinformation such as the age, breed, sex,and physical condition of animals withsuspected liver disease.

Veterinarians must keep in mindthat serial evaluation of the completeblood count and urinalysis findingsadd to the overall interpretation ofliver disease diagnosis, progression, andregression.Also, serial evaluations oflaboratory data and diagnostic imagingevaluations in patients with confirmedliver disease can be extremely helpfulin characterizing the development ofdisease as well as the patient’s responseto therapy.

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Experimental portal fibrosis produced by intra-

portal injection of killed nonpathogenic

Escherichia coli in rabbits. Gastroenterologu

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2. Sugita S, Ohnishi K, Iida S, et al.

Histological changes in the liver and portal

hypertension subsequent to repeated intraportal

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3. Boomkens SY, Slump E, Egberink HF,

et al. PCR screening for candidate etiological

agents of canine hepatitis. Vet Microbiol

2005;108:49-55.

4. Dossin O, Rives A, Germain C, et al.

Pharmacokinetics of liver transaminases in

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5.Wiedmeyer CE, Solter PE, Hoffmann

WE: Kinetics of mRNA expression of alkaline

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glucocorticoid-treated dogs. Am J Vet Res

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6.Wiedmeyer CE, Solter PE, Hoffmann

WE.Alkaline phosphatase expression in tissues

from glucocorticoid-treated dogs. Am J Vet Res

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7. Sanecki RK, Hoffmann WE, Gelberg HB,

et al. Subcellular location of corticosteroid-

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hepatocytes. Vet Pathol 1987;24:296-301.

8. Center SA, Baldwin BH, Dillingham S, et

al. Diagnostic value of serum gamma-glutamyl

transferase and alkaline phosphatase activities in

hepatobiliary disease in the cat. J Am Vet Med

Assoc 1986;188:507-10.

9. Center SA, Leveille CR, Baldwin BH, et

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15

Cover art by Paul Chason.Radiographs courtesy of Brian Poteet, MS, DVM, DACVR, DABSNM; Gulf Coast Veterinary Diagnostic Imaging; Gulf Coast Veterinary Specialists, Houston, Texas

The views in this publication represent those of the participants and do not necessarily reflect those of IDEXX Laboratories.© 2005 IDEXX Laboratories. All rights reserved.


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